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Lucchesi S, Montesi G, Polvere J, Fiorino F, Pastore G, Sambo M, Lusini M, Montagnani F, Ciabattini A, Santoro F, Garosi G, Medaglini D. Transcriptomic analysis after SARS-CoV-2 mRNA vaccination reveals a specific gene signature in low-responder hemodialysis patients. Front Immunol 2025; 16:1508659. [PMID: 40370459 PMCID: PMC12075225 DOI: 10.3389/fimmu.2025.1508659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 03/28/2025] [Indexed: 05/16/2025] Open
Abstract
Introduction Individuals with comorbidities, such as chronic kidney disease and hemodialysis patients (HDP), are particularly susceptible to severe COVID-19 and to its complications. Furthermore, their immune response to vaccines is impaired, requiring tailored vaccination strategies. In this study, we investigated through transcriptomic profiling the immune response heterogeneity of HDP vaccinated with two doses of mRNA BNT162b2 vaccine. Methods Transcriptomic analyses were conducted in peripheral blood mononuclear cells (PBMC) collected from HDP and healthy controls (HC) before and 7 days after each dose. The HDP were stratified into high- and low-responders based on their humoral response after the second dose. Results Significant differences in gene expression related to B cell abundance and regulation, CD4 T cell proliferation, and inflammation pathways were observed at baseline and day 7 between HDP-low responders and HC, while the HDP high-responders displayed an intermediate expression profile for these genes. Discussion Results were consistent with the known immunologic alterations occurring in HDP cohorts related to lymphopenia, chronic inflammation, and dysregulated proliferation of CD4+. Our analyses identified an early transcriptional signature correlated with a diminished immune response in HDP low-responders, highlighting the importance of conducting a characterization of immunocompromised cohorts.
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Affiliation(s)
- Simone Lucchesi
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Giorgio Montesi
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Jacopo Polvere
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Fabio Fiorino
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Department of Medicine and Surgery, LUM University “Giuseppe Degennaro”, Bari, Italy
| | - Gabiria Pastore
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Margherita Sambo
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
| | - Marialetizia Lusini
- Nephrology, Dialysis, and Transplantation Unit, University Hospital of Siena, Siena, Italy
| | - Francesca Montagnani
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
| | - Annalisa Ciabattini
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Francesco Santoro
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Guido Garosi
- Nephrology, Dialysis, and Transplantation Unit, University Hospital of Siena, Siena, Italy
| | - Donata Medaglini
- Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
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Araji G, Keesari PR, Chowdhry V, Valsechi-Diaz J, Afif S, Diab W, El-Sayegh S. Vitamin B12 deficiency in dialysis patients: risk factors, diagnosis, complications, and treatment: A comprehensive review. World J Nephrol 2024; 13:100268. [PMID: 39723360 PMCID: PMC11572648 DOI: 10.5527/wjn.v13.i4.100268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 09/24/2024] [Accepted: 10/08/2024] [Indexed: 11/07/2024] Open
Abstract
Vitamin B12 deficiency is a significant concern among patients with end-stage renal disease undergoing dialysis. However, there hasn't been extensive research conducted on this particular patient group. The reported incidence rates vary widely, ranging from 20% to 90%, reflecting the complexity of its diagnosis. Dialysis patients often face multiple nutritional deficiencies, including a lack of essential vitamins, due to factors such as dietary restrictions, impaired absorption, and nutrient loss during dialysis. Diagnosing vitamin B12 deficiency in these patients is challenging, and addressing it is crucial to prevent complications and improve their overall quality of life. This review paper delves into the available body of evidence on vitamin B12 deficiency in dialysis patients, examining the contributing risk factors, diagnostic challenges, potential complications, and available treatment options. It provides a well-rounded perspective on the topic, making it a valuable resource for researchers, healthcare practitioners, and policymakers interested in addressing the nutritional needs of dialysis patients.
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Affiliation(s)
- Ghada Araji
- Department of Internal Medicine, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Praneeth R Keesari
- Department of Internal Medicine, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Varun Chowdhry
- Department of Internal Medicine, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Jonathan Valsechi-Diaz
- Department of Internal Medicine, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Sarah Afif
- Department of Internal Medicine, CUNY School of Medicine, New York, NY 10031, United States
| | - Wassim Diab
- Department of Internal Medicine, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Suzanne El-Sayegh
- Department of Nephrology, Northwell Health-Staten Island University Hospital, Staten Island, NY 10305, United States
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Men R, Zhu M, Li P, Liu S, Zhan Y, Wang J, Pang H, Lu R, Gu L, Zhang W. Associations between serum potassium variability and mortality in patients undergoing maintenance hemodialysis: a retrospective study. Sci Rep 2024; 14:29998. [PMID: 39622893 PMCID: PMC11611915 DOI: 10.1038/s41598-024-80709-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
Dyskalemia are associated with an increased risk of mortality in patients undergoing maintenance hemodialysis (MHD). However, studies evaluating the impact of serum potassium variability on mortality in MHD patients are scarce. To investigate serum potassium variability and its association with prognosis in MHD patients, we conducted a retrospective study on maintenance hemodialysis patients from three campus of Renji Hospital between June 2018 and December 2022. The exposure of interest was serum potassium variability defined as the coefficient of variation of serum potassium levels (CVSP). Cox regression models and Kaplan-Meier survival analysis were used to assess the prognostic significance of serum potassium variability. In a subgroup analysis, the association between serum potassium variability and prognosis was investigated in patients within normal serum potassium concentration range. Total of 588 maintenance hemodialysis patients were included. During a median follow-up of 45 months (24, 54), 121 patients (20.6%) died. The survival analysis suggested significantly higher survival rates for both all-cause (p < 0.01) and cardiovascular (p < 0.01) death in patients in the highest group of CVSP (H-CVSP) compared with those in the the lowest group (L-CVSP). After adjustment, the all-cause mortality hazard ratio compared to L-CVSP was 2.17 [95% confidence interval (CI) 1.18, 3.97] for H-CVSP (p < 0.05) and was 2.53 [95%CI 1.03, 6.22] for cardiovascular mortality (p < 0.05). In the subgroup analysis, 493 patients (83.8%) presented normokalemia (the mean of serum potassium levels ≥ 3.5mmol/L and ≤ 5.0mmol/L) were included. Similar association was found between serum potassium variability and accumulated survival rates, and higher serum potassium variablity was remained an independent risk factor for cardiovascular mortality (2.69, 95% CI 1.07-6.78, p < 0.05) in patients within normal serum potassium concentration range. In conclusion, a higher serum potassium variability was associated with all-cause and cardiovascular mortality in maintenance haemodialysis patients, even in the normal range.
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Affiliation(s)
- Ru Men
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Minxia Zhu
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Ping Li
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
- Department of Nursing, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Shang Liu
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Yaping Zhan
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Jieying Wang
- Clinical research center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Huihua Pang
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Renhua Lu
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Leyi Gu
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China
| | - Weiming Zhang
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.160, Pujian Road, Shanghai, China.
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Otsuka E, Kitamura M, Funakoshi S, Mukae H, Nishino T. Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study. Ren Fail 2024; 46:2410375. [PMID: 39378117 PMCID: PMC11463015 DOI: 10.1080/0886022x.2024.2410375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/21/2024] [Accepted: 09/24/2024] [Indexed: 10/10/2024] Open
Abstract
Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60-4.51) mU/L before roxadustat treatment to 1.36 (0.72-2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78-4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97-1.24) ng/dL before roxadustat treatment to 0.92 (0.71-1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93-1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78-2.31) pg/mL before starting roxadustat, 1.97 (1.69-2.27) pg/mL during treatment, and 1.90 (1.63-2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.
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Affiliation(s)
- Emiko Otsuka
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Nagasaki Renal Center, Nagasaki, Japan
| | - Mineaki Kitamura
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Nagasaki Renal Center, Nagasaki, Japan
| | | | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Katakami N, Mita T, Sato Y, Watada H, Shimomura I. Changes in serum levels of liver-related parameters, uric acid, and hemoglobin in patients with type 2 diabetes mellitus under treatment with tofogliflozin-a post-hoc analysis of the UTOPIA study. Diabetol Int 2024; 15:379-388. [PMID: 39101158 PMCID: PMC11291786 DOI: 10.1007/s13340-024-00693-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 01/08/2024] [Indexed: 08/06/2024]
Abstract
Aims/Introduction The aim of the study was to evaluate the effects of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, on circulating levels of hepatic enzymes, uric acid and hemoglobin levels in patients with type 2 diabetes mellitus (T2DM). Materials and methods We evaluated longitudinal changes in circulating aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, and hemoglobin levels in tofogliflozin (n = 169) and conventional treatment groups (n = 170) using data obtained from the UTOPIA trial, a randomized prospective study conducted to evaluate the efficacy of tofogliflozin in preventing atherosclerosis. Results Within 104 weeks, tofogliflozin treatment, but not conventional treatment, significantly reduced AST, ALT, and γ-GTP levels. This reduction was significantly greater in the tofogliflozin group than in the conventional group. Stratified analysis showed that, in patients with obesity (defined as body mass index (BMI) ≥ 25.0 kg/m2), significant differences were observed in AST, ALT, and γ-GTP changes from baseline to 104 weeks between treatment groups. However, in patients without obesity, there were no significant differences in AST and γ-GTP changes from baseline to 104 weeks between treatment groups. Multivariable regression analysis showed that changes in BMI and HbA1c levels were independently associated with changes in AST, ALT, and γ-GTP levels. The reduction of uric acid and the increase of hemoglobin from baseline to 104 weeks were significantly greater in the tofogliflozin group than in the conventional group. Conclusions The beneficial effects of tofogliflozin on circulating levels of hepatic enzymes, uric acid, and Hb lasted for 2 years in patients with T2DM. Clinical trial registration UMIN000017607 (https://www.umin.ac.jp/icdr/index.html). Supplementary Information The online version contains supplementary material available at 10.1007/s13340-024-00693-x.
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Affiliation(s)
- Naoto Katakami
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Tomoya Mita
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-Ku, Tokyo 113-8421 Japan
| | - Yasunori Sato
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 45 Shinanomachi, Shinjuku-Ku, Tokyo 160-8582 Japan
| | - Hirotaka Watada
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-Ku, Tokyo 113-8421 Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871 Japan
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Tsai CH, Shih DH, Tu JH, Wu TW, Tsai MG, Shih MH. Analyzing Monthly Blood Test Data to Forecast 30-Day Hospital Readmissions among Maintenance Hemodialysis Patients. J Clin Med 2024; 13:2283. [PMID: 38673554 PMCID: PMC11051209 DOI: 10.3390/jcm13082283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 03/27/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Background: The increase in the global population of hemodialysis patients is linked to aging demographics and the prevalence of conditions such as arterial hypertension and diabetes mellitus. While previous research in hemodialysis has mainly focused on mortality predictions, there is a gap in studies targeting short-term hospitalization predictions using detailed, monthly blood test data. Methods: This study employs advanced data preprocessing and machine learning techniques to predict hospitalizations within a 30-day period among hemodialysis patients. Initial steps include employing K-Nearest Neighbor (KNN) imputation to address missing data and using the Synthesized Minority Oversampling Technique (SMOTE) to ensure data balance. The study then applies a Support Vector Machine (SVM) algorithm for the predictive analysis, with an additional enhancement through ensemble learning techniques, in order to improve prediction accuracy. Results: The application of SVM in predicting hospitalizations within a 30-day period among hemodialysis patients resulted in an impressive accuracy rate of 93%. This accuracy rate further improved to 96% upon incorporating ensemble learning methods, demonstrating the efficacy of the chosen machine learning approach in this context. Conclusions: This study highlights the potential of utilizing machine learning to predict hospital readmissions within a 30-day period among hemodialysis patients based on monthly blood test data. It represents a significant leap towards precision medicine and personalized healthcare for this patient group, suggesting a paradigm shift in patient care through the proactive identification of hospitalization risks.
