|
1
|
Zhao Z, Sun N, Li C, Kong B, Xia X, Sun F, Liu Q, Cao C. Application of psyllium husk powder addition on the textural properties, oxidative stability and sensory attributes of non-phosphates luncheon meat. Meat Sci 2025; 222:109760. [PMID: 39854910 DOI: 10.1016/j.meatsci.2025.109760] [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: 07/23/2024] [Revised: 11/24/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
This study assessed the textural properties, oxidative stability and sensory attributes of non-phosphates luncheon meat containing different concentrations (0.75 %, 1.00 %, 1.25 %, 1.50 % and 1.75 %, w/w) of psyllium husk powder (PHP). The addition of PHP effectively promoted the emulsion stability and textural properties of non-phosphates luncheon meat, as verified by the changes noted in cooking loss and microstructural observations. Meanwhile, PHP successfully retarded lipid oxidation of non-phosphate luncheon meat during storage in a dose-dependent manner (P < 0.05). Moreover, 1.50 % PHP-addition overcame the quality defects in non-phosphates luncheon meat and was statistically no significant difference or better than the phosphate-added luncheon meat. Thus, 1.50 % PHP-addition exhibited the optimal phosphates-replacing effect in luncheon meat. However, a higher concentration of PHP (1.75 % in present work) exhibited a negative effect on the sensory attributes of non-phosphates luncheon meat. Additionally, hydrogen bonds and disulphide bonds were the major molecular forces in PHP-containing non-phosphates luncheon meat. Our results indicate that the application of PHP could be considered a feasible and practical strategy for processing non-phosphates luncheon meat with superior textural properties and sensory attributes.
Collapse
Affiliation(s)
- Zihan Zhao
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Nan Sun
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Cheng Li
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Baohua Kong
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Xiufang Xia
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Fangda Sun
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China
| | - Qian Liu
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China; Heilongjiang Green Food Science & Research Institute, Harbin, Heilongjiang 150028, China.
| | - Chuanai Cao
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China.
| |
Collapse
|
|
2
|
Gu C, Zhang T, Gao Y, Li X, Yuan X, Wang Q, Liu H, Han R, Li G. Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone Disorder: A Rat Model. Curr Vasc Pharmacol 2024; 22:122-136. [PMID: 37961858 DOI: 10.2174/0115701611254269231105063028] [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: 03/21/2023] [Revised: 08/27/2023] [Accepted: 10/16/2023] [Indexed: 11/15/2023]
Abstract
OBJECTIVE To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI). METHODS Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. LH was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins. RESULTS Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (p<0.01), calcification of the thoracic aorta was reduced (p<0.05, p<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (p<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (p<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (p<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (p<0.05). CONCLUSION LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.
Collapse
Affiliation(s)
- Chao Gu
- Department of Pharmacy, Ordos City Hospital, Dongsheng District, Ordos City, 017000, Inner Mongolia Autonomous Region, China
| | - Ting Zhang
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Yuan Gao
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Xiaojia Li
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Xiaorong Yuan
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Qiwen Wang
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Hong Liu
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Ruilan Han
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| | - Gang Li
- Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China
| |
Collapse
|
|
3
|
Adi M, Ghanbari F, Downie ML, Hung A, Robinson-Cohen C, Manousaki D. Effects of 25-Hydroxyvitamin D Levels on Renal Function: A Bidirectional Mendelian Randomization Study. J Clin Endocrinol Metab 2023; 108:1442-1451. [PMID: 36510827 PMCID: PMC10413421 DOI: 10.1210/clinem/dgac724] [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: 05/16/2022] [Revised: 12/07/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022]
Abstract
CONTEXT Observational studies investigating the role of vitamin D in renal function have yielded inconsistent results. OBJECTIVE We tested whether 25-hydroxyvitamin D (25[OH]D) serum levels are associated with renal function, and inversely, whether altered renal function causes changes in 25(OH)D, using Mendelian randomization (MR). METHODS In this two-sample MR study, we used single nucleotide polymorphisms (SNP) associated with 25(OH)D in 443 734 Europeans and evaluated their effects on estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), chronic kidney disease (CKD) risk and progression in genome-wide association studies totaling over 1 million Europeans. To control for pleiotropy, we also used SNPs solely in DHCR7, CYP2R1, and GC, all genes with known roles in vitamin D metabolism. We performed a reverse MR, using SNPs for the above indices of renal function to study causal effects on 25(OH)D levels. RESULTS We did not find robust evidence supporting effects of 25(OH)D on eGFR, BUN, and CKD or its progression. Our inverse variance weighted MR demonstrated a 0.56 decrease in standardized log-transformed 25(OH)D (95% CI -0.73, -0.41; P = 2.89 × 10-12) per unit increase in log-transformed eGFR. Increased BUN was associated with increased 25(OH)D (β = 0.25, 95% CI 0.15, 0.36; P = 4.12 × 10-6 per unit increase in log-transformed BUN). Finally, genetically predicted CKD conferred a 0.05 increase in standardized log-transformed 25(OH)D level (95% CI 0.04, 0.06; P = 1.06 × 10-13). Other MR methods confirmed the findings of the main analyses. CONCLUSION Genetically predicted CKD, increased BUN, and decreased eGFR are associated with increased 25(OH)D levels, but we found no causal effect of 25(OH)D on renal function in Europeans.
Collapse
Affiliation(s)
- Manel Adi
- Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3T1J4, Canada
| | - Faegheh Ghanbari
- Research Center of the Sainte-Justine University Hospital, University of Montreal, Montreal, QC H3TAC5, Canada
| | - Mallory L Downie
- Department of Renal Medicine, University College London, London NW32PF, UK
| | - Adriana Hung
- Department of Medicine, Vanderbilt University Medical Center, Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37212, USA
| | | | - Despoina Manousaki
- Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3T1J4, Canada
- Research Center of the Sainte-Justine University Hospital, University of Montreal, Montreal, QC H3TAC5, Canada
- Department of Pediatrics, University of Montreal, Montreal, QC H3T1C5, Canada
| |
Collapse
|
|
4
|
Liao J, Zhang Y, Zhang W, Zeng Y, Zhao J, Zhang J, Yao T, Li H, Shen X, Wu G, Zhang W. Different software processing affects the peak picking and metabolic pathway recognition of metabolomics data. J Chromatogr A 2023; 1687:463700. [PMID: 36508769 DOI: 10.1016/j.chroma.2022.463700] [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: 04/05/2022] [Revised: 11/30/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
In untargeted liquid chromatography‒mass spectrometry (LC‒MS) metabolomics studies, data preprocessing and metabolic pathway recognition are crucial for screening important pathways that are disturbed by diseases or restored by drugs. Here, we collected high-resolution mass spectrometry data of serum samples from 221 coronary heart disease (CHD) patients under two different chromatographic columns (BEH amide and C18 column) and evaluated the three commonly used software programs (XCMS, Progenesis QI, MarkerView) from four aspects (including signal drift, peak number, metabolite annotation and metabolic pathway enrichment). The results showed that the data preprocessed by the three software programs have different degrees of signal drift, but the StatTarget could improve the data quality to meet the data analysis requirement after correction. In addition, XCMS surpassed other software in detection of real chromatographic peaks and Progenesis QI was the best performer in terms of the number of metabolite annotation. XCMS and Progenesis QI showed different performance in pathway enrichment. However, metabolic pathways based on the combination of XCMS and Progenesis QI had a high coincidence with Progenesis QI. In addition, we also reported that C18 and amide columns were highly complementary and have great potential for cooperation in the context of metabolic pathways. In this study, the effects of different chromatographic columns and software pretreatments on metabolomics data were evaluated based on clinical large cohort samples, which will provide a reference for the metabolomics of clinical samples and guide subsequent mechanistic research.
