Intravenous fluids should be used with caution as regards the tonicity and volume administered, and with appropriate monitoring of serum electrolytes.
The biochemical mechanism underlying cyclosporine (CsA)* induced nephrotoxicity is far from clear. Increased generation of oxygen derived free radicals (ODFR) and enhanced activity of phospholipase A2 (PLA2) have been observed in experimental animals following treatment with CsA. Several recent reports have shown that quinacrine, besides being a potent inhibitor of PLA2, suppresses the generation of ODFR. The present study was designed to investigate the effect of quinacrine on CsA induced nephrotoxicity in rats. Male Wistar rats (weighing 280-300 g) were randomized into eight groups of eight animals each. Group 1 (control) received appropriate vehicles only, whereas the rats in groups 2, 3, 4, and 5 received subcutaneous injection of CsA (17.5 mg/kg dissolved in olive oil) daily for 8 weeks. The animals in groups 3, 4, and 5 were also given intraperitoneal injections of quinacrine in three different doses of 2.5 mg/kg, 5 mg/kg, and 10 mg/kg body weight, respectively, in addition to CsA. The animals in groups 6, 7, and 8 received intraperitoneal injection of quinacrine alone at doses of 2.5 mg/kg, 5 mg/kg, and 10 mg/kg respectively for eight weeks. After 8 weeks, animals were sacrificed under light ether anesthesia and blood and kidney samples were collected for various biochemical and histological studies. The biochemical parameters included blood urea nitrogen (BUN), serum creatinine (Scr), potassium, and sodium. The blood was also analyzed for the level of CsA. The kidney samples were analyzed for malondialdehyde (MDA), glutathione, and vitamin E (VE). Kidney sections were prepared for histopathological studies using hematoxylin-eosin staining. There was an increase in BUN, Scr, and potassium levels and decrease in sodium levels in cyclosporine alone treated group, suggesting a significant nephrotoxicity. Quinacrine treatment significantly protected animals against CsA induced biochemical changes. Our studies on free radical indices showed that quinacrine treatment protected animals against cyclosporine induced increase in MDA and depletion of glutathione and VE. The beneficial effect of quinacrine against CsA induced nephrotoxicity was also confirmed by histological studies.
Although inulin clearance measured during constant infusion is still considered the reference method, single-injection of 51Cr-EDTA with subsequent plasma sampling has become the most popular technique for the routine assessment of glomerular filtration rate. Despite the fact that the technique has been in use for 30 years, there are only a few reports of normal values calculated directly from 51Cr-EDTA data and normal ranges have generally been produced by conversions of inulin data. The aim of this study was to measure the variation in total plasma clearance, calculated directly from 51Cr-EDTA measurements, in normal males and females, of Saudi Arabian origin, over a wide range. Altogether, 201 potential kidney donors aged 16-60 years were studied. No statistically significant association of total plasma clearance with age or sex could be demonstrated; however, predictive equations suggesting a small decline in total plasma clearance with age were developed. The figures presented suggest that the reduction in total plasma clearance of 51Cr-EDTA with age is relatively shallow up to the age of at least 60 years and that normal ranges produced by conversion of inulin data may overestimate the decline with age.
A simple ultrasonic method was used for measuring transplanted kidney volume in 29 patients. Five of these patients developed diabetes mellitus and six women became pregnant following transplantation. Serial measurements were performed over periods of 6-12 months after transplantation. The kidney volume became stable 6 months after transplantation and this volume correlated positively with the renal function. Renal hypertrophy was noted in those transplant patients who developed diabetes mellitus following transplantation and this hypertrophy was associated with improvement in graft function. Transplant volume also rose in acute rejection and returned to normal after appropriate treatment. During pregnancy following transplantation, the transplant volume increased early in pregnancy to return to normal before delivery. This volume increase was also associated with graft function improvement.
Cyclosporin (CSA) has been universally used as an immunosuppressant for the management of allotransplantation and autoimmune diseases. However, nephrotoxicity of CSA limits its use to optimum level. Aluminum (Al) is an extensively distributed element in the environment and human exposure to this metal is unavoidable. Recent studies suggest that even a slight impairment of renal function may increase the Al body burden significantly, which may lead to neurotoxicity, nephrotoxicity, osteodystrophy or hypochromic anemia. In the present study, an attempt was made to study the effect of concomitant use of Al and CSA on structure and function of kidney in rats. This study was undertaken in two steps. In the first set of experiments, the effect of single dose of Al (1% Al2(SO4)3 18H2O) on the nephrotoxicity of multiple doses of CSA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) was studied, where as in the second set of experiments the effect of multiple doses of Al (0.25%, 0.5% and 1%) on single dose of CSA (50 mg/kg) was undertaken. Male Sprague-Dawley rats (weighing 230 +/- 20 g) were used in this study. CSA was given once a day by gavage for seven days, where as Al was given in drinking water for the same period. Twenty four hours after the last dose of CSA, animals were sacrificed and blood and kidney were collected for biochemical and histopathological studies. The bio-chemical parameters included blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Al levels. The kidney homogenates were assayed for malondialdehyde (MDA) and lipid hydroperoxides (LPH). Treatment of rats with CSA alone produced dose-dependent structural and functional changes in kidney. Although Al alone failed to produce any deleterious effect on renal function, it significantly increased the bioavailability and nephrotoxicity of CSA. Al also exacerbated CSA induced increase in oxidative stress (as evident by increased MDA and LPH). Thus, the exacerbation of CSA nephrotoxicity by Al may be attributed to increased bioavailability of CSA and excessive generation of free radicals following concomitant use of these drugs.
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