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Affiliation(s)
- Cheng-Han Tsai
- Department of Information Management and Institute of Healthcare Information Management, National Chung Cheng University, Chiayi City 62102, Taiwan or
- Department of Emergency Medicine, Chiayi Branch, Taichung Veteran’s General Hospital, Chiayi City 60090, Taiwan
| | - Dong-Her Shih
- Department of Information Management, National Yunlin University of Science and Technology, Douliu 64002, Taiwan;
| | - Jue-Hong Tu
- Department of Nephrology, St. Joseph’s Hospital, Yunlin 63241, Taiwan; (J.-H.T.); (M.-G.T.)
| | - Ting-Wei Wu
- Department of Information Management, National Yunlin University of Science and Technology, Douliu 64002, Taiwan;
| | - Ming-Guei Tsai
- Department of Nephrology, St. Joseph’s Hospital, Yunlin 63241, Taiwan; (J.-H.T.); (M.-G.T.)
| | - Ming-Hung Shih
- Department of Electrical and Computer Engineering, Iowa State University, 2520 Osborn Drive, Ames, IA 50011, USA;
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Kohlhas L, Studer M, Rutten-Jacobs L, Reigner SM, Sander A, Yap HK, Vondrak K, Coccia PA, Cano F, Schmitt CP, Warady BA, Schaefer F. Real-world evidence on the dosing and safety of C.E.R.A. in pediatric dialysis patients: findings from the International Pediatric Dialysis Network registries. Pediatr Nephrol 2024; 39:807-818. [PMID: 37566114 PMCID: PMC10817843 DOI: 10.1007/s00467-023-05977-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 04/05/2023] [Accepted: 04/05/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND This retrospective real-world study used data from two registries, International Pediatric Peritoneal Dialysis Network (IPPN) and International Pediatric Hemodialysis Network (IPHN), to characterize the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) in pediatric patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) or hemodialysis (HD). METHODS IPPN and IPHN collect prospective data (baseline and every 6 months) from pediatric PD and HD centers worldwide. Demographics, clinical characteristics, dialysis information, treatment, laboratory parameters, number and causes of hospitalization events, and deaths were extracted for patients on C.E.R.A. treatment (IPPN: 2007-2021; IPHN: 2013-2021). RESULTS We analyzed 177 patients on PD (median age 10.6 years) and 52 patients on HD (median age 14.1 years) who had ≥ 1 observation while being treated with C.E.R.A. The median (interquartile range [IQR]) observation time under C.E.R.A. exposure was 6 (0-12.5) and 12 (0-18) months, respectively. Hemoglobin concentrations were stable over time; respective means (standard deviation) at last observation were 10.9 (1.7) g/dL and 10.4 (1.7) g/dL. Respective median (IQR) monthly C.E.R.A. doses at last observation were 3.5 (2.3-5.1) µg/kg, or 95 (62-145) µg/m2 and 2.1 (1.2-3.4) µg/kg, or 63 (40-98) µg/m2. Non-elective hospitalizations occurred in 102 (58%) PD and 32 (62%) HD patients. Seven deaths occurred (19.8 deaths per 1000 observation years). CONCLUSIONS C.E.R.A. was associated with efficient maintenance of hemoglobin concentrations in pediatric patients with CKD on dialysis, and appeared to have a favorable safety profile. The current analysis revealed no safety signals.
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Affiliation(s)
- Laura Kohlhas
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | | | | | | | - Anja Sander
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | - Hui-Kim Yap
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
| | - Karel Vondrak
- Department of Pediatrics and Transplantation Center, University Hospital Motol, 2nd Medical Faculty Prague, Charles University Prague, Prague, Czech Republic
| | - Paula A Coccia
- Division of Pediatric Nephrology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Francisco Cano
- Division of Pediatric Nephrology, Hospital Dr. Luis Calvo Mackenna, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Claus Peter Schmitt
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany
| | - Bradley A Warady
- Division of Pediatric Nephrology, Children's Mercy Kansas City, Kansas City, MO, USA
| | - Franz Schaefer
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
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Seirafian S, Feizi A, Shahidi S, Badri SS, Rouhani MH, Najafabadi PP, Naeini EK. The effect of oral zinc on hemoglobin and dose of erythropoietin in hemodialysis patients. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 28:85. [PMID: 38510781 PMCID: PMC10953733 DOI: 10.4103/jrms.jrms_271_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/15/2023] [Accepted: 10/16/2023] [Indexed: 03/22/2024]
Abstract
Background In hemodialysis (HD) patients, low serum zinc level could cause hyporesponsivity to erythropoiesis-stimulating agents and lead to anemia. This study investigated the effects of oral zinc supplements on the required dose of erythropoietin in patients undergoing HD. Materials and Methods In a double-blinded randomized trial, 76 HD patients were assigned to 2 groups of 38. One group (intervention) was treated with oral zinc supplements of 210 mg, daily for 6 months, and the other group (control) used placebo capsules for 6 months. The serum zinc level, hemoglobin level, and required dose of erythropoietin, albumin, ferritin, ferrous, and total iron-binding capacity were evaluated 3 and 6 months after intervention. Results Repeated measures ANOVA did not show a significant increase in Hb level after 6 months of intervention (P = 0.28). However, the required dose of erythropoietin was decreased, but the changes were not statistically significant (P > 0.05). The changes in the other variables were not statistically significant. Conclusion Oral zinc supplementation in HD patients could not increase hemoglobin level irrespective of their serum zinc level.
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Affiliation(s)
- Shiva Seirafian
- Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Science, Isfahan, Iran
| | - Shahrzad Shahidi
- Department of Internal Medicine, Isfahan Kidney Diseases Research Center, Khorshid Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shirin Sadat Badri
- Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hossein Rouhani
- Food Security Research Center, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Elham Kabiri Naeini
- Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Miura T, Sato T, Yano T, Takaguri A, Miki T, Tohse N, Nishizawa K. Role of Erythropoiesis-Stimulating Agents in Cardiovascular Protection in CKD Patients: Reappraisal of Their Impact and Mechanisms. Cardiovasc Drugs Ther 2023; 37:1175-1192. [PMID: 35150385 DOI: 10.1007/s10557-022-07321-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/28/2022] [Indexed: 11/28/2022]
Abstract
Erythropoiesis-stimulating agents (ESAs) have markedly reduced the need for blood transfusion for renal anemia and are included in standard therapies for patients with chronic kidney disease (CKD). Various protective effects of ESAs on the cardiovascular system have been discovered through basic research, and the effects have received much attention because the rates of cardiovascular events and mortality are high in CKD patients. However, randomized clinical trials did not provide strong evidence that ESAs exert cardioprotection in humans, including CKD patients. It is difficult to assess the cardioprotective effects of ESAs in CKD patients through the clinical data that has been reported to date because the relationship between hemoglobin level rather than ESA dose and cardiovascular event rates was examined in most studies. Interestingly, recent studies using a rat model of CKD showed that the infarct size-limiting effect of an ESA was lost when its dose was increased to a level that normalized blood hemoglobin levels, suggesting that the optimal dose of an ESA for myocardial protection is less than the dose required to normalize hemoglobin levels. Furthermore, animal models of traditional coronary risk factors or comorbidities were resistant to the cardioprotective effects of ESAs because of interruptions in signal-mediated mechanisms downstream of erythropoietin receptors. In this review, we briefly discuss basic and clinical data on the impact of anemia on coronary and systemic circulation, the effects of CKD on the cardiovascular system, and the multiple pharmacological actions of ESAs to examine whether the ESAs that are prescribed for renal anemia exert any cardioprotection in patients with CKD.
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Affiliation(s)
- Tetsuji Miura
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 15-4-1, Maeda-7, Teine-ku, Sapporo, Japan.
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
| | - Tatsuya Sato
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toshiyuki Yano
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Akira Takaguri
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Japan
| | - Takayuki Miki
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cardiology and Diabetes, Oji General Hospital, Tomakomai, Japan
| | - Noritsugu Tohse
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keitaro Nishizawa
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Nephrology, Asahikawa Red Cross, Hospital, Asahikawa, Japan
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10
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Zoccali C, Mallamaci F, Adamczak M, de Oliveira RB, Massy ZA, Sarafidis P, Agarwal R, Mark PB, Kotanko P, Ferro CJ, Wanner C, Burnier M, Vanholder R, Wiecek A. Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association. Cardiovasc Res 2023; 119:2017-2032. [PMID: 37249051 PMCID: PMC10478756 DOI: 10.1093/cvr/cvad083] [Citation(s) in RCA: 81] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 12/29/2022] [Accepted: 01/09/2023] [Indexed: 05/31/2023] Open
Abstract
Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.
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Affiliation(s)
- Carmine Zoccali
- Renal Research Institute, 315 E, 62nd St., New York, NY 10065, USA
- Associazione Ipertensione Nefrologia e Trapianto Renale (IPNET) c/o Nefrologia e CNR, Grande Ospedale Metropolitano, Contrada Camporeale, 83031 Ariano Irpino Avellino, Italy
| | - Francesca Mallamaci
- Nephrology and Transplantation Unit, Grande Ospedale Metropolitano Reggio Cal and CNR-IFC, Via Giuseppe Melacrino 21, 89124 Reggio Calabria, Italy
| | - Marcin Adamczak
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Francuska 20-24 St. 40-027 Katowice, Poland
| | - Rodrigo Bueno de Oliveira
- Department of Internal Medicine (Nephrology), School of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil
| | - Ziad A Massy
- Ambroise Paré University Hospital, APHP, Boulogne Billancourt/Paris, and INSERM U-1018, Centre de recherche en épidémiologie et santé des populations (CESP), Equipe 5, Paris-Saclay University (PSU) and University of Paris Ouest-Versailles-Saint-Quentin-en-Yvelines (UVSQ), FCRIN INI-CRCT, Villejuif, France
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Rajiv Agarwal
- Indiana University School of Medicine and Richard L. Roudebush VA Medical Center, 1481 W 10th St, Indianapolis, IN 46202, USA
| | - Patrick B Mark
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Peter Kotanko
- Renal Research Institute, LLC Icahn School of Medicine at Mount Sinai, 315 East 62nd Street, 3rd Floor, New York, NY 10065, USA
| | - Charles J Ferro
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK
| | - Christoph Wanner
- Division of Nephrology, University Hospital of Würzburg, Würzburg, Germany
| | - Michel Burnier
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Raymond Vanholder
- Nephrology Section, Department of Internal Medicine and Pediatrics, University Hospital, Ghent, Belgium
| | - Andrzej Wiecek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Francuska 20-24 St. 40-027 Katowice, Poland
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11
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Asmar J, Chelala D, El Hajj Chehade R, Azar H, Finianos S, Aoun M. Anemia biomarkers and mortality in hemodialysis patients with or without diabetes: A 10-year follow-up study. PLoS One 2023; 18:e0280871. [PMID: 36719878 PMCID: PMC9888689 DOI: 10.1371/journal.pone.0280871] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 01/10/2023] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Many studies have assessed the association between anemia and mortality in hemodialysis but few compared patients with and without diabetes. Our study aims to investigate the impact of hemoglobin and iron parameters on mortality in hemodialysis patients with or without diabetes. METHODS This is a two-center retrospective study that included all adult patients who started hemodialysis between February 2012 and February 2020, followed until January 2021. Averages of hemoglobin, ferritin and transferrin saturation of entire follow-up were recorded. Kaplan Meier survival, log rank test and cox regression analyses were performed to assess the association between anemia biomarkers and mortality. RESULTS A total of 214 patients were included. Mean age was 67.98 ±12.41 years, mean hemoglobin was 10.92 ±0.75 g/dL, mean ferritin was 504.43 ± 221.42 ng/mL and mean transferrin saturation was 26.23 ±7.77%. Log rank test showed an association between hemoglobin ≥11 g/dL and better survival in patients without diabetes (P = 0.028). Based on cox regression analysis, hemoglobin was associated with all-cause mortality in all patients (HR = 0.66; CI:0.49,0.89; P = 0.007). When comparing patients with and without diabetes, this association remained significant only in patients without diabetes (HR = 0.53; CI:0.37,0.77; P<0.001). Based on different multivariate models, hemoglobin, ferritin and age were independent factors associated with mortality in patients without diabetes. CONCLUSIONS This study showed that hemoglobin ≥11 g/dL is associated with better survival in hemodialysis patients without diabetes but not in those with diabetes. These differences need to be further explored in other countries and settings. An individualization of the hemoglobin target level might be necessary to improve patients' outcomes.
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Affiliation(s)
- Jihane Asmar
- Department of Internal Medicine, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Dania Chelala
- Department of Nephrology, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
- Department of Nephrology, Hotel-Dieu de France Hospital, Beirut, Lebanon
| | - Razane El Hajj Chehade
- Department of Internal Medicine, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Hiba Azar
- Department of Nephrology, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
- Department of Nephrology, Hotel-Dieu de France Hospital, Beirut, Lebanon
| | - Serge Finianos
- Department of Nephrology, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
- Department of Nephrology, Hotel-Dieu de France Hospital, Beirut, Lebanon
| | - Mabel Aoun
- Department of Nephrology, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
- Department of Nephrology, Saint-George Hospital, Ajaltoun, Lebanon
- * E-mail:
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12
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Mazahir R, Anand K, Pruthi PK. Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India. Eur J Pediatr 2023; 182:101-109. [PMID: 36220980 DOI: 10.1007/s00431-022-04650-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/26/2022] [Accepted: 10/05/2022] [Indexed: 01/20/2023]
Abstract
To determine whether or not Darbepoetin alpha (DA) was non-inferior to recombinant human erythropoietin (rHuEPO) in the treatment of anemia in children with chronic kidney disease (CKD) stage 3-5 (on or not on dialysis). This was a randomized, open-label, two-arm, parallel group, active-controlled, non-inferiority trial conducted at a tertiary care center in New Delhi, India. Fifty patients of either gender (aged 1-18 years) with CKD stage 3-5 (on or not on dialysis) who had baseline hemoglobin (Hb) between 9 and 12 g/dL and were on stable erythropoietin therapy for at least 8 weeks were randomized (1:1) to either continue rHuEPO or switch to DA therapy for a period of 28 weeks. Doses were titrated in the initial 23 weeks to maintain the Hb between 11 and 12 g/dL, and efficacy was assessed between weeks 24 and 28. The primary efficacy outcome was the mean change in Hb between baseline and the evaluation period. In the intention-to-treat population (n = 50), the adjusted between-group difference in mean Hb change between the baseline and the evaluation period was 0.131 g/dL (95% CI: - 0.439 to 0.719, p = 0.629). The lower limit of the two-sided 95% CI for the difference in the mean change in Hb between the two treatment groups was well above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar pattern of non-inferiority was seen for per protocol population. The safety profile of DA and rHuEPO was also comparable (injection site pain:rHuEPO-3, DA-7; p-0.296). Conclusion: DA is non-inferior to rHuEPO for the treatment of anemia of CKD (stage 3-5) in pediatric population with a comparable safety profile. Trial registration: ClinicalTrials.gov Identifier: NCT04959578 (retrospectively registered), Date: July 13, 2021. What is Known: • Limited studies showing darbepoetin alpha is effective in children as an erythropoiesis stimulating agent. • No RCT from Indian subcontinent addressing this topic. What is New: • Darbepoetin alpha is non inferior to recombinant human erythropoietin for treatment of anemia in children with CKD stage 3-5 (on or not on dialysis) with safety comparable to recombinant human erythropoietin. • A cost reduction of approximately 8.6% per patient by shifting to darbepoetin alpha.