Collapse
Affiliation(s)
- Jingyu Liao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Guangdong Pharmaceutical University, Guangdong 510006, China
| | - Yuhao Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wendan Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuanyuan Zeng
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Jing Zhao
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Jingfang Zhang
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Tingting Yao
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Houkai Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaoxu Shen
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
| | - Gaosong Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Weidong Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China
| |
Collapse
|
|
5
|
Caracciolo A, Scalise RFM, Ceresa F, Bagnato G, Versace AG, Licordari R, Perfetti S, Lofrumento F, Irrera N, Santoro D, Patanè F, Di Bella G, Costa F, Micari A. Optimizing the Outcomes of Percutaneous Coronary Intervention in Patients with Chronic Kidney Disease. J Clin Med 2022; 11:2380. [PMID: 35566504 PMCID: PMC9100167 DOI: 10.3390/jcm11092380] [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: 03/12/2022] [Revised: 04/16/2022] [Accepted: 04/20/2022] [Indexed: 12/15/2022] Open
Abstract
Percutaneous coronary intervention (PCI) is one of the most common procedures performed in medicine. However, its net benefit among patients with chronic kidney disease (CKD) is less well established than in the general population. The prevalence of patients suffering from both CAD and CKD is high, and is likely to increase in the coming years. Planning the adequate management of this group of patients is crucial to improve their outcome after PCI. This starts with proper preparation before the procedure, the use of all available means to reduce contrast during the procedure, and the implementation of modern strategies such as radial access and drug-eluting stents. At the end of the procedure, personalized antithrombotic therapy for the patient's specific characteristics is advisable to account for the elevated ischemic and bleeding risk of these patients.
Collapse
Affiliation(s)
- Alessandro Caracciolo
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Renato Francesco Maria Scalise
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Fabrizio Ceresa
- Department of Cardio-Thoraco-Vascular Surgery, Division of Cardiac Surgery, Papardo Hospital, 98158 Messina, Italy; (F.C.); (F.P.)
| | - Gianluca Bagnato
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Antonio Giovanni Versace
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Roberto Licordari
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Silvia Perfetti
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Francesca Lofrumento
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Natasha Irrera
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Domenico Santoro
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Francesco Patanè
- Department of Cardio-Thoraco-Vascular Surgery, Division of Cardiac Surgery, Papardo Hospital, 98158 Messina, Italy; (F.C.); (F.P.)
| | - Gianluca Di Bella
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Francesco Costa
- Department of Clinical and Experimental Medicine, Policlinic “Gaetano Martino”, University of Messina, 98100 Messina, Italy; (A.C.); (R.F.M.S.); (G.B.); (A.G.V.); (R.L.); (S.P.); (F.L.); (N.I.); (D.S.); (G.D.B.)
| | - Antonio Micari
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98100 Messina, Italy
| |
Collapse
|
|
6
|
Liu Q, Qi H, Yao L. A long non-coding RNA H19/microRNA-138/TLR3 network is involved in high phosphorus-mediated vascular calcification and chronic kidney disease. Cell Cycle 2022; 21:1667-1683. [PMID: 35435133 PMCID: PMC9302514 DOI: 10.1080/15384101.2022.2064957] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Vascular calcification, characterized by the accumulation of calcium-phosphate crystals in blood vessels, is a major cause of cardiovascular complications and chronic kidney disease (CKD)-related death. This work focuses on the molecules involved in high-phosphorus-mediated vascular calcification in CKD. A rat model of CKD was established by 5/6 nephrectomy, and the rats were given normal phosphorus diet (NPD) or high phosphorus diet (HPD). HPD decreased kidney function, increased the concentration of calcium ion and damaged vascular structure in the thoracic aorta of diseased rats. A high phosphorus condition enhanced calcium deposition in vascular smooth muscle cells (VSMCs). High phosphorus also increased the expression of RUNX2 whereas reduced the expression of α-SM actin in the aortic tissues and VSMCs. Long non-coding RNA (lncRNA) H19 was upregulated in the aortic tissues after HPD treatment. H19 bound to microRNA (miR)-138 to block its inhibitory effect on TLR3 mRNA and activated the NF-κB signaling pathway. Downregulation of H19 or TLR3 alleviated, whereas downregulation of miR-138 aggravated the calcification and vascular damage in model rats and VSMCs. In conclusion, this study demonstrates that the H19/miR-138/TLR3 axis is involved in high phosphorus-mediated vascular calcification in rats with CKD.
Collapse
Affiliation(s)
- Qiang Liu
- Department of Nephrology, Fuyang Hospital of Anhui Medical University, Fuyang Anhui, P.R. China
| | - Huimeng Qi
- Department of General Practice, Fuyang Hospital of Anhui Medical University, Fuyang Anhui, P.R. China
| | - Li Yao
- Department of Nephrology, The First Hospital of China Medical University, Shenyang Liaoning, P.R. China
| |
Collapse
|
|
7
|
Troost JP, Trachtman H, Spino C, Kaskel FJ, Friedman A, Moxey-Mims MM, Fine RN, Gassman JJ, Kopp JB, Walsh L, Wang R, Gipson DS. Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis. Am J Kidney Dis 2021; 77:216-225. [PMID: 32791086 PMCID: PMC7854818 DOI: 10.1053/j.ajkd.2020.04.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 04/18/2020] [Indexed: 01/01/2023]
Abstract
RATIONALE & OBJECTIVE Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. STUDY DESIGN Cohort analysis of clinical trial participants. SETTING & PARTICIPANTS Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. PREDICTORS Reduction in proteinuria measured during 26 weeks after initiating treatment. OUTCOMES Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. ANALYTICAL APPROACH Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. RESULTS 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). LIMITATIONS Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. CONCLUSIONS These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.
Collapse
Affiliation(s)
- Jonathan P Troost
- Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI.
