Urinary interleukin-37 as a suggested protective biomarker of renal prognosis in autosomal dominant polycystic kidney disease.

BACKGROUND

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst expansion and chronic inflammation. Interleukin-37 (IL-37) is an anti-inflammatory cytokine, but its role in ADPKD remains unclear. This study aimed to evaluate IL-37 expression in ADPKD patients and assess its clinical relevance in disease severity and renal prognosis.

METHODS

IL-37 expression in kidney tissues and cell lines was examined by real-time PCR, Western blot, and immunofluorescence. IL-37 levels were measured by ELISA. This retrospective observational cohort study analyzed longitudinal follow-up data of ADPKD patients using Cox proportional hazards models to explore the prognostic value of IL-37 for progression to end-stage kidney disease (ESKD).

RESULTS

78 ADPKD patients and 20 normal controls were included. IL-37 expression was significantly elevated in kidney tissues, cyst fluid, serum, and urine from ADPKD patients compared with normal controls. Urinary IL-37, adjusted for creatinine (uIL-37/uCr), rose with advancing CKD stages, and it showed a positive correlation with tubular injury markers-NGAL, L-FABP, MCP-1, and α1-MG-and a negative correlation with eGFR and hemoglobin levels. After adjusting for baseline eGFR, age, and inflammation-associated biomarkers (MCP1), elevated urinary IL-37 was independently associated with better kidney survival (HR = 0.954, 95% CI: 0.912-0.998, P = 0.041), suggesting a protective role in ADPKD progression.

CONCLUSIONS

IL-37 is elevated in ADPKD, reflecting inflammation and tubular injury in disease pathogenesis. Despite higher levels in advanced disease, urinary IL-37 independently predicts better renal survival, suggesting its potential as both a disease activity marker and prognostic indicator.