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Affiliation(s)
- Rufaida Mazahir
- Department of Pediatrics, Teerthanker Mahaveer Medical College and Research Centre, TMU, Uttar Pradesh, Moradabad, India. .,Division of Pediatric Nephrology, Department of Pediatrics, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India.
| | - Kanav Anand
- Division of Pediatric Nephrology, Department of Pediatrics, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
| | - P K Pruthi
- Division of Pediatric Nephrology, Department of Pediatrics, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
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13
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Factors Associated with Pressure Injury Among Critically Ill Patients in a Coronary Care Unit. Adv Skin Wound Care 2022; 35:1-10. [PMID: 36125458 DOI: 10.1097/01.asw.0000872172.83299.0d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To ascertain the incidence of pressure injuries (PIs) in patients in the coronary care unit (CCU), identify PI characteristics, and determine associated risk factors. METHODS Researchers conducted a retrospective investigational study of patients' medical records. A total of 820 patients who were admitted to the CCU between January 2018 and December 2020 met the study criteria. Of these, 200 patients who developed PIs after admission to the CCU were included in this study. This study examined the clinical features of PIs, as well as five PI risk factors: patient characteristics; length of stay; intrinsic factors; care factors, including medical devices; and vasopressor agents. RESULTS The incidence of PIs among patients in the CCU was 24.4%. At initial detection, 79.5% of these injuries were already at stage 2 or higher. The results indicated a significant correlation between PI stage and hemoglobin level. Moreover, the authors also found relationships between the use of medical devices (eg, arterial catheters, oxygen tubes, and Levin tubes) and PI onset. CONCLUSIONS Critically ill patients in the CCU use various medical devices for an extended period with severe consequences. The risk factors affecting PI are multifactorial. Therefore, the implementation of PI prevention and early detection strategies for patients in the CCU are crucial.
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14
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Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev 2022; 8:CD013751. [PMID: 36005278 PMCID: PMC9404697 DOI: 10.1002/14651858.cd013751.pub2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Anaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD. OBJECTIVES We aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA Randomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included. DATA COLLECTION AND ANALYSIS Five authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE. MAIN RESULTS We included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA. Compared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence). Compared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA. The effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain. None of the included studies reported life participation. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS HIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.
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Affiliation(s)
- Patrizia Natale
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Suetonia C Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Allison Jaure
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Elisabeth M Hodson
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Marinella Ruospo
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Tess E Cooper
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Deirdre Hahn
- Department of Nephrology, The Children's Hospital at Westmead, Westmead, Australia
| | - Valeria M Saglimbene
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Giovanni Fm Strippoli
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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15
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Liu S, Zhao Q, Huang F, Yang Q, Wang Y, Wang H, Sun Y, Yan Y, He G, Zhao G, Dong R, Chen B. Exposure to melamine and its derivatives in Chinese adults: The cumulative risk assessment and the effect on routine blood parameters. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 241:113714. [PMID: 35660378 DOI: 10.1016/j.ecoenv.2022.113714] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 05/22/2022] [Accepted: 05/25/2022] [Indexed: 06/15/2023]
Abstract
Melamine (MEL) and its derivatives, ammeline (AMN), ammelide (AMD), cyanuric acid (CYA) are widely existed in environmental media. Animal studies have reported the cumulative risk assessment (CRA) of simultaneous exposure to MEL and its derivatives and explored the associations between exposure and routine blood parameters. Such information is largely unknown in human studies. In this study, we detected the urinary concentrations of MEL and its derivatives in 239 Chinese adults to conduct the CRA by evaluating their hazard quotients (HQ) and hazard Index (HI), and also explored the possible associations between exposure and measured routine blood parameters in study population. The detectable frequencies of MEL, AMN, AMD and CYA were 96.65%, 41.00%, 97.91% and 97.07%, respectively. The median values of creatinine (Cr)-adjusted MEL, AMN, AMD, CYA and the total concentrations of MEL and its derivatives (∑MEL) were 11.41 μg/g Cr, not detected (ND), 2.64 μg/g Cr, 15.30 μg/g Cr, 35.02 μg/g Cr, respectively. There were 9 (3.77%) participants with estimated daily intakes (EDIs) of CYA exceeding the tolerable daily intake (TDI) of 2500 ng/kg bw/day, and 12 (5.02%) participants with HI of ∑MEL exposure exceeding 1 based on the strictest TDI value. Urinary concentrations of MEL and its derivatives were positively associated with specific routine blood parameters, including hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, white blood cell, neutrophil count (P < 0.05). Meanwhile, exposure to MEL and its derivatives increased the risk of red blood cell abnormality (P < 0.05). Our study is the first study to provide evidence-based data on the CRA of exposure to MEL and its derivatives in Chinese adults, and to propose a possible association between such exposure and routine blood parameters in human.
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Affiliation(s)
- ShaoJie Liu
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - Qi Zhao
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - FeiFei Huang
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - QiFan Yang
- Chemical Laboratory, Jing'an District Center for Disease Control and Prevention, Shanghai 200041, China
| | - YiFei Wang
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - HangWei Wang
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - YongYun Sun
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - YuJia Yan
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - GengSheng He
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - GenMing Zhao
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China
| | - RuiHua Dong
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
| | - Bo Chen
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
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16
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Aronson L, Phillips H, Oyama M. Characterization of preoperative cardiovascular status and association with outcome following feline renal allograft transplantation: 166 cases. J Am Vet Med Assoc 2022; 260:1518-1525. [DOI: 10.2460/javma.22.03.0120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
OBJECTIVES
To retrospectively evaluate preoperative historical, biochemical, and cardiovascular screening data for predictors of survival to discharge and long-term survival in feline renal allograft recipients from 1 institution.
ANIMALS
166 cats that underwent renal transplantation at the University of Pennsylvania between 1998 and 2018.
PROCEDURES
Medical records were reviewed for preoperative historical information, biochemical data, and cardiac assessment including auscultation findings, pre- and postoperative systolic blood pressure measurements, thoracic radiographic evaluation, and echocardiographic measurements. The need for hemodialysis, the number of surgical procedures, native kidney biopsy diagnosis and survival time was also recorded. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% CI. Univariable and multivariable analysis were performed to determine variables that were independently associated with survival to discharge and long-term survival.
RESULTS
The patient population primarily consisted of adult male DSH cats (70%) diagnosed with IRIS stage 4 CKD (66.3%). Abnormalities identified on preoperative cardiac assessment, including hypertension, the presence of a murmur, echocardiographic changes, and radiographic signs of congestive heart failure, were not associated with survival to discharge or long-term survival. Age was the only single significant variable associated with survival, and the risk of death increased by 11% (95% CI, 6% to 17%) for every 1 year in patient age.
CLINICAL RELEVANCE
The presence of cardiac abnormalities identified during the screening process of cats presenting for transplantation should not immediately exclude a potential candidate for the procedure. Owners considering transplantation should be educated on the impact of age on survival following surgery.
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Affiliation(s)
- Lillian Aronson
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
| | - Heidi Phillips
- Department of Veterinary Clinical Medicine, Veterinary Medical Teaching Hospital, College of Veterinary Medicine, University of Illinois, Urbana, IL
| | - Mark Oyama
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
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17
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Zuo S, Liu M, Liu Y, Xu S, Zhong X, Qiu J, Qin D, Tan R, Liu Y. Association Between the Blood Copper-Zinc (Cu/Zn) Ratio and Anemia in Patients Undergoing Maintenance Hemodialysis. Biol Trace Elem Res 2022; 200:2629-2638. [PMID: 34480666 DOI: 10.1007/s12011-021-02888-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/12/2021] [Indexed: 10/20/2022]
Abstract
Copper (Cu) and zinc (Zn) imbalances are common in dialysis patients. This study aimed to investigate the relationship between the blood Cu/Zn ratio and anemia in patients undergoing maintenance hemodialysis (MHD) treatment. This cross-sectional study included patients undergoing MHD at our center in September 2019. Clinical and demographic data and blood samples were collected before the hemodialysis sessions, and the blood levels of Zn and Cu were measured by inductively coupled plasma mass spectrometry. Multivariable linear and binary logistic regression analyses were performed to study the relationship between blood Cu/Zn ratio and anemia. A total of 144 MHD patients were enrolled in this study. The patients had a mean age of 64.33 ± 13.39 years, a median dialysis vintage of 33.50 (16.25-57.50) months, with 66 being females (45.8%). The median blood Cu/Zn ratio was 15.55 (interquartile range: 12.47-20.31). Anemia was present in 99 patients (68.8%). Groups with higher hemoglobin levels had decreased blood Cu/Zn ratios (p < 0.05). After adjustments for confounding factors, higher blood Cu/Zn ratios were independently associated with lower hemoglobin levels and anemia in MHD patients based on multivariate linear and multivariate binary logistic regression, respectively, in different models. Our study found that the blood Cu/Zn ratio is independently associated with anemia in MHD patients, but prospective multicenter studies with larger sample sizes are still needed to determine the appropriate cutoff values for blood zinc, blood copper, and blood Cu/Zn levels in this patient population.
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Affiliation(s)
- Sujun Zuo
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Mengmeng Liu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Yun Liu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou City, Guangdong province, China
| | - Shilin Xu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Xiaoshi Zhong
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Jingxian Qiu
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou City, Guangdong province, China
| | - Danping Qin
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.
| | - Rongshao Tan
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou City, Guangdong province, China
| | - Yan Liu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou City, Guangdong province, China
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Liu Y, Hu J, Tang R, Guo H, Chen Q, Qiu J, Liu Y, Tan R, Zhong X. Association between the blood manganese (Mn) and hemoglobin in patients undergoing maintenance hemodialysis. J Trace Elem Med Biol 2022; 71:126947. [PMID: 35176578 DOI: 10.1016/j.jtemb.2022.126947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/04/2022] [Accepted: 02/08/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND AIMS Manganese (Mn) and iron metabolism are closely related. Iron metabolism disorders often lead to anemia in patients undergoing maintenance hemodialysis (MHD). Here, we aimed to investigate the relationship between blood Mn and hemoglobin (Hb) in patients undergoing MHD. METHODS Patients undergoing MHD in September 2019 were included in a cross-sectional study. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and blood levels of Mn were measured by inductively coupled plasma mass spectrometry. Both multivariable linear and binary logistic regression analyses were performed to study the relationship between the blood Mn and Hb. RESULTS A total of 144 patients undergoing MHD were enrolled in the study. The patients had a mean age of 64.33 ± 13.39 years, median vintage of 33.50 (16.25-57.50) months. Among them, 66 were females (45.8%). The median blood Mn level was 13.55 µg/L (IQR:9.92-17.48). Ninety-nine patients were anemic (68.8%). The mean Hb level was 99.83 ± 19.68 g/L. The patient group with high blood Mn had a high proportion of females, and these patients had high levels of RBC, hemoglobin, Hct, UIBC, serum TCHOL, and serum LDL, yet short dialysis vintage, low prevalence of anemia, low levels of serum ferritin, serum iron, and TSAT. Following adjustment for confounding factors, we found that low blood Mn level was independently associated with lower Hb level and anemia in patients undergoing MHD by multivariate linear and multivariate binary logistic regression, respectively, in different models. CONCLUSION Whilst our study showed that high levels of blood Mn were independently associated with high hemoglobin in patients undergoing MHD, further multicenter studies with large sample sizes are still required.
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Affiliation(s)
- Yun Liu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China
| | - Jianguang Hu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China
| | - Ruiying Tang
- Department of Nephrology, Jiangmen Central Hospital, Jiangmen City, Guangdong Province 510220, China
| | - Haonan Guo
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China
| | - Qiongmei Chen
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China
| | - Jingxian Qiu
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou, Guangdong Province 510220, China
| | - Yan Liu
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China; Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou, Guangdong Province 510220, China
| | - Rongshao Tan
- Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou, Guangdong Province 510220, China
| | - Xiaoshi Zhong
- Department of Nephrology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong Province 510220, China.