| | - Howard Trachtman
- Division of Nephrology, Department of Pediatrics, New York University Langone Health, New York, NY
| | - Cathie Spino
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI
| | - Frederick J Kaskel
- Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, NY
| | - Aaron Friedman
- Division of Nephrology, Department of Pediatrics, University of Minnesota, Minneapolis, MN
| | - Marva M Moxey-Mims
- Division of Nephrology, Children's National Hospital, Department of Pediatrics, The George Washington University School of Medicine, Washington, DC
| | - Richard N Fine
- Stony Brook University Medical Center, School of Medicine, Stony Brook, NY
| | - Jennifer J Gassman
- Department of Quantitative Health Sciences at the Cleveland Clinic, Cleveland, OH
| | - Jeffrey B Kopp
- Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | | | | | - Debbie S Gipson
- Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI
| |
Collapse
|
|
8
|
Jha AK, Lata S. Kidney transplantation and cardiomyopathy: Concepts and controversies in clinical decision-making. Clin Transplant 2020; 34:e13795. [PMID: 31991012 DOI: 10.1111/ctr.13795] [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: 06/04/2019] [Revised: 08/21/2019] [Accepted: 01/24/2020] [Indexed: 11/30/2022]
Abstract
Increasing comorbidities and an aging population have led to a tremendous increase in the burden of both kidney and cardiac dysfunction. Concomitant cardiomyopathy exposes the patients with kidney disease to further physiological, hemodynamic, and pathologic alterations. Kidney transplantation imposes lesser anesthetic and surgical complexities compared to another solid organ transplant. The surgical decision-making remains an unsettled issue in these conditions. The surgical choices, techniques, and sequences in kidney transplant and cardiac surgery depend on the pathophysiological perturbations and perioperative outcomes. The absence of randomized controlled trials eludes us from suggesting definite management protocol in patients with end-stage kidney disease with cardiomyopathy. Nevertheless, in this review, we extracted data from published literature to understand the pathophysiologic interactions between end-stage renal diseases with cardiomyopathy and also proposed the management algorithm in this challenging scenario. The proposed management algorithm would ensure consensus across all stakeholders involved in decision-making. Our simplistic evidence-based approach would augur future randomized trials and would further ensure refinement in our management approach after the emergence of more definitive evidence.
Collapse
Affiliation(s)
- Ajay Kumar Jha
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Suman Lata
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| |
Collapse
|
|
9
|
Lioufas N, Toussaint ND, Pedagogos E, Elder G, Badve SV, Pascoe E, Valks A, Hawley C. Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study. BMJ Open 2019; 9:e024382. [PMID: 30796122 PMCID: PMC6398689 DOI: 10.1136/bmjopen-2018-024382] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 10/09/2018] [Accepted: 01/08/2019] [Indexed: 12/25/2022] Open
Abstract
INTRODUCTION Patients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD. METHODS AND ANALYSIS We outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population-the IM pact of P hosphate R eduction O n V ascular E nd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels. ETHICS AND DISSEMINATION Ethical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER ACTRN12610000650099.
Collapse
Affiliation(s)
- Nicole Lioufas
- Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Nigel D Toussaint
- Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | | | - Grahame Elder
- Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia
| | - Sunil V Badve
- Department of Nephrology, St. George Hospital, Sydney, New South Wales, Australia
| | - Elaine Pascoe
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Australasian Kidney Trials Network, Brisbane, Queensland, Australia
| | - Andrea Valks
- University of Queensland, Australasian Kidney Trials Network, Brisbane, Queensland, Australia
| | - Carmel Hawley
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Australasian Kidney Trials Network, Brisbane, Queensland, Australia
| |
Collapse
|
|
10
|
Shimada M, Shutto-Uchita Y, Yamabe H. Lack of Awareness of Dietary Sources of Phosphorus Is a Clinical Concern. In Vivo 2019; 33:11-16. [PMID: 30587596 PMCID: PMC6364062 DOI: 10.21873/invivo.11432] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 10/23/2018] [Accepted: 10/24/2018] [Indexed: 01/04/2023]
Abstract
Hyperphosphatemia is a serious complication in patients with chronic kidney disease (CKD), and is associated with more rapid progression as well as higher risk of mortality, and higher rate of cardiovascular disease accidents. CKD patients are usually advised to adopt a low phosphate diet in addition to phosphate-lowering medications, if necessary. However, there is a lack of awareness of the dietary sources of phosphate, especially hidden phosphate intake from phosphate additives in processed foods and carbonated beverages. Appropriate nutritional education could be an effective solution in reducing phosphate toxicity without introducing an additional pill burden or malnutrition.
Collapse
Affiliation(s)
- Michiko Shimada
- Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | | | | |
Collapse
|
|
11
|
Guedeney P, Sorrentino S, Vogel B, Baber U, Claessen BE, Mehran R. Assessing and minimizing the risk of percutaneous coronary intervention in patients with chronic kidney disease. Expert Rev Cardiovasc Ther 2018; 16:825-835. [DOI: 10.1080/14779072.2018.1526082] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Paul Guedeney
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
- Department of Cardiology, ACTION Study Group, Sorbonne Université - Univ Paris 06 (UPMC), INSERM UMRS 1166, Institut de Cardiologie, Paris, France
| | - Sabato Sorrentino
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
- Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Birgit Vogel
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
| | - Usman Baber
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
| | - Bimmer E. Claessen
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
| | - Roxana Mehran
- The Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, New York, New York, USA
| |
Collapse
|
|
12
|
Zhang H, Chen J, Shen Z, Gu Y, Xu L, Hu J, Zhang X, Ding X. Indoxyl sulfate accelerates vascular smooth muscle cell calcification via microRNA-29b dependent regulation of Wnt/β-catenin signaling. Toxicol Lett 2017; 284:29-36. [PMID: 29195902 DOI: 10.1016/j.toxlet.2017.11.033] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Revised: 11/16/2017] [Accepted: 11/27/2017] [Indexed: 01/21/2023]
Abstract
Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification. We found that vascular miR-29b was down-regulated in radial arteries of patients with end-stage renal disease. Consistently, IS also decreased miR-29b expression in human aortic smooth muscle cells (HASMCs) and potentiated their calcification. MiR-29b mimics significantly suppressed, while miR-29b anti-miR markedly enhanced, IS-induced runt-related transcription factor 2 and osteopontin expression. The expression of Wnt7b/β-catenin in radial arteries was higher in end stage renal disease than in control group, and IS increased Wnt7b/β-catenin expression in HASMCs as early as 3days after stimulation. Furthermore, miR-29b mimics potently repressed Wnt7b/β-catenin protein expression in HASMCs, whereas miR-29b anti-miR increased their expression, indicating miR-29b indeed negatively regulates Wnt7b/β-catenin signaling. Dickkopf-1 protein, the Wnt/β-catenin signaling inhibitor, suppressed anti-miR-29b-enhanced HASMCs calcification. Our data thus indicate that miR-29b downregulation and Wnt/β-catenin signaling activation may be the key mechanism of IS induced vascular calcification in chronic kidney disease.
Collapse
Affiliation(s)
- Han Zhang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
| | - Jing Chen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
| | - Ziyan Shen
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
| | - Yulu Gu
- Shanghai Institute of Kidney and Dialysis, Shanghai, China
| | - Linghan Xu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China
| | - Jiachang Hu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
| | - Xiaoyan Zhang
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.
| |
Collapse
|
|
13
|
Kim KI, Jeong S, Han N, Oh JM, Oh KH, Kim IW. Identification of differentially expressed miRNAs associated with chronic kidney disease-mineral bone disorder. Front Med 2017. [PMID: 28623542 DOI: 10.1007/s11684-017-0541-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD-mineral bone disorder (CKD-MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD-MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational analyses were performed with the imputed microRNA regulation based on weighted ranked expression and putative microRNA targets (IMRE) method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD-MBD. TLR4 levels were significantly downregulated, whereas primiR- 146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.
