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Scott J, Yates M, Tanaka T, Ferrucci L, Cameron D, Welch AA. Cross-Sectional Associations between Clinical Biochemistry and Nutritional Biomarkers and Sarcopenic Indices of Skeletal Muscle in the Baltimore Longitudinal Study of Aging. J Nutr 2025; 155:1535-1548. [PMID: 40064424 DOI: 10.1016/j.tjnut.2025.03.006] [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: 10/08/2024] [Revised: 02/12/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Investigating relationships between nutritional and clinical biochemistry biomarkers and skeletal muscle mass, strength and function (sarcopenic indices) may 1) highlight micronutrients of interest for potential preventive or treatment strategies for sarcopenia, or 2) highlight biomarkers that may be useful for identifying individuals at risk of sarcopenia. OBJECTIVES Investigate associations between nutritional biomarkers (vitamin D, vitamin B12, folate, magnesium, potassium, calcium, and iron), clinical biomarkers (hemoglobin, ferritin, albumin, creatinine, and hemoglobin A1c: HbA1c), and sarcopenic indices (appendicular lean mass: ALM); height-adjusted ALM: ALMht; fat-free mass as a percentage of total body weight; extended short physical performance battery score: extSPPB; height-adjusted hand grip strength: HGSht; height-adjusted knee extension concentric strength, and; height-adjusted knee extension isometric strength) in males and females. METHODS Using multivariable linear regression analysis, we investigated cross-sectional associations between biomarkers and sarcopenic indices in data collected from 1761 participants (age 22-103 y) from the Baltimore Longitudinal Study of Aging. RESULTS Hemoglobin was positively associated with ALM (β = 0.20, P = 0.021), HGSht (β = 0.25, P = 0.001), and extSPPB (β = 0.13, P = 0.024) in males, and with extSPPB in females (β = 0.15, P = 0.019). In males, serum iron was positively associated with ALMht (β = 0.0021, P = 0.038) and extSPPB (β = 0.0043, P = 0.045). In females, ferritin was positively associated with knee-extension strength measurements. Serum creatinine was positively associated with lean mass measures in males and females and with muscle strength and function measures in males with normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2). In males, high HbA1c was associated with lower ALMht (β = -0.21, P = 0.023), extSPPB (β = -0.40, P = 0.027), and HGSht (β = -0.56, P = 0.031). In males and females, magnesium was positively associated with extSPPB, and potassium was positively associated with measures of knee-extension strength. CONCLUSIONS The associations found between measures of iron status and creatinine and sarcopenic indices, in males in particular, indicate potential importance for muscle health. Future longitudinal and intervention studies are warranted to confirm these findings.
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Affiliation(s)
- Jamie Scott
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Centre for Population Health Research, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom; Norwich Epidemiology Centre, Faculty of Medicine and Health Sciences, Population Health, University of East Anglia, Norwich, United Kingdom.
| | - Max Yates
- Norwich Epidemiology Centre, Faculty of Medicine and Health Sciences, Population Health, University of East Anglia, Norwich, United Kingdom; Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, United Kingdom
| | - Toshiko Tanaka
- Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
| | - Luigi Ferrucci
- Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
| | - Donnie Cameron
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ailsa A Welch
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Centre for Population Health Research, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom; Norwich Epidemiology Centre, Faculty of Medicine and Health Sciences, Population Health, University of East Anglia, Norwich, United Kingdom
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Akad N, Bilha SC, Apetrii M, Akad F, Bilha M, Hogas M, Hogas S, Ungureanu MC, Preda C, Covic A. Calciphylaxis Following Parathyroidectomy in Chronic Kidney Disease Patients-Case Report and Literature Review. Biomedicines 2025; 13:715. [PMID: 40149691 PMCID: PMC11940037 DOI: 10.3390/biomedicines13030715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 02/28/2025] [Accepted: 03/12/2025] [Indexed: 03/29/2025] Open
Abstract
Calcific uremic arteriolopathy, also known as calciphylaxis, is a rare and often fatal condition most commonly occurring in patients with end-stage renal disease (ESRD). It is marked by extensive vascular calcification, resulting in tissue ischemia and the development of distinctive skin lesions. We report the case of a 38-year-old male with ESRD due to polycystic kidney disease, who developed calciphylaxis lesions following total parathyroidectomy (PTx). We also performed an electronic search of PubMed and Google Scholar from inception until December 2024, using the following keywords: 'chronic kidney disease', 'dialysis', 'calciphylaxis', 'calcific uremic arteriolopathy', 'secondary hyperparathyroidism', and 'parathyroidectomy'. A literature review of calciphylaxis cases following PTx in chronic kidney disease (CKD) patients identified 14 cases reported up to the manuscript's writing. Although PTx can be a treatment option for calciphylaxis related to severe secondary hyperparathyroidism (SHPT), leading to clinical improvement in some patients, there are atypical calciphylaxis cases occurring after PTx. While the mechanism is not fully understood, the sudden reduction in parathormone (PTH) levels leading to hypocalcemia and decreased bone turnover, together with an increased calcium loading in a patient at risk for abnormal mineralization, may promote vascular and soft tissue calcification. However, the long-term impact of severe SHPT with a delayed post-PTx manifestation cannot be ruled out. Clinicians should consider calciphylaxis in CKD patients with new painful skin lesions. Skin biopsy remains controversial, but a thorough clinical examination, and, in some cases, imaging are essential for a correct diagnosis. A multidisciplinary, personalized approach is crucial, with careful management of post-PTx hypocalcemia and calcium supplementation. Further research is needed to enhance understanding and treatment strategies.
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Affiliation(s)
- Nada Akad
- Nephrology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (A.C.)
| | - Stefana Catalina Bilha
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Mugurel Apetrii
- Nephrology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (A.C.)
| | - Fawzy Akad
- Anatomy Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Madalina Bilha
- Pathology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Mihai Hogas
- Physiology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Simona Hogas
- Nephrology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (A.C.)
| | - Maria-Christina Ungureanu
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Cristina Preda
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Adrian Covic
- Nephrology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (A.C.)
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Otis JL, Parker NM, Busch RA. Nutrition support for patients with renal dysfunction in the intensive care unit: A narrative review. Nutr Clin Pract 2025; 40:35-53. [PMID: 39446967 PMCID: PMC11713211 DOI: 10.1002/ncp.11231] [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: 04/03/2024] [Revised: 09/20/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
Providing optimal nutrition support in the intensive care unit (ICU) is a challenging and dynamic process. Energy, protein, fluid, electrolyte, and micronutrient requirements all can be altered in patients with acute, chronic, and acute-on-chronic kidney disease. Given that renal dysfunction occurs in up to one-half of ICU patients, it is imperative that nutrition support providers understand how renal dysfunction, its metabolic consequences, and its treatments, including renal replacement therapy (RRT), affect patients' nutrition needs. Data on nutrient requirements in critically ill patients with renal dysfunction are sparse. This article provides an overview of renal dysfunction in the ICU and identifies and addresses the unique nutrition challenges present among these patients, including those receiving RRT, as supported by the available literature and guidelines.
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Affiliation(s)
- Joanna L. Otis
- Department of Clinical NutritionUniversity of Wisconsin Hospital and ClinicsMadisonWisconsinUSA
| | - Nicholas M. Parker
- Department of PharmacyUniversity of Wisconsin Hospital and ClinicsMadisonWisconsinUSA
| | - Rebecca A. Busch
- Division of Acute Care and Regional General Surgery, Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
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Dehghan A, Ardekani A, Akabri M, Sadeghi Y, Radmard AR, Merat S, Khoshnia M, Sharafkhah M, Khuzani AS, Poustchi H, Malekzadeh R, Molavi Vardanjani H. Carotid intima media thickness and glomerular filtration rate: a baseline analysis of the PolyIran-L trial. J Nephrol 2025; 38:181-188. [PMID: 39521753 DOI: 10.1007/s40620-024-02122-3] [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: 05/01/2024] [Accepted: 09/17/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The relationship between kidney and vascular health is acknowledged, but detailed information is still missing. This study examines the relationship of estimated glomerular filtration rate (eGFR) and carotid intima media thickness, providing insights into the association between atherosclerosis and kidney function. METHODS Participants older than 50 years of age who were part of the PolyIran-L study, a trial nested in the Golestan Cohort Study, were included. The maximal intima media thickness of both common carotid arteries was evaluated using B-mode ultrasonography. Four different cut-off values for abnormal carotid intima media thickness were considered. Correlation of carotid intima media thickness and eGFR was assessed with linear correlation and multivariable binary logistic regression models after adjusting for several confounders. RESULTS In total, 1562 participants (750 females, 48%) were included in this population-based study. Assuming the eGFR < 45 [mL/min/1.73 m2] group as reference in the crude analysis, those with eGFR ≥ 45 and < 60 [mL/min/1.73 m2] showed an association of being less likely to have carotid intima media thickness above the 0.8 cutoff. However, the fully adjusted analysis showed no significant statistical association between carotid intima media thickness and eGFR. CONCLUSION This study did not support the independent association of eGFR and different carotid intima media thickness cutoffs. This pattern may be different in patients with severely decreased eGFR, a subset of cases in which it should be further investigated.
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Affiliation(s)
- Alireza Dehghan
- MPH Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Medical Imaging Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Ardekani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadreza Akabri
- Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yasaman Sadeghi
- MPH Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Reza Radmard
- Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Merat
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Khoshnia
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Maryam Sharafkhah
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Molavi Vardanjani
- MD-MPH Department, School of Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Calderón-Juárez M, Saavedra-Fuentes N, Del Castillo-Loreto KG, Castillo-Salinas JC, Lerma C. Diet Supplementation with Ketoanalogues, Inulin, and Calcium Citrate in Chronic Kidney Disease: A Retrospective Cohort. Life (Basel) 2024; 14:1638. [PMID: 39768345 PMCID: PMC11677553 DOI: 10.3390/life14121638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
The addition of ketoanalogues (KAs) to a low-protein diet has been shown to mitigate the progression of pre-dialysis chronic kidney disease (CKD). The addition of inulin and calcium citrate may add further benefits, given their nephroprotective effects. In this study, we tested the changes in estimated glomerular filtration rate (eGFR), CKD symptoms, body composition, and biochemical parameters after 6 months of diet supplementation with Cetolán III, a combination of KA, inulin, and calcium citrate. We included 76 adult patients diagnosed with CKD stages 3 and 4 and not treated with renal replacement therapy in a retrospective cohort. In this cohort, participants were followed through two clinic visits at 3 and 6 months after diet supplementation. We found a slight increase in eGFR at 3 and 6 months compared with baseline, as well as a decrease in the severity of CDK-related symptoms, fat mass, and muscle mass. We observed only a slight decrease in creatinine and uric acid after 6 months of follow-up. We did not find a remarkable change in anthropometric parameters (e.g., body mass index, waist circumference, and arm muscle area). This observational study suggests that addition of KA, inulin, and calcium citrate to a low protein- diet could be associated with an improvement in eGFR and symptom severity in CKD pre-dialysis.