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Akizawa T, Tanaka-Amino K, Otsuka T, Yamaguchi Y. Clinical parameters among patients in Japan with anemia and non-dialysis-dependent chronic kidney disease with and without diabetes mellitus who received roxadustat. Clin Exp Nephrol 2022; 26:843-850. [PMID: 35462610 PMCID: PMC9385792 DOI: 10.1007/s10157-022-02225-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/05/2022] [Indexed: 12/14/2022]
Abstract
Background Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia of chronic kidney disease (CKD). This post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in patients with non-dialysis-dependent (NDD) CKD evaluated disease state–related parameters among patients with and without diabetes mellitus who received roxadustat. In the 1517-CL-0310 study (NCT02988973), roxadustat was noninferior to darbepoetin alfa for change in average hemoglobin levels at Weeks 18–24 from baseline who received roxadustat. Methods Patients enrolled in the 1517-CL-0310 study who received roxadustat were included in this post hoc analysis. Hematologic (hemoglobin, reticulocyte/erythrocyte ratio, mean corpuscular volume [MCV], and mean corpuscular hemoglobin [MCH]), iron-related (ferritin, total iron-binding capacity, transferrin, ceruloplasmin, and hepcidin), metabolic (HbA1c, glycated albumin, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), and renal (eGFR) parameters were summarized descriptively by visit through Week 52. Results Among 201 included patients, 105 (52.2%) and 96 (47.8%) were in the Diabetes and No Diabetes subgroups, respectively. There were no clinically meaningful differences through Week 52 for most hematologic, iron-related, metabolic, or renal parameters between patients in the Diabetes and No Diabetes subgroups. MCV and MCH remained lower and HbA1c and glycated albumin remained higher in patients in the Diabetes subgroup through Week 52. Both subgroups experienced a similar benefit from roxadustat in maintaining hemoglobin levels in the target range of 10–12 g/dL. Conclusion Roxadustat maintained hemoglobin levels in the target range with similar clinical parameters irrespective of diabetes mellitus presence at baseline. Supplementary Information The online version contains supplementary material available at 10.1007/s10157-022-02225-w.
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Affiliation(s)
- Tadao Akizawa
- Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
| | - Keiko Tanaka-Amino
- Medical Specialty, Japan Medical Affairs, Astellas Pharma, Inc., 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411, Japan.
| | - Tetsuro Otsuka
- Japan-Asia Clinical Development, Astellas Pharma, Inc., Tokyo, Japan
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Elsayed M, Mahmoud SM, Mohamed LH, Omar W, Abdelaziz K. Prediction of Outcome in Anemic Critically ill Patients in Intensive Care Unit: A Retrospective Observational Study. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.7659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective: Anemia is a universal finding in critically-ill patients which add to the risk of poor outcomes. We aimed to evaluate the prevalence of anemic critically-ill patients and to detect predictors of outcome.
Methods: A retrospective study from 5-year data in the electronic medical record of the critical care department at Cairo University. All medical ICU patients that were admitted with or developed anemia during their ICU stay were included. All data of admission, ICU stay, and APACHE II were recorded and their association with the final outcome was determined.
Results: The study included 301 patients. Anemia was detected in 84.6% of patients. Blood transfusion was given to 61.8% of patients while not given to 38.2% and was not significantly associated with outcome. Non-survivors were 37.5%. Only DM, IHD and CKD were associated with poor outcome (P values 0.045, 0.026, 0.001 respectively). Need for MV or vasopressors was associated with poor outcome (P values 0.0001 for both). WBC, platelets at admission, and Hb at day 14 (P values 0.014, 0.002, 0.0001) respectively. The Multi-variate analysis detected these variables (need for MV, vasopressors, and Hb at the 14 th day ≤7.3 g/dl) could correctly detect outcome with sensitivity 91.6%, specificity 73.6%, PPV 76.7%, and NPV 90.3% and total accuracy 82.4%.
Conclusions: Anemia in critically-ill patients is common and associated with poor outcomes. Blood transfusion was not associated with a better outcome. Combination of MV need and vasopressors with persistent anemia at day 14 were the best predictors of poor outcomes.
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Ghosh S, Das P, Banerjee U. Study of hematological changes in patients with chronic renal failure undergoing hemodialysis (pre and post). MULLER JOURNAL OF MEDICAL SCIENCES AND RESEARCH 2022. [DOI: 10.4103/mjmsr.mjmsr_34_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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Sá Martins V, Adragão T, Aguiar L, Pinto I, Dias C, Figueiredo R, Lourenço P, Pascoal T, Pereira J, Pinheiro T, Ramião I, Velez B, Papoila AL, Borges N, Calhau C, Macário F. Prognostic Value of the Malnutrition-inflammation Score in Hospitalization and Mortality on Long-term Hemodialysis. J Ren Nutr 2021; 32:569-577. [PMID: 34922814 DOI: 10.1053/j.jrn.2021.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 10/11/2021] [Accepted: 11/07/2021] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVE Since its development, cumulative evidence has accumulated regarding the prognostic value of the Malnutrition-Inflammation Score (MIS/Kalantar score) prognostic value; however, there is a shortage of recent and large studies with comprehensive statistical methodologies that contribute to support a higher level of evidence and a consensual cutoff. The aim of this study was to assess the strength of MIS association with hospitalization and mortality in a nationwide cohort. METHODS This was a historical cohort study of hemodialysis patients from 25 outpatient centers followed up for 48 months. Univariable and multivariable Cox additive regression models were used to analyze the data. The C-index was estimated to assess the performance of the final model. RESULTS Two thousand four hundred forty-four patients were analyzed, 59.0% males, 32.0% diabetic, and median age of 71 years (P25 = 60, P75 = 79). During a median period of 45-month follow-up, with a maximum of 48 months (P25 = 31; P75 = 48), 875 patients presented an MIS <5 (35.8%) and 860 patients (35.2%) died. The proportion of deaths was 23.1% for patients with the MIS <5 and 41.9% if the MIS ≥5 (P < .001). A total of 1,528 patients (62.5%) were hospitalized with a median time to the first hospitalization of 26 months (P25 = 9; P75 = 45). A new cutoff point regarding the risk of death, MIS ≥6, was identified for this study data set. In multivariable analysis for hospitalization risk, a higher MIS, higher comorbidity index, and arteriovenous graft or catheter increased the risk, whereas higher Kt/V and higher albumin had a protective effect. In multivariable analysis for mortality risk, adjusting for age, albumin, normalized protein catabolic rate, Charlson comorbidity index, interdialytic weight gain, Kt/V, diabetes, hematocrit, and vascular access, patients with the MIS ≥6 showed a hazard ratio of 1.469 (95% confidence interval: 1.262-1.711; P < .001). Higher age, higher interdialytic weight gain, higher comorbidity index, and catheter increased significantly the risk, whereas higher Kt/V, higher albumin, and higher normalized protein catabolic rate (≥1.05 g/kg/d) reduced the risk. CONCLUSION The MIS maintains its relevant and significant association with hospitalization and mortality.
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Affiliation(s)
- Vítor Sá Martins
- Medical Department DIAVERUM Portugal, Sintra, Portugal; Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, Porto, Portugal; CINTESIS, Center for Health Technology Services Research, Rua Doutor Plácido da Costa, Porto, Portugal.
| | - Teresa Adragão
- Medical Department DIAVERUM Portugal, Sintra, Portugal; Nephrology Department, Santa Cruz Hospital, Carnaxide, Portugal
| | - Leila Aguiar
- Medical Department DIAVERUM Portugal, Sintra, Portugal
| | - Iola Pinto
- CMA, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Lisboa, Portugal; ISEL, Instituto Superior de Engenharia de Lisboa, Lisboa, Portugal
| | - Catarina Dias
- Medical Department DIAVERUM Portugal, Sintra, Portugal
| | | | | | - Tânia Pascoal
- Medical Department DIAVERUM Portugal, Sintra, Portugal
| | | | | | - Inês Ramião
- Medical Department DIAVERUM Portugal, Sintra, Portugal
| | - Brígida Velez
- Medical Department DIAVERUM Portugal, Sintra, Portugal
| | - Ana Luisa Papoila
- CEAUL, Centro de Estatística e Aplicações da Universidade de Lisboa, Lisboa, Portugal; NOVA Medical School
- Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal
| | - Nuno Borges
- Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, Porto, Portugal; CINTESIS, Center for Health Technology Services Research, Rua Doutor Plácido da Costa, Porto, Portugal
| | - Conceição Calhau
- CINTESIS, Center for Health Technology Services Research, Rua Doutor Plácido da Costa, Porto, Portugal; NOVA Medical School
- Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal; Unidade Universitária Lifestyle Medicine José de Mello Saúde by NOVA Medical School, Lisboa, Portugal
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Esmaeili M. Blood Performance: A New Formula for Fish Growth and Health. BIOLOGY 2021; 10:biology10121236. [PMID: 34943151 PMCID: PMC8698978 DOI: 10.3390/biology10121236] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 12/28/2022]
Abstract
Simple Summary The use of haematological and blood biochemistry parameters has proven to be effective and repeatable ways to monitor fish health. Testing these parameters is becoming more common in aquaculture studies. Further, it is widely accepted that fish with better health status are more likely to grow faster as less energy should be consumed for non-growth purposes. Here, a new formula (Blood Performance) is introduced, which contains five common haematological and blood biochemistry parameters: red blood cells, white blood cells, haemoglobin, haematocrit, and total protein. The idea behind this formula is that any single component of this formula cannot be reliable enough as a biomarker of fish health and growth. However, interestingly, Blood Performance can be much more reliable and accurate for monitoring fish health and growth. Abstract Monitoring fish health in a repeatable and accurate manner can contribute to the profitability and sustainability of aquaculture. Haematological and blood biochemistry parameters have been powerful tools and becoming increasingly common in aquaculture studies. Fish growth is closely related to its health status. A fish with a higher growth rate is more likely to be a healthy one. Any change in the physiological status of the fish, from pollution to nutritional stress, can cause changes in the blood parameters. Various aquaculture studies have measured the following components: red blood cells, white blood cells, haemoglobin, haematocrit, and total protein. However, because these parameters do not always follow the same trend across experimental fish, it is difficult to draw a firm conclusion about which parameter should be considered. Therefore, Blood Performance (BP) as a new formula is introduced, which is a more reliable indicator. This formula is simple and sums up the natural logarithm of the five above-mentioned parameters. More than 90 published peer-reviewed articles that measured these five parameters in the last six years confirmed the reliability and validity of this formula. Regardless of which supplements were added to the diets, the fish with a higher growth rate had higher BP as well. In addition, in 44 studies out of 53 articles, there was a significant positive correlation between specific growth rate and BP. Under different stressful situations, from pollution to thermal stress, the fish under stress had a lower BP than the control. Fish meal and fish oil replacement studies were further evidence for this formula and showed that adding excessive alternative proteins decreased growth along with BP. In conclusion, BP can be a reliable indicator of fish health and growth when it is compared between groups in the same experiment or farm. Although there was a positive correlation between specific growth rate and BP, comparing BP between experiments is not recommended. Standardising the haematological assays can improve the reliability and accuracy of BP across experiments.
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Affiliation(s)
- Moha Esmaeili
- Institute for Marine and Antarctic Studies, University of Tasmania, Hobart Private Bag 49, 15-21 Nubeena Cres, Taroona, TAS 7053, Australia
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Elmi C, Fan MM, Le M, Cheng G, Khalighi K. Association of serum 25-Hydroxy Vitamin D level with lipid, lipoprotein, and apolipoprotein level. J Community Hosp Intern Med Perspect 2021; 11:812-816. [PMID: 34804396 PMCID: PMC8604514 DOI: 10.1080/20009666.2021.1968571] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 08/11/2021] [Indexed: 11/18/2022] Open
Abstract
Introduction 25-Hydroxy vitamin D (Vit D3) deficiency was found to be associated with vascular dysfunction, arterial stiffening, extent of coronary artery disease and cardiovascular mortality. Previous studies showed positive correlation between serum Vit D3 and HDL-C and negative correlation between Vit D3 and LDL-C. The aim of this study is to investigate more details about the possible association of serum Vit D3 level with lipid, lipoprotein and apolipoprotein level. Methods Totally 101 patients were included in this study and Vit D3, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C), total triglyceride (TG), non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein particle (LDL-P), small dense low-density lipoprotein particle (sLDL-P), small dense low-density lipoprotein cholesterol (sdLDL-C), High-density lipoprotein cholesterol particles (HDL-P), High-density lipoprotein 2-cholesterol (HDL2-C), Apolipoprotein B(ApoB), Apolipoprotein A1 (Apo A1) and Apolipoprotein B/Apolipoprotein A1 ratio (ApoB/A ratio) were tested. Results Our results show that patients with Vit D3 deficiency (Vit D3 < 30 ng/ml) have significantly higher level of LDL-C, TG, Non-HDL-C, LDL-P, sLDL-P, sdLDL-C, ApoB and ApoB/A ratio compare with patients have normal Vit D3 level (Vit D3 > 30 ng/ml). Patients with normal Vit D3 level have significantly higher level of HDL-C and HDL2-C. Correlation study shows that Vit D3 level is negative correlated with TC, LDL-C, TG, Non-HDL-C, LDL-P, sLDL-P, sdLDL-C, ApoB and ApoB/A ratio and positive correlated with HDL2-C level. Conclusion Our results show that Vit D3 deficiency links to an increased risk for dyslipidemia and that may be the reason that patients with vitamin D deficiency tend to have higher risk of coronary artery disease.
