Urinary d-lactate levels reflect renal function in aristolochic acid-induced nephropathy in mice

Urinary d-lactate is highly correlated to diabetic nephropathy - a progressive kidney disease in renal glomeruli. In this study, we used a C3H/3e mouse model to investigate the relationship between urinary d-lactate and aristolochic acid nephropathy where the glomerular structure is not affected. The nephropathy was induced using intravenous injections of aristolochic acid at a dosage of 10 mg/kg per day for 5 days and was characterized biochemically and histologically. The urinary excretions of proteins, N-acetyl-β-d-glucosaminidase and serum creatinine were determined and connected to histological conventional findings. Urinary d-lactate was analyzed using column-switching high-performance liquid chromatography with fluorescence detection. The results showed a remarkable increase of urinary markers, including of urinary proteins and N-acetyl-β-d-glucosaminidase, and the histological examination confirmed a diagnosis of acute tubule necrosis. The ratio of d-lactate to creatinine in the urine of aristolochic acid-treated mice was approximately 36 times greater than that of the mice in the control group (p < 0.05). The ratios for the two groups of mice were 311.00 ± 71.70 and 8.60 ± 1.80 µmol/mmol creatinine, respectively. These data confirm in vivo that urinary d-lactate reflects renal injury conditions in aristolochic acid-treated mice and may be a marker for the assessment of nephropathy.