Circulating KIM-1 Tracks Lupus Nephritis Relapse Risk

Key Takeaways

• In a 46-patient biopsy-confirmed lupus nephritis cohort, baseline circulating KIM-1 at or above the median was associated with lower relapse-free survival and lower ESKD-free survival, while overall survival was not significantly different
• After adjustment for serum creatinine and urinary protein, circulating KIM-1 remained associated with lupus nephritis relapse
• Patients with higher circulating KIM-1 had higher serum creatinine, lower eGFR, greater proteinuria, lower serum albumin, more hypertension, dyslipidemia, Class IV histology, and higher activity index scores; circulating and urinary KIM-1 were strongly correlated, while median-stratified urinary KIM-1 was not associated with relapse or ESKD in Kaplan-Meier analyses

In this single-center retrospective cohort, serum was collected at renal biopsy before treatment or additional treatment, 63 patients were screened and 46 were analyzed, and the investigators reported in that the biomarker remained associated with relapse after adjustment for serum creatinine and urinary protein, with a per-IQR HR of 1.92 (95% CI 1.07 to 3.45; p=0.029).

At Kanazawa University Hospital, the investigators followed Japanese patients with biopsy-confirmed lupus nephritis diagnosed between 1990 and 2022, with observation through 31 October 2025. According to renal biopsy–timed serum KIM-1 cohort details, 17 patients were excluded because of incomplete records, fewer than five scorable glomeruli, coexisting glomerular disease, or unavailable pretreatment serum samples. Complete remission required proteinuria below 0.5 g/g Cr with inactive urinary sediment and no worsening kidney function, and relapse was defined as a UPCR doubling to >0.5 g/g Cr, reappearance of active urinary sediment, or a serum creatinine increase of at least 25% after remission. Over follow-up, the cohort experienced nine relapses (20%), four ESKD events (9%), and six deaths (13%), and patients were divided at the median baseline circulating KIM-1 value of 153 pg/mL, with low- and high-KIM-1 group medians of 63 pg/mL and 453 pg/mL.

The high-KIM-1 group entered biopsy with a more adverse renal profile, including serum creatinine 0.70 vs 0.55 mg/dL, eGFR 83.6 vs 107.7 mL/min/1.73 m², UPCR 1.95 vs 0.20 g/g Cr, and serum albumin 2.90 vs 3.60 g/dL. Hypertension and dyslipidemia were more frequent, Class IV histology was present in 48% vs 13%, and biopsy activity index scores were higher in the high-KIM-1 group. Circulating KIM-1 also correlated strongly with urinary KIM-1, but median-stratified urinary KIM-1 was not associated with relapse or ESKD in Kaplan-Meier analyses.

Sensitivity analyses were generally directionally similar: the relapse association persisted in a competing-risk model (p=0.033), the ESKD competing-risk analysis showed a near-threshold signal (p=0.053), and adding circulating KIM-1 to serum creatinine plus urinary protein changed Harrell’s C from 0.776 to 0.781; however, with only nine relapse events, the investigators described the multivariable estimates as exploratory, and the relapse association was no longer statistically significant after additional adjustment for hypertension. The investigators also noted that interpretation was constrained by the retrospective observational design, the small single-center cohort, only nine relapse events and four ESKD events, the absence of a multivariable ESKD model because of event scarcity, and measurement of KIM-1 at baseline only. Within that scope, the findings linked biopsy-timed circulating KIM-1 to later relapse and kidney failure events in this lupus nephritis cohort.

Clinician Questions

What baseline circulating KIM-1 level was used to stratify risk in biopsy-confirmed lupus nephritis?

In this study, patients were split at the cohort median circulating KIM-1 level of 153 pg/mL measured in serum collected at renal biopsy before treatment or additional treatment; the investigators noted that no established clinical cutoff exists and that this threshold requires prospective validation. The low- and high-KIM-1 groups had median values of 63 pg/mL and 453 pg/mL, respectively.

How did higher circulating KIM-1 relate to relapse and kidney failure outcomes in lupus nephritis?

In the 46-patient biopsy-confirmed lupus nephritis cohort, higher baseline circulating KIM-1 was associated with lower relapse-free survival (p=0.027) and lower ESKD-free survival (p=0.049), while overall survival did not differ significantly (p=0.104) over a median follow-up of 127 months.

Did circulating KIM-1 remain associated with lupus nephritis relapse after accounting for serum creatinine and proteinuria?

Yes. In biopsy-confirmed lupus nephritis, the multivariable Cox model that included circulating KIM-1, serum creatinine, and urinary protein reported a per-IQR hazard ratio for relapse of 1.92 with a 95% CI of 1.07 to 3.45 and p=0.029, and the study described the added discrimination beyond conventional markers as modest.

What baseline renal and biopsy features were more common in the high-KIM-1 lupus nephritis group?

The high-KIM-1 lupus nephritis group showed higher serum creatinine, lower eGFR, greater proteinuria, lower serum albumin, more hypertension and dyslipidemia, more frequent Class IV histology, and higher biopsy activity index scores at baseline.