Collapse
Affiliation(s)
- Kyung Im Kim
- College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea
| | - Sohyun Jeong
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Nayoung Han
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Jung Mi Oh
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Kook-Hwan Oh
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea
| | - In-Wha Kim
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
| |
Collapse
|
|
14
|
Harada K, Suzuki S, Ishii H, Hirayama K, Aoki T, Shibata Y, Negishi Y, Sumi T, Kawashima K, Kunimura A, Tatami Y, Kawamiya T, Yamamoto D, Morimoto R, Yasuda Y, Murohara T. Nutrition Status Predicts Severity of Vascular Calcification in Non-Dialyzed Chronic Kidney Disease. Circ J 2017; 81:316-321. [PMID: 28077811 DOI: 10.1253/circj.cj-16-0911] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Vascular calcification is a major complication in chronic kidney disease (CKD) that increases the risk of adverse clinical outcomes. Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that predicts poor prognosis in elderly subjects. The purpose of the present study was to evaluate the correlation between GNRI and severity of vascular calcification in non-dialyzed CKD patients. METHODS AND RESULTS We enrolled 323 asymptomatic CKD patients. To evaluate abdominal aortic calcification (AAC), we used aortic calcification index (ACI) determined on non-contrast computed tomography. The patients were divided into three groups according to GNRI tertile. Median ACI significantly decreased with increasing GNRI tertile (15.5%, 13.6%, and 7.9%, respectively; P=0.001). On multivariate regression analysis GNRI was significantly correlated with ACI (β=-0.15, P=0.009). We also investigated the combination of GNRI and C-reactive-protein (CRP) for predicting the severity of AAC. Low GNRI and high CRP were significantly associated with severe AAC, compared with high GNRI and low CRP (OR, 4.07; P=0.004). CONCLUSIONS GNRI was significantly associated with AAC in non-dialyzed CKD patients.
Collapse
Affiliation(s)
- Kazuhiro Harada
- Department of Cardiology, Nagoya University Graduate School of Medicine
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Keith M, de Sequera P, Clair F, Pedersini R. Lanthanum carbonate oral powder: satisfaction, preference and adherence in French and Spanish patients with end-stage renal disease. Drugs Context 2016; 5:212300. [PMID: 27803726 PMCID: PMC5081242 DOI: 10.7573/dic.212300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Phosphate binders, such as lanthanum carbonate, control elevated serum-phosphate levels in patients with end-stage renal disease (ESRD). Lanthanum carbonate is available in oral powder and tablet form. The aim of this survey was to investigate satisfaction with, preference for, and adherence to lanthanum carbonate oral powder in patients with ESRD. SCOPE Patients from France and Spain who had been taking lanthanum carbonate powder for at least 4 weeks, and who had experience of other phosphate binders of any formulation, were asked to complete an online or telephone survey. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication-9; preference was measured using 5-point Likert scale agreement ratings; and adherence was measured using the Morisky Medication Adherence Scale-4. Data were evaluated using bivariate analyses. FINDINGS Overall, 160 patients participated (80 per country). Lanthanum carbonate powder was reported to have a higher effectiveness rating (p<0.05), be more convenient (p<0.05), and provide a higher level of satisfaction (p<0.01) than previous binders. There was an overall preference for lanthanum carbonate powder over previous binders of any formulation (p<0.001). Adherence to medication was similar for all binders analysed: 66.3% of French patients adhered to lanthanum carbonate powder, and 65.0% adhered to previous binder treatment (p=not significant); 52.5% of Spanish patients adhered to lanthanum carbonate powder, and 56.3% adhered to previous binder treatment (p=not significant). LIMITATIONS The survey enrolled patients who had already experienced phosphate binders before the study began. Information on patient preferences for and adherence to previous phosphate binders was therefore based on the patients' memories of these experiences, which may have been subject to change over time. Although most participants completed the online survey in this study, a telephone survey was used for individuals who could not access the online version; if only one method of data recording had been used, there may have been reduced variation in responses. CONCLUSION Patients with ESRD report increased satisfaction with and preference for lanthanum carbonate powder over other formulations, suggesting that lanthanum carbonate powder is more convenient and easier to use than other formulations.
Collapse
Affiliation(s)
- Michael Keith
- Global Health Economics & Outcomes Research, Shire, Lexington, MA, USA
| | | | - François Clair
- Clinique Néphrologique Maison Blanche, Vernouillet, France
| | | |
Collapse
|
|
16
|
Yamamoto D, Suzuki S, Ishii H, Hirayama K, Harada K, Aoki T, Shibata Y, Negishi Y, Tatami Y, Sumi T, Ichii T, Kawashima K, Kunimura A, Kawamiya T, Morimoto R, Yasuda Y, Murohara T. Predictors of abdominal aortic calcification progression in patients with chronic kidney disease without hemodialysis. Atherosclerosis 2016; 253:15-21. [PMID: 27573734 DOI: 10.1016/j.atherosclerosis.2016.08.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 08/08/2016] [Accepted: 08/17/2016] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS Abdominal aortic calcification (AAC) is an important predictor of cardiovascular mortality in patients with chronic kidney disease (CKD). However, little is known regarding AAC progression in these patients. This study aimed to identify risk factors associated with AAC progression in patients with CKD without hemodialysis. METHODS We recruited 141 asymptomatic patients with CKD without hemodialysis [median estimated glomerular filtration rate (eGFR), 40.3 mL/min/1.73 m2] and evaluated the progression of the abdominal aortic calcification index (ACI) over 3 years. To identify risk factors contributing to the rate of ACI progression, the associations between baseline clinical characteristics and annual change in ACI for each CKD category were analyzed. The annual change of ACI (ΔACI/year) was calculated as follows: (second ACI - first ACI)/duration between the two evaluations. RESULTS Median ΔACI/year values significantly increased in advanced CKD stages (0.73%, 0.87%, and 2.24%/year for CKD stages G1-2, G3, and G4-5, respectively; p for trend = 0.041). The only independent risk factor for AAC progression in mild to moderate CKD (G1-3, eGFR ≥ 30 mL/min/1.73 m2) was pulse pressure level (β = 0.258, p = 0.012). In contrast, parathyroid hormone (PTH) level was significantly correlated with ΔACI/year (β = 0.426, p = 0.007) among patients with advanced CKD (G4-5, eGFR < 30 mL/min/1.73 m2). CONCLUSIONS This study suggests that the AAC progression rate was significantly accelerated in patients with advanced CKD. In addition, measuring PTH is useful to evaluate both bone turnover and AAC progression in patients with advanced CKD.