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Affiliation(s)
- Cyrus Elmi
- Easton Cardiovascular Associates, Easton, PA, USA
- Moravian Academy, Bethlehem, PA, USA
| | - Melton Mingtian Fan
- Easton Cardiovascular Associates, Easton, PA, USA
- Thurgood Marshall College, University of California San Diego, San Diego, CA, USA
| | - Marjolein Le
- Department of Medicine, St Luke’s University Hospital, Easton Campus, Easton, PA, USA
| | - Gang Cheng
- Department of Cardiovascular Medicine, University of Louisville, Louisville, KY, USA
| | - Koroush Khalighi
- Easton Cardiovascular Associates, Easton, PA, USA
- Lehigh Valley Heart Institute, Easton, PA, USA
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Lee SH, Kim M, Han KD, Lee JH. Low hemoglobin levels and an increased risk of psoriasis in patients with chronic kidney disease. Sci Rep 2021; 11:14741. [PMID: 34285267 PMCID: PMC8292392 DOI: 10.1038/s41598-021-94165-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 07/07/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic diseases, such as chronic kidney disease (CKD), are frequently accompanied by various comorbidities, including anemia, which is considered a surrogate marker of systemic inflammation. Psoriasis is a chronic inflammatory skin disease prevalent in patients with chronic disease. Psoriasis risk in patients with CKD, however, especially in patients with low hemoglobin levels, has never been investigated. In this study, we investigated associations between low hemoglobin levels and psoriasis in patients with CKD using data from the National Health Insurance Service of Korea. During a mean follow-up period of 6.16 ± 1.02 years, psoriasis was recorded in 13,803 patients with CKD (2.39% of CKD patients). The cumulative incidence of psoriasis was significantly higher in CKD patients with anemia (hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) than those without. In multivariate-adjusted Cox proportional hazards regression models, the risk of psoriasis was significantly higher in anemic CKD patients than nonanemic CKD patients (hazard ratio [HR] 1.136, 95% CI 1.089–1.185, p < 0.001). Additionally, we noted that the incidence of psoriasis decreased with increasing hemoglobin levels in CKD patients (HR 0.953, 95% CI 0.942–0.965, p < 0.001). Altogether, our findings indicate that low hemoglobin levels are significantly related to psoriasis risk in patients with CKD. Further study is required to elucidate whether low hemoglobin levels have an impact on the development of psoriasis or are merely a surrogate marker of psoriasis risk in patients with CKD.
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Affiliation(s)
- Si-Hyung Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
| | - Miri Kim
- Department of Dermatology, College of Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Kyung-Do Han
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Hyun Lee
- Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Korea.
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Weir MR. Managing Anemia across the Stages of Kidney Disease in Those Hyporesponsive to Erythropoiesis-Stimulating Agents. Am J Nephrol 2021; 52:450-466. [PMID: 34280923 DOI: 10.1159/000516901] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/26/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Patients with CKD frequently have anemia that results from iron-restricted erythropoiesis and inflammation. Anemia of CKD is currently managed with iron supplements and erythropoiesis-stimulating agents (ESAs) to promote erythropoiesis and with RBC transfusion in severe cases. Hyporesponse to ESAs, or the need for larger than usual doses to attain a given hemoglobin (Hb) level, is associated with increased morbidity and mortality and presents a pressing clinical challenge, particularly for patients on dialysis. This paper reviews ESA hyporesponse and potential new therapeutic options in the management of anemia of CKD. SUMMARY The most common causes of ESA hyporesponse include iron deficiency and inflammation, and to a lesser degree, secondary hyperparathyroidism, inadequate dialysis, malnutrition, and concomitant medications. Management of ESA hyporesponse is multipronged and involves treating low level infections, ensuring adequate nutrition, and optimizing iron status and dialysis modality, although some patients can remain refractory. Inflammation directly increases production and secretion of hepcidin, contributes to an impaired response to hypoxia, and suppresses proliferation of erythroid progenitors. Coordination of renal and hepatic erythropoietin (EPO) production and iron metabolism is under the control of hypoxia-inducible factors (HIF), which are in turn regulated by HIF-prolyl hydroxylases (HIF-PHs). HIF-PHs and hepcidin are therefore attractive potential drug targets particularly in patients with ESA hyporesponse. Several oral HIF-PH inhibitors have been evaluated in patients with anemia of CKD and have been shown to increase Hb and reduce hepcidin regardless of inflammation, iron status, or dialysis modality. These sustained effects are achieved through more modest increases in endogenous EPO compared with ESAs. Key Messages: Treatments that address ESA hyporesponse remain a significant unmet clinical need in patients with anemia of CKD. New therapies such as HIF-PH inhibitors have the potential to address fundamental aspects of ESA hyporesponse and provide a new therapeutic option in these patients.
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Affiliation(s)
- Matthew R Weir
- Division of Nephrology, University of Maryland Medical Center, Baltimore, Maryland, USA
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Suresh S, Wright EC, Wright DG, Abbott KC, Noguchi CT. Erythropoietin treatment and the risk of hip fractures in hemodialysis patients. J Bone Miner Res 2021; 36:1211-1219. [PMID: 33949002 PMCID: PMC8360057 DOI: 10.1002/jbmr.4297] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 03/08/2021] [Accepted: 03/25/2021] [Indexed: 12/19/2022]
Abstract
Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO-stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production. EPO has been used clinically for three decades to treat anemia in end-stage renal disease, and notably, although the incidence of hip fractures decreased in the United States generally after 1990, it rose among hemodialysis patients coincident with the introduction and subsequent dose escalation of EPO treatment. Given this clinical paradox and findings from studies in mice that elevated EPO affects bone health, we examined EPO treatment as a risk factor for fractures in hemodialysis patients. Relationships between EPO treatment and hip fractures were analyzed using United States Renal Data System (USRDS) datasets from 1997 to 2013 and Consolidated Renal Operations in a Web-enabled Network (CROWNWeb) datasets for 2013. Fracture risks for patients treated with <50 units of EPO/kg/week were compared to those receiving higher doses by multivariable Cox regression. Hip fracture rates for 747,832 patients in USRDS datasets (1997-2013) increased from 12.0 per 1000 patient years in 1997 to 18.9 in 2004, then decreased to 13.1 by 2013. Concomitantly, average EPO doses increased from 11,900 units/week in 1997 to 18,300 in 2004, then decreased to 8,800 by 2013. During this time, adjusted hazard ratios for hip fractures with EPO doses of 50-149, 150-299, and ≥ 300 units/kg/week compared to <50 units/kg/week were 1.08 (95% confidence interval [CI], 1.01-1.15), 1.22 (95% CI, 1.14-1.31), and 1.41 (95% CI, 1.31-1.52), respectively. Multivariable analyses of 128,941 patients in CROWNWeb datasets (2013) replicated these findings. This study implicates EPO treatment as an independent risk factor for hip fractures in hemodialysis patients and supports the conclusion that EPO treatment may have contributed to changing trends in fracture incidence for these patients during recent decades. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Sukanya Suresh
- Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Elizabeth C Wright
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Daniel G Wright
- Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Kevin C Abbott
- Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Constance T Noguchi
- Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Gilbertson DT, Yan H, Xu H, Sinsakul M, Peng Y, Wetmore JB, Liu J, Li S. Development and Validation of a Transfusion Risk Score for Patients Receiving Maintenance Hemodialysis. KIDNEY360 2021; 2:948-954. [PMID: 35373092 PMCID: PMC8791373 DOI: 10.34067/kid.0004512020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 04/02/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND In patients on dialysis with anemia, avoiding red blood cell transfusions is preferable. We sought to develop and validate a novel transfusion prediction risk score for patients receiving maintenance hemodialysis. METHODS This retrospective cohort study used United States Renal Data System data to create a model development cohort (patients who were point prevalent and on hemodialysis on November 1, 2012) and a validation cohort (patients who were point prevalent and on hemodialysis on August 1, 2013). We characterized comorbidity, inflammatory conditions, hospitalizations, anemia and anemia management, iron parameters, intravenous iron use, and vitamin D use during a 6-month baseline period to predict subsequent 3-month transfusion risk. We used logistic least absolute shrinkage and selection operator regression. In an exploratory analysis, model results were used to calculate a score to predict 6- and 12-month hospitalization and mortality. RESULTS Variables most predictive of transfusion were prior transfusion, hemoglobin, ferritin, and number of hospital days in the baseline period. The resulting c-statistic in the validation cohort was 0.74, indicating relatively good predictive power. The score was associated with a significantly increased risk of subsequent mortality (hazard ratios 1.0, 1.22, 1.26, 1.54, 1.71, grouped from lowest to highest score), but not with hospitalization. CONCLUSIONS We developed a transfusion prediction risk score with good performance characteristics that was associated with mortality. This score could be further developed into a clinically useful application, allowing clinicians to identify patients on hemodialysis most likely to benefit from a timely, proactive anemia treatment approach, with the goal of avoiding red blood cell transfusions and attendant risks of adverse clinical outcomes.
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Affiliation(s)
- David T. Gilbertson
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
| | - Heng Yan
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
| | | | | | - Yi Peng
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
| | - James B. Wetmore
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
| | - Jiannong Liu
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
| | - Suying Li
- Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
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Noonan ML, Ni P, Agoro R, Sacks SA, Swallow EA, Wheeler JA, Clinkenbeard EL, Capitano ML, Prideaux M, Atkins GJ, Thompson WR, Allen MR, Broxmeyer HE, White KE. The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model. J Bone Miner Res 2021; 36:1117-1130. [PMID: 33592127 PMCID: PMC8255270 DOI: 10.1002/jbmr.4272] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 02/01/2021] [Accepted: 02/10/2021] [Indexed: 12/15/2022]
Abstract
Fibroblast growth factor-23 (FGF23) is a critical factor in chronic kidney disease (CKD), with elevated levels causing alterations in mineral metabolism and increased odds for mortality. Patients with CKD develop anemia as the kidneys progressively lose the ability to produce erythropoietin (EPO). Anemia is a potent driver of FGF23 secretion; therefore, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) currently in clinical trials to elevate endogenous EPO to resolve anemia was tested for effects on iron utilization and FGF23-related parameters in a CKD mouse model. Mice were fed either a casein control diet or an adenine-containing diet to induce CKD. The CKD mice had markedly elevated iFGF23 and blood urea nitrogen (BUN), hyperphosphatemia, and anemia. Cohorts of mice were then treated with a patient-equivalent dose of BAY 85-3934 (BAY; Molidustat), which elevated EPO and completely resolved aberrant complete blood counts (CBCs) in the CKD mice. iFGF23 was elevated in vehicle-treated CKD mice (120-fold), whereas circulating iFGF23 was significantly attenuated (>60%) in the BAY-treated CKD mice. The BAY-treated mice with CKD also had reduced BUN, but there was no effect on renal vitamin D metabolic enzyme expression. Consistent with increased EPO, bone marrow Erfe, Transferrin receptor (Tfrc), and EpoR mRNAs were increased in BAY-treated CKD mice, and in vitro hypoxic marrow cultures increased FGF23 with direct EPO treatment. Liver Bmp-6 and hepcidin expression were downregulated in all BAY-treated groups. Femur trabecular parameters and cortical porosity were not worsened with BAY administration. In vitro, differentiated osteocyte-like cells exposed to an iron chelator to simulate iron depletion/hypoxia increased FGF23; repletion with holo-transferrin completely suppressed FGF23 and normalized Tfrc1. Collectively, these results support that resolving anemia using a HIF-PHI during CKD was associated with lower BUN and reduced FGF23, potentially through direct restoration of iron utilization, thus providing modifiable outcomes beyond improving anemia for this patient population. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Megan L Noonan
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Pu Ni
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Rafiou Agoro
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Spencer A Sacks
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN
| | - Elizabeth A Swallow
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN
| | - Jonathan A Wheeler
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Erica L Clinkenbeard
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Maegan L Capitano
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN
| | - Matthew Prideaux
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN
| | - Gerald J Atkins
- Centre for Orthopaedic and Trauma Research, The University of Adelaide, Adelaide, Australia
| | - William R Thompson
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN
| | - Matthew R Allen
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN
| | - Hal E Broxmeyer
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN
| | - Kenneth E White
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN
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30
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Zhang Y, Ren S, Xue H, Wang AY, Zou Y, Cai Y, He J, Yuan X, Jiang F, Wei J, Yang D, He D, Hu S, Lei M, Deng F, Chen J, Wang X, He Q, Li G, Hong D. Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study. BMC Nephrol 2021; 22:28. [PMID: 33441103 PMCID: PMC7805134 DOI: 10.1186/s12882-021-02229-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/01/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .
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Affiliation(s)
- Yaling Zhang
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China
| | - Song Ren
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China
| | - Hen Xue
- Department of Nephrology, Ya'an People's Hospital, 625000, Ya'an, Sichuan, China
| | - Amanda Y Wang
- The Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, 2042, Australia.
- Concord Clinical School, The University of Sydney, Sydney, 2042, Australia.
- Department of Renal Medicine, Concord Repatriation General Hospital, Beijing Friendship Hospital, Beijing, China.
| | - Yang Zou
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China
| | - Yanrong Cai
- Department of Nephrology, 610000, Gao Xin Boli Hospital,Chengdu, China
| | - Jingdong He
- Department of Nephrology, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 Hospital, 610000, Chengdu, China
| | - Xiaoling Yuan
- Department of Nephrology, Sichuan Science City Hospital, 621000, Mianyang, China
| | - Feifei Jiang
- Department of Nephrology, Chengdu Jinniu District People's Hospital, 610036, Chengdu, China
| | - Jinxi Wei
- Hemodialysis center,Pidu District People's Hospital, 611730, Chengdu, China
| | - Dongmei Yang
- Department of Nephrology, Mianyang Anzhou People's Hospital, 621000, Mianyang, China
| | - Dong He
- Department of Nephrology, The People's Hospital of Mianyang, 621000, Mianyang, China
| | - Shide Hu
- Department of Nephrology, Sichuan Mianyang 404 Hospital, 621000, Mianyang, China
| | - Min Lei
- Department of Nephrology, Affiliated Hospital of Chengdu University, 610081, Chengdu, China
| | - Fei Deng
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China
| | - Jin Chen
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China
| | - Xia Wang
- The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Qiang He
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China.
| | - Guisen Li
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China.
| | - Daqing Hong
- Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West 2nd Duan, 1st Circle Road, Qingyang District, Chengdu, Sichuan, China.
