Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Details

• Personal Author:
  Anderson AH ; Bonventre JV ; Chen J ; Coca S ; Feldman HI ; Furth SL ; Greenberg JH ; Gutierrez OM ; Ix JH ; Kimmel PL ; Lash JP ; Parikh CR ; Rebholz CM ; Sabbisetti V ; Sarnak MJ ; Schelling JR ; Schrauben SJ ; Shlipak MG ; Shou H ; Vasan RS ; Waikar SS ; Zhang X
• Corporate Authors:
  CKD Biomarkers Consortium and the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Aging Biomarkers Blood Genetics Hematologic Diseases Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Author Keywords: Biomarker Blood Sugar Disorders Chronic Diabetic Complications Chronic Kidney Disease Diabetes Diabetic Kidney Disease Diabetic Nephropathy End Stage Kidney Disease Epidemiology And Outcomes Kidney Disorders Kidneys Proteins Risk Factors

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• ISSN:
  1046-6673
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; California ; Connecticut ; Illinois ; Louisiana ; Maryland ; Massachusetts ; New York ; Ohio ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  115-126
• Volume:
  32
• Issue:
  1
• NIOSHTIC Number:
  nn:20063041
• Citation:
  J Am Soc Nephrol 2021 Jan; 32(1):115-126
• Contact Point Address:
  Dr. Sarah Schrauben, Department of Medicine, University of Pennsylvania, 930 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19103
• Email:
  Sarah.Schrauben@pennmedicine.upenn.edu
• Federal Fiscal Year:
  2021
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  Journal of the American Society of Nephrology
• End Date:
  20200630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:28587a875140df3a2562a928d20f0ddba90238e6b9e23c3a3a60b7925798ad3013d8789f252db4d54863868e6b55216b25252ea43bfcc53b931cc284ad72c925
• Download URL:
  https://stacks.cdc.gov/view/cdc/226170/cdc_226170_DS1.pdf
• File Type:
  [PDF - 9.32 MB ]