Caracterização de um modelo pré-clínico de lesão renal aguda associada a nefrolitíase por cristais de oxalato de cálcio

Abstract

Acute kidney injury (AKI) is a common syndrome characterized by a rapid decline in the excretory function of the kidneys and by the accumulation of nitrogen metabolism byproducts, such as creatinine, urea, and uric acid. Among the causes of AKI, nephrolithiasis- commonly known as kidney stones4stands out, resulting from the formation of calculi due to an imbalance between the solubility and precipitation of salts in the urinary tract. Given the importance of kidney function in maintaining homeostasis, studying the pathogenesis of renal diseases such as nephrolithiasis is essential for the development of new therapeutic approaches. Previous studies using animal models indicate that oxidative stress is involved in the pathophysiology of AKI induced by nephrolithiasis. The present study aimed to characterize acute kidney injury associated with nephrolithiasis caused by calcium oxalate crystals in mice. For this purpose, glyoxylate, a precursor compound of oxalate capable of promoting the formation of calcium oxalate crystals in the renal tubules- thus mimicking the process of nephrolithiasis- was used. Male Swiss mice were used and divided into the following experimental groups (n=8 per group): control (CT) and calcium oxalate-induced injury at glyoxylate doses of 100 mg/kg (OC100), 150 mg/kg (OC150), and 225 mg/kg (OC225), administered intraperitoneally (IP) for seven consecutive days. The procedures were carried out in accordance with the guidelines established by the National Council for the Control of Animal Experimentation (CONCEA) and were previously approved by the Animal Use Ethics Committee of the Federal University of Ceará (CEUA/UFC), under protocol no. 4829260424. After the induction period, the animals were observed for another seven days to allow the development of symptoms associated with nephrolithiasis. On the 15th day, the animals were euthanized for the collection of biological materials such as blood, urine, and organs, including kidneys, liver, and bladder. The proposed injury model was able to induce significant changes in several physiological parameters analyzed, such as body mass loss, water intake, urinary flow, and tissue weight. Indicators such as creatinine clearance, serum urea, and proteinuria showed relevant alterations at the 225 mg/kg dose. Furthermore, MDA and GSH concentrations were significantly reduced compared to the control group. The presence of calcium oxalate crystals in the urine confirmed stone formation, reinforcing the model's effectiveness. It was concluded that the 225 mg/kg glyoxylate dose was effective in promoting functional changes consistent with the clinical picture of acute kidney injury associated with nephrolithiasis.