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Liang M, Wu Y, Su N, Liu Y, Lin W, Li S, Zhong W, Jiang Z. Prevalence, associated factors and cardiocerebral vascular prognosis of anaemia among patients on chronic haemodialysis in South Guangdong, China. J Int Med Res 2020; 48:300060520965791. [PMID: 33203278 PMCID: PMC7683930 DOI: 10.1177/0300060520965791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 09/21/2020] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE To assess the prevalence, associated factors and cardiocerebral vascular prognosis of anaemia in patients undergoing haemodialysis. METHODS This multicentre, retrospective, observational cohort study included patients on maintenance haemodialysis in South Guangdong, China. Anaemia in haemodialysis was defined as haemoglobin (Hb) <90 g/l. A proportion of patients were enrolled in a follow-up of the cardiocerebral vascular prognosis. RESULTS A total of 1161 patients were enrolled and 938 were followed-up for cardiocerebral vascular events. Of 1161 patients, 250 (21.5%) had anaemia and 524 (45.1%) had an Hb level of 100-120 g/l. Adjusted multivariate logistic regression analysis demonstrated that frequency of dialysis ≤ twice weekly, hypoalbuminaemia and use of unfractionated heparin were independent factors associated with anaemia. Kaplan-Meier survival curve analysis for no myocardial infarction was 100%, 100%, 100% and 100% after 3, 6, 9 and 12 months, respectively, in patients with Hb < 90 g/l; compared with 97%, 95%, 93% and 93%, respectively, in patients with Hb ≥ 130 g/l. Adjusted Cox proportional hazards regression demonstrated that Hb ≥ 130 g/l was an independent risk factor for myocardial infarction. CONCLUSION Anaemia is highly prevalent among patients undergoing haemodialysis in South Guangdong and requires careful management.
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Affiliation(s)
- Mengjun Liang
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Yong Wu
- Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China
| | - Ning Su
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Ying Liu
- Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China
| | - Weiping Lin
- Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China
| | - Siyi Li
- Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China
| | - Weiqiang Zhong
- Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China
| | - Zongpei Jiang
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
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High prevalence of parvovirus B19 infection in patients with chronic kidney disease under hemodialysis: A multicenter study. Int J Infect Dis 2020; 100:350-356. [PMID: 32927082 DOI: 10.1016/j.ijid.2020.09.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/01/2020] [Accepted: 09/04/2020] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVES Parvovirus B19 (B19V) infection is commonly acute and self-limited, but in chronic kidney disease (CKD) patients under dialysis treatment, this infection could increase susceptibility to acute and chronic anemia. The aim of this study was to evaluate the frequency and risk of B19V infection among Brazilian CKD patients under dialysis. METHODS A study was conducted among 221 CKD patients and a control group of 142 blood donors. B19V infection was evaluated in serum samples by real-time PCR, and ELISA (anti-B19V IgM and IgG). RESULTS B19V DNA was detected in 65% (145/221) of CKD patients, which was significantly higher (p < 0.001) than in the blood donors (6.3%). Simultaneous detection of B19V IgG and viremia was shown in 40.3% of CKD patients, which was indicative of persistent B19V infection. CKD patients showed an increased risk of developing B19V infection (OR = 28.1, CI = 13.5-58.5, p = 0.001). CONCLUSIONS Despite an absence of clinical signs of B19V infection, these data highlight the importance of B19V infection in this high-risk population, since a persistent B19V infection could become clinically significant after renal transplant. Moreover, the persistent viremia should be considered as a potential risk, mainly because of the contamination of dialysis equipment.
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Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies. Kidney Med 2020; 1:271-280. [PMID: 32734207 PMCID: PMC7380401 DOI: 10.1016/j.xkme.2019.06.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Rationale & Objective Epoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-term safety of epoetin alfa-epbx. Study Design Pooled analyses of previously conducted studies. Setting & Participants Hemodialysis patients with anemia. Interventions Data from patients who received 1 or more subcutaneous or intravenous doses of study drug were integrated across route of administration in combined randomized groups (epoetin alfa-epbx, n = 423; epoetin alfa, n = 426). Data from patients who received 1 or more doses of epoetin alfa-epbx in either open-label extension trial were integrated across route of administration in a combined long-term safety studies group (n = 576). Outcomes Adverse events (AEs), immunogenicity, and other outcomes were assessed. Results Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were similar between combined randomized epoetin alfa-epbx and epoetin alfa, which had mean treatment durations of 18.1 and 17.7 weeks, respectively. Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were 86.5%, 39.4%, and 6.6%, respectively, for the combined long-term safety studies group, which had a mean treatment duration of 40.0 weeks. In total, 12 patients across the combined randomized groups (epoetin alfa-epbx, n = 5; epoetin alfa, n = 7) and 9 patients in the combined long-term safety studies group tested anti-recombinant human erythropoietin antibody positive in 1 or more visits during study conduct. No patient in any group developed neutralizing antibodies or pure red blood cell aplasia. Limitations Epoetin alfa comparator not included in the long-term safety studies, greater cumulative exposure to study drug for epoetin alfa-epbx, shorter follow-up in the randomized studies, and potential for selection bias among patients in the open-label long-term safety studies. Conclusions This analysis reinforces previous conclusions of similar safety profiles between epoetin alfa-epbx and epoetin alfa. Furthermore, epoetin alfa-epbx had no unexpected safety signals during long-term treatment. Funding This study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015. Trial Registration ClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107).
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Lim M, Dharmaraj V, Gong B, Jung BT, Xu T. Estimating Tumor Vascular Permeability of Nanoparticles Using an Accessible Diffusive Flux Model. ACS Biomater Sci Eng 2020; 6:2879-2892. [DOI: 10.1021/acsbiomaterials.9b01590] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Marc Lim
- UC Berkeley - UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California 94720, United States
- Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720, United States
| | - Vishnu Dharmaraj
- Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, United States
| | - Boying Gong
- Department of Biostatistics, University of California, Berkeley, Berkeley, California 94720, United States
| | - Benson T. Jung
- Department of Materials Science & Engineering, University of California, Berkeley, Berkeley, California 94720, United States
| | - Ting Xu
- Department of Materials Science & Engineering, University of California, Berkeley, Berkeley, California 94720, United States
- Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States
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Silverberg DS, Wexler D, Blum M, Sheps D, Schwartz D, Yachnin T, Baruch R, Tchebiner J, Zubkov A, Shaked M, Steinbruch S, Keren G, Iaina A. Aggressive Therapy of Congestive Heart Failure and Associated Chronic Renal Failure with Medications and Correction of Anemia Stops or Slows the Progression of Both Diseases. Perit Dial Int 2020. [DOI: 10.1177/089686080102103s42] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.
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Affiliation(s)
- Donald S. Silverberg
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Dov Wexler
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Miriam Blum
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - David Sheps
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Doron Schwartz
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Tatyana Yachnin
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ron Baruch
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Joseph Tchebiner
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Alexander Zubkov
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Meital Shaked
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Shoshana Steinbruch
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Gad Keren
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Adrian Iaina
- Department of Nephrology, Congestive Heart Failure Unit, Cardiology Department, and Internal Medicine B Department, Tel Aviv Medical Center, Tel Aviv, Israel
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Wong JH, Pierratos A, Oreopoulos DG, Mohammad R, Benjamin–Wong F, Chan CT. The Use of Nocturnal Home Hemodialysis as Salvage Therapy for Patients Experiencing Peritoneal Dialysis Failure. Perit Dial Int 2020. [DOI: 10.1177/089686080702700613] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background Failure of peritoneal dialysis (PD) results in poor quality of life and worsening morbidity in patients with end-stage renal disease (ESRD). Traditionally, hospital-based conventional hemodialysis has been the only option for this patient population. We hypothesized that nocturnal home hemodialysis (NHD), 3 – 6 sessions per week, 6 – 8 hours per session, is a suitable alternative salvage therapy for this vulnerable patient group. Methods This is a descriptive cohort study of all consecutive ESRD patients failing PD that were converted to NHD at the University Health Network and Humber River Regional Hospital from 2003 to 2005. Our primary objective was to describe the changes in clinical and biochemical indices before and after conversion from PD to NHD. Results 69 patients required transfer from PD to another form of renal replacement therapy during the period of interest. Our pilot cohort included 8 ESRD patients (5 males, 3 females; age 53 ± 7 years). Mean duration on PD was 4.8 ± 4.6 years. NHD delivered a higher dose of dialysis, as reflected by lower plasma creatinine concentration 1 year after beginning NHD (from 1107 ± 312 μmol/L with PD to 649 ± 309 μmol/L, p = 0.01) and a rise in standardized Kt/V (from 2.21 ± 0.73 with PD to 4.49 ± 1.92 after 6 months of NHD, to 4.51 ± 1.77 after 1 year of NHD; p < 0.001). There was a progressive and sustained rise in plasma albumin after conversion to NHD (from 31 ± 4 g/L with PD to 36 ± 4 g/L after 6 months of NHD, to 39 ± 2 g/L after 1 year of NHD; p = 0.001). Hemoglobin concentrations increased (from 102 ± 13 to 125 ± 7 g/L, p = 0.03), while erythropoietin requirement tended to fall (from 17500 ± 8669 to 9197 ± 7573 U/week). Plasma phosphate fell (from 2.1 ± 0.6 to 1.1 ± 0.3 mmol/L, p = 0.01) despite a decrease in phosphate binder requirement. Blood pressure profile also tended to improve after conversion to NHD. Conclusion Nocturnal HD represents a promising, viable, alternative renal replacement therapy for patients experiencing PD failure. The clinical impact of transferring ESRD patients failing PD to NHD deserves further investigation.
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Affiliation(s)
- Joseph H.S. Wong
- Division of Nephrology, Queen Elizabeth Hospital, Hong Kong, China
| | | | | | - Reem Mohammad
- Division of Nephrology, University Health Network, Toronto, Ontario, Canada
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Decaro C, Montanari GB, Molinari R, Gilberti A, Bagnoli D, Bianconi M, Bellanca G. Machine Learning Approach for Prediction of Hematic Parameters in Hemodialysis Patients. IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE-JTEHM 2019; 7:4100308. [PMID: 32309060 PMCID: PMC6788674 DOI: 10.1109/jtehm.2019.2938951] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/30/2019] [Accepted: 08/25/2019] [Indexed: 11/23/2022]
Abstract
Objective: This paper shows the application of machine learning techniques to predict hematic parameters using blood visible spectra during ex-vivo treatments. Methods: A spectroscopic setup was prepared for acquisition of blood absorbance spectrum and tested in an operational environment. This setup is non invasive and can be applied during dialysis sessions. A support vector machine and an artificial neural network, trained with a dataset of spectra, have been implemented for the prediction of hematocrit and oxygen saturation. Results & Conclusion: Results of different machine learning algorithms are compared, showing that support vector machine is the best technique for the prediction of hematocrit and oxygen saturation.
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Affiliation(s)
| | | | | | | | | | - Marco Bianconi
- 2MIST E-R40129BolognaItaly.,5CNR-IMM-UOS di Bologna40129BolognaItaly
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Moradi Z, Maali A, Shad JS, Farasat A, Kouchaki R, Moghadami M, Ahmadi MH, Azad M. Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach. Indian J Hematol Blood Transfus 2019; 36:26-36. [PMID: 32174689 DOI: 10.1007/s12288-019-01170-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 08/05/2019] [Indexed: 02/07/2023] Open
Abstract
Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.
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Affiliation(s)
- Zahra Moradi
- 1Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhosein Maali
- 2Student Research Committee, Babol University of Medical Sciences, Babol, Iran.,3Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Javad Sadeghi Shad
- 2Student Research Committee, Babol University of Medical Sciences, Babol, Iran.,4Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Alireza Farasat
- 5Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Reza Kouchaki
- 6Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mona Moghadami
- 2Student Research Committee, Babol University of Medical Sciences, Babol, Iran.,3Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | | | - Mehdi Azad
- 6Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
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Pérez-García R, Varas J, Cives A, Martín-Malo A, Aljama P, Ramos R, Pascual J, Stuard S, Canaud B, Merello JI. Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis. Nephrol Dial Transplant 2019; 33:690-699. [PMID: 29036505 DOI: 10.1093/ndt/gfx269] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 07/22/2017] [Indexed: 12/13/2022] Open
Abstract
Background Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure. Methods A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA administration was according to standard medical practice. Patients were grouped as quintiles, according to ESA dose, in order to compare mortality and hospitalization data. Using propensity score matching (PSM), we defined two groups of 324 patients receiving weekly threshold ESA doses of either > or ≤8000 IU. Results Kaplan-Meier survival curves indicated significant increases in the risk of mortality in patients administered with high doses of ESAs (>8127.4 IU/week). Multivariate Cox models identified a high ESA dose as an independent predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic regression models identified high ESA doses as an independent predictor for all-cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA doses of >8000 IU constitute an independent predictor of all-cause mortality and hospitalization, even though the adjusted cohort displayed the same demographic features, inflammatory profile, clinical HD parameters and haemoglobin levels. Conclusions Our data suggest that ESA doses of >8000 IU/week are associated with an increased risk of all-cause mortality and hospitalization in HD patients.
