Urinary and Plasma KIM-1 in Chronic Kidney Disease: Prognostic Insights and Remaining Questions

Le résumé fourni par la source

Dear Editor,We read with great interest the article by McDonnell et al. [1] evaluating plasma and urinary kidney injury molecule-1 (KIM-1) in chronic kidney disease (CKD). Their findings that plasma KIM-1 is independently associated with kidney failure, whereas urinary KIM-1 is more strongly linked to mortality provide important insights into biomarker biology in CKD. We commend the authors for their contribution and would like to place these results in the context of broader biomarker research.KIM-1 was originally described as a proximal tubular injury marker in acute kidney injury (AKI), detectable in urine before serum creatinine rises [2, 3]. Beyond its role in acute injury, sustained expression has been shown to promote tubular dedifferentiation, lipid uptake, and fibrogenesis, linking early injury to long-term maladaptive repair [4, 5]. This dual biology explains why KIM-1 is increasingly recognized as a bridge between AKI and CKD, reflecting both acute tubular stress and chronic remodeling processes [6, 7].The strong association between urinary KIM-1 and mortality observed by McDonnell et al. is particularly noteworthy. Urinary KIM-1 likely reflects ongoing tubular stress that not only accelerates CKD progression but also signals systemic pathways of inflammation and fibrosis linked to cardiovascular and non-renal outcomes. Broader biomarker research in CKD has similarly shown that KIM-1, together with markers such as MCP-1 and suPAR, provides prognostic information for progression and survival, capturing interstitial injury and inflammation not reflected by creatinine [6]. This aligns with evidence that maladaptive repair after AKI, reflected by biomarkers including KIM-1 and cell cycle arrest proteins (TIMP-2/IGFBP7), drives both CKD progression and long-term mortality risk [7, 8]. The observation that urinary KIM-1 is more strongly associated with death than kidney failure suggests that it may serve as a systemic health marker rather than a purely renal endpoint predictor.The interaction with albuminuria is biologically plausible but complicates interpretation. Albuminuria induces tubular stress and inflammation, and KIM-1 levels have been shown to parallel albumin-induced tubular injury in experimental and clinical studies [9]. It therefore remains uncertain whether KIM-1 provides information entirely independent of uACR or largely mirrors albuminuric burden. Mediation analyses could help clarify this relationship.For clinical translation, benchmarking against established tools such as the Kidney Failure Risk Equation (KFRE) is essential [10, 11]. Small improvements in discrimination, as reported, may not justify routine measurement unless accompanied by gains in calibration, risk reclassification, and clinical decision-making. Moreover, with therapies such as SGLT2 inhibitors and finerenone demonstrating robust benefits across CKD populations [12, 13], an important question is whether KIM-1 can identify patients who derive greater benefit or serve as a responsive pharmacodynamic biomarker. Although KIM-1 has been proposed as a promising follow-up parameter, recent data suggest that short-term changes in urinary KIM-1 may not consistently predict subsequent kidney function decline, indicating that its role as a longitudinal marker remains uncertain and requires further validation [14].Finally, methodological and population aspects deserve attention. Competing risk models should be applied to account for the high mortality hazard in CKD when assessing kidney failure risk. External validation in more diverse populations is also needed, since biomarker levels and trajectories may vary across ethnic and genetic backgrounds.In conclusion, McDonnell et al. provide valuable evidence on the prognostic role of KIM-1 in CKD. When integrated with AKI and CKD biomarker research, these findings highlight KIM-1 as a marker of both renal and systemic health. Future studies should determine whether KIM-1 adds meaningful predictive value beyond existing models, whether its trajectories can guide therapeutic decisions, and whether it can be applied across diverse patient populations. Only through such steps can KIM-1 advance from a promising research biomarker to an actionable tool in CKD care.The author has no conflicts of interest to declare.The author declares no funding was obtained or used for this study.O.F.A. contributed to the concept, editing, and writing of the study.

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