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Affiliation(s)
| | | | | | | | - Claudia Lerma
- Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan 14080, Mexico
- Faculty of Health Sciences, Universidad Anahuac Mexico, Huixquilucan 52786, Mexico
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Zaimi M, Grapsa E. Current therapeutic approach of chronic kidney disease-mineral and bone disorder. Ther Apher Dial 2024; 28:671-689. [PMID: 38898685 DOI: 10.1111/1744-9987.14177] [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: 02/29/2024] [Revised: 05/14/2024] [Accepted: 05/31/2024] [Indexed: 06/21/2024]
Abstract
Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances.
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Affiliation(s)
- Maria Zaimi
- National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
| | - Eirini Grapsa
- National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
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Montenegro J, Simas Torres Klein MR, Prado CM, Barreto Silva MI. Changes in Bone Mineral Density in Patients With Non-dialysis-Dependent Chronic Kidney Disease Are Associated With Body Composition. J Ren Nutr 2024; 34:391-400. [PMID: 38621430 DOI: 10.1053/j.jrn.2024.03.011] [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: 06/29/2023] [Revised: 11/20/2023] [Accepted: 03/17/2024] [Indexed: 04/17/2024] Open
Abstract
OBJECTIVE Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with nondialysis-dependent CKD (NDD-CKD). METHODS Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry. The ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as T-score ≤ -1.0. RESULTS The mean time between assessments was 2.8 ± 1.3 years; 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (P = .031), ALSTI (P = .021), a trend for BMD (P = .053), and an increase in percentage fat mass (P = .044) and LCI (P = .032). Females had a reduction in BMD (P = .034), ALST (P = .026), and ALSTI (P = .037). Patients with low BMD at baseline had lower LST (P = .013), ALST (P = .023), and percentage fat mass (P = .037) than those with normal BMD. Additionally, reductions in LST (P = .041), ALST (P = .006), and ALSTI (P = .008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (odds ratio [OR]: 0.899, 95% confidence interval [CI]: 0.829-0.976, P = .010), ALST (OR: 0.825, 95% CI: 0.704-0.967, P = .017), and ALSTI (OR: 0.586, 95% CI: 0.354-0.968, P = .037), independent of fat mass and LCI. CONCLUSIONS Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.
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Affiliation(s)
- Julia Montenegro
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada
| | | | - Carla M Prado
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada
| | - Maria Inês Barreto Silva
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada; Department of Applied Nutrition, Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil.
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Rajiah PS, Suman G, Vijay K, Venugopal N, Mansoori B, Chalian M, Agarwal AK. Multisystem Imaging Manifestations of Kidney Failure. Radiographics 2024; 44:e230124. [PMID: 39052499 DOI: 10.1148/rg.230124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
Kidney failure (KF) refers to a progressive decline in glomerular filtration rate to below 15 ml/min per 1.73 m2, necessitating renal replacement therapy with dialysis or renal transplant. The hemodynamic and metabolic alterations in KF combined with a proinflammatory and coagulopathic state leads to complex multisystemic complications. The imaging hallmark of systemic manifestations of KF is bone resorption caused by secondary hyperparathyroidism. Other musculoskeletal complications include brown tumor, osteosclerosis, calcinosis, soft-tissue calcification, and amyloid arthropathy. Cardiovascular complications and infections are the leading causes of death in KF. Cardiovascular complications include accelerated atherosclerosis, cardiomyopathy, pericarditis, myocardial calcinosis, and venous thromboembolism. Neurologic complications such as encephalopathy, osmotic demyelination, cerebrovascular disease, and opportunistic infections are also frequently encountered. Pulmonary complications include edema and calcifications. Radiography and CT are used in assessing musculoskeletal and thoracic complications, while MRI plays a key role in assessing neurologic and cardiovascular complications. CT iodinated contrast material is generally avoided in patients with KF except in situations where the benefit of contrast-enhanced CT outweighs the risks and in patients already undergoing maintenance dialysis. At MRI, group II gadolinium-based contrast material can be safely administered in patients with KF. The authors discuss the extrarenal systemic manifestations of KF, the choice of imaging modality in their assessment, and imaging findings of complications. ©RSNA, 2024 Supplemental material is available for this article.
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Affiliation(s)
- Prabhakar Shantha Rajiah
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Garima Suman
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Kanupriya Vijay
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Nitin Venugopal
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Bahar Mansoori
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Majid Chalian
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Amit Kumar Agarwal
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.S.R., G.S.); UT Southwestern Medical Center, Dallas, Tex (K.V.); University of Washington, Seattle, Wash (N.V., B.M., M.C.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
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Yong MHA, Seng JJB, Tan YLC, Wong J, How P. Prevalence and outcomes associated with hypocalcaemia and hypercalcaemia among pre-dialysis chronic kidney disease patients with mineral and bone disorder. Singapore Med J 2024; 65:421-429. [PMID: 36453429 PMCID: PMC11382823 DOI: 10.4103/singaporemedj.smj-2021-391] [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: 10/20/2021] [Accepted: 02/09/2022] [Indexed: 11/10/2022]
Abstract
INTRODUCTION Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients. METHODS A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca 2+ ) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca 2+ : between 1.90 and 2.10 mmol/L) and 'severe' (Ca 2+ : <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca 2+ : between 2.47 and 3.00 mmol/L), moderate (Ca 2+ : between 3.01 and 3.50 mmol/L) and severe (Ca 2+ : >3.50 mmol/L). RESULTS Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality ( P > 0.05) or the occurrence of cardiovascular events ( P > 0.05). CONCLUSION Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes.
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Affiliation(s)
| | | | | | - Jiunn Wong
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Priscilla How
- Department of Pharmacy, National University of Singapore, Singapore
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Biruete A, Shin A, Kistler BM, Moe SM. Feeling gutted in chronic kidney disease (CKD): Gastrointestinal disorders and therapies to improve gastrointestinal health in individuals CKD, including those undergoing dialysis. Semin Dial 2024; 37:334-349. [PMID: 34708456 PMCID: PMC9043041 DOI: 10.1111/sdi.13030] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 09/21/2021] [Indexed: 12/15/2022]
Abstract
Chronic kidney disease (CKD) affects 9.1% of the population worldwide. CKD may lead to structural and functional gastrointestinal alterations, including impairment in the intestinal barrier, digestion and absorption of nutrients, motility, and changes to the gut microbiome. These changes can lead to increased gastrointestinal symptoms in people with CKD, even in early grades of kidney dysfunction. Gastrointestinal symptoms have been associated with lower quality of life and reduced nutritional status. Therefore, there has been considerable interest in improving gastrointestinal health in this clinical population. Gastrointestinal health can be influenced by lifestyle and medications, particularly in advanced grades of kidney dysfunction. Therapies focused on gastrointestinal health have been studied, including the use of probiotics, prebiotics, and synbiotics, yielding limited and conflicting results. This review summarizes the alterations in the gastrointestinal tract structure and function and provides an overview of potential nutritional interventions that kidney disease professionals can provide to improve gastrointestinal health in individuals with CKD.
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Affiliation(s)
- Annabel Biruete
- Department of Nutrition and Dietetics, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA
- Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Brandon M. Kistler
- Department of Nutrition and Health Science, Ball State University, Muncie, Indiana, USA
| | - Sharon M. Moe
- Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Anatomy, Cell Biology, and Anatomy, Indiana University School of Medicine, Indianapolis, Indiana, USA
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11
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Sivaprasad M, Shalini T, Sahay M, Sahay R, Satyanarayanan M, Reddy GB. Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study. J Trace Elem Med Biol 2024; 84:127425. [PMID: 38484635 DOI: 10.1016/j.jtemb.2024.127425] [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: 10/06/2023] [Revised: 02/25/2024] [Accepted: 03/03/2024] [Indexed: 05/27/2024]
Abstract
BACKGROUND AND AIM Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. METHODS A hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman's rank correlation was used to evaluate the relationship between the categorical variables. RESULTS The median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= -0.486, p<0.001). CONCLUSION Plasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.
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Affiliation(s)
- Mudili Sivaprasad
- Biochemistry Division, ICMR-National Institute of Nutrition, Hyderabad, India
| | - Tattari Shalini
- Biochemistry Division, ICMR-National Institute of Nutrition, Hyderabad, India
| | - Manisha Sahay
- Nephrology Division, Osmania General Hospital and Medical College, Hyderabad, India
| | - Rakesh Sahay
- Endocrinology Division, Osmania General Hospital and Medical College, Hyderabad, India
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12
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Mendapara K. Development and evaluation of a chronic kidney disease risk prediction model using random forest. Front Genet 2024; 15:1409755. [PMID: 38993480 PMCID: PMC11236722 DOI: 10.3389/fgene.2024.1409755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/29/2024] [Indexed: 07/13/2024] Open
Abstract
This research aims to advance the detection of Chronic Kidney Disease (CKD) through a novel gene-based predictive model, leveraging recent breakthroughs in gene sequencing. We sourced and merged gene expression profiles of CKD-affected renal tissues from the Gene Expression Omnibus (GEO) database, classifying them into two sets for training and validation in a 7:3 ratio. The training set included 141 CKD and 33 non-CKD specimens, while the validation set had 60 and 14, respectively. The disease risk prediction model was constructed using the training dataset, while the validation dataset confirmed the model's identification capabilities. The development of our predictive model began with evaluating differentially expressed genes (DEGs) between the two groups. We isolated six genes using Lasso and random forest (RF) methods-DUSP1, GADD45B, IFI44L, IFI30, ATF3, and LYZ-which are critical in differentiating CKD from non-CKD tissues. We refined our random forest (RF) model through 10-fold cross-validation, repeated five times, to optimize the mtry parameter. The performance of our model was robust, with an average AUC of 0.979 across the folds, translating to a 91.18% accuracy. Validation tests further confirmed its efficacy, with a 94.59% accuracy and an AUC of 0.990. External validation using dataset GSE180394 yielded an AUC of 0.913, 89.83% accuracy, and a sensitivity rate of 0.889, underscoring the model's reliability. In summary, the study identified critical genetic biomarkers and successfully developed a novel disease risk prediction model for CKD. This model can serve as a valuable tool for CKD disease risk assessment and contribute significantly to CKD identification.
