Bismuth overdosing-induced reversible nephropathy in rats

Overdosing of colloidal bismuth subcitrate (CBS), used to treat peptic ulce rs and Helicobacter pylori infections, has been reported to result in serio us, though reversible, nephrotoxicity in humans. However, little is known a bout the nature of the renal damage induced by bismuth (Bi), and no well-de scribed experimental model exists. Single large oral CBS doses (0.75, 1.5, and 3.0 mmol Bi/kg) were administered to three groups of 20 female Wistar r ats. A control group (n = 20) received only the vehicle. Standard kidney fu nction parameters, urinary excretion of N-acetyl-beta -D-glucosaminidase (N AG) and the Bi content were monitored in blood, urine, liver, and kidneys f or 14 days. A dose of 3.0 mmol Bi/kg, 100 times the daily therapeutic dose, caused kidney damage within 6 h as detected by proteinuria, glucosuria, an d elevated plasma urea and plasma creatinine levels. The kidneys of all ani mals, except two that died, recovered functionally within 10 days. At a dos e of 1.5 mmol Bi/kg, clinical parameters changed less and normalized within 48 h, whereas a dose of 0.75 mmol Bi/kg induced no changes. Histological e valuation revealed that the S3 tubular segment necrotized first with additi onal necrotization of the S1/S2 segment when more Bi was absorbed. The lesi ons were accompanied by interstitial infiltrates of CD45(+) leukocytes. In summary, we developed a rat model for Bi-induced reversible nephropathy. A large single oral overdose of CBS administered to Wistar rats led to damage to the proximal tubule, especially in the last segment.