Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years

Nephrol Dial Transplant. 2020 Feb 1;35(2):265-273. doi: 10.1093/ndt/gfy382.

Abstract

Background: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.

Methods: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.

Results: During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years.

Conclusion: Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.

Keywords: CKD; KIM-1; TIM-1; eGFR; kidney function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Creatinine / blood
  • Cystatin C / blood
  • Female
  • Glomerular Filtration Rate
  • Hepatitis A Virus Cellular Receptor 1 / blood*
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / pathology*
  • Sweden / epidemiology

Substances

  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Creatinine