Collapse
Affiliation(s)
- Dai Yamamoto
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Susumu Suzuki
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Hideki Ishii
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenshi Hirayama
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiro Harada
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshijiro Aoki
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yohei Shibata
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yosuke Negishi
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yosuke Tatami
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takuya Sumi
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takeo Ichii
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiro Kawashima
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ayako Kunimura
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshiki Kawamiya
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ryota Morimoto
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of CKD Initiatives Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshinari Yasuda
- Department of CKD Initiatives Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| |
Collapse
|
|
17
|
Bhatti NK, Karimi Galougahi K, Paz Y, Nazif T, Moses JW, Leon MB, Stone GW, Kirtane AJ, Karmpaliotis D, Bokhari S, Hardy MA, Dube G, Mohan S, Ratner LE, Cohen DJ, Ali ZA. Diagnosis and Management of Cardiovascular Disease in Advanced and End-Stage Renal Disease. J Am Heart Assoc 2016; 5:JAHA.116.003648. [PMID: 27491836 PMCID: PMC5015288 DOI: 10.1161/jaha.116.003648] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Navdeep K Bhatti
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Keyvan Karimi Galougahi
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Yehuda Paz
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Tamim Nazif
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Jeffrey W Moses
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Martin B Leon
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Gregg W Stone
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Ajay J Kirtane
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Dimitri Karmpaliotis
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| | - Sabahat Bokhari
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Mark A Hardy
- Department of Surgery, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Geoffrey Dube
- Division of Nephrology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Sumit Mohan
- Division of Nephrology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Lloyd E Ratner
- Department of Surgery, New York Presbyterian Hospital and Columbia University, New York, NY
| | - David J Cohen
- Division of Nephrology, New York Presbyterian Hospital and Columbia University, New York, NY
| | - Ziad A Ali
- Division of Cardiology, New York Presbyterian Hospital and Columbia University, New York, NY Cardiovascular Research Foundation, New York, NY
| |
Collapse
|
|
18
|
Liu J, Zhang L, Zhou Y, Zhu D, Wang Q, Hao L. Aberrant activation of Wnt pathways in arteries associates with vascular calcification in chronic kidney disease. Int Urol Nephrol 2016; 48:1313-1319. [DOI: 10.1007/s11255-016-1291-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 04/11/2016] [Indexed: 12/12/2022]
|
|
19
|
Kaur M, Chandran DS, Jaryal AK, Bhowmik D, Agarwal SK, Deepak KK. Baroreflex dysfunction in chronic kidney disease. World J Nephrol 2016; 5:53-65. [PMID: 26788464 PMCID: PMC4707168 DOI: 10.5527/wjn.v5.i1.53] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 10/04/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired baroreflex sensitivity (BRS) resulting in augmented blood pressure (BP) variability and hampered BP regulation. Baroreflex plays a vital role in short term regulation of BP. This review discusses the normal baroreflex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of baroreflex dysfunction in CKD.
Collapse
|
|
20
|
Abstract
A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone-related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes.
Collapse
Affiliation(s)
- Edward R Smith
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
| |
Collapse
|
|
21
|
Hortells L, Sosa C, Millán Á, Sorribas V. Critical Parameters of the In Vitro Method of Vascular Smooth Muscle Cell Calcification. PLoS One 2015; 10:e0141751. [PMID: 26554928 PMCID: PMC4640663 DOI: 10.1371/journal.pone.0141751] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 10/13/2015] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Vascular calcification (VC) is primarily studied using cultures of vascular smooth muscle cells. However, the use of very different protocols and extreme conditions can provide findings unrelated to VC. In this work we aimed to determine the critical experimental parameters that affect calcification in vitro and to determine the relevance to calcification in vivo. EXPERIMENTAL PROCEDURES AND RESULTS Rat VSMC calcification in vitro was studied using different concentrations of fetal calf serum, calcium, and phosphate, in different types of culture media, and using various volumes and rates of change. The bicarbonate content of the media critically affected pH and resulted in supersaturation, depending on the concentration of Ca2+ and Pi. Such supersaturation is a consequence of the high dependence of bicarbonate buffers on CO2 vapor pressure and bicarbonate concentration at pHs above 7.40. Such buffer systems cause considerable pH variations as a result of minor experimental changes. The variations are more critical for DMEM and are negligible when the bicarbonate concentration is reduced to ¼. Particle nucleation and growth were observed by dynamic light scattering and electron microscopy. Using 2mM Pi, particles of ~200nm were observed at 24 hours in MEM and at 1 hour in DMEM. These nuclei grew over time, were deposited in the cells, and caused osteogene expression or cell death, depending on the precipitation rate. TEM observations showed that the initial precipitate was amorphous calcium phosphate (ACP), which converts into hydroxyapatite over time. In blood, the scenario is different, because supersaturation is avoided by a tightly controlled pH of 7.4, which prevents the formation of PO43--containing ACP. CONCLUSIONS The precipitation of ACP in vitro is unrelated to VC in vivo. The model needs to be refined through controlled pH and the use of additional procalcifying agents other than Pi in order to reproduce calcium phosphate deposition in vivo.
Collapse
Affiliation(s)
- Luis Hortells
- Department of Toxicology, University of Zaragoza, Veterinary Faculty, Zaragoza, Spain
| | - Cecilia Sosa
- Department of Toxicology, University of Zaragoza, Veterinary Faculty, Zaragoza, Spain
| | - Ángel Millán
- Institute of Materials Science of Aragón, CSIC – Universidad de Zaragoza, Zaragoza, Spain
| | - Víctor Sorribas
- Department of Toxicology, University of Zaragoza, Veterinary Faculty, Zaragoza, Spain
| |
Collapse
|
|
22
|
Qu Z, Guan Y, Cui L, Song J, Gu J, Zhao H, Xu L, Lu L, Jin Y, Xu GT. Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration. Stem Cell Res Ther 2015; 6:219. [PMID: 26553210 PMCID: PMC4640237 DOI: 10.1186/s13287-015-0207-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 09/08/2015] [Accepted: 09/09/2015] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. METHODS The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. RESULTS We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. CONCLUSIONS We have successfully differentiated rESCs to glia enriched RPCs and retinal neuron enriched RPCs in vitro. The retinal neuron enriched rESC-RPC2 protected the structure and function of retina in rats with genetic retinal degeneration and could be a candidate cell source for treating some degenerative retinal diseases in human trials.
Collapse
Affiliation(s)
- Zepeng Qu
- Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, Room 208, Building 5, 280 South Chongqing Road, Shanghai, 200025, China.
| | - Yuan Guan
- Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, Room 208, Building 5, 280 South Chongqing Road, Shanghai, 200025, China.
| | - Lu Cui
- Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, Room 208, Building 5, 280 South Chongqing Road, Shanghai, 200025, China.
| | - Jian Song
- ShanghaiTech University School of Life Science and Technology, Shanghai, 201210, China.
| | - Junjie Gu
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China.
| | - Hanzhi Zhao
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China.
| | - Lei Xu
- Department of Regenerative Medicine, Stem Cell Research Center, and Institute for Nutritional Sciences, Tongji University School of Medicine, Shanghai, 200092, China.
| | - Lixia Lu
- Department of Ophthalmology of Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University School of Medicine, 1239 Siping Road, Medical Building, Room 521, Shanghai, 200092, China.
- Department of Regenerative Medicine, Stem Cell Research Center, and Institute for Nutritional Sciences, Tongji University School of Medicine, Shanghai, 200092, China.
| | - Ying Jin
- Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, Room 208, Building 5, 280 South Chongqing Road, Shanghai, 200025, China.
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China.
- ShanghaiTech University School of Life Science and Technology, Shanghai, 201210, China.
| | - Guo-Tong Xu
- Department of Ophthalmology of Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Science of Tongji Eye Institute, Tongji University School of Medicine, 1239 Siping Road, Medical Building, Room 521, Shanghai, 200092, China.