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Affiliation(s)
| | - Javier Varas
- Medical Department, Fresenius Medical Care, Tres Cantos, Madrid, Spain
| | - Alejandro Cives
- Medical Department, Fresenius Medical Care, Tres Cantos, Madrid, Spain
| | | | - Pedro Aljama
- Nephrology Department, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Rosa Ramos
- Medical Department, Fresenius Medical Care, Tres Cantos, Madrid, Spain
| | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | - Stefano Stuard
- Care Value Management EMEA, Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany
| | - Bernard Canaud
- Center of Excellence Medical, Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany
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Yamamoto H, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Akizawa T. Molidustat for the treatment of renal anaemia in patients with non-dialysis-dependent chronic kidney disease: design and rationale of two phase III studies. BMJ Open 2019; 9:e026704. [PMID: 31203242 PMCID: PMC6588957 DOI: 10.1136/bmjopen-2018-026704] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 04/11/2019] [Accepted: 05/15/2019] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Anaemia is a common complication of chronic kidney disease (CKD). Owing to the limitations of erythropoiesis-stimulating agents (ESAs), the current standard of care, there is a need to develop new therapies. Hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitors might be a promising new treatment option. Molidustat is an oral HIF-PH inhibitor that stimulates the endogenous, predominantly renal, production of erythropoietin and was generally well tolerated in phase IIb clinical trials. Here, we report the design and rationale of two studies from the molidustat phase III programme: MolIdustat once dailY improves renal Anaemia By Inducing erythropoietin (MIYABI). METHODS AND ANALYSIS MIYABI Non-Dialysis-Correction (ND-C) and MIYABI Non-Dialysis-Maintenance (ND-M) are randomised, open-label, parallel-group, multicentre studies that aim to demonstrate the efficacy of molidustat treatment compared with darbepoetin alfa in patients with anaemia and non-dialysis-dependent CKD. The secondary objectives are to assess the safety, pharmacokinetics and pharmacodynamics of molidustat treatment. MIYABI ND-C will recruit patients currently untreated with ESAs, whereas patients treated with an ESA will enter MIYABI ND-M. Each study will recruit 150 patients who will be randomised in a 1:1 ratio to receive either molidustat or darbepoetin alfa for 52 weeks, with efficacy evaluated during weeks 30-36. Study drug doses will be titrated regularly using an interactive voice/web response system with the aim of maintaining the patients' haemoglobin (Hb) levels between ≥110 and <130 g/L. The primary objective will be achieved if, in molidustat-treated patients, the mean Hb level remains within the target range during the evaluation period, and if the change in the mean Hb level at evaluation time points from baseline is non-inferior to darbepoetin alfa. ETHICS AND DISSEMINATION The protocols were approved by ethics committees at all participating sites. These studies will be conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines. Results arising from these studies will be published in peer-reviewed journal(s). TRIAL REGISTRATION NUMBERS NCT03350321; Pre-results, NCT03350347; Pre-results.
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Affiliation(s)
- Hiroyasu Yamamoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Megumi Taguchi
- MAF Pulmonology & Cardiology, Medical Affairs, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Yoshimi Matsuda
- Statistics & Data Insights, Data Sciences & Analytics, Research & Development, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Kazuma Iekushi
- MAF Pulmonology & Cardiology, Medical Affairs, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Takashi Yamada
- TA Thrombosis & Nephrology, Clinical Development & Operations, Research & Development, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Tadao Akizawa
- Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
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Sakaguchi Y, Hamano T, Wada A, Masakane I. Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis. J Am Soc Nephrol 2019; 30:1037-1048. [PMID: 31015255 DOI: 10.1681/asn.2018101007] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 03/01/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Despite the widespread use of erythropoietin-stimulating agents (ESAs) to treat anemia in patients undergoing hemodialysis, the relative mortality risks associated with use of different types of ESAs are unknown. METHODS To compare the mortality risk associated with use of short-acting ESAs versus long-acting ESAs, we conducted a nationwide cohort study of 194,698 hemodialysis patients in Japan who received either a short-acting (epoetin α/β or epoetin κ) or a long-acting (darbepoetin or epoetin β pegol) ESA. Study outcomes were 2-year all-cause and cause-specific mortality. In addition to Cox proportional hazards models, we performed an instrumental variable analysis in which facility-level long-acting ESA prescription rates were taken as the instrumental variable. RESULTS During the 2-year follow-up period, 31,557 deaths occurred. In a multivariable Cox model, long-acting ESA users had a 13% higher rate of deaths compared with short-acting ESA users, a significant difference (P<0.001). Similar results were obtained in other analyses. This difference in risk was pronounced among patients receiving high doses of ESA (for whom the adjusted 2-year number needed to harm for death was 30.8). Long-acting ESA use was associated with an increased rate of death from cardiovascular diseases, infection, and malignancies. In the instrumental variable analysis, long-acting ESA users remained at a significantly higher risk of death. Compared with anemic (hemoglobin 9.0-9.9 g/dl) short-acting ESA users, long-acting ESA users who achieved more optimal hemoglobin levels (10.0-10.9 g/dl) showed a higher mortality rate. CONCLUSIONS Among patients undergoing hemodialysis, use of long-acting ESAs might be associated with a higher risk of death than use of short-acting ESAs.
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Affiliation(s)
- Yusuke Sakaguchi
- Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
| | - Takayuki Hamano
- Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
| | - Atsushi Wada
- Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
| | - Ikuto Masakane
- Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
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Pan CF, Lin CJ, Chen SH, Huang CF, Lee CC. Association between trace element concentrations and anemia in patients with chronic kidney disease: a cross-sectional population-based study. J Investig Med 2019; 67:995-1001. [PMID: 30723120 DOI: 10.1136/jim-2018-000833] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/30/2018] [Indexed: 12/27/2022]
Abstract
Anemia is common in chronic kidney disease (CKD) and may be affected by trace element concentrations. While the concentrations of trace elements are known to be altered in CKD, the relationship between trace element and hemoglobin concentrations has not been systematically investigated in a large cohort. This study aims to examine associations between trace element concentrations and anemia in patients with CKD. Data from the National Health and Nutrition Examination Survey collected from 2011 to 2014 were used for this analysis. The participants who were more than 20 years old were included. A total of 3057 participants were included; the final cohort was divided into two groups based on CKD status. The concentrations of hemoglobin, iron, zinc, and manganese were significantly lower in participants with than without CKD (all p<0.05). Multivariate analyses showed that in patients without CKD, hemoglobin concentrations correlated positively with iron, zinc, and cadmium (β=0.005, 0.009, and 0.33, respectively), but correlated negatively with copper levels (β=-0.002). In patients with CKD, hemoglobin concentrations correlated positively with cadmium and selenium, but negatively with copper levels (β=0.57, 0.007, and -0.008, respectively). The serum iron concentration was found to correlate positively with zinc, cadmium, and selenium, but negatively with copper and manganese concentrations in the total study population (all p<0.05). The associations between serum concentrations of trace elements and hemoglobin differ between patients with and without CKD. Further investigations are warranted to determine whether patients with CKD have distinct trace element requirements.
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Affiliation(s)
- Chi-Feng Pan
- Department of Internal Medicine, Division of Nephrology, Mackay Memorial Hospital, Taipei, Taiwan.,Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.,Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Cheng-Jui Lin
- Department of Internal Medicine, Division of Nephrology, Mackay Memorial Hospital, Taipei, Taiwan.,Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
| | - Shu-Hua Chen
- Department of Internal Medicine, Division of Nephrology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chi-Feng Huang
- Department of Internal Medicine, Division of Nephrology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chun-Chuan Lee
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.,Department of Internal Medicine, Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan
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Aapro M, Gascón P, Patel K, Rodgers GM, Fung S, Arantes LH, Wish J. Erythropoiesis-Stimulating Agents in the Management of Anemia in Chronic Kidney Disease or Cancer: A Historical Perspective. Front Pharmacol 2019; 9:1498. [PMID: 30687083 PMCID: PMC6333861 DOI: 10.3389/fphar.2018.01498] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 12/07/2018] [Indexed: 11/23/2022] Open
Abstract
Anemia is common in patients with cancer or with chronic kidney disease (CKD). Although the introduction of erythropoiesis-stimulating agents (ESAs) has transformed the management of anemia, their use has been complicated by a number of factors including frequent guideline updates, safety concerns and, in the United States, a Risk Evaluation and Mitigation Strategy (REMS) program, which aimed to ensure that the benefits of ESAs outweigh the risks. Many previous concerns around ESA use in cancer and CKD have been addressed by the reassuring results of post-approval studies, and biosimilar ESAs have been used in Europe for many years, with safety and efficacy profiles similar to originator products. This review describes the evolution of the use of ESAs from approval to the present day, discussing results from clinical studies of ESAs in cancer and CKD, and the influence of these findings on product labeling and guideline updates. We also discuss the impact of the introduction of ESA biosimilars in Europe, bringing cost savings and increased access to patients.
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Affiliation(s)
- Matti Aapro
- Genolier Cancer Centre, Clinique de Genolier, Genolier, Switzerland
| | - Pere Gascón
- Division of Medical Oncology, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Kashyap Patel
- Carolina Blood and Cancer Care, Rock Hill, SC, United States
| | - George M. Rodgers
- Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
| | - Selwyn Fung
- Supportive Care Biosimilars, Pfizer Inc., New York, NY, United States
| | - Luiz H. Arantes
- Supportive Care Biosimilars, Pfizer Inc., New York, NY, United States
| | - Jay Wish
- Division of Nephrology, Indiana University Health, Indianapolis, IN, United States
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Mc Causland FR, Claggett B, Burdmann EA, Chertow GM, Cooper ME, Eckardt KU, Ivanovich P, Levey AS, Lewis EF, McGill JB, McMurray JJV, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto RD, Pfeffer MA. Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Am J Kidney Dis 2018; 73:309-315. [PMID: 30578152 DOI: 10.1053/j.ajkd.2018.10.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 10/08/2018] [Indexed: 12/19/2022]
Abstract
RATIONALE & OBJECTIVE Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. STUDY DESIGN Post hoc analysis of a randomized controlled trial. SETTING & PARTICIPANTS Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n=590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). EXPOSURE Randomized treatment assignment (darbepoetin vs placebo). OUTCOMES All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. ANALYTICAL APPROACH Proportional hazards regression. RESULTS Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n=298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3±1.6 and 9.5±1.5g/dL (P<0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). LIMITATIONS Post hoc analyses of a subgroup of study participants. CONCLUSIONS Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.
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Affiliation(s)
- Finnian R Mc Causland
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
| | - Brian Claggett
- Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Emmanuel A Burdmann
- Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo, Brazil
| | - Glenn M Chertow
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA
| | - Mark E Cooper
- Monash University Central Clinical School, Melbourne, VIC, Australia
| | - Kai-Uwe Eckardt
- Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany
| | | | - Andrew S Levey
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - Eldrin F Lewis
- Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Janet B McGill
- Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO
| | - John J V McMurray
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland
| | - Patrick Parfrey
- Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Hans-Henrik Parving
- Department of Medical Endocrinology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
| | - Giuseppe Remuzzi
- IRCCS-Istituto di Ricerche Farmacologiche Mario Negri; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Ajay K Singh
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA
| | - Scott D Solomon
- Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Robert D Toto
- Renal Division, University of Texas Southwestern, Dallas, TX
| | - Marc A Pfeffer
- Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA
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Kim CH, Kim MS, Kang MJ, Kim HH, Park NJ, Jung HK. Oral mucosa pressure ulcers in intensive care unit patients: A preliminary observational study of incidence and risk factors. J Tissue Viability 2018; 28:27-34. [PMID: 30551969 DOI: 10.1016/j.jtv.2018.11.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 11/03/2018] [Accepted: 11/28/2018] [Indexed: 12/11/2022]
Abstract
PURPOSE This study examined the incidence of oral mucosa pressure ulcers (PUs) in intensive care unit (ICU) patients and the relationship between biomechanical and physiological variables in onset of PUs. METHODS A prospective observational descriptive study design was used. We recruited patients over 18 years of age with endotracheal tube (ETT) insertion in three ICUs in a tertiary hospital in Korea. We analysed 113 patient-days of data. Patient assessments and medical record reviews were conducted to gather biomechanical and physiological data. Fisher's exact tests and χ2 test and Spearman's rank correlations were used to compare data. RESULTS The highest incidence of oral mucosa PUs occurred in lower oral mucosa (36.3%). There was a significant relationship between lower oral mucosa PU stage and bite-block or airway use (r = .20, p = .036), commercial ETT holder use (r = 0.19, p = .048), sedative use (r = -0.22, p = .022), and plasma protein (r = 0.20, p = .033). Upper oral mucosa PU stage was related to commercial ETT holder use (r = 0.19, p = .044), haemoglobin(r = 0.24, p = .011), haematocrit (r = 0.27, p = .004), and serum albumin (r = -0.24, p = .012). Stage was related to commercial ETT holder use in both sites (r = 0.28, p = .003), haematocrit (r = 0.19, p = .039), and serum albumin (r = -0.23, p = .015). CONCLUSION Oral mucosa PUs developed more frequently and healed more quickly than general skin PUs. Taken together, these data indicate that biomechanical and haematological variables are risk factors associated with PU incidence should be considered in intensive care patients.
