Endothelial Injury and Oxidative Stress in Patients with Schistosomal Hepatic Fibrosis: Relation to Renal Dysfunction and Hemodynamics

BACKGROUND: Schistosomiasis mansoni is associated with immune-mediated glomerulopathy; however, the mechanism of renal involvement is not well established. Endothelial injury plays an important role in the pathogenesis of chronic renal diseases and may be related to oxidative stress. The present work was designed to study markers of endothelial injury and oxidative stress in patients with schistosomal hepatic fibrosis (SHF) in relation to renal dysfunction and hemodynamics. METHODS: Forty-five patients with SHF (15 without albuminuria, 15 with mild/moderate albuminuria, and 15 with severe albuminuria) and 15 healthy subjects were included in the study. Endothelial injury was assessed by plasma von Willibrand factor (vWF) activity and serum angiotensin converting enzyme (ACE) levels. Serum malondialdehyde (MDA) levels and 24-hour urinary levels of leucine aminopeptidase (LAP) were measured as markers for oxidative stress and tubular damage respectively. Renal hemodynamics were assessed using Duplex-Doppler ultrasonography by calculating the diastolic/systolic renal flow velocity ratio (d/s), intrarenal resistive index (RI), and hilar renal blood flow (RBF). RESULTS: Patients with SHF showed significant increases in plasma vWF activity, serum levels of ACE and MDA, urinary LAP levels and RI and significant decreases in d/s and RBF compared with healthy subjects (P < 0.05). The increase in plasma vWF activity and the changes in renal hemodynamics were positively correlated but were not related to the severity of glomerular injury (P > 0.05). Serum MDA and urinary LAP levels were significantly higher in patients with albuminuria than in patients without albuminuria while serum ACE level was significantly higher in patients with severe albuminuria than in other patients (P < 0.05). There was a significant positive correlation between serum MDA levels and severity of liver disease in patients with SHF (P < 0.05). CONCLUSION: Endothelial injury, possibly due to oxidative stress, may play an important role in the pathogenesis of renal dysfunction and increased renovascular impedence in SHF and in the initiation of schistosomal nephropathy in this disease. DISCLOSURES: All authors: No reported disclosures.