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.