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Affiliation(s)
- Krish Mendapara
- Faculty of Health Sciences, Queen's University, Kingston, ON, Canada
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13
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Vue Z, Prasad P, Le H, Neikirk K, Harris C, Garza-Lopez E, Wang E, Murphy A, Jenkins B, Vang L, Scudese E, Shao B, Kadam A, Shao J, Marshall AG, Crabtree A, Kirk B, Koh A, Wilson G, Oliver A, Rodman T, Kabugi K, Koh HJ, Smith Q, Zaganjor E, Wanjalla CN, Dash C, Evans C, Phillips MA, Hubert D, Ajijola O, Whiteside A, Do Koo Y, Kinder A, Demirci M, Albritton CF, Wandira N, Jamison S, Ahmed T, Saleem M, Tomar D, Williams CR, Sweetwyne MT, Murray SA, Cooper A, Kirabo A, Jadiya P, Quintana A, Katti P, Fu Dai D, McReynolds MR, Hinton A. The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.09.598108. [PMID: 38915644 PMCID: PMC11195114 DOI: 10.1101/2024.06.09.598108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health.
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Affiliation(s)
- Zer Vue
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Praveena Prasad
- Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801
| | - Han Le
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Kit Neikirk
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Chanel Harris
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Edgar Garza-Lopez
- Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA
| | - Eric Wang
- Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA
| | - Alexandria Murphy
- Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801
| | - Brenita Jenkins
- Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801
| | - Larry Vang
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Estevão Scudese
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Bryanna Shao
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Ashlesha Kadam
- Department of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
| | - Jianqiang Shao
- Central Microscopy Research Facility, University of Iowa, Iowa City, IA, 52242, USA
| | - Andrea G. Marshall
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Amber Crabtree
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Benjamin Kirk
- Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA
| | - Alice Koh
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Genesis Wilson
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Ashton Oliver
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Taylor Rodman
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Kinuthia Kabugi
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | - Ho-Jin Koh
- Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA
| | - Quinton Smith
- Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA
| | - Elma Zaganjor
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
| | | | - Chandravanu Dash
- Department of Biochemistry, Cancer Biology, Pharmacology and Neuroscience, Meharry Medical College, Nashville, TN, United States
| | - Chantell Evans
- Department of Cell Biology, Duke University School of Medicine, Durham, NC, 27708, USA
| | - Mark A. Phillips
- Department of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA
| | - David Hubert
- Department of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA
| | - Olujimi Ajijola
- UCLA Cardiac Arrhythmia Center, University of California, Los Angeles, CA, USA
| | - Aaron Whiteside
- Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435 USA
| | - Young Do Koo
- Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA
- Fraternal Order of Eagles Diabetes Research Center, Iowa City, Iowa, USA
| | - André Kinder
- Artur Sá Earp Neto University Center - UNIFASE-FMP, Petrópolis Medical School, Brazil
| | - Mert Demirci
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Claude F. Albritton
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
- Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208-3501, USA
| | - Nelson Wandira
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Sydney Jamison
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Taseer Ahmed
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Mohammad Saleem
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Dhanendra Tomar
- Department of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
| | - Clintoria R. Williams
- Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435 USA
| | - Mariya T. Sweetwyne
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA
| | - Sandra A. Murray
- Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Anthonya Cooper
- Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Annet Kirabo
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
- Vanderbilt Center for Immunobiology, Vanderbilt University, Nashville, TN, 37232, USA
- Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University, Nashville, TN, 37232, USA
- Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN, 37232, USA
| | - Pooja Jadiya
- Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Anita Quintana
- Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, Texas, USA
| | - Prasanna Katti
- National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
- Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, AP, 517619, India
| | - Dao Fu Dai
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Melanie R. McReynolds
- Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801
| | - Antentor Hinton
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
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Pereira R, Vinayakumar KB, Sillankorva S. Polymeric Microneedles for Health Care Monitoring: An Emerging Trend. ACS Sens 2024; 9:2294-2309. [PMID: 38654679 PMCID: PMC11129353 DOI: 10.1021/acssensors.4c00612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 04/09/2024] [Accepted: 04/17/2024] [Indexed: 04/26/2024]
Abstract
Bioanalyte collection by blood draw is a painful process, prone to needle phobia and injuries. Microneedles can be engineered to penetrate the epidermal skin barrier and collect analytes from the interstitial fluid, arising as a safe, painless, and effective alternative to hypodermic needles. Although there are plenty of reviews on the various types of microneedles and their use as drug delivery systems, there is a lack of systematization on the application of polymeric microneedles for diagnosis. In this review, we focus on the current state of the art of this field, while providing information on safety, preclinical and clinical trials, and market distribution, to outline what we believe will be the future of health monitoring.
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Affiliation(s)
- Raquel
L. Pereira
- INL − International Iberian
Nanotechnology Laboratory, Av. Mestre José Veiga, 4715-330 Braga, Portugal
| | - K. B. Vinayakumar
- INL − International Iberian
Nanotechnology Laboratory, Av. Mestre José Veiga, 4715-330 Braga, Portugal
| | - Sanna Sillankorva
- INL − International Iberian
Nanotechnology Laboratory, Av. Mestre José Veiga, 4715-330 Braga, Portugal
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15
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Wu M, Hou W, Qin R, Wang G, Sun D, Geng Y, Du Y. Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease. Front Endocrinol (Lausanne) 2024; 15:1362085. [PMID: 38752174 PMCID: PMC11094205 DOI: 10.3389/fendo.2024.1362085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/15/2024] [Indexed: 05/18/2024] Open
Abstract
Background Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.
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Affiliation(s)
- Miaoling Wu
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang, China
| | - Weiming Hou
- Department of Medical Engineering, Air Force Medical Center, PLA, Beijing, China
| | - Ruonan Qin
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang, China
| | - Gang Wang
- Experimental and Teaching Center, School of Public Health, China Medical University, Shenyang, China
| | - Da Sun
- Department of Nephrology, The First Hospital of China Medical University, Shenyang, China
| | - Ye Geng
- Blood Purification Center, The First Hospital of China Medical University, Shenyang, China
| | - Yinke Du
- Department of Nephrology, The First Hospital of China Medical University, Shenyang, China
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16
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Maranduca MA, Cozma CT, Clim A, Pinzariu AC, Tudorancea I, Popa IP, Lazar CI, Moscalu R, Filip N, Moscalu M, Constantin M, Scripcariu DV, Serban DN, Serban IL. The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease. Curr Issues Mol Biol 2024; 46:3877-3905. [PMID: 38785509 PMCID: PMC11120161 DOI: 10.3390/cimb46050241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024] Open
Abstract
Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.
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Affiliation(s)
- Minela Aida Maranduca
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Cristian Tudor Cozma
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Andreea Clim
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Alin Constantin Pinzariu
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Ionut Tudorancea
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Irene Paula Popa
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Cristina Iuliana Lazar
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Roxana Moscalu
- Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK;
| | - Nina Filip
- Discipline of Biochemistry, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Mihaela Moscalu
- Department of Preventive Medicine and Interdisciplinarity, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Mihai Constantin
- Internal Medicine Department, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Dragos Viorel Scripcariu
- Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania;
| | - Dragomir Nicolae Serban
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
| | - Ionela Lacramioara Serban
- Discipline of Physiology, Department of Morpho-Functional Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.M.); (C.T.C.); (A.C.); (A.C.P.); (I.T.); (I.P.P.); (C.I.L.); (D.N.S.); (I.L.S.)
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Liu H, Xiao H, Lin S, Zhou H, Cheng Y, Xie B, Xu D. Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis. Front Pharmacol 2024; 15:1372399. [PMID: 38725663 PMCID: PMC11079205 DOI: 10.3389/fphar.2024.1372399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 03/25/2024] [Indexed: 05/12/2024] Open
Abstract
Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.
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Affiliation(s)
- Hongyu Liu
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
| | - Huimin Xiao
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
| | - Sufen Lin
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
| | - Huan Zhou
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
| | - Yizhao Cheng
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
| | - Baocheng Xie
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Department of Pharmacy, The 10th Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, China
| | - Daohua Xu
- Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China
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18
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Lalayiannis AD, Soeiro EMD, Moysés RMA, Shroff R. Chronic kidney disease mineral bone disorder in childhood and young adulthood: a 'growing' understanding. Pediatr Nephrol 2024; 39:723-739. [PMID: 37624528 PMCID: PMC10817832 DOI: 10.1007/s00467-023-06109-3] [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: 04/19/2023] [Revised: 07/06/2023] [Accepted: 07/19/2023] [Indexed: 08/26/2023]
Abstract
Chronic kidney disease (CKD) mineral and bone disorder (MBD) comprises a triad of biochemical abnormalities (of calcium, phosphate, parathyroid hormone and vitamin D), bone abnormalities (turnover, mineralization and growth) and extra-skeletal calcification. Mineral dysregulation leads to bone demineralization causing bone pain and an increased fracture risk compared to healthy peers. Vascular calcification, with hydroxyapatite deposition in the vessel wall, is a part of the CKD-MBD spectrum and, in turn, leads to vascular stiffness, left ventricular hypertrophy and a very high cardiovascular mortality risk. While the growing bone requires calcium, excess calcium can deposit in the vessels, such that the intake of calcium, calcium- containing medications and high calcium dialysate need to be carefully regulated. Normal physiological bone mineralization continues into the third decade of life, many years beyond the rapid growth in childhood and adolescence, implying that skeletal calcium requirements are much higher in younger people compared to the elderly. Much of the research into the link between bone (de)mineralization and vascular calcification in CKD has been performed in older adults and these data must not be extrapolated to children or younger adults. In this article, we explore the physiological changes in bone turnover and mineralization in children and young adults, the pathophysiology of mineral bone disease in CKD and a potential link between bone demineralization and vascular calcification.
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Affiliation(s)
- Alexander D Lalayiannis
- Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
- University College London Great Ormond Street Hospital Institute of Child Health, London, UK.
| | | | - Rosa M A Moysés
- Sao Paulo University Faculty of Medicine, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, Brazil
| | - Rukshana Shroff
- University College London Great Ormond Street Hospital Institute of Child Health, London, UK
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19
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Chang TH, Chen YD, Lu HHS, Wu JL, Mak K, Yu CS. Specific patterns and potential risk factors to predict 3-year risk of death among non-cancer patients with advanced chronic kidney disease by machine learning. Medicine (Baltimore) 2024; 103:e37112. [PMID: 38363886 PMCID: PMC10869094 DOI: 10.1097/md.0000000000037112] [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: 10/17/2023] [Accepted: 01/09/2024] [Indexed: 02/18/2024] Open
Abstract
Chronic kidney disease (CKD) is a major public health concern. But there are limited machine learning studies on non-cancer patients with advanced CKD, and the results of machine learning studies on cancer patients with CKD may not apply directly on non-cancer patients. We aimed to conduct a comprehensive investigation of risk factors for a 3-year risk of death among non-cancer advanced CKD patients with an estimated glomerular filtration rate < 60.0 mL/min/1.73m2 by several machine learning algorithms. In this retrospective cohort study, we collected data from in-hospital and emergency care patients from 2 hospitals in Taiwan from 2009 to 2019, including their international classification of disease at admission and laboratory data from the hospital's electronic medical records (EMRs). Several machine learning algorithms were used to analyze the potential impact and degree of influence of each factor on mortality and survival. Data from 2 hospitals in northern Taiwan were collected with 6565 enrolled patients. After data cleaning, 26 risk factors and approximately 3887 advanced CKD patients from Shuang Ho Hospital were used as the training set. The validation set contained 2299 patients from Taipei Medical University Hospital. Predictive variables, such as albumin, PT-INR, and age, were the top 3 significant risk factors with paramount influence on mortality prediction. In the receiver operating characteristic curve, the random forest had the highest values for accuracy above 0.80. MLP, and Adaboost had better performance on sensitivity and F1-score compared to other methods. Additionally, SVM with linear kernel function had the highest specificity of 0.9983, while its sensitivity and F1-score were poor. Logistic regression had the best performance, with an area under the curve of 0.8527. Evaluating Taiwanese advanced CKD patients' EMRs could provide physicians with a good approximation of the patients' 3-year risk of death by machine learning algorithms.
