Renal Salt-Wasting Syndrome Induced by Neoadjuvant Chemotherapy Containing Cisplatin - A Case Report.

Hyponatremia is one of the most common electrolyte abnormality seen in oncology practice. The underlying pathogenetic mechanism for chemotherapy-induced hyponatremia is renal salt-wasting syndrome (RSWS) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction is the treatment of choice in SIADH, whereas salt supplements is the mode of treatment in RSWS. Hence, differentiation between RSWS and SIADH is very important though difficult. Case reports of cisplatin (cis-dichloro-diammine-platinum-2)-induced RSWS and SIADH are rare in the literature. We report about a patient who developed hyponatremia, hypokalemia with excessive urinary excretion of sodium and potassium, renal glycosuria, and aminoaciduria on the third day of the first cycle of cisplatin-containing chemotherapy.

Polymorphism of the CYP3A5 gene and its effect on tacrolimus blood level.

OBJECTIVES: Tacrolimus is the cornerstone for immunosuppression in renal transplant and is metabolized by the cytochrome P 450 3A (CYP3A) subfamily of enzymes in the liver and small intestine. A polymorphism in intron 3 of the CYP3A5 gene affects the expression of this enzyme and tacrolimus trough blood levels. The purpose of this study was to identify the proportion of CYP3A5 gene polymorphisms in South Indian renal transplant patients and determine the effect of CYP3A5 gene polymorphisms on tacrolimus trough blood levels in patients with and without CYP3A5 expression. MATERIALS AND METHODS: We included 25 adult patients who underwent renal transplant at Government Medical College, Trivandrum. All patients received tacrolimus (dose, 0.1 mg/kg/body weight, in 2 divided doses). Tacrolimus trough blood levels were determined on postoperative day 6. The CYP3A5 genotype analysis was performed by polymerase chain reaction amplification of target and detection by restriction fragment length polymorphism analysis. RESULTS: The CYP3A5*1/*1 genotype was detected in 5 recipients (20%), *1/*3 genotype in 5 recipients (20%), and *3/*3 genotypes in 15 recipients (60%) of the total 25 graft recipients. Mean tacrolimus level in the CYP3A5*1/*1 group was 5.154 ng/mL (range, 4.42 to 6.5 ng/mL), CYP3A5*1/*3 group was 5.348 ng/mL (range, 3.1 to 9.87 ng/mL), and CYP3A5*3/*3 group was 9.483 ng/mL (range, 4.5 to14.1 ng/mL). Acute rejection episodes were significantly more frequent for CYP3A5*1/*1 homozygous patients (40%) than patients with CYP3A5*1/*3 (20%) or CYP3A5*3/*3 (13%) genotypes. CONCLUSIONS: Most patients carried the mutant allele CYP3A5*3 (A6986G). Tacrolimus drug level correlated well with presence or absence of CYP3A5 polymorphisms. Acute rejection episodes were more frequent in expressors, and they may require higher doses of tacrolimus. Similarly, tacrolimus nephrotoxicity was more frequent in non-expressors. Therefore, CYP3A5 polymorphism analysis before renal transplant may help determine the optimal dose of tacrolimus in this population and prevent acute rejection episodes or tacrolimus toxicity.