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Affiliation(s)
- Chul-Hoon Kim
- Department of Oral and Maxillofacial Surgery, College of Medicine, Dong-A University, Busan, South Korea
| | - Myoung Soo Kim
- Department of Nursing, Pukyong National University, Busan, South Korea.
| | - Myung Ja Kang
- Department of Nursing, Pukyong National University, Busan, South Korea
| | - Hyun Hee Kim
- Respiratory Intensive Care Unit, Pusan National University Hospital, Busan, South Korea
| | - Nam Jung Park
- Infection Control Team, Pusan National University Hospital, Busan, South Korea
| | - Hyun Kyeong Jung
- Urology Ward, Pusan National University Hospital, Busan, South Korea
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Bansal N, Zelnick LR, Himmelfarb J, Chertow GM. Bioelectrical Impedance Analysis Measures and Clinical Outcomes in CKD. Am J Kidney Dis 2018; 72:662-672. [PMID: 29885923 DOI: 10.1053/j.ajkd.2018.03.030] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 03/27/2018] [Indexed: 11/11/2022]
Abstract
RATIONALE & OBJECTIVE Bioelectrical impedance analysis (BIA) provides a noninvasive assessment of body composition. BIA measures of cell integrity (phase angle) and hydration (vector length) have been associated with mortality among patients receiving dialysis. Whether these measures are associated with clinical outcomes in patients with chronic kidney disease (CKD) is unknown. STUDY DESIGN Observational study. SETTINGS & PARTICIPANTS We studied 3,751 participants with CKD in the prospective multicenter Chronic Renal Insufficiency Cohort (CRIC) who had baseline single-frequency BIA performed. PREDICTORS Predictors included phase angle and vector length, which were calculated from measurements of resistance and reactance from BIA. We ranked phase angle and vector length into quartiles and compared the 2 narrower quartiles of phase angle and shorter quartiles of vector length with the 2 upper quartiles. OUTCOMES Mortality, heart failure, atherosclerotic cardiovascular disease, and progression of CKD (30% decline in estimated glomerular filtration rate or end-stage kidney disease). ANALYTIC APPROACH We tested associations of phase angle and vector length with risks for mortality and progression of CKD using Cox proportional hazard models and the association with heart failure and atherosclerotic cardiovascular disease using Fine and Gray models. All models were adjusted for demographics, comorbid conditions, and kidney function. RESULTS Mean phase angle and vector length were 6.6°±1.8° and 470 ± 96 Ω/m, respectively. Relative to phase angle ≥ 6.40o, narrower phase angle (<5.59o) was significantly associated with mortality (HR, 1.31; 95% CI, 1.09-1.58). Relative to vector length ≥ 459 Ω/m, shorter vector length (<401 Ω/m) was significantly associated with heart failure (HR, 1.28; 95% CI, 1.01-1.61). Neither measure was associated with atherosclerotic cardiovascular disease or a composite renal end point. LIMITATIONS Observational study. CONCLUSIONS Adjusted for key confounders, BIA-derived measures of cellular integrity and tissue hydration were significantly associated with death and incident heart failure, respectively.
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Affiliation(s)
- Nisha Bansal
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA.
| | - Leila R Zelnick
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA
| | - Jonathan Himmelfarb
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA
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Wetmore JB, Li S, Yan H, Xu H, Peng Y, Sinsakul MV, Liu J, Gilbertson DT. Predialysis anemia management and outcomes following dialysis initiation: A retrospective cohort analysis. PLoS One 2018; 13:e0203767. [PMID: 30256836 PMCID: PMC6157862 DOI: 10.1371/journal.pone.0203767] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 08/27/2018] [Indexed: 01/08/2023] Open
Abstract
Whether and how anemia treatment with erythropoiesis stimulating agents (ESAs) before hemodialysis initiation may be associated with lower mortality after dialysis initiation is unknown. We compared all-cause and cardiovascular mortality in two groups of patients who experienced distinct anemia treatment patterns with ESAs before and after hemodialysis initiation. This retrospective cohort analysis included patients initiating hemodialysis April 1, 2012-June 30, 2013, identified from United States Renal Data System end-stage renal disease (ESRD) and pre-ESRD files. Patients treated with ESAs before and after hemodialysis initiation who maintained Hb ≥ 9.0 g/dL throughout (comparator group, n = 3662) were compared with patients with Hb < 9.0 g/dL before hemodialysis initiation (with or without ESAs) whose levels increased with ESAs after hemodialysis initiation (referent group, n = 4461). Cox proportional hazards models were used to calculate the hazard ratio of all-cause and cardiovascular mortality after hemodialysis initiation. Of 20,454 patients, 4855 (23.7%) had Hb < 9.0 g/dL upon hemodialysis initiation; of these 4855, 26.6% received ESAs before initiation. Comparator group Hb levels increased from 8.2 ± 0.8 mg/dL upon initiation to 10.9 ± 1.2 with ESAs afterward. Comparator patients were more likely than referent patients to be younger (76.3 ± 6.7 versus 77.2 ± 6.9 years), male (51.5% versus 49.8%), and black (24.6% versus 18.6%). Risk of all-cause mortality was lower for the comparator group versus the referent group at 3 (HR 0.83, 95% CI 0.68–1.00, P = 0.052), 6 (0.86, 0.74–1.00, P = 0.047), and 12 (0.88, 0.78–0.99, P = 0.036) months. The pattern was similar for cardiovascular mortality. Hb ≥ 9.0 with ESAs before and after hemodialysis initiation was generally associated with lower post-initiation all-cause and cardiovascular mortality compared with predialysis Hb < 9.0 g/dL in patients whose Hb levels subsequently improved with ESAs after hemodialysis initiation.
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Affiliation(s)
- James B. Wetmore
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
- Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, United States of America
- * E-mail:
| | - Suying Li
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
| | - Heng Yan
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
| | - Hairong Xu
- AstraZeneca, Gaithersburg, Maryland, United States of America
| | - Yi Peng
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
| | | | - Jiannong Liu
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
| | - David T. Gilbertson
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America
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O'Donnell TFX, Shean KE, Deery SE, Bodewes TCF, Wyers MC, O'Brien KL, Matyal R, Schermerhorn ML. A preoperative risk score for transfusion in infrarenal endovascular aneurysm repair to avoid type and cross. J Vasc Surg 2018; 67:442-448. [PMID: 28756046 PMCID: PMC5785583 DOI: 10.1016/j.jvs.2017.05.108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 05/12/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Preoperative type and cross are often routinely ordered before elective endovascular aneurysm repair (EVAR), but the cost of this practice is high, and transfusion is rare. We therefore aimed to stratify patients by their risk of transfusion to identify a cohort in whom a type and screen would be sufficient. METHODS We queried the targeted vascular module of the National Surgical Quality Improvement Program (NSQIP) for all elective EVARs from 2011 to 2015. We included only infrarenal aneurysms and excluded ruptured aneurysms and patients transfused within 72 hours preoperatively. Two-thirds of the cases were randomly assigned to a model derivation cohort and one third to a validation cohort. We created and subsequently validated a risk model for transfusion within the first 24 hours of surgery (including intraoperatively), using logistic regression. RESULTS Between 2011 and 2015, there were 4875 patients who underwent elective infrarenal EVAR, only 221 (4.5%) of whom received a transfusion within 24 hours of surgery. The frequency of transfusion during the study period declined monotonously from 6.5% in 2011 to 3.2% in 2015. The factors independently associated with transfusion were preoperative hematocrit <36% (odds ratio [OR], 3.4 [95% confidence interval, 2.1-5.4]; P < .001), aortic diameter (per centimeter increase: OR, 1.2 [1.03-1.4]; P = .02), preoperative dependent functional status (OR, 2.5 [1.1-5.5]; P = .03), and chronic obstructive pulmonary disease (OR, 1.7 [1.04-2.9]; P = .04). A risk prediction model based on these criteria produced a C statistic of 0.69 in the prediction cohort and 0.76 in the validation cohort and a Hosmer-Lemeshow goodness of fit of 0.62 and 0.14, respectively. A score of <3 of 9, corresponding to a <5% probability of transfusion, would avoid preoperative type and cross in 86% of patients. Of the 4203 patients (86%) with a hematocrit >36%, only 6 (0.1%) had a risk score of >3. CONCLUSIONS Perioperative transfusion for EVAR is becoming increasingly uncommon and is predicted well by a transfusion risk score or simply a hematocrit of <36%. Application of this risk score would avoid unnecessary type and cross in the majority of patients, leading to significant savings in both time and cost.
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Affiliation(s)
- Thomas F X O'Donnell
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Katie E Shean
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Sarah E Deery
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Thomas C F Bodewes
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Mark C Wyers
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Kerry L O'Brien
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Robina Matyal
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Marc L Schermerhorn
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass.
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49
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Shine JS, Kim SJ, Lee JH, Yu M. [Factors Predicting the Interface Pressure Related to Pressure Injury in Intensive Care Unit Patients]. J Korean Acad Nurs 2018; 47:794-805. [PMID: 29326410 DOI: 10.4040/jkan.2017.47.6.794] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 11/22/2017] [Accepted: 11/22/2017] [Indexed: 11/09/2022]
Abstract
PURPOSE Interface pressure is a factor that contributes to the occurrence of pressure injuries. This study aimed to investigate interface pressure at common sites of pressure injury (occipital, gluteal and peritrochanteric areas), to explore the relationships among risk factors, skin condition and interface pressure, and to identify risk factors influencing interface pressure. METHODS A total of 100 patients admitted to the intensive care unit were enrolled at a tertiary teaching hospital in Korea. Interface pressure was recorded by a scanning aid device (PalmQ). Patient data regarding age, pulmonary disease, Braden Scale score, body mass index, serum albumin, hemoglobin, mean blood pressure, body temperature, and oxygen saturation were included as risk factors. Data collected from July to September 2016 were analyzed using binary logistic regression. RESULTS The mean interface pressure of the occipital, gluteal, and right and left peritrochanteric areas were 37.96 (±14.90), 41.15 (±16.04), 53.44 (±24.67), and 54.33 (±22.80) mmHg, respectively. Predictive factors for pressure injuries in the occipital area were age ≥70 years (OR 3.45, 95% confidence interval [CI]: 1.19~9.98), serum albumin deficit (OR 2.88, 95% CI: 1.00~8.26) and body temperature ≥36.5℃ (OR 3.12, 95% CI: 1.17~8.17); age ≥70 years (OR 2.81, 95% CI: 1.10~7.15) in the right peritrochanteric area; and body temperature ≥36.5℃ (OR 2.86, 95% CI: 1.17~6.98) in the left peritrochanteric area. CONCLUSION Our findings suggest that old age, hypoalbuminemia, and high body temperature may be contributory factors to increasing interface pressure; therefore, careful assessment and nursing care of these patients are needed to prevent pressure injury. Further studies are needed to establish cutoff values of interface pressure for patients with pressure ulcers.
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Affiliation(s)
- Ji Seon Shine
- Surgical Intensive Care Unit, Gyeongsang National University Hospital, Jinju, Korea
| | - Soo Jin Kim
- Adequate Medical Support Department, Gyeongsang National University Hospital, Jinju, Korea
| | - Ji Hyun Lee
- Surgical Outpatient Team, Gyeongsang National University Hospital, Jinju, Korea
| | - Mi Yu
- College of Nursing · Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
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50
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Restrepo C, Patel SK, Rethnam V, Werden E, Ramchand J, Churilov L, Burrell LM, Brodtmann A. Left ventricular hypertrophy and cognitive function: a systematic review. J Hum Hypertens 2018; 32:171-179. [PMID: 29330420 DOI: 10.1038/s41371-017-0023-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/11/2017] [Accepted: 07/26/2017] [Indexed: 02/07/2023]
Abstract
Cognitive impairment is common in patients with hypertension. Left ventricular hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage and is a strong predictor of coronary artery disease, heart failure and stroke. There is evidence that LVH is independently associated with cognitive impairment, even after adjustment for the presence of hypertension. We conducted a systematic review that examined cognitive impairment in adults with LVH. Independent searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms left ventricular hypertrophy and cognition. Seventy-three studies were identified when both searches were combined. After limiting the search to studies that were: (1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and older; and (4) investigated the relationship between LVH and cognitive performance, nine papers were included in this systematic review. The majority of studies found an association between LVH and cognitive performance. Inspection of results indicated that individuals with LVH exhibited a lower performance in cognitive tests, when compared to individuals without LVH. Memory and executive functions were the cognitive domains that showed a specific vulnerability to the presence of LVH. A possible mechanism for the relationship between LVH and cognition is the presence of cerebral white matter damage. White matter lesions occur frequently in patients with LVH and may contribute to cognitive dysfunction. Together, the results of this review suggest that memory impairment and executive dysfunction are the cognitive domains that showed a particular association with the presence of LVH.
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Affiliation(s)
- C Restrepo
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia
| | - S K Patel
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia.,Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, VIC, Australia
| | - V Rethnam
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia
| | - E Werden
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia
| | - J Ramchand
- Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, VIC, Australia.,Department of Cardiology, Austin Health, Heidelberg, VIC, Australia
| | - L Churilov
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia
| | - L M Burrell
- Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, VIC, Australia. .,Department of Cardiology, Austin Health, Heidelberg, VIC, Australia.
| | - A Brodtmann
- The Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, VIC, Australia.,Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, VIC, Australia.,Department of Neurology, Austin Health, Heidelberg, VIC, Australia
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