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Affiliation(s)
- Tzu-Hao Chang
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Da Chen
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Henry Horng-Shing Lu
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Institute of Data Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Jenny L. Wu
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | | | - Cheng-Sheng Yu
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
- Clinical Data Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan
- Fintech RD Center, Nan Shan Life Insurance Co., Ltd
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20
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Rafiee MJ, Bandegi P, Taylor JL. Extensive myocardial calcifications in a dialysis patient: A porcelain heart manifesting with abdominal pain. Radiol Case Rep 2024; 19:523-530. [PMID: 38044898 PMCID: PMC10686893 DOI: 10.1016/j.radcr.2023.10.081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/28/2023] [Accepted: 10/30/2023] [Indexed: 12/05/2023] Open
Abstract
This case report describes a 41-year-old male patient with chronic kidney disease on peritoneal dialysis presenting with upper abdominal pain and mild thigh numbness. CT chest demonstrated extensive myocardial calcifications and left atrial thrombus. This case emphasizes the clinical relevance of myocardial calcifications, especially in patients with end-stage renal disease. It also highlights the potential association between these calcifications and complications such as atrial fibrillation and thromboembolic events. The findings emphasize the need for diagnostic vigilance and an improved understanding of the pathophysiology of myocardial calcifications in the context of renal disease.
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Affiliation(s)
- Moezedin Javad Rafiee
- Department of Diagnostic Radiology, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
- Research Institute, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
| | - Pouya Bandegi
- Department of Diagnostic Radiology, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
| | - Jana Lyn Taylor
- Research Institute, McGill University Health Centre, 1001 Blvd Decarie, Montreal, Québec, H4A3J1 Canada
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21
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R, Hasan S, Hamza MB. Renal calcification in children with renal tubular acidosis: What a paediatrician should know. World J Clin Pediatr 2023; 12:295-309. [PMID: 38178934 PMCID: PMC10762599 DOI: 10.5409/wjcp.v12.i5.295] [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: 07/29/2023] [Revised: 09/15/2023] [Accepted: 10/16/2023] [Indexed: 12/08/2023] Open
Abstract
Renal tubular acidosis (RTA) can lead to renal calcification in children, which can cause various complications and impair renal function. This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification, highlighting essential aspects for clinical management. The article analyzed relevant studies to explore the prevalence, risk factors, underlying mechanisms, and clinical implications of renal calcification in children with RTA. Results show that distal RTA (type 1) is particularly associated with nephrocalcinosis, which presents a higher risk of renal calcification. However, there are limitations to the existing literature, including a small number of studies, heterogeneity in methodologies, and potential publication bias. Longitudinal data and control groups are also lacking, which limits our understanding of long-term outcomes and optimal management strategies for children with RTA and renal calcification. Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications. In addition, alkaline therapy remains a cornerstone in the treatment of RTA, aimed at correcting the acid-base imbalance and reducing the formation of kidney stones. Therefore, early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children. Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama, Bahrain, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama, Manama 26671, Manama, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Samir Hasan
- Department of Pediatrics, Faculty of Medicine, Tanta University Hospital, Tanta 31511, Algharbia, Egypt
| | - Mohamed Basiony Hamza
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
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22
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Liu F, Chen H, Cao C, Liang Y, Zhou Y. The role of toll-like receptors (TLRs) and their therapeutic applications in glomerulonephritis. Int Urol Nephrol 2023; 55:2845-2856. [PMID: 37060433 DOI: 10.1007/s11255-023-03592-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 04/07/2023] [Indexed: 04/16/2023]
Abstract
One of the most important features of innate immunity is the presence of a special group of pattern recognition receptors (PRRs) called toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), resulting in a quick and effective immune response to them. Glomerulonephritis (GN) is one of the most important categories of renal disorders characterized by destructive responses of the immune system to the glomerulus. To date, the association of TLRs as important innate immune system members with GN has been one of the topics that attracted the attention of researchers in this field. However, the exact role of these receptors in the immunopathogenesis of GN has not yet been fully discussed. Therefore, this study aims to overview the role of TLRs in GN and the possibility of using them as a potential therapeutic target.
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Affiliation(s)
- Feiyan Liu
- Hemodialysis Room, Nanchang First Hospital, No. 128, Xiangshan North Road, Nanchang, Jiangxi, China
| | - Huimin Chen
- Hemodialysis Room, Nanchang First Hospital, No. 128, Xiangshan North Road, Nanchang, Jiangxi, China
| | - Caixia Cao
- Hemodialysis Room, Nanchang First Hospital, No. 128, Xiangshan North Road, Nanchang, Jiangxi, China
| | - Yanlin Liang
- Hemodialysis Room, Nanchang First Hospital, No. 128, Xiangshan North Road, Nanchang, Jiangxi, China
| | - Ying Zhou
- Hemodialysis Room, Nanchang First Hospital, No. 128, Xiangshan North Road, Nanchang, Jiangxi, China.
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23
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Hung WL, Huang CF, Tsai MH, Liou HH, Liu PY, Fang YW. A New Predictive Equation for Estimating Serum Ionized Calcium Levels in Patients on Chronic Hemodialysis. Med Sci Monit 2023; 29:e941321. [PMID: 37807497 PMCID: PMC10572016 DOI: 10.12659/msm.941321] [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: 06/02/2023] [Accepted: 08/20/2023] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND Circulating calcium mainly carries out its physiologic function in its ionized form (iCa). Clinically, iCa is usually estimated by multiplying the total calcium (TCa) level by 0.5 in the general population, but this method is not accurate when applied to patients on long-term hemodialysis (CHD). Accordingly, this study aimed to develop a predictive function for iCa in patients on CHD by incorporating TCa and other additional variables. MATERIAL AND METHODS This was a retrospective cross-sectional study consisting of 2 cross-sectional datasets: a derivation set including 469 CHD patients in June 2019, and a validation set including 446 CHD patients in September 2019. The derivation set's data were analyzed using the stepwise model selection of machine learning with 10-fold cross-validation to develop a predictive function for iCa. This predictive function was then applied to the validation set's data, and the predictive function's estimated iCa was compared with the actual laboratory iCa by using the paired-samples t test and intraclass correlation coefficient. RESULTS After analyzing the routine laboratory data parameters of patients in the derivation set, the following 5 variables were included in the predictive function of iCa: blood urea nitrogen, creatinine, phosphate, TCa, and albumin. This predictive function was applied to the validation set to yield an estimated iCa level that was not significantly different from the laboratory-measured iCa level of the validation dataset (P=0.676) with an excellent ICC of 0.905. CONCLUSIONS We developed a new predictive function that accurately measures the iCa in patients on CHD by using routine laboratory data.
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Affiliation(s)
- Wei-Li Hung
- Division of General Medicine, Department of Education, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chi-Feng Huang
- Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Ming-Hsien Tsai
- Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- Department of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Hung-Hsiang Liou
- Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan
| | - Pei-Yang Liu
- School of Nutrition and Dietetics, University of Akron, Akron, OH, USA
| | - Yu-Wei Fang
- Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- Department of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
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24
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Davenport A. Calcium balance in peritoneal dialysis patients treated by continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) cyclers. J Nephrol 2023; 36:1867-1876. [PMID: 36862284 PMCID: PMC10543882 DOI: 10.1007/s40620-023-01575-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 12/31/2022] [Indexed: 03/03/2023]
Abstract
INTRODUCTION Although vascular calcification is a recognised complication for haemodialysis patients, peritoneal dialysis (PD) patients are also at risk. As such we wished to review peritoneal and urinary calcium balance and the effect of calcium containing phosphate binders (CCPBs). METHODS Twenty-four-hour peritoneal calcium balance and urinary calcium were reviewed in PD patients undergoing their first assessment of peritoneal membrane function. RESULTS Results from 183 patients, 56.3% male, 30.1% diabetic, mean age 59.4 ± 16.4 years, median 2.0 (2-6) months of PD, 29% treated by automated PD (APD), 26.8% continuous ambulatory (CAPD) and 44.2% APD with a day-time exchange (CCPD) were reviewed. Peritoneal calcium balance was positive in 42.6%, and remained positive in 21.3% after including urinary calcium losses. PD calcium balance was negatively associated with ultrafiltration (odds ratio 0.99 (95% confidence limits 0.98-0.99), p = 0.005. PD calcium balance was lowest with APD (APD - 0.45 (- 0.78 to 0.05) vs CAPD - 0.14 (- 1.18 to 0.59) vs CCPD - 0.03) - 0.48 to 0.5) mmol/day), p < 0.05, with 82.1% of patients with a positive balance prescribed icodextrin, when combining peritoneal and urinary losses. When considering CCPB prescription, then 97.8% of subjects prescribed CCPD had an over-all positive calcium balance. DISCUSSION Over 40% of PD patients had a positive peritoneal calcium balance. Elemental calcium intake from CCPB had a major effect on calcium balance, as median combined peritoneal and urinary calcium losses were < 0.7 mmol/day (26 mg), so caution is required to prevent excessive CCPB prescribing, increasing the exchangeable calcium pool and thus potentially increasing vascular calcification, particularly for anuric patients.
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Affiliation(s)
- Andrew Davenport
- UCL Department of Renal Medicine, Royal Free Hospital, University College London Medical School, London, UK.
- UCL Department of Nephrology, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK.
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25
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Stepanova N. Oxalate Homeostasis in Non-Stone-Forming Chronic Kidney Disease: A Review of Key Findings and Perspectives. Biomedicines 2023; 11:1654. [PMID: 37371749 PMCID: PMC10296321 DOI: 10.3390/biomedicines11061654] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/03/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Chronic kidney disease (CKD) is a significant global public health concern associated with high morbidity and mortality rates. The maintenance of oxalate homeostasis plays a critical role in preserving kidney health, particularly in the context of CKD. Although the relationship between oxalate and kidney stone formation has been extensively investigated, our understanding of oxalate homeostasis in non-stone-forming CKD remains limited. This review aims to present an updated analysis of the existing literature, focusing on the intricate mechanisms involved in oxalate homeostasis in patients with CKD. Furthermore, it explores the key factors that influence oxalate accumulation and discusses the potential role of oxalate in CKD progression and prognosis. The review also emphasizes the significance of the gut-kidney axis in CKD oxalate homeostasis and provides an overview of current therapeutic strategies, as well as potential future approaches. By consolidating important findings and perspectives, this review offers a comprehensive understanding of the present knowledge in this field and identifies promising avenues for further research.
