Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
- 29 October 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 32 (1), 115-126
- https://doi.org/10.1681/asn.2020040487
Abstract
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 2 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.Keywords
Funding Information
- NIDDK (K23DK118198-01A1)
- NIDDK (U01-DK103225)
- NIDDK (U01DK106962)
- National Heart, Lung, and Blood Institute (R01DK115562, R01HL85757, R01DK112258)
- National Institute for Occupational Safety and Health (U01OH011326)
- National Heart, Lung, and Blood Institute (R37DK039773, R01DKD072381)
- NIDDK (U01DK085660)
- NIDDK (U01DK085660)
- NIDDK (U01DK102730)
- NIDDK (U01DK106965)
- NIH (K08DK110536)
- Charles H. Hood Foundation
- NIDDK (U01DK103225, U01DK060990, U01DK060963, R01DK104730)
- NIDDK (K01 DK107782)
- National Heart, Lung, and Blood Institute (R21 HL143089)
- NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902, U24DK060990)
- National Center for Advancing Translational Sciences (UL1TR000003, UL1 TR-000424, M01 RR-16500, UL1TR000439, UL1TR000433, UL1RR029879)
- NIH (P20 GM109036)
- National Center for Research Resources (NCRR UCSF-CTSI UL1 RR-024131)
- National Heart, Lung, and Blood Institute (R01DK119199)
This publication has 59 references indexed in Scilit:
- Circulating TNF Receptors 1 and 2 Predict Stage 3 CKD in Type 1 DiabetesJournal of the American Society of Nephrology, 2012
- Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 DiabetesJournal of the American Society of Nephrology, 2012
- In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuriaKidney International, 2010
- Chronic Renal Insufficiency Cohort (CRIC) StudyClinical Journal of the American Society of Nephrology, 2009
- The estimation of average hazard ratios by weighted Cox regressionStatistics in Medicine, 2009
- Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine: A Pooled Analysis of 3,418 Individuals With CKDAmerican Journal of Kidney Diseases, 2008
- The Role of Inflammatory Cytokines in Diabetic NephropathyJournal of the American Society of Nephrology, 2008
- Adjusting batch effects in microarray expression data using empirical Bayes methodsBiostatistics, 2006
- Does Microalbuminuria Predict Diabetic Nephropathy?Diabetes Care, 2001
- Expression and colocalization of cytokeratin 1 and urokinase plasminogen activator receptor on endothelial cellsBlood, 2001