Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease.

Publisher: Wolters Kluwer Health Country of Publication: United States NLM ID: 101271570 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-905X (Electronic) Linking ISSN: 15559041 NLM ISO Abbreviation: Clin J Am Soc Nephrol Subsets: MEDLINE

Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health
Original Publication: Washington, D.C. : American Society of Nephrology, c2005-

Diabetes Mellitus, Type 2/*etiology ; Diabetic Nephropathies/*etiology ; Hepatitis A Virus Cellular Receptor 1/*physiology ; Receptors, Tumor Necrosis Factor/*physiology ; Renal Insufficiency, Chronic/*etiology; Aged ; Canagliflozin/therapeutic use ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Diabetic Nephropathies/complications ; Disease Progression ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Renal Insufficiency, Chronic/complications ; Severity of Illness Index ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

Background and Objectives: Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. TNF receptor-1, TNF receptor-2, and kidney injury marker-1 (KIM-1) are known to be associated with kidney disease progression in patients with micro- or macroalbuminuria. We assessed the value of TNF receptor-1, TNF receptor-2, and KIM-1 as prognostic biomarkers for CKD progression in patients with type 2 diabetes and normoalbuminuria.
Design, Setting, Participants, & Measurements: TNF receptor-1, TNF receptor-2, and KIM-1 were measured using immunoassays in plasma samples from patients with type 2 diabetes at high cardiovascular risk participating in the Canagliflozin Cardiovascular Assessment Study trial. We used multivariable adjusted Cox proportional hazards analyses to estimate hazard ratios per doubling of each biomarker for the kidney outcome, stratified the population by the fourth quartile of each biomarker distribution, and assessed the number of events and event rates.
Results: In patients with normoalbuminuria ( n =2553), 51 kidney outcomes were recorded during a median follow-up of 6.1 (interquartile range, 5.8-6.4) years (event rate, 3.5; 95% confidence interval, 2.6 to 4.6 per 1000 patient-years). Each doubling of baseline TNF receptor-1 (hazard ratio, 4.2; 95% confidence interval, 1.8 to 9.6) and TNF receptor-2 (hazard ratio, 2.3; 95% confidence interval, 1.5 to 3.6) was associated with a higher risk for the kidney outcome. Baseline KIM-1, urinary albumin-creatinine ratio, and eGFR were not associated with kidney outcomes. The event rates in the highest quartile of TNF receptor-1 (≥2992 ng/ml) and TNF receptor-2 (≥11,394 ng/ml) were 5.6 and 7.0 events per 1000 patient-years, respectively, compared with 2.8 and 2.3, respectively, in the lower three quartiles.
Conclusions: TNF receptor-1 and TNF receptor-2 are associated with kidney outcomes in patients with type 2 diabetes and normoalbuminuria.
Clinical Trial Registry Name and Registration Number: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629.
(Copyright © 2022 by the American Society of Nephrology.)

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UL1 TR001863 United States TR NCATS NIH HHS; R01 DK126477 United States DK NIDDK NIH HHS; UH3 DK114920 United States DK NIDDK NIH HHS; R01 HL085757 United States HL NHLBI NIH HHS; R01 DK118222 United States DK NIDDK NIH HHS; R01 DK093770 United States DK NIDDK NIH HHS; UH3 DK114866 United States DK NIDDK NIH HHS; R01 DK115562 United States DK NIDDK NIH HHS; U01 DK106962 United States DK NIDDK NIH HHS; R01 DK112258 United States DK NIDDK NIH HHS

Keywords: KIM-1; TNFR-1; TNFR-2; biomarkers; clinical trial design; hepatitis a virus cellular receptor 1; kidney outcomes; normoalbuminuria; prognosis; risk prediction

ClinicalTrials.gov NCT01032629

0 (HAVCR1 protein, human)
0 (Hepatitis A Virus Cellular Receptor 1)
0 (Receptors, Tumor Necrosis Factor)
0 (Sodium-Glucose Transporter 2 Inhibitors)
0SAC974Z85 (Canagliflozin)

Date Created: 20211208 Date Completed: 20220317 Latest Revision: 20230421

20230422

PMC8823939

10.2215/CJN.08780621

34876454