Interleukin-37 does not confer protection against stone formation or kidney injury at the peak of disease in a murine calcium oxalate model.

Calcium oxalate (CaOx) stones are the most prevalent form of nephrolithiasis in adults. While murine models of CaOx stone disease are established, many lack translational features for therapeutic evaluation, including in vivo assessment of kidney function and molecular profiling of renal inflammation. We refined the glyoxylate‑induced CaOx mouse model by incorporating non‑invasive transdermal glomerular filtration rate (tGFR) measurements to enable longitudinal assessment of kidney function. This platform was used to investigate the renoprotective role of the anti‑inflammatory cytokine interleukin‑37 (IL‑37). Because mice do not express IL‑37, we used IL‑37 transgenic (IL‑37tg) mice that express the human IL37b isoform. Male wild‑type and IL‑37tg mice received daily intraperitoneal glyoxylate to induce CaOx deposition. Crystal burden and tubular injury were quantified using digital image analysis of whole‑kidney sections. Kidney function was assessed using tGFR and validated by serum creatinine, blood urea nitrogen (BUN), and symmetric dimethylarginine (SDMA). Renal inflammation was profiled using an RT² Profiler PCR Array, with key transcripts validated by qPCR. CaOx deposition peaked on day 6, coinciding with tubular injury and impaired kidney function in both wild‑type and IL‑37tg mice, as evidenced by reduced tGFR and elevated BUN, creatinine, and SDMA. Stone formation triggered a robust inflammatory response, with 46 of 84 genes upregulated > 3‑fold in wild‑type mice. IL‑37 expression did not alter crystal burden, kidney injury, kidney function, or inflammatory gene expression. These findings establish a refined murine CaOx model incorporating kidney function and molecular endpoints and demonstrate that IL‑37 does not confer renal protection in glyoxylate‑induced stone disease.