- Department of Regenerative Medicine, Stem Cell Research Center, and Institute for Nutritional Sciences, Tongji University School of Medicine, Shanghai, 200092, China.
| |
Collapse
|
|
23
|
Zoccali C, Mallamaci F, Cannata-Andía J. Phosphate Binders and Clinical Outcomes in Patients with Stage 5D Chronic Kidney Disease. Semin Dial 2015; 28:587-93. [PMID: 26278591 DOI: 10.1111/sdi.12416] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Knowledge informing the prescription and the choice of phosphate binders in end stage kidney disease (ESKD) patients has a weak evidentiary base. To date, no placebo-controlled trial based on meaningful clinical endpoints (death, cardiovascular events, bone fractures) has been performed to test the efficacy of these drugs. By the same token, we still lack solid proof that noncalcium binders afford better clinical outcomes as compared with calcium-based binders. Without proper trials, clinical decisions about the treatment of hyperphosphatemia rest on experience and contingent clinical judgment. The use of huge doses of calcium-based binders typically prescribed in the nineties now appears unwarranted. The relationship between phosphate and the risk of death is U shaped and moderate hyperphosphatemia carries just a mild-to-moderate risk excess and may not be seen as a compelling indication for the prescription of phosphate binders. Placebo-controlled randomized clinical trials assessing whether non-calcium and calcium-based binders reduce the risk of death and cardiovascular disease events in ESKD patients remain a public health priority.
Collapse
Affiliation(s)
- Carmine Zoccali
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Cal c/o Ospedali Riuniti, Reggio Cal, Italy
| | - Francesca Mallamaci
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Cal c/o Ospedali Riuniti, Reggio Cal, Italy.,Nephrology, Transplantation and Hypertension Division, Ospedali Riuniti, Reggio Cal, Italy
| | - Jorge Cannata-Andía
- Bone and Mineral Research Unit, Reina Sofia Research Institute of the Hospital, Universitario Central de Asturias.,Department of Medicine, University of Oviedo, Oviedo, Spain
| |
Collapse
|
|
24
|
Cannata-Andía JB, Martin KJ. The challenge of controlling phosphorus in chronic kidney disease. Nephrol Dial Transplant 2015; 31:541-7. [PMID: 25770169 DOI: 10.1093/ndt/gfv055] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 01/30/2015] [Indexed: 01/26/2023] Open
Abstract
The pathogenesis and management of chronic kidney disease-mineral bone disorders (CKD-MBD) has experienced major changes, but the control of serum phosphorus at all stages of CKD still seems to be a key factor to improve clinical outcomes. High serum phosphorus is the most important uremia-related, non-traditional risk factor associated with vascular calcification in CKD patients and in the general population. Phosphorus may also be one of the key elements linking vascular calcification with low bone turnover. The main hormones and factors that contribute to the kidney regulation of phosphorus and calcium include parathyroid hormone, FGF-23, klotho and 1,25-dihydroxyvitamin D (1,25(OH)2D). Serum phosphorus did not start rising until CKD 3b in contrast with the earlier changes observed with fibroblast growth factor-23 (FGF-23), Klotho, calcitriol and parathyroid hormone (PTH). Despite FGF-23 and PTH having synergic effects regarding phosphorus removal, they have opposite effects on 1,25(OH)2D3. At the same stages of CKD in which phosphorus retention appears to occur, calcium retention also occurs. As phosphorus accumulation is associated with poor outcomes, an important question without a clear answer is at which level-range should serum phosphorus be maintained at different stages of CKD to improve clinical outcomes. There are four main strategies to manage phosphate homeostasis; phosphorus dietary intake, administration of phosphate binder agents, effective control of hyperparathyroidism and to ensure in the CKD 5D setting, an adequate scheme of dialysis. Despite all the available strategies, and the introduction of new phosphate binder agents in the market, controlling serum phosphorus remains challenging, and hyperphosphatemia continues to be extremely common in CKD 5 patients. Furthermore, despite phosphate binding agents having proved to be effective in reducing serum phosphorus, their ultimate effects on clinical outcomes remain controversial. Thus, we still need well-designed, large-scale, placebo-controlled studies to definitively prove that the reduction of serum phosphorus by phosphate binders improves clinical outcomes.
Collapse
Affiliation(s)
- Jorge B Cannata-Andía
- Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, University of Oviedo, Asturias, Spain
| | - Kevin J Martin
- Division of Nephrology, Saint Louis University School of Medicine, St. Louis, MO, USA
| |
Collapse
|
|
25
|
Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register TC, Freedman BI, Monier-Faugere MC, Malluche H, Hruska KA. CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol 2014; 25:1760-73. [PMID: 24578135 DOI: 10.1681/asn.2013080818] [Citation(s) in RCA: 119] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
In chronic kidney disease, vascular calcification, renal osteodystrophy, and phosphate contribute substantially to cardiovascular risk and are components of CKD-mineral and bone disorder (CKD-MBD). The cause of this syndrome is unknown. Additionally, no therapy addresses cardiovascular risk in CKD. In its inception, CKD-MBD is characterized by osteodystrophy, vascular calcification, and stimulation of osteocyte secretion. We tested the hypothesis that increased production of circulating factors by diseased kidneys causes the CKD-MBD in diabetic mice subjected to renal injury to induce stage 2 CKD (CKD-2 mice). Compared with non-CKD diabetic controls, CKD-2 mice showed increased renal production of Wnt inhibitor family members and higher levels of circulating Dickkopf-1 (Dkk1), sclerostin, and secreted klotho. Neutralization of Dkk1 in CKD-2 mice by administration of a monoclonal antibody after renal injury stimulated bone formation rates, corrected the osteodystrophy, and prevented CKD-stimulated vascular calcification. Mechanistically, neutralization of Dkk1 suppressed aortic expression of the osteoblastic transcription factor Runx2, increased expression of vascular smooth muscle protein 22-α, and restored aortic expression of klotho. Neutralization of Dkk1 did not affect the elevated plasma levels of osteocytic fibroblast growth factor 23 but decreased the elevated levels of sclerostin. Phosphate binder therapy restored plasma fibroblast growth factor 23 levels but had no effect on vascular calcification or osteodystrophy. The combination of the Dkk1 antibody and phosphate binder therapy completely treated the CKD-MBD. These results show that circulating Wnt inhibitors are involved in the pathogenesis of CKD-MBD and that the combination of Dkk1 neutralization and phosphate binding may have therapeutic potential for this disorder.
Collapse
Affiliation(s)
- Yifu Fang
- Departments of Pediatrics/Nephrology and
| | | | - Michael Seifert
- Departments of Pediatrics/Nephrology and Department of Pediatric Nephrology, Southern Illinois School of Medicine, Springfield, Illinois
| | | | | | | | - Barry I Freedman
- Internal Medicine/Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina; and
| | | | - Hartmut Malluche
- Department of Medicine/Nephrology, University of Kentucky, Lexington, Kentucky
| | - Keith A Hruska
- Departments of Pediatrics/Nephrology and Medicine, Washington University, St. Louis, Missouri;
| |
Collapse
|
|
26
|
Jimbo R, Shimosawa T. Cardiovascular Risk Factors and Chronic Kidney Disease-FGF23: A Key Molecule in the Cardiovascular Disease. Int J Hypertens 2014; 2014:381082. [PMID: 24678415 PMCID: PMC3941790 DOI: 10.1155/2014/381082] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Accepted: 12/23/2013] [Indexed: 02/06/2023] Open
Abstract
Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients.
Collapse
Affiliation(s)
- Rika Jimbo
- Department of Internal Medicine, Odaira-Memorial Tokyo Hitachi Hospital, 3-5-7 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Tatsuo Shimosawa
- Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
| |
Collapse
|
|
27
|
Fang Y, Ginsberg C, Sugatani T, Monier-Faugere MC, Malluche H, Hruska KA. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int 2014; 85:142-50. [PMID: 23884339 PMCID: PMC3836911 DOI: 10.1038/ki.2013.271] [Citation(s) in RCA: 156] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Revised: 05/09/2013] [Accepted: 05/16/2013] [Indexed: 01/15/2023]
Abstract
The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor Runx2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham-operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low-turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low-turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD.