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Affiliation(s)
- Natalia Stepanova
- State Institution «Institute of Nephrology of the National Academy of Medical Sciences of Ukraine», 04050 Kyiv, Ukraine
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26
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Gelli R, Ridi F. Reconsidering the role of albumin towards amorphous calcium phosphate-based calciprotein particles formation and stability from a physico-chemical perspective. Colloids Surf B Biointerfaces 2023; 227:113372. [PMID: 37257300 DOI: 10.1016/j.colsurfb.2023.113372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 03/03/2023] [Accepted: 05/24/2023] [Indexed: 06/02/2023]
Abstract
The formation of calciprotein particles (CPPs) in serum is a physiological phenomenon fundamental to prevent the rise of ectopic calcifications. CPPs are colloidal hybrid particles made of amorphous calcium phosphate stabilized by a protein, fetuin-A. Since albumin is the most abundant protein present in serum, we aimed at understanding if it plays a synergic action together with fetuin-A towards CPPs formation and stability. CPPs were prepared using a constant fetuin-A concentration (5 µM) and different concentrations of albumin (0-606 µM). The stability of CPPs, their crystallization and sedimentation were followed in situ by combining turbidimetry, precipitation analysis and dynamic light scattering. The morphology was investigated by scanning electron microscopy and cryo-transmission electron microscopy, while crystallinity was inspected by infrared spectroscopy. The effect of albumin on the amount of formed CPPs was also studied, as well as the amount of protein adsorbed on CPPs. We found that albumin is not able to prolong the lifetime of the amorphous phase, but it is very effective in delaying the sedimentation of CPPs after crystallization. Albumin also significantly decreases the amount and size of CPPs when present in their synthetic medium, likely playing a fundamental role in our organism together with fetuin-A towards the stabilization of CPPs.
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Affiliation(s)
- Rita Gelli
- Department of Chemistry "Ugo Schiff" and CSGI, University of Florence, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
| | - Francesca Ridi
- Department of Chemistry "Ugo Schiff" and CSGI, University of Florence, via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy
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27
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Coimbra S, Catarino C, Sameiro Faria M, Nunes JPL, Rocha S, Valente MJ, Rocha-Pereira P, Bronze-da-Rocha E, Bettencourt N, Beco A, Marques SHDM, Oliveira JG, Madureira J, Fernandes JC, Miranda V, Belo L, Santos-Silva A. The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis. Biomedicines 2023; 11:biomedicines11041026. [PMID: 37189644 DOI: 10.3390/biomedicines11041026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.
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28
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Fonseca RID, Menezes LRA, Santana-Filho AP, Schiefer EM, Pecoits-Filho R, Stinghen AEM, Sassaki GL. Untargeted plasma 1H NMR-based metabolomic profiling in different stages of chronic kidney disease. J Pharm Biomed Anal 2023; 229:115339. [PMID: 36963247 DOI: 10.1016/j.jpba.2023.115339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/13/2023]
Abstract
Chronic kidney disease (CKD) is a serious public health issue affecting thousands of people worldwide. CKD diagnosis is usually made by Estimated Glomerular Filtration Rate (eGFR) and albuminuria, which limit the knowledge of the mechanisms behind CKD progression. The aim of the present study was to identify changes in the metabolomic profile that occur as CKD advances. In this sense, 77 plasma samples from patients with CDK were evaluated by 1D and 2D Nuclear Magnetic Resonance Spectroscopy (NMR). The NMR data showed significant changes in the metabolomic profile of CKD patients and the control group. Principal component analysis (PCA) clustered CKD and control patients into three distinct groups, control, stage 1 (G1)-stage 4 (G4) and stage 5 (G5). Lactate, glucose, acetate and creatinine were responsible for discriminating the control group from all the others CKD stages. Valine, alanine, glucose, creatinine, glutamate and lactate were responsible for the clustering of G1-G4 stages. G5 was discriminated by calcium ethylenediamine tetraacetic acid, magnesium ethylenediamine tetraacetic acid, creatinine, betaine/choline/trimethylamine N-oxide (TMAO), lactate and acetate. CKD G5 plasma pool which was submitted in MetaboAnalyst 4.0 platform (MetPA) analysis and showed 13 metabolic pathways involved in CKD physiopathology. Metabolic changes associated with glycolysis and gluconeogenesis allowed discriminating between CKD and control patients. The determination of involved molecules in TMAO generation in G5 suggests an important role in this uremic toxin linked to CKD and cardiovascular diseases. The aforementioned results propose the feasibility of metabolic assessment of CKD by NMR during treatment and disease progression.
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Affiliation(s)
| | | | | | - Elberth Manfron Schiefer
- Universidade Tecnológica Federal do Paraná, Av. Sete de Setembro, 3165, Curitiba 80230-901, Brazil
| | - Roberto Pecoits-Filho
- Center for Health and Biological Sciences, Pontifícia Universidade Católica do Paraná, Curitiba CEP 80215-901, Brazil
| | | | - Guilherme Lanzi Sassaki
- Department of Biochemistry and Molecular Biology, Universidade Federal do Paraná, Curitiba 80050-540, Brazil.
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29
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Gaeini Z, Bahadoran Z, Mirmiran P, Feyzi Z, Azizi F. High-Fat Dairy Products May Decrease the Risk of Chronic Kidney Disease Incidence: A Long-Term Prospective Cohort Study. J Ren Nutr 2023; 33:307-315. [PMID: 36270480 DOI: 10.1053/j.jrn.2022.10.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 10/01/2022] [Accepted: 10/11/2022] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE The association between consumption of dairy products and risk of chronic kidney disease (CKD) is under debate. We aimed to determine the potential effects of total and subtypes of dairy intake on the occurrence of CKD. METHODS This study was conducted within the Tehran Lipid and Glucose Study (TLGS) on 2416 CKD-free adults. At baseline, consumption of dairy products was estimated using a validated 168-items semiquantitative food frequency questionnaire. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CKD were calculated in tertile categories of dairy products. Also, the CKD risk was estimated with multivariable Cox regression to substitute total dairy with other dietary protein sources. RESULTS During 8.4 years of follow-up, the incidence rate of CKD was 21%. The participants' mean (±SD) age was 38 (±13) years and 46% were men. Dietary intakes of total dairy, low-fat dairy, and fermented dairy were not associated with CKD risk. There were significant lower risks of CKD in the highest compared to the lowest tertiles of high-fat dairy (HR = 0.76, 95% CI = 0.60-0.95) and high-fat milk (HR = 0.75, 95% CI = 0.59-0.96). However, no significant associations were found between other categories of dairy products and CKD incidence. Substitutions of total dairy with other dietary protein sources were not associated with CKD risk. CONCLUSIONS In this study, higher intakes of high-fat dairy and high-fat milk were associated with lower risks of CKD. No significant associations were found between other dairy products and CKD. More prospective and clinical trials are needed to clarify the issue.
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Affiliation(s)
- Zahra Gaeini
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Feyzi
- Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Song Q, Ruffalo M, Bar-Joseph Z. Using single cell atlas data to reconstruct regulatory networks. Nucleic Acids Res 2023; 51:e38. [PMID: 36762475 PMCID: PMC10123116 DOI: 10.1093/nar/gkad053] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/16/2022] [Accepted: 01/19/2023] [Indexed: 02/11/2023] Open
Abstract
Inference of global gene regulatory networks from omics data is a long-term goal of systems biology. Most methods developed for inferring transcription factor (TF)-gene interactions either relied on a small dataset or used snapshot data which is not suitable for inferring a process that is inherently temporal. Here, we developed a new computational method that combines neural networks and multi-task learning to predict RNA velocity rather than gene expression values. This allows our method to overcome many of the problems faced by prior methods leading to more accurate and more comprehensive set of identified regulatory interactions. Application of our method to atlas scale single cell data from 6 HuBMAP tissues led to several validated and novel predictions and greatly improved on prior methods proposed for this task.
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Affiliation(s)
- Qi Song
- Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
| | - Matthew Ruffalo
- Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
| | - Ziv Bar-Joseph
- Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.,Machine Learning Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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31
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Pediatric CKD-MBD: existing and emerging treatment approaches. Pediatr Nephrol 2022; 37:2599-2614. [PMID: 35038008 DOI: 10.1007/s00467-021-05265-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 07/08/2021] [Accepted: 07/08/2021] [Indexed: 12/13/2022]
Abstract
The effects of bone and mineral metabolism on skeletal formation, as well as vascular and soft tissue calcifications, define chronic kidney disease-metabolic bone disease (CKD-MBD). Treatment recommendations center on establishing adequate vitamin D status, phosphate control through diet restriction and phosphate binders, and the use of vitamin D analogs for specific indications. Several emerging bone-promoting therapies have now been studied in adults with CKD, including bisphosphonates and denosumab. These approaches are associated with improved bone mass and, in some cases, decreased fracture rates in adults with CKD-MBD and are of potential interest for some children with CKD-MBD. In children with CKD and immobilization and/or muscle weakness, bisphosphonates appear to be an effective treatment to increase bone mass; baseline assessment and careful monitoring of bone density and/or bone biopsy findings are important in consideration of any new bone therapies for children with CKD-MBD.
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32
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Hsu CP, Maddox J, Block G, Bartley Y, Yu Z. Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab. J Clin Pharmacol 2022; 62:1132-1141. [PMID: 35304747 PMCID: PMC9542825 DOI: 10.1002/jcph.2050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 03/16/2022] [Indexed: 11/08/2022]
Abstract
We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open-label, parallel-group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end-stage renal disease requiring hemodialysis (ESRD-RH; n = 8), or healthy participants with normal renal function (n = 8). Compared with the group with normal renal function, the mean romosozumab exposure was 31% and 43% higher as measured by Cmax and AUC, respectively, in the severe RI group and similar to those in the ESRD-RH group. For all 3 groups, the maximum mean percent increase in procollagen type 1 N terminal propeptide (P1NP) and decrease in serum C-telopeptide (sCTX) levels from baseline were observed on day 15. Changes in P1NP and sCTX were of similar patterns in all 3 groups. The single dose of romosozumab 210 mg was well tolerated. Adverse events (AEs) were reported for 13 patients (7 patients with severe RI and 6 with ESRD-RH), with no deaths, AEs, or serious AEs leading to withdrawal. The incidence of subjects with postbaseline transient decreases in serum calcium (severe RI, n = 1; ESRD-RH, n = 5) and increases in intact parathyroid hormone (severe RI, n = 7; ESRD-RH, n = 7; healthy, n = 3) were greater in severe RI and ESRD-RH groups than in the healthy group. All reported events of hypocalcemia (severe RI, n = 1; ESRD-RH, n = 4) were asymptomatic. These results support the use of romosozumab without dose adjustment in patients with severe RI or ESRD-RH. This article is protected by copyright. All rights reserved.
