Uromodulin as a kidney protective factor in acute oxalate urolithiasis: a dose-dependent mouse model

INTRODUCTION . Urolithiasis is a common urological pathology with a high recurrence rate. Experimental models on rodents are the main tool for studying the pathogenesis of stone formation and the search for therapeutic targets.

THE AIM: To develop models of acute oxalate urolithiasis in ICR mice and evaluate the role of uromodulin (UMO) in protecting the kidneys from crystal-induced damage.

MATERIALS AND METHODS. The study was performed on 18 male ICR mice (CD 1). Mice were intraperitoneally injected with sodium oxalate in two doses: 2.5 mg/100 g body weight (NaOx L) and 5 mg/100 g body weight (NaOx H). The biochemical parameters of blood, glomerular filtration rate by FITC inulin clearance, colloidal composition of urine, urinary excretion of UMO and ions, morphology of sediment and internal organs were evaluated in the experiment.

RESULTS . A high dose of the pathology inducer caused severe acute nephropathy with pronounced azotemia, decreased GFR, accumulation of large CaOx containing nanoparticles, and deep tubulointerstitial damage. A dose of 2.5 mg/100 g of body weight formed a milder, generally compensated lesion with a transient peak of crystalluria. In this group, the dynamics of urinary UMO excretion and colloidal profile most convincingly demonstrated its nephroprotective and anti-crystallogenic role.

CONCLUSIONS. The developed two-dose model of acute Ox urolithiasis in mice allows differentiated study of severe crystal-induced kidney damage (5 mg/100 g) and mechanisms of effective crystal clearance with the participation of UMO (2.5 mg/100 g), which creates the basis for molecular genetic studies on transgenic and knockout lines of mice.

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