Collapse
Affiliation(s)
- Yifu Fang
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA
| | - Charles Ginsberg
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA
| | - Toshifumi Sugatani
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA
| | | | - Hartmut Malluche
- Division of Nephrology, Department of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Keith A Hruska
- Division of Pediatric Nephrology, Department of Pediatrics, Washington University, St Louis, Missouri, USA
| |
Collapse
|
|
28
|
In and out of the bone: can the osteocyte escape skeletal jail and yet regulate mineralization? Kidney Int 2014; 85:11-2. [DOI: 10.1038/ki.2013.296] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
29
|
Shutto Y, Shimada M, Kitajima M, Yamabe H, Saitoh Y, Saitoh H, Razzaque MS. Inadequate awareness among chronic kidney disease patients regarding food and drinks containing artificially added phosphate. PLoS One 2013; 8:e78660. [PMID: 24236030 PMCID: PMC3827266 DOI: 10.1371/journal.pone.0078660] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Accepted: 09/21/2013] [Indexed: 12/03/2022] Open
Abstract
Hyperphosphatemia is an important determinant of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with CKD are advised to consume a low phosphate diet and are often prescribed phosphate-lowering drug therapy. However, commercially processed food and drinks often contain phosphate compounds, but the phosphate level is not usually provided in the ingredient list, which makes it difficult for CKD patients to choose a correct diet. We conducted a survey of the awareness of food/beverages containing artificially added phosphate among CKD patients undergoing hemodialysis. The subjects were 153 patients (77 males and 76 females; average age 56±11 years) who were randomly selected from the Dialysis Center of Hirosaki City, Japan. The subjects were provided with a list of questions. The survey results showed that 93% of the subjects were aware of the presence of high sugar content in soda, whereas only 25% were aware of the presence of phosphate (phosphoric acid) in such drinks. Despite 78% of the subjects being aware of the detrimental effects of consumption of a high phosphate diet, 43% drank at least 1 to 5 cans of soda per week and about 17% consumed “fast food” once each week. We also assessed the immediate effects of high-phosphate containing carbonated soda consumption by determining urinary calcium, phosphate, protein and sugar contents in overnight fasted healthy volunteers (n = 55; average age 20.7±0.3 years old, 20 males and 35 females). Significantly higher urinary calcium (adjusted using urinary creatinine) excretion was found 2 h after consuming 350 ml of carbonated soda compared to the fasting baseline level (0.15±0.01 vs. 0.09±0.01, p = 0.001). Our survey results suggest that CKD patients undergoing hemodialysis are not adequately aware of the hidden source of phosphate in their diet, and emphasize the need for educational initiatives to raise awareness of this issue among CKD patients.
Collapse
Affiliation(s)
- Yoshiko Shutto
- Department of Health Promotion, Hirosaki University Graduate School of Health Sciences, Hirosaki, Japan
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Phan O, Maillard M, Peregaux C, Mordasini D, Stehle JC, Funk F, Burnier M. PA21, a new iron-based noncalcium phosphate binder, prevents vascular calcification in chronic renal failure rats. J Pharmacol Exp Ther 2013; 346:281-9. [PMID: 23697346 DOI: 10.1124/jpet.113.204792] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.
Collapse
Affiliation(s)
- Olivier Phan
- Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
| | | | | | | | | | | | | |
Collapse
|
|
31
|
Cannata-Andía JB, Fernández-Martín JL, Locatelli F, London G, Gorriz JL, Floege J, Ketteler M, Ferreira A, Covic A, Rutkowski B, Memmos D, Bos WJ, Teplan V, Nagy J, Tielemans C, Verbeelen D, Goldsmith D, Kramar R, Martin PY, Wüthrich RP, Pavlovic D, Benedik M, Sánchez JE, Martínez-Camblor P, Naves-Díaz M, Carrero JJ, Zoccali C. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int 2013; 84:998-1008. [PMID: 23823605 DOI: 10.1038/ki.2013.185] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 01/31/2013] [Accepted: 02/14/2013] [Indexed: 11/09/2022]
Abstract
Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.
Collapse
Affiliation(s)
- Jorge B Cannata-Andía
- Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Hajhosseiny R, Khavandi K, Goldsmith DJ. Cardiovascular disease in chronic kidney disease: untying the Gordian knot. Int J Clin Pract 2013; 67:14-31. [PMID: 22780692 DOI: 10.1111/j.1742-1241.2012.02954.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Chronic kidney disease (CKD) affects around 10-13% of the general population, with only a small proportion in end stage renal disease (ESRD), either on dialysis or awaiting renal transplantation. It is well documented that CKD patients have an extremely high risk of developing cardiovascular disease (CVD) compared with the general population, so much so that in the early stages of CKD patients are more likely to develop CVD than they are to progress to ESRD. Various pathophysiological pathways and explanations have been advanced and suggested to account for this, including endothelial dysfunction, dyslipidaemia, inflammation, left ventricular hypertrophy and cardiac autonomic dysfunction. In this review, we try to understand and further explore the link between CKD and CVD, as well as offering interventional advice where available, while exposing the current lack of RCT-based research and trial evidence in this area. We also suggest pragmatic Interim measures we could take while we wait for definitive RCTs.
Collapse
Affiliation(s)
- R Hajhosseiny
- MRC Centre for Transplantation and Renal Unit, Guy's & St. Thomas' NHS Foundation Trust, King's College Academic Health Partners, London, UK
| | | | | |
Collapse
|
|
33
|
|
|
34
|
Sharain K, Hoppensteadt D, Bansal V, Singh A, Fareed J. Progressive Increase of Inflammatory Biomarkers in Chronic Kidney Disease and End-Stage Renal Disease. Clin Appl Thromb Hemost 2012; 19:303-8. [DOI: 10.1177/1076029612454935] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Chronic kidney disease (CKD) has reached epidemic levels. It is a multisystem disease associated with elevated systemic inflammatory and hypercoagulable states. Most concerning are the cardiovascular risks associated with all stages of kidney disease. It is difficult to assess kidney disease stage progression and cardiovascular risk with current indicators such as estimated glomerular filtration rate and conventional cardiovascular risk factors. However, the use of biomarkers to assess the underlying pathological disease state may bridge the gap. This study evaluated biomarkers of inflammation including C-reactive protein, d-dimer, neuron-specific enolase, neutrophil gelatinase–associated lipocalin, tumor necrosis factor receptor I, and thrombomodulin in 3 groups of patients: CKD stages 2-4, end-stage renal disease (ESRD), and age-matched controls. The study demonstrated a statistically significant progressive upregulation in mean concentration of all markers when comparing controls to CKD and ESRD. Therefore, biomarkers may be able to evaluate the inflammatory state in kidney disease and potentially predict the cardiovascular risk.
