Plasma Kidney Injury Molecule 1 in CKD: Findings From the Boston Kidney Biopsy Cohort and CRIC Studies.

Abstract Rationale & Objective Plasma kidney injury molecule-1 (KIM-1) is a sensitive marker of proximal tubule injury, but its association with risks of adverse clinical outcomes across a spectrum of kidney diseases is unknown. Study Design Prospective, observational cohort study. Setting & Participants 524 individuals undergoing clinically indicated native kidney biopsy with biopsy specimens adjudicated for semiquantitative scores of histopathology by two kidney pathologists enrolled into the Boston Kidney Biopsy Cohort (BKBC) Study and 3,800 individuals with common forms of chronic kidney disease (CKD) enrolled into the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure Histopathologic lesions and clinicopathologic diagnosis in cross-sectional analyses, baseline plasma KIM-1 in prospective analyses. Outcomes Baseline plasma KIM-1 in cross-sectional analyses, kidney failure (defined as initiation of kidney replacement therapy) and death in prospective analyses. Analytical Approach Multivariable-adjusted linear regression models tested associations of plasma KIM-1 with histopathologic lesions and clinicopathologic diagnoses. Cox proportional hazards models tested associations of plasma KIM-1 with future kidney failure and death. Results In the BKBC Study, higher plasma KIM-levels were associated with more severe acute tubular injury, tubulointerstitial inflammation, and more severe mesangial expansion after multivariable adjustment. Participants with diabetic nephropathy, glomerulopathies, and tubulointerstitial disease had significantly higher plasma KIM-1 levels after multivariable adjustment. In the BKBC Study, 124 participants progressed to kidney failure and 85 participants died during a median follow-up time of 5 years. In the CRIC Study, 1153 participants progressed to kidney failure and 1356 participants died during a median follow-up time of 11.5 years. In both cohorts, each doubling of plasma KIM-1 was associated with an increased risk of kidney failure after multivariable adjustment (BKBC: HR 1.19, 95% CI 1.03 to 1.38 and CRIC: HR 1.10, 95% CI 1.06 to 1.15). There was no statistically significant association of plasma KIM-1 with death in either cohort. Limitations Generalizability and unmeasured confounding. Conclusions Plasma KIM-1 is associated with underlying tubulointerstitial and mesangial lesions and progression to kidney failure in two cohort studies of individuals with kidney diseases.