TY - JOUR
T1 - Association of multiple plasma biomarker concentrations with progression of prevalent diabetic kidney disease
T2 - Findings from the Chronic Renal Insufficiency Cohort (CRIC) study
AU - CKD Biomarkers Consortium and the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators
AU - Schrauben, Sarah J.
AU - Shou, Haochang
AU - Zhang, Xiaoming
AU - Anderson, Amanda Hyre
AU - Bonventre, Joseph V.
AU - Chen, Jing
AU - Coca, Steven
AU - Furth, Susan L.
AU - Greenberg, Jason H.
AU - Gutierrez, Orlando M.
AU - Ix, Joachim H.
AU - Lash, James P.
AU - Parikh, Chirag R.
AU - Rebholz, Casey M.
AU - Sabbisetti, Venkata
AU - Sarnak, Mark J.
AU - Shlipak, Michael G.
AU - Waikar, Sushrut S.
AU - Kimmel, Paul L.
AU - Vasan, Ramachandran S.
AU - Feldman, Harold I.
AU - Schelling, Jeffrey R.
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - He, Jiang
AU - Nelson, Robert G.
AU - Rao, Panduranga S.
AU - Rahman, Mahboob
AU - Shah, Vallabh O.
AU - Townsend, Raymond R.
AU - Unruh, Mark L.
AU - Denburg, Michelle
AU - Warady, Bradley
AU - Coresh, Josef
AU - Grams, Morgan
AU - Abraham, Alison
AU - Rhee, Eugene
AU - Gutiérrez, Orlando M.
AU - Dubin, Ruth
AU - Hostetter, Tom
AU - Deo, Rajat
AU - Xie, Dawei
AU - Ballard, Shawn
AU - Whitehead, Krista
AU - Collins, Heather
AU - Ganz, Peter
N1 - Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. Methods: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. Results: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. Conclusions: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
AB - Background: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. Methods: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. Results: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. Conclusions: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
UR - http://www.scopus.com/inward/record.url?scp=85098515474&partnerID=8YFLogxK
U2 - 10.1681/ASN.2020040487
DO - 10.1681/ASN.2020040487
M3 - Article
C2 - 33122288
AN - SCOPUS:85098515474
SN - 1046-6673
VL - 32
SP - 115
EP - 126
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 1
ER -