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Hasparyk UG, Vigil FMB, Bartolomei VS, Nunes VM, Simões e Silva AC. Chronic Kidney Disease-Mineral Bone Disease biomarkers in kidney transplant patients. Curr Med Chem 2022; 29:5230-5253. [DOI: 10.2174/0929867329666220318105856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/16/2022] [Accepted: 01/20/2022] [Indexed: 11/22/2022]
Abstract
Background:
Chronic Kidney Disease associated with Mineral Bone Disease (CKD-MBD) is frequent in kidney transplant patients. Post-transplantation bone disease is complex, especially in patients with pre-existing metabolic bone disorders that are further affected by immunosuppressive medications and changes in renal allograft function. Main biochemical abnormalities of mineral metabolism in kidney transplantation (KTx) include hypophosphatemia, hyperparathyroidism (HPTH), insufficiency or deficiency of vitamin D, and hypercalcemia.
Objective:
This review aimed to summarize the pathophysiology and main biomarkers of CKD-MBD in KTx.
Methods:
A comprehensive and non-systematic search in PubMed was independently made with an emphasis on biomarkers in mineral bone disease in KTx.
Results:
CKD-MBD can be associated with numerous factors including secondary HPTH, metabolic dysregulations before KTx, and glucocorticoids therapy in post-transplant subjects. Fibroblast growth factor 23 (FGF23) reaches normal levels after KTx with good allograft function, while calcium, vitamin D and phosphorus, ultimately, result in hypercalcemia, persistent vitamin D insufficiency, and hypophosphatemia respectively. As for PTH levels, there is an initial tendency of a significant decrease, followed by a raise due to secondary or tertiary HPTH. In regard to sclerostin levels, there is no consensus in the literature.
Conclusion:
KTx patients should be continuously evaluated for mineral homeostasis and bone status, both cases with successful kidney transplantation and those with reduced functionality. Additional research on CKD-MBD pathophysiology, diagnosis, and management is essential to guarantee long-term graft function, better prognosis, good quality of life, and reduced mortality for KTx patients.
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Affiliation(s)
- Ursula Gramiscelli Hasparyk
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Flávia Maria Borges Vigil
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Victória Soares Bartolomei
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Vitor Moreira Nunes
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Ana Cristina Simões e Silva
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
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Yang YQ, Wang X, Zhang YJ, Chen YF, Wang L, Hu XW, Niu L, Pu HM, Zhang X, Zhang Z, Wang L, Chen FW, Shi J, Ji YQ. Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism. Respirology 2022; 27:645-652. [PMID: 35297140 PMCID: PMC9540334 DOI: 10.1111/resp.14243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 02/10/2022] [Accepted: 02/28/2022] [Indexed: 12/19/2022]
Abstract
Background and objective The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. Methods This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. Results In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid‐ and long‐term mortalities (p <0.05). By including hypocalcaemia, the new 30‐day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well‐performing predictive validity was also verified on a constructed external validation cohort. Conclusion Hypocalcaemia is independently associated with mid‐ and long‐term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE. Currently, pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize pulmonary thromboembolism (PTE) patients with low prognosis risk. In this multicentre research, a new prognosis assessment model including hypocalcaemia, which is confirmed to be independently associated with mid‐ and long‐term PTE mortalities, showed significantly higher specificity with PESI and sPESI and similar sensitivity. See relatedEditorial
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Affiliation(s)
- Yu-Qing Yang
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, China
| | - Xin Wang
- Department of Ultrasound, Peking Union Medical College Hospital, Beijing, China.,Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yun-Jian Zhang
- Department of Respiration, Beijing Jishuitan Hospital, Beijing, China
| | - Yan-Fan Chen
- Department of Respiration, the First Affiliated Hospital of Wenzhou Medical College, Zhejiang, China
| | - Ling Wang
- Department of Respiration, Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Uygur, China
| | - Xiao-Wen Hu
- Department of Respiration, Anhui Provincial Hospital, Hefei, China
| | - Ling Niu
- Department of Respiration, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Uygur, China
| | - Hong-Mei Pu
- Department of Respiration, Yanbian University Affiliated Hospital Organization, Yanji, China
| | - Xin Zhang
- Department of Respiration, Hebei Chest Hospital, Hebei, China
| | - Zhen Zhang
- Department of Respiration, BaoDing No. 1 Hospital, Hebei, China
| | - Lan Wang
- Department of Respiration, Shanghai Pulmonary Hospital, Shanghai, China
| | - Fang-Wei Chen
- Department of Respiration, Zhuzhou People's Hospital of Hunan Province, Hunan, China
| | - Juhong Shi
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.,Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Ying-Qun Ji
- Department of Pulmonary and Critical Care Medicine, East Hospital, Shanghai, China
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35
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Roberts WE, Mangum JE, Schneider PM. Pathophysiology of Demineralization, Part I: Attrition, Erosion, Abfraction, and Noncarious Cervical Lesions. Curr Osteoporos Rep 2022; 20:90-105. [PMID: 35129809 PMCID: PMC8930910 DOI: 10.1007/s11914-022-00722-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2021] [Indexed: 12/14/2022]
Abstract
PURPOSE OF THE REVIEW Compare pathophysiology for infectious and noninfectious demineralization disease relative to mineral maintenance, physiologic fluoride levels, and mechanical degradation. RECENT FINDINGS Environmental acidity, biomechanics, and intercrystalline percolation of endemic fluoride regulate resistance to demineralization relative to osteopenia, noncarious cervical lesions, and dental caries. Demineralization is the most prevalent chronic disease in the world: osteoporosis (OP) >10%, dental caries ~100%. OP is severely debilitating while caries is potentially fatal. Mineralized tissues have a common physiology: cell-mediated apposition, protein matrix, fluid logistics (blood, saliva), intercrystalline ion percolation, cyclic demineralization/remineralization, and acid-based degradation (microbes, clastic cells). Etiology of demineralization involves fluid percolation, metabolism, homeostasis, biomechanics, mechanical wear (attrition or abrasion), and biofilm-related infections. Bone mineral density measurement assesses skeletal mass. Attrition, abrasion, erosion, and abfraction are diagnosed visually, but invisible subsurface caries <400μm cannot be detected. Controlling demineralization at all levels is an important horizon for cost-effective wellness worldwide.
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Affiliation(s)
- W. Eugene Roberts
- grid.257413.60000 0001 2287 3919Indiana University & Purdue University at Indianapolis, 8260 Skipjack Drive, Indianapolis, IN 46236 USA
| | - Jonathan E. Mangum
- grid.1008.90000 0001 2179 088XDepartment of Biochemistry and Pharmacology, Dentistry and Health Sciences, University of Melbourne, Corner Grattan Street and Royal Parade, Parkville, Victoria 3010 Australia
| | - Paul M. Schneider
- grid.1008.90000 0001 2179 088XMelbourne Dental School, University of Melbourne, 720 Swanston St, Melbourne, Victoria 3010 Australia
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Udomkarnjananun S, Phannajit J, Takkavatakarn K, Tumkosit M, Kingpetch K, Avihingsanon Y, Praditpornsilpa K, Eiam-Ong S, Susantitaphong P. Effects of Phosphate Binders on Bone Biomarkers and Bone Density in Hemodialysis Patients. Nephrology (Carlton) 2022; 27:441-449. [PMID: 35044029 DOI: 10.1111/nep.14022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUNDS The incidences of osteoporosis, fracture, and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD-mineral bone disease (CKD-MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in hemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD-MBD. METHODS We conducted a prospective cohort of 65 hemodialysis patients to investigate the effect of 12-month monotherapy of phosphate binders composing calcium-based phosphate binders (CPB) or non-calcium-based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. RESULTS When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1 N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in hemodialysis patients. CONCLUSIONS Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in hemodialysis patients who already had low BMD. P1NP, BALP, and TRAP5b could be used to guide the appropriate management, including anti-resorptive and anabolic medications, and predict low BMD in hemodialysis patients treated with phosphate binders. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Jeerath Phannajit
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kullaya Takkavatakarn
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Monravee Tumkosit
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kanaungnit Kingpetch
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Yingyos Avihingsanon
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kearkiat Praditpornsilpa
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Somchai Eiam-Ong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Paweena Susantitaphong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Sonkar SK, Singh PK, Chandra S, Sonkar GK, Bhosale V, Sharma S. Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients. J Bras Nefrol 2022; 44:329-335. [PMID: 35023538 PMCID: PMC9518627 DOI: 10.1590/2175-8239-jbn-2021-0135] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 10/08/2021] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. OBJECTIVE To investigate cathepsin S as an early biomarker for CVD in patients with CKD. METHODS A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. RESULTS The level of serum Cat S was increased in CKD patients with CVD (p <0.05) as well as in later stages of CKD (p <0.05). CVD was also more common in patients in early stage CKD. In early stages CKD, Cat S and CVD were positively correlated. CONCLUSION These findings suggest that serum Cat S might be useful as an early biomarker for CVD in CKD patients.
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Affiliation(s)
| | | | - Sharad Chandra
- King George's Medical University, Cardiology Department, Lucknow, India
| | | | - Vivek Bhosale
- Central Drug Research Institute, Clinical & Experimental Medicine, Lucknow, India
| | - Sharad Sharma
- Central Drug Research Institute, Clinical & Experimental Medicine, Lucknow, India
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Murthi M, Shaka H, El-Amir Z, Velagapudi S, Jamil A, Wani F, Atluri R, Kumar A, Kichloo A. Association of hypocalcemia with in-hospital mortality and complications in patients with acute pulmonary embolism: results from the 2017 Nationwide Inpatient Sample. BMC Pulm Med 2021; 21:410. [PMID: 34895211 PMCID: PMC8665606 DOI: 10.1186/s12890-021-01784-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 12/09/2021] [Indexed: 12/20/2022] Open
Abstract
Background Acute pulmonary embolism (PE) is a common cause for hospitalization associated with significant mortality and morbidity. Disorders of calcium metabolism are a frequently encountered medical problem. The effect of hypocalcemia is not well defined on the outcomes of patients with PE. We aimed to identify the prognostic value of hypocalcemia in hospitalized PE patients utilizing the 2017 Nationwide Inpatient Sample (NIS).
