Protein carbamylation and chronic kidney disease progression in the Chronic Renal Insufficiency Cohort Study
Autor: | Jing Chen, Matthew R. Weir, Dominic S. Raj, Anand Srivastava, Sophia Zhao, Sagar U. Nigwekar, Anne Frydrych, Tariq Shafi, Andrew S. Allegretti, Rajat Deo, James H. Sondheimer, James P. Lash, Ravi Thadhani, Anders H. Berg, Subbian Ananth Karumanchi, Cric Study Investigators, Sahir Kalim |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty 030232 urology & nephrology Renal function Gastroenterology Cohort Studies 03 medical and health sciences 0302 clinical medicine Internal medicine Humans Medicine Renal Insufficiency Chronic Blood urea nitrogen Transplantation Protein Carbamylation Proteinuria business.industry Albumin Odds ratio medicine.disease Confidence interval 030104 developmental biology Nephrology Disease Progression Kidney Failure Chronic medicine.symptom business Glomerular Filtration Rate Kidney disease Cohort study |
Zdroj: | Nephrology Dialysis Transplantation. 37:139-147 |
ISSN: | 1460-2385 0931-0509 |
Popis: | Background Protein carbamylation is a post-translational protein modification caused, in part, by exposure to urea’s dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis-dependent end-stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established. Methods We conducted two nested case–control studies within the Chronic Renal Insufficiency Cohort Study. First, we matched 75 cases demonstrating CKD progression [50% estimated glomerular filtration rate (eGFR) reduction or reaching ESKD] to 75 controls (matched on baseline eGFR, 24-h proteinuria, age, sex and race). In the second study, we similarly matched 75 subjects who died during follow-up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study. Results At baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other parameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression [odds ratio (OR) = 7.9; 95% confidence interval (CI) 1.9–32.8; P = 0.004] and mortality (OR = 3.4; 95% CI 1.0–11.4; P = 0.05) when compared with the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN. Conclusions Our data suggest that protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation’s association with mortality was smaller in this limited sample size. |
Databáze: | OpenAIRE |
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