Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 35, Issue 2, Pages 265-273Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfy382
Keywords
CKD; eGFR; kidney function; KIM-1; TIM-1
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Funding
- European Research Council [649021]
- Swedish Research Council
- Swedish Heart and Lung Foundation
- Novo Nordic Foundation
- Swedish Diabetes Foundation
- Pahlsson Foundation
- Knut and Alice Wallenberg Foundation
- Region Skane
- Skane University Hospital
- Linneus Foundation for the Lund University Diabetes Center
- Swedish Foundation for Strategic Research [IRC15-0067]
- European Research Council (ERC) [649021] Funding Source: European Research Council (ERC)
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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 Malmo 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<60mL/min/1.73 m(2) at follow-up. Results During a mean follow-up time of 16.6years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54mL/min/1.73 m(2); 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 19.2years. 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.
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