Reversal Of Nephrotoxicity Research Articles

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.

Aim:To compare the effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.Materials and Methods:Rabbits and rats of either sex in weight range of 1.5–2.5 kg and 175–225 g, respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5 g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day i.m. were administered for 6 days in either species containing 7 groups. Blood urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for histopathplogical examination and kidney superoxide dismutase levels (SOD) were measured. Statistical analysis was done using student's unpaired t-test, analysis of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was considered significant.Results:The results showed that calcium was able to reverse significantly increased BUN, serum creatinine, urine protein, and reduced kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose-dependent manner while verapamil had no protective or nephrotoxic effect.Conclusion:Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals. There was no species-sensitive variation in reversal of nephrotoxicity by calcium in rats and rabbits.

Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans

Vancomycin troughs of 15-20 mg/L are recommended in the treatment of invasive staphylococcal disease, higher levels than previously recommended. We sought to determine if there was an association between vancomycin trough and nephrotoxicity, defined as 0.5 mg/L or 50% increase in serum creatinine, at a large Veterans Affairs medical center. We reviewed records of 348 inpatients at our institution who received ≥5 days of vancomycin during 2 time periods when vancomycin dosing protocols differed (May 2005-April 2006 and January 2007-December 2007). Potential risk factors for nephrotoxicity were collected prior to nephrotoxicity onset, and all patients with nephrotoxicity events occurring within 5 days of starting vancomycin were excluded. Overall incidence of nephrotoxicity was 31/348 patients (8.9%). A similar percentage of patients experienced nephrotoxicity in 2005-2006 versus 2007 (16/201 vs 15/147, respectively; P = 0.57), despite a rise in mean (9.7 mg/L in 2005-2006 vs 13.2 mg/L in 2007; P < 0.0001) and highest (11.8 mg/L in 2005-2006 vs 15.7 mg/L in 2007; P < 0.0001) vancomycin trough levels achieved. In a multivariate logistic regression model, only receipt of intravenous contrast dye was significantly associated with nephrotoxicity (OR 4.01, P < 0.001), though there was a trend toward an association between maximum vancomycin trough ≥15 mg/L and nephrotoxicity (OR 2.05, P = 0.082). Overall reversibility of nephrotoxicity either prior to or within 72 hours of vancomycin discontinuation was 77.8%. We conclude that nephrotoxicity, with higher trough levels occurring at ≥5 days of vancomycin therapy, was uncommon at our institution and typically reversible.

Reversibility of nephrotoxicity and severe gastrointestinal symptoms associated with FK506 immunosuppression in liver transplant recipients

Reversibility of nephrotoxicity and severe gastrointestinal symptoms associated with FK506 immunosuppression in liver transplant recipients