Urinary 8-hydroxydeoxyguanosine is elevated in patients with nephrolithiasis

Abstract

8-hydroxydeoxyguanosine (8-OHdG) is an oxidatively modified guanosine, which has been widely used as an oxidative DNA damage marker in various diseases. The present study aimed to determine urinary 8-OHdG in nephrolithiasis patients and evaluate its clinical significance. Thirty-six nephrolithiasis patients and 30 healthy subjects were recruited. Urine volume, creatinine, malondialdehyde, beta-N-acetylglucosaminidase (NAG) activity and proteins were measured in 24 h urine samples. Urinary 8-OHdG was determined by competitive enzyme-linked immunosorbent assay. Mineral composition of stones was analyzed using Fourier-transformed infrared spectroscopy. Nephrolithiasis patients excreted urinary 8-OHdG significantly higher than healthy controls. Urinary 8-OHdG levels compared among patients with calcium oxalate, struvite and uric acid stones were insignificantly different. The urinary NAG activity correlated positively with urinary 8-OHdG. Multiple linear regression showed that urinary NAG activity was an independent predictor of urinary 8-OHdG level. Receiver operating characteristic analysis revealed that the urinary 8-OHdG test was adequate for diagnosing nephrolithiasis. At 10 mug/g creatinine cutoff, the 8-OHdG test imparted high specificity (96.67%) and a positive predictive value (91.67%). In conclusion, this is the first report of elevated urinary 8-OHdG excretion in nephrolithiasis patients indicating increased oxidative DNA damage. Increased renal tubular damage was independently associated with elevated urinary 8-OHdG. Elevated urinary 8-OHdG levels adjunct with metabolic profile may be useful for identifying people at risk of stone development.