Abstract
INTRODUCTION: Kidney injury molecule-1 (KIM-1) expression reflects proximal renal tubular damage, but plasma and urine KIM-1 have not been jointly studied in a CKD cohort. METHODS: Plasma and urine KIM-1 were measured in 2,581 adults from the NURTuRE-CKD cohort, a multicentre, non-dialysis-dependent CKD cohort. Survival analyses, C-statistics, and net reclassification improvement were used to assess associations and predictive performance of plasma and urine KIM-1 for kidney failure (KF), all-cause mortality, and a secondary endpoint of combined CKD progression endpoint (CKE) (KF or >40% decline in eGFR) in the total cohort and in KDIGO albuminuria categories, early CKD (eGFR >45 mL/min/1.73 m2), and four plasma/urine KIM-1 groups, dichotomised above and below the median value. RESULTS: Median age was 65 years, baseline eGFR 34.8 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (uACR) 22.3 mg/mmol. During median follow-up of 48.8 months, 616 (23.9%) participants developed KF, 817 (32%) experienced CKE, and 344 (13.3%) died. Plasma and urine KIM-1 levels increased with lower eGFR, higher uACR, and diabetes. Plasma KIM-1 was independently associated with KF, while urine KIM-1 was associated with pre-KF death. The combination of high plasma and high urine KIM-1 conferred the greatest hazards of KF and all-cause mortality. Combining plasma and urine KIM-1 led to a 24.1% improvement in net reclassification index for KF. In earlier stages of CKD, both biomarkers were associated with CKD progression and there were large improvements in risk prediction for plasma KIM-1 alone. Increased albuminuria amplified the relationship between plasma and urine KIM-1 and KF risk. CONCLUSION: This study highlights distinct prognostic associations of plasma and urine KIM-1 in CKD. Measuring both may be useful in improving risk stratification in people with CKD. For early-stage CKD, the need to use a combined CKE, including decline in eGFR, is emphasised as few of these people developed KF.