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Background: Kidney disease was ranked 10th as the leading cause of death in Indonesia according to WHO Country Health Profiles in 2012. In conducting alternative therapies research, preclinic study using animal model is performed before the drug can be tested into human beings. Objective: This study was designed to investigate alternative therapies on kidney disease and to evaluate nephrotoxicity in rat models. Materials and Methods: Evaluation of nephrotoxicity in rat models is conducted using 27 rats which divided into 7 groups: normal, 3 groups of gentamycin (80, 100, and 120 mg/kg w/day), and 3 groups of diclofenac sodium (10, 50, and 100 mg/kg w/day). Meanwhile, to evaluate the therapeutic effect of losartan, 3 dosage variations (5, 10, and 20 mg/kg w/day) were given to the nephrotoxic rat model. Results: Induction of gentamycin elevated the levels of serum creatinine, BUN, and the relative kidney weight. Specifically, the administration of gentamycin at a dose of 120 mg/kg w/day for 5 and 10 days, also reduced albumin serum levels. Meanwhile, administration of diclofenac sodium did not provide a significant difference in serum creatinine, urea, and BUN parameters. In addition, administering diclofenac sodium at a dose of 50 and 100 mg/kg w/day has toxic effect on rats, killing the rats in less than 5 days. The administration of losartan as a kidney disease therapy elevated the biomarkers of kidney damage but increased levels of serum antioxidant on the 7th day when compared to negative control groups. Conclusion: Gentamycin has a higher nephrotoxic effect compared with sodium diclofenac, so it is further used as a nephrotoxic model in rats for the next experiment with a dosage given 120 mg/kg w/day for 5 days. Meanwhile, the effect of administering losartan does not have therapeutic effect, reversely, exacerbate kidney damage despite elevating the levels of serum antioxidant.