Kidney medicine · 2025
Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT.
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Wettersten Nicholas, Katz Ronit, Ascher Simon B, Scherzer Rebecca, Bullen Alexander L, Chen Teresa K, Campos Kasey, Garimella Pranav S, Estrella Michelle M, Shlipak Michael G, Ix Joachim H
Аннотация
RATIONALE & OBJECTIVE: Among individuals with chronic kidney disease (CKD), higher blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with greater risk of CKD progression. Their associations with risk of cardiovascular disease (CVD) and all-cause mortality in individuals with CKD remain uncertain.
STUDY DESIGN: An observational cohort study.
SETTING & PARTICIPANTS: Systolic Blood Pressure Intervention Trial participants with hypertension and CKD (eGFR <60 mL/min/1.73 m2) but without diabetes.
PREDICTORS: Plasma KIM-1, TNFR-1, and TNFR-2.
OUTCOMES: A composite CVD outcome (acute coronary syndrome/myocardial infarction, stroke, heart failure, and CVD death) and all-cause mortality.
ANALYTIC APPROACH: Cox proportional hazards models, adjusting for CVD risk factors, eGFR, and urine albumin-to-creatinine ratio.
RESULTS: Total of 2,350 participants with a mean age of 73 ± 9 years, eGFR of 46 ± 10 mL/min/1.73m2 and 25% prevalence of CVD. Over more than 3 years follow-up, 293 CVD events (12%) and 160 deaths (7%) occurred. Higher KIM-1, TNFR-1, and TNFR-2 were associated with higher risk of the composite CVD outcome after adjusting for CVD risk factors, but associations were no longer significant after adjusting for eGFR and urine albumin-to-creatinine ratio (KIM-1: HR = 1.13, 95% CI, 0.99-1.30; TNFR-1: HR = 1.03, 95% CI, 0.72-1.46; TNFR-2: HR = 0.98, 95% CI, 0.76-1.26). In contrast, in fully adjusted models, higher plasma KIM-1 and TNFR-1, but not TNFR-2, were associated with higher risk of all-cause mortality (KIM-1: HR = 1.23, 95% CI, 1.01-1.49; TNFR-1: HR = 2.09, 95% CI, 1.14-3.83; TNFR-2: HR = 1.19, 95% CI, 0.85-1.66).
LIMITATIONS: No individuals with diabetes or stroke.
CONCLUSIONS: In individuals with hypertension and nondiabetic CKD, associations of higher plasma KIM-1, TNFR-1, and TNFR-2 concentrations with CVD events were not independent of eGFR and albuminuria, whereas higher levels of plasma KIM-1 and TNFR-1 were independently associated with greater risk of all-cause mortality.
STUDY DESIGN: An observational cohort study.
SETTING & PARTICIPANTS: Systolic Blood Pressure Intervention Trial participants with hypertension and CKD (eGFR <60 mL/min/1.73 m2) but without diabetes.
PREDICTORS: Plasma KIM-1, TNFR-1, and TNFR-2.
OUTCOMES: A composite CVD outcome (acute coronary syndrome/myocardial infarction, stroke, heart failure, and CVD death) and all-cause mortality.
ANALYTIC APPROACH: Cox proportional hazards models, adjusting for CVD risk factors, eGFR, and urine albumin-to-creatinine ratio.
RESULTS: Total of 2,350 participants with a mean age of 73 ± 9 years, eGFR of 46 ± 10 mL/min/1.73m2 and 25% prevalence of CVD. Over more than 3 years follow-up, 293 CVD events (12%) and 160 deaths (7%) occurred. Higher KIM-1, TNFR-1, and TNFR-2 were associated with higher risk of the composite CVD outcome after adjusting for CVD risk factors, but associations were no longer significant after adjusting for eGFR and urine albumin-to-creatinine ratio (KIM-1: HR = 1.13, 95% CI, 0.99-1.30; TNFR-1: HR = 1.03, 95% CI, 0.72-1.46; TNFR-2: HR = 0.98, 95% CI, 0.76-1.26). In contrast, in fully adjusted models, higher plasma KIM-1 and TNFR-1, but not TNFR-2, were associated with higher risk of all-cause mortality (KIM-1: HR = 1.23, 95% CI, 1.01-1.49; TNFR-1: HR = 2.09, 95% CI, 1.14-3.83; TNFR-2: HR = 1.19, 95% CI, 0.85-1.66).
LIMITATIONS: No individuals with diabetes or stroke.
CONCLUSIONS: In individuals with hypertension and nondiabetic CKD, associations of higher plasma KIM-1, TNFR-1, and TNFR-2 concentrations with CVD events were not independent of eGFR and albuminuria, whereas higher levels of plasma KIM-1 and TNFR-1 were independently associated with greater risk of all-cause mortality.