Collapse
Affiliation(s)
- Korosh Sharain
- Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Debra Hoppensteadt
- Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Vinod Bansal
- Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Ajay Singh
- Department of Medicine and Renal Division, Brigham and Women’s Hospital, Boston, MA, USA
| | - Jawed Fareed
- Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| |
Collapse
|
|
35
|
TOUSSAINT NIGELD, PEDAGOGOS EUGENIE, TAN SVENJEAN, BADVE SUNILV, HAWLEY CARMELM, PERKOVIC VLADO, ELDER GRAHAMEJ. Phosphate in early chronic kidney disease: Associations with clinical outcomes and a target to reduce cardiovascular risk. Nephrology (Carlton) 2012; 17:433-44. [DOI: 10.1111/j.1440-1797.2012.01618.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
36
|
Choo JCJ, Ong SY, Krishnasamy T, Foo MWY. The Singapore General Hospital Peritoneal Dialysis Programme from 2000–2008. PROCEEDINGS OF SINGAPORE HEALTHCARE 2012. [DOI: 10.1177/201010581202100207] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Introduction: There is lack of data regarding outcomes of peritoneal dialysis (PD) in Singapore. The aim of this study is to retrospectively evaluate the patient characteristics, technique survival, and patient survival in a single centre. Methods: The retrospective review included 1,015 adults (47.3% female, 72.6% Chinese, mean age 58±12.4 years, mean follow-up 39.7±27.7 months) initiated on PD at the Singapore General Hospital from January 2000 to December 2008. Baseline characteristics, including cause of end-stage renal disease (ESRD), comorbid conditions, and endpoints (ie. death, transfer to HD or transplantation, renal recovery or until last follow-up on 31 December 2010) were collected. Demographic variables and patient and technique survival rates were analysed. Results: The main causes of ESRD were diabetes mellitus (DM) (58.0%), glomerulonephritis (GN) (23.3%) and hypertension (15.4%). The 1, 2, 5 and 10-year patient survival rates were 88.7%, 77.7%, 39.8% and 15.4%, respectively. Causes of death were related to infection (43.1%) and cardiac (37.8%). Patient survival rates were significantly better in PD patients with ESRD due to GN, compared with DM (5-year survival rates of 70.2% versus 22.3%, P <0.001). Patients aged 65 years and older had lower survival rates compared with those aged less than 65 years ( P <0.001). The 1, 2, 5 and 10-year technique survival rates were 92.9%, 85.0%, 64.8% and 32.9%, respectively. Peritonitis was the main cause of technique failure (63.5%), and caused 13.8% of deaths. Technique survival rates were better in patients with ESRD due to GN, compared with DM (5-year survival rates of 70.9% versus 62.0%, P <0.05). Conclusion: In our single-centre retrospective review, technique survival was comparable to other East Asian centres. The poorer patient survival observed in this study may be due to older age and higher comorbidity.
Collapse
|
|
37
|
Vervloet MG, van Zuilen AD, Heijboer AC, ter Wee PM, Bots ML, Blankestijn PJ, Wetzels JFM. Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: an analysis of the MASTERPLAN cohort. BMC Nephrol 2012; 13:20. [PMID: 22530966 PMCID: PMC3366907 DOI: 10.1186/1471-2369-13-20] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 04/24/2012] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fibroblast growth factor 23 (FGF23) has emerged as a risk factor for cardiovascular disease and mortality throughout all stages of chronic kidney disease (CKD), independent from established risk factors and markers of mineral homeostasis. The relation of FGF23 with other renal and non-renal cardiovascular risk factors is not well established. METHODS Using stored samples, plasma FGF23 was determined in 604 patients with moderate to severe kidney disease that participated in the MASTERPLAN study (ISRCTN73187232). The association of FGF23 with demographic and clinical parameters was evaluated using multivariable regression models. RESULTS Mean age in the study population was 60 years and eGFR was 37 (± 14) ml/min/1.73 m(2). Median proteinuria was 0.3 g/24 hours [IQR 0.1-0.9]. FGF23 level was 116 RU/ml [67-203] median and IQR. Using multivariable analysis the natural logarithm of FGF23 was positively associated with history of cardiovascular disease (B = 0.224 RU/ml; p = 0.002), presence of diabetes (B = 0.159 RU/ml; p = 0.035), smoking (B = 0.313 RU/ml; p < 0.001), phosphate level (B = 0.297 per mmol/l; p = 0.0024), lnPTH (B = 0.244 per pmol/l; p < 0.001) and proteinuria (B = 0.064 per gram/24 hrs; p = 0.002) and negatively associated with eGFR (B = -0.022 per ml/min/1.73 m(2); p < 0.001). CONCLUSIONS Our study demonstrates that in patients with CKD, FGF23 is related to proteinuria and smoking. We confirm the relation between FGF23 and other cardiovascular risk factors.
Collapse
Affiliation(s)
- Marc G Vervloet
- Department of Nephrology and ICaR-VU, VU university medical centre, Amsterdam, The Netherlands.
| | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Di Iorio B, Di Micco L, Torraca S, Sirico ML, Russo L, Pota A, Mirenghi F, Russo D. Acute Effects of Very-Low-Protein Diet on FGF23 Levels: A Randomized Study. Clin J Am Soc Nephrol 2012; 7:581-7. [DOI: 10.2215/cjn.07640711] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
|
|
39
|
Shutto Y, Shimada M, Kitajima M, Yamabe H, Razzaque MS. Lack of awareness among future medical professionals about the risk of consuming hidden phosphate-containing processed food and drinks. PLoS One 2011; 6:e29105. [PMID: 22220204 PMCID: PMC3248402 DOI: 10.1371/journal.pone.0029105] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Accepted: 11/21/2011] [Indexed: 12/17/2022] Open
Abstract
Phosphate toxicity is an important determinant of mortality in patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis treatments. CKD patients are advised to take a low phosphate-containing diet, and are additionally prescribed with phosphate-lowering drugs. Since these patients usually seek guidance from their physicians and nurses for their dietary options, we conducted a survey to determine the levels of awareness regarding the high phosphate content in commercially processed food and drinks among medical and nursing students at the Hirosaki University School of Medicine in Japan. For this survey, 190 medical and nursing students (average age 21.7±3 years) were randomly selected, and provided with a list of questions aimed at evaluating their awareness of food and drinks containing artificially added phosphate ingredients. While 98.9% of these students were aware of the presence of sugar in commercially available soda drinks, only 6.9% were aware of the presence of phosphate (phosphoric acid). Similarly, only 11.6% of these students were aware of the presence of phosphate in commercially processed food, such as hamburgers and pizza. Moreover, around two thirds of the surveyed students (67.7%) were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. About 28% of the surveyed students consume such "fast food" once a week, while 40% drink at least 1∼5 cans of soda drinks/week. After realizing the potential long-term risks of consuming excessive phosphate-containing food and drinks, 40.5% of the survey participants considered reducing their phosphate intake by minimizing the consumption of commercially processed "fast food" items and soda drinks. Moreover, another 48.4% of students showed interest in obtaining more information on the negative health effects of consuming excessive amounts of phosphate. This survey emphasizes the need for educational initiative to raise awareness of the health risks posed by excessive consumption of phosphate additives.
Collapse
Affiliation(s)
- Yoshiko Shutto
- Department of Health Promotion, Hirosaki University Graduate School of Health Sciences, Hirosaki, Japan
| | - Michiko Shimada
- Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Maiko Kitajima
- Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hideaki Yamabe
- Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Mohammed S. Razzaque
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America
| |
Collapse
|