Methods In this retrospective study, we selected patients with a primary diagnosis of Acute PE using ICD 10 codes. They were further stratified based on the presence of hypocalcemia. We primarily aimed to compare in-hospital mortality for PE patients with and without hypocalcemia. We performed multivariate logistic regression analysis to adjust for potential confounders. We also used propensity‐matched cohort of patients to compare mortality. Results In the 2017 NIS, 187,989 patients had a principal diagnosis of acute PE. Among the above study group, 1565 (0.8%) had an additional diagnosis of hypocalcemia. 12.4% of PE patients with hypocalcemia died in the hospital in comparison to 2.95% without hypocalcemia. On multivariate regression analysis, PE and hypocalcemia patients had 4 times higher odds (aOR-4.03, 95% CI 2.78–5.84, p < 0.001) of in-hospital mortality compared to those with only PE. We observed a similarly high odds of mortality (aOR = 4.4) on 1:1 propensity-matched analysis. The incidence of acute kidney injury (aOR = 2.62, CI 1.95–3.52, p < 0.001), acute respiratory failure (a0R = 1.84, CI 1.42–2.38, p < 0.001), sepsis (aOR = 4.99, CI 3.08–8.11, p < 0.001) and arrhythmias (aOR = 2.63, CI 1.99–3.48, p < 0.001) were also higher for PE patients with hypocalcemia. Conclusion PE patients with hypocalcemia have higher in-hospital mortality than those without hypocalcemia. The in-hospital complications were also higher, along with longer length of stay.
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Affiliation(s)
- Mukunthan Murthi
- John H Stroger Hospital of Cook County, 1969 W Ogden Ave, Chicago, IL, 60612, USA.
| | - Hafeez Shaka
- John H Stroger Hospital of Cook County, 1969 W Ogden Ave, Chicago, IL, 60612, USA
| | - Zain El-Amir
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Sujitha Velagapudi
- John H Stroger Hospital of Cook County, 1969 W Ogden Ave, Chicago, IL, 60612, USA
| | - Abdul Jamil
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Farah Wani
- Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
| | - Ramtej Atluri
- John H Stroger Hospital of Cook County, 1969 W Ogden Ave, Chicago, IL, 60612, USA
| | - Akshay Kumar
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Centre, Pittsburgh, USA
| | - Asim Kichloo
- Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
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Hsieh CC, Chan MJ, Su YJ, Fu JF, Wang IK, Chen CY, Weng CH, Huang WH, Hsu CW, Yen TH. Bone Marrow Hypocellularity in Patients with End-Stage Kidney Disease. Healthcare (Basel) 2021; 9:1452. [PMID: 34828498 PMCID: PMC8621268 DOI: 10.3390/healthcare9111452] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 10/12/2021] [Accepted: 10/22/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. METHODS This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. RESULTS Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66-53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29-0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. CONCLUSION Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.
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Affiliation(s)
- Chia-Chen Hsieh
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Ming-Jen Chan
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Yi-Jiun Su
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333, Taiwan;
| | - Jen-Fen Fu
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
- Department of Medical Research, Chang Gung Memorial Hospital, Linkou 333, Taiwan
| | - I-Kuan Wang
- Department of Nephrology, China Medical University Hospital, Taichung 404, Taiwan;
- College of Medicine, China Medical University, Taichung 406, Taiwan
| | - Chao-Yu Chen
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Cheng-Hao Weng
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Wen-Hung Huang
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Ching-Wei Hsu
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Tzung-Hai Yen
- Clinical Poison Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; (C.-C.H.); (M.-J.C.); (C.-Y.C.); (C.-H.W.); (W.-H.H.); (C.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
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Prenggono MD, Yasmina A, Ariyah M, Wanahari TA, Hasrianti N. The effect of imatinib and nilotinib on blood calcium and blood potassium levels in chronic myeloid leukemia patients: a literature review. Oncol Rev 2021; 15:547. [PMID: 34976304 PMCID: PMC8649642 DOI: 10.4081/oncol.2021.547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/27/2021] [Indexed: 11/24/2022] Open
Abstract
Imatinib and nilotinib are first-line treatments for chronic myeloid leukemia (CML) patients, which act specifically against target cells. However, these drugs may cause side effects, such as electrolyte disturbances. This literature review aimed to provide a comparison of the effects of imatinib and nilotinib on blood potassium and calcium levels. It also summarized their hypothetical mechanism. A comprehensive electronic search of the different databases was conducted using ‘chronic myeloid leukemia’, ‘tyrosine kinase inhibitors’, ‘imatinib’, ‘nilotinib’, ‘potassium’, ‘calcium’, ‘electrolytes’ as keywords. This review used PubMed- MEDLINE, Cochrane Library, and Google Scholar as the source databases. Sixteen articles published from 2006 to 2020 were reviewed. Changes in blood potassium levels range from increased to decreased levels, while changes in blood calcium levels range from the lower normal values to below normal values (hypocalcemia). Tyrosine kinase inhibitors (TKIs), including imatinib and nilotinib, have a non-specific target, namely plateletderived growth factor receptor (PDGFR), which indirectly affects blood potassium and calcium levels in CML patients. The clinical manifestations of these changes vary from being visible only in laboratory tests to displaying a variety of clinical signs and symptoms.
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Affiliation(s)
- Muhammad Darwin Prenggono
- Division of Medical Oncology-Hematology, Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat/Ulin General Hospital, Banjarmasin
| | - Alfi Yasmina
- Department of Pharmacology, Faculty of Medicine, Universitas Lambung Mangkurat, Banjarmasin
| | - Misna Ariyah
- Medical Education Study Program, Faculty of Medicine, Universitas Lambung Mangkurat, Banjarmasin
| | - Tenri Ashari Wanahari
- Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat/Ulin General Hospital, Banjarmasin, Indonesia
| | - Nuvita Hasrianti
- Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat/Ulin General Hospital, Banjarmasin, Indonesia
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Oxlund CS, Hansen H, Hansen S, Rohold A. Progressive valvular calcifications with critical aortic stenosis in a 25-year-old woman with end-stage renal disease on haemodialysis: a case report. EUROPEAN HEART JOURNAL-CASE REPORTS 2021; 5:ytab061. [PMID: 34345761 PMCID: PMC8323062 DOI: 10.1093/ehjcr/ytab061] [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: 05/19/2020] [Revised: 08/26/2020] [Accepted: 01/27/2021] [Indexed: 11/15/2022]
Abstract
Background The increased risk of cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) seems particularly pronounced in patients with concomitant aortic and mitral valvular calcifications. Valvular calcification (VC) is accelerated in patients with CKD and even more so with ESRD and haemodialysis (HD) due to premature endothelial cell dysfunction. Mineral and bone disorder (CKD-MBD) is a common complication of CKD/ESRD and may play a pivotal role in VC. Case summary A 25-year-old woman with congenital hypoplastic kidneys and ESRD on HD from the age of 19 was admitted to the emergency department suffering from chest pain and dyspnoea. Transthoracic echocardiogram (TTE) revealed critical aortic stenosis (AS) with indexed aortic valve area 0.4 cm2/m2, a mean gradient 58 mmHg and a moderate mitral stenosis with a mean gradient 6–8 mmHg developed over the course of 2 years, as a normal TTE was performed at that time. During HD, the patient had longstanding alterations in calcium and phosphate metabolism including secondary hyperparathyroidism that eventually progressed into tertiary hyperparathyroidism. Efforts were made to treat CKD-MBD but patient compliance was low. Subtotal parathyroidectomy was performed 6 months prior to admission. The patient had dual mechanical valve replacement. Discussion Valvular calcification is common in patients with CKD/ESRD and in particular in patients on HD. Rapid progression of valve disease in this case may be related to the combination of low patient adherence and sustained disturbed calcium and phosphate metabolism with tertiary hyperparathyroidism. Transthoracic echocardiogram should be performed in patients on HD even with minor suspicion of VC and in patients with low adherence and disturbance of calcium and phosphate metabolism.
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Affiliation(s)
| | - Helle Hansen
- Department of Nephrology, Sydvestjysk University Hospital, Finsensgade 35, DK-6700 Esbjerg, Denmark
| | - Stinus Hansen
- Department of Endocrinology, Sydvestjysk University Hospital, Finsensgade 35, DK-6700 Esbjerg, Denmark.,Department of Regional Health Research, University of Southern Denmark, J.B Winslowsvej 19,3, DK-5000 Odense C, Denmark
| | - Allan Rohold
- Department of Cardiology, Sydvestjysk University Hospital, Finsensgade 35, DK-6700 Esbjerg, Denmark
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Phannajit J, Wonghakaeo N, Takkavatakarn K, Asawavichienjinda T, Praditpornsilpa K, Eiam-Ong S, Susantitaphong P. The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials. J Nephrol 2021; 35:473-491. [PMID: 34061337 DOI: 10.1007/s40620-021-01065-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/09/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients. METHOD A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables. RESULTS This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed. CONCLUSIONS In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
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Affiliation(s)
- Jeerath Phannajit
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand.,Division of Clinical Epidemiology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Natthaphon Wonghakaeo
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand
| | - Kullaya Takkavatakarn
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand
| | - Thanin Asawavichienjinda
- Division of Clinical Epidemiology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kearkiat Praditpornsilpa
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand
| | - Somchai Eiam-Ong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand
| | - Paweena Susantitaphong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand. .,Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Wu CH, Su HA, Chou CA, Liu JW, Lee CT, Dai LH, Yang CC. An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan. J Formos Med Assoc 2021; 120:1350-1360. [DOI: 10.1016/j.jfma.2020.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/03/2020] [Accepted: 10/12/2020] [Indexed: 01/20/2023] Open
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Nielsen CV, Underbjerg L, Grove-Laugesen D, Sikjaer T, Rejnmark L. Lower Leg Arterial Calcifications Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Hypoparathyroid and Pseudohypoparathyroid Patients. Calcif Tissue Int 2021; 108:775-784. [PMID: 33576839 DOI: 10.1007/s00223-021-00814-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 01/19/2021] [Indexed: 10/22/2022]
Abstract
Hypoparathyroidism (HypoPT) and pseudohypoparathyroidism (PHP) are diseases with abnormal calcium and phosphate homeostasis and low and high PTH levels, respectively. It has been hypothesized that this could dispose to vascular calcifications and thereby perhaps also cardiovascular morbidity. The aim of this study was to assess lower leg arterial calcifications (LLAC) in patients with HypoPT or PHP. Using a cross-sectional design, we measured the LLAC using a high-resolution peripheral quantitative computed tomography (HR-pQCT) scanner in 72 patients with HypoPT and 25 patients with PHP and compared them with findings in 61 controls. LLAC were found in only two (3%) of the controls. Compared to the controls, LLAC were significantly more prevalent in patients with HypoPT (N = 12, [17%], p < 0.01) and PHP (N = 4, [16%], p < 0.04). Compared to the patients without calcifications, patients with calcifications had higher plasma calcium levels and a lower eGFR, as well as they were older and more often males. Plasma phosphate levels and the calcium-phosphate product were not associated with LLAC. In conclusion, we found that HypoPT and PHP are associated with an increased prevalence of vascular calcifications.
