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

TitleAssociation of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsSchrauben SJ, Shou H, Zhang X, Anderson AHyre, Bonventre JV, Chen J, Coca S, Furth SL, Greenberg JH, Gutierrez OM, Ix JH, Lash JP, Parikh CR, Rebholz CM, Sabbisetti V, Sarnak MJ, Shlipak MG, Waikar SS, Kimmel PL, Vasan RS, Feldman HI, Schelling JR
Corporate AuthorsCKD Biomarkers Consortium and the Chronic Renal Insufficiency Cohort(CRIC) Study Investigators
JournalJ Am Soc Nephrol
Volume32
Issue1
Pagination115-126
Date Published2021 01
ISSN1533-3450
KeywordsAdult, Aged, Biomarkers, Chemokine CCL2, Chitinase-3-Like Protein 1, Cohort Studies, Diabetic Nephropathies, Disease Progression, Female, Glomerular Filtration Rate, Hepatitis A Virus Cellular Receptor 1, Humans, Kidney Failure, Chronic, Male, Middle Aged, Phenotype, Prevalence, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Receptors, Urokinase Plasminogen Activator, Renal Insufficiency, Chronic, Risk, Young Adult
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 <60 ml/min per 1.73 m 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.

DOI10.1681/ASN.2020040487
Alternate JournalJ Am Soc Nephrol
PubMed ID33122288
PubMed Central IDPMC7894671
Grant ListUL1 TR000439 / TR / NCATS NIH HHS / United States
UL1 TR000424 / TR / NCATS NIH HHS / United States
U01 DK102730 / DK / NIDDK NIH HHS / United States
R01 DK115562 / DK / NIDDK NIH HHS / United States
UL1 TR002548 / TR / NCATS NIH HHS / United States
U01 DK061021 / DK / NIDDK NIH HHS / United States
U24 DK060990 / DK / NIDDK NIH HHS / United States
U01 DK060963 / DK / NIDDK NIH HHS / United States
U01 DK061022 / DK / NIDDK NIH HHS / United States
UL1 TR000003 / TR / NCATS NIH HHS / United States
R21 HL143089 / HL / NHLBI NIH HHS / United States
U01 DK106965 / DK / NIDDK NIH HHS / United States
U01 DK060990 / DK / NIDDK NIH HHS / United States
U01 DK061028 / DK / NIDDK NIH HHS / United States
U01 DK085660 / DK / NIDDK NIH HHS / United States
K08 DK110536 / DK / NIDDK NIH HHS / United States
P20 GM109036 / GM / NIGMS NIH HHS / United States
R01 DK119199 / DK / NIDDK NIH HHS / United States
K23 DK118198 / DK / NIDDK NIH HHS / United States
U01 DK103225 / DK / NIDDK NIH HHS / United States
R01 DK104730 / DK / NIDDK NIH HHS / United States
U01 DK060980 / DK / NIDDK NIH HHS / United States
R37 DK039773 / DK / NIDDK NIH HHS / United States
U01 DK060984 / DK / NIDDK NIH HHS / United States
K01 DK107782 / DK / NIDDK NIH HHS / United States
M01 RR016500 / RR / NCRR NIH HHS / United States
U01 DK060902 / DK / NIDDK NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
R01 HL085757 / HL / NHLBI NIH HHS / United States
L30 DK110819 / DK / NIDDK NIH HHS / United States
U01 OH011326 / OH / NIOSH CDC HHS / United States
UL1 TR000433 / TR / NCATS NIH HHS / United States
UL1 RR029879 / RR / NCRR NIH HHS / United States
U01 DK106962 / DK / NIDDK NIH HHS / United States
R01 DK112258 / DK / NIDDK NIH HHS / United States