Sahir Kalim1, Caitlin A Trottier2, Julia B Wenger2, Josh Wibecan2, Rayhnuma Ahmed2, Elizabeth Ankers2, S Ananth Karumanchi3, Ravi Thadhani2, Anders H Berg4. 1. Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and skalim@mgh.harvard.edu. 2. Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and. 3. Department of Medicine, Division of Nephrology and Center for Vascular Biology Research and. 4. Department of Pathology, Division of Clinical Chemistry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND AND OBJECTIVES: Carbamylation describes a post-translational protein modification associated with adverse outcomes in ESRD, but the risk implications of changes in carbamylation over time are not well understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the 1-year natural history of protein carbamylation in patients initiating maintenance hemodialysis and determined the prognostic value of longitudinal carbamylation changes in relation to mortality. In a nested patient-control study, we measured serial carbamylated albumin concentrations in select participants from a large incident dialysis cohort followed from 2004 to 2005 (n=10,044); 122 individuals who survived at least 90 days but died within 1 year of initiating hemodialysis (patients) were randomly selected along with 244 individuals who survived for at least 1 year (controls; matched for demographics). Carbamylated albumin concentration was measured using plasma collected at dialysis initiation and every subsequent 90-day period until 1 year or death. RESULTS: Baseline carbamylated albumin concentration was similar between controls and patients (mean±SD; 18.9±0.7 and 19.8±1.1 mmol/mol, respectively; P=0.94). From dialysis initiation to day 90, carbamylated albumin concentration markedly fell in all patients, with controls -9.9±0.8 mmol/mol (P<0.001) and patients -10.0±1.2 mmol/mol (P<0.001). Adjusted repeated measures analysis of carbamylated albumin concentration from dialysis initiation to 1 year or death showed that the mean change (95% confidence interval) in carbamylated albumin concentration from baseline to final measure differed significantly between groups (-9.3; 95% confidence interval, -10.8 to -7.7 for controls and -6.3; 95% confidence interval, -7.7 to -2.8 for patients; P<0.01). There were no such between-group differences in blood urea levels, Kt/V, or normalized protein catabolic rate. Mortality prediction assessed using c statistics showed that carbamylated albumin concentration, when modeled continuously as the difference from baseline to final, improved a fully adjusted model from 0.76 to 0.87 (P=0.03). CONCLUSIONS: Protein carbamylation decreased with dialysis initiation, and a greater reduction over time was associated with a lower risk for mortality. Carbamylation changes were able to predict individuals' mortality risk beyond traditional variables, including markers of dialysis adequacy and nutrition.
BACKGROUND AND OBJECTIVES: Carbamylation describes a post-translational protein modification associated with adverse outcomes in ESRD, but the risk implications of changes in carbamylation over time are not well understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the 1-year natural history of protein carbamylation in patients initiating maintenance hemodialysis and determined the prognostic value of longitudinal carbamylation changes in relation to mortality. In a nested patient-control study, we measured serial carbamylated albumin concentrations in select participants from a large incident dialysis cohort followed from 2004 to 2005 (n=10,044); 122 individuals who survived at least 90 days but died within 1 year of initiating hemodialysis (patients) were randomly selected along with 244 individuals who survived for at least 1 year (controls; matched for demographics). Carbamylated albumin concentration was measured using plasma collected at dialysis initiation and every subsequent 90-day period until 1 year or death. RESULTS: Baseline carbamylated albumin concentration was similar between controls and patients (mean±SD; 18.9±0.7 and 19.8±1.1 mmol/mol, respectively; P=0.94). From dialysis initiation to day 90, carbamylated albumin concentration markedly fell in all patients, with controls -9.9±0.8 mmol/mol (P<0.001) and patients -10.0±1.2 mmol/mol (P<0.001). Adjusted repeated measures analysis of carbamylated albumin concentration from dialysis initiation to 1 year or death showed that the mean change (95% confidence interval) in carbamylated albumin concentration from baseline to final measure differed significantly between groups (-9.3; 95% confidence interval, -10.8 to -7.7 for controls and -6.3; 95% confidence interval, -7.7 to -2.8 for patients; P<0.01). There were no such between-group differences in blood urea levels, Kt/V, or normalized protein catabolic rate. Mortality prediction assessed using c statistics showed that carbamylated albumin concentration, when modeled continuously as the difference from baseline to final, improved a fully adjusted model from 0.76 to 0.87 (P=0.03). CONCLUSIONS: Protein carbamylation decreased with dialysis initiation, and a greater reduction over time was associated with a lower risk for mortality. Carbamylation changes were able to predict individuals' mortality risk beyond traditional variables, including markers of dialysis adequacy and nutrition.
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Authors: Sahir Kalim; Anders H Berg; Subbian Ananth Karumanchi; Ravi Thadhani; Andrew S Allegretti; Sagar Nigwekar; Sophia Zhao; Anand Srivastava; Dominic Raj; Rajat Deo; Anne Frydrych; Jing Chen; James Sondheimer; Tariq Shafi; Matthew Weir; James P Lash Journal: Nephrol Dial Transplant Date: 2021-12-31 Impact factor: 7.186