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Affiliation(s)
- Catharina Vind Nielsen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
| | - Line Underbjerg
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Diana Grove-Laugesen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Tanja Sikjaer
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Rejnmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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Song Y, Lobene AJ, Wang Y, Hill Gallant KM. The DASH Diet and Cardiometabolic Health and Chronic Kidney Disease: A Narrative Review of the Evidence in East Asian Countries. Nutrients 2021; 13:984. [PMID: 33803731 PMCID: PMC8003274 DOI: 10.3390/nu13030984] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 03/16/2021] [Accepted: 03/16/2021] [Indexed: 02/07/2023] Open
Abstract
The rising incidence of cardiometabolic diseases and chronic kidney disease (CKD) is a leading public health problem in East Asia. Diet is an important modifiable risk factor; thus, adopting a healthy diet such as the Dietary Approaches to Stop Hypertension (DASH) diet may help combat these chronic diseases. The DASH diet was originally developed in a U.S. population, and East Asia is demographically and culturally different from the U.S. Therefore, it is important to examine the evidence regarding the DASH diet and chronic disease in this unique population. This narrative review summarizes the evidence on the DASH diet and cardiometabolic health and CKD in East Asia. Culturally-modified DASH diets have been developed in some East Asian countries. Studies suggest the DASH diet is effective at lowering blood pressure in this population, though the long-term benefits remain unclear. Evidence also suggests the DASH diet may reduce the risk of type 2 diabetes and metabolic syndrome. Further research indicates the DASH diet and its components may reduce CKD risk. However, recommending the DASH diet in those who already have CKD is controversial, as it conflicts with current CKD dietary guidelines, especially in advanced CKD. Notably, current intakes in the general population differ from the DASH dietary pattern, suggesting public health efforts would be needed to encourage adoption of the DASH diet.
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Affiliation(s)
- Yazhen Song
- Peking University Clinical Research Institute, Beijing 100191, China; (Y.S.); (Y.W.)
| | - Andrea J. Lobene
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA;
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE 19713, USA
| | - Yanfang Wang
- Peking University Clinical Research Institute, Beijing 100191, China; (Y.S.); (Y.W.)
| | - Kathleen M. Hill Gallant
- Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA;
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108, USA
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Hashimoto H, Shikuma S, Mandai S, Adachi S, Uchida S. Calcium-based phosphate binder use is associated with lower risk of osteoporosis in hemodialysis patients. Sci Rep 2021; 11:1648. [PMID: 33462371 PMCID: PMC7814124 DOI: 10.1038/s41598-021-81287-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 01/04/2021] [Indexed: 01/29/2023] Open
Abstract
Loss of bone mineral density (BMD) is a substantial risk of mortality in addition to fracture in hemodialysis patients. However, the factors affecting BMD are not fully determined. We conducted a single-center, cross-sectional study on 321 maintenance hemodialysis patients who underwent evaluation of femoral neck BMD using dual-energy X-ray absorptiometry from August 1, 2018, to July 31, 2019. We examined factors associated with osteoporosis defined by T-score of ≤ - 2.5, using logistic regression models. Median age of patients was 66 years, and 131 patients (41%) were diagnosed with osteoporosis. Older age, female, lower body mass index, diabetes mellitus, and higher Kt/V ratios were associated with higher osteoporosis risk. The only medication associated with lower osteoporosis risk was calcium-based phosphate binders (CBPBs) [odds ratio (OR), 0.41; 95% confidence interval (CI), 0.21-0.81]. In particular, CBPB reduced the osteoporosis risk within subgroups with dialysis vintage of ≥ 10 years, albumin level of < 3.5 mg/dL, active vitamin D analog use, and no proton pump inhibitor (PPI) use. In conclusion, CBPB use was associated with lower osteoporosis risk in hemodialysis patients. This effect might be partially attributable to calcium supplementation, given its higher impact in users of active vitamin D analogs or non-users of PPI, which modulate calcium absorption.
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Affiliation(s)
- Hiroko Hashimoto
- Department of Nephrology, Shuuwa General Hospital, 1200 Yaharashinden, Kasukabe, Saitama 344-0035 Japan
| | - Satomi Shikuma
- Department of Nephrology, Shuuwa General Hospital, 1200 Yaharashinden, Kasukabe, Saitama 344-0035 Japan
| | - Shintaro Mandai
- grid.265073.50000 0001 1014 9130Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519 Japan
| | - Susumu Adachi
- Department of Cardiology, Shuuwa General Hospital, 1200 Yaharashinden, Kasukabe, Saitama 344-0035 Japan
| | - Shinichi Uchida
- grid.265073.50000 0001 1014 9130Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519 Japan
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Tang PK, Geddes RF, Chang YM, Jepson RE, Bijsmans E, Elliott J. Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease. J Vet Intern Med 2020; 35:321-332. [PMID: 33368694 PMCID: PMC7848342 DOI: 10.1111/jvim.15996] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 11/23/2020] [Accepted: 12/01/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate-restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats. OBJECTIVES To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate-restricted diet and to explore its role in CKD-mineral and bone disorder (CKD-MBD) in cats. ANIMALS Seventy-one geriatric (≥9 years) euthyroid client-owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD. METHODS Retrospective cross-sectional cohort study. Changes in plasma tCa concentration in the first 200 days of diet transition were assessed using linear regression. Binary logistic regressions were performed to identify risk factors for increasing calcium concentration. Changes in clinicopathological variables associated with CKD-MBD over time were explored using linear mixed model and generalized linear mixed model analyses. RESULTS Lower baseline plasma potassium (odds ratio [OR] = 1.19 per 0.1 mmol/L decrease; P = .003) and phosphate (OR = 1.15 per 0.1 mmol/L decrease; P = .01) concentrations remained independent risk factors for increasing plasma tCa concentration. Plasma creatinine (β = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (β = .64 ± .29 μg/dL; P = .03), phosphate (β = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (β = .103 ± .035 pg/mL; P = .004) concentrations had significantly increased rates of change in cats with increasing plasma tCa concentration over time. CONCLUSION AND CLINICAL IMPORTANCE Lower plasma potassium or phosphate concentrations or both at the time of transition of cats with CKD to a phosphate-restricted diet are independently associated with increased risk of an increase in plasma tCa concentration. Increasing plasma tCa concentration is associated with progression of CKD.
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Affiliation(s)
- Pak-Kan Tang
- Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK
| | - Rebecca F Geddes
- Department of Clinical Science and Services, Royal Veterinary College, University of London, London, UK
| | - Yu-Mei Chang
- Research Support Office, Royal Veterinary College, University of London, London, UK
| | - Rosanne E Jepson
- Department of Clinical Science and Services, Royal Veterinary College, University of London, London, UK
| | | | - Jonathan Elliott
- Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK
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Hanna RM, Ferrey A, Rhee CM, Kalantar-Zadeh K. Renal-Cerebral Pathophysiology: The Interplay Between Chronic Kidney Disease and Cerebrovascular Disease. J Stroke Cerebrovasc Dis 2020; 30:105461. [PMID: 33199089 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105461] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/01/2020] [Accepted: 11/03/2020] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVES Cerebrovascular disease has increasingly been linked to overall vascular health. Pathologic conditions like diabetes, hypertension, and kidney disease have been shown to affect brain health and cerebrovascular and nervous systems. Acute kidney injury (AKI) and chronic Kidney Disease (CKD) represent a variety of vascular insults that can adversely affect cerebral health. Hypertension, fluctuations in blood pressure, and diabetic vasculopathy are known risk factors for cerebrovascular disease associated with CKD. Other emerging areas of interest include endothelial dysfunction, vascular calcification due to calcium and phosphorus metabolism dysregulation, and uremic neuropathy present the next frontier of investigation in CKD and cerebrovascular health. METHODS It has become apparent that the interrelation of AKI and CKD with vascular health, chemical homeostasis, and hormonal regulation upset many aspects of cerebral health and functioning. Stroke is an obvious connection, with CKD patients demonstrating a higher proclivity for cerebrovascular accidents. Cerebral bleeding risk, uremic neuropathies, sodium dysregulation with impacts on nervous system, vascular calcification, and endothelial dysfunction are the next salient areas of research that are likely to reveal key breakthroughs in renal-cerebral pathophysiology. RESULTS In this review nephrological definition are discussed in a neuro-centric manner, and the areas of key overlap between CKD and cerebrovascular pathology are discussed. The multifaceted effects of renal function on the health of the brain are also examined. CONCLUSION This review article aims to create the background for ongoing and future neurological-nephrological collaboration on understanding the special challenges in caring for patients with cerebrovascular disease who also have CKD.
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Affiliation(s)
- Ramy M Hanna
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Antoney Ferrey
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Connie M Rhee
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
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Tang CF, Ding H, Jiao RQ, Wu XX, Kong LD. Possibility of magnesium supplementation for supportive treatment in patients with COVID-19. Eur J Pharmacol 2020; 886:173546. [PMID: 32931782 PMCID: PMC7486870 DOI: 10.1016/j.ejphar.2020.173546] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/30/2020] [Accepted: 09/08/2020] [Indexed: 12/16/2022]
Abstract
Magnesium as an enzymatic activator is essential for various physiological functions such as cell cycle, metabolic regulation, muscle contraction, and vasomotor tone. A growing body of evidence supports that magnesium supplementation (mainly magnesium sulfate and magnesium oxide) prevents or treats various types of disorders or diseases related to respiratory system, reproductive system, nervous system, digestive system, and cardiovascular system as well as kidney injury, diabetes and cancer. The ongoing pandemic coronavirus disease 19 (COVID-19) characterized by respiratory tract symptoms with different degrees of important organ and tissue damages has attracted global attention. Particularly, effective drugs are still lacking in the COVID-19 therapy. In this review, we find and summarize the effectiveness of magnesium supplementation on the disorders or diseases, and provide a reference to the possibility of magnesium supplementation for supportive treatment in patients with COVID-19.
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Affiliation(s)
- Chuan-Feng Tang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China
| | - Hong Ding
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China
| | - Rui-Qing Jiao
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China
| | - Xing-Xin Wu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China
| | - Ling-Dong Kong
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China.
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Hsu CY, Chen LR, Chen KH. Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review. Int J Mol Sci 2020; 21:6846. [PMID: 32961953 PMCID: PMC7555655 DOI: 10.3390/ijms21186846] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 09/13/2020] [Accepted: 09/16/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.
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Affiliation(s)
- Chia-Yu Hsu
- Department of Rehabilitation Medicine, Ten-Chan General Hospital, Zhongli, Taoyuan 320, Taiwan;
- Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan 320, Taiwan
| | - Li-Ru Chen
- Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 104, Taiwan;
- Department of Mechanical Engineering, National Chiao-Tung University, Hsinchu 300, Taiwan
| | - Kuo-Hu Chen
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 231, Taiwan
- Department of Medicine, School of Medicine, Tzu-Chi University, Hualien 970, Taiwan
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