The effect of mdr-1, cyp3a5 and cyp3a4 gene polymorphisms in determining steroid response in children with nephrotic syndrome

Nephrotic syndrome, is a chronic disease of childhood which is characterized by a protein loss with the urine and hypoalbuminemia, hyperlipidemia and edema that can be seen as a result of impairment of the glomerular capillary wall semi permeability. Nephrotic syndrome is clinically classified according to the responsiveness to oral steroid treatment, which is the first line therapy of the disease. Although genetic mutations of glomerular capillary wall proteins are blamed in the development of steroid resistance, some patients who carry these mutations can respond well to steroid treatment. Therefore, effects of other factors should be also investigated in the case of steroid resistance. In this study, we aimed to determine MDR 1, CYP3A5 and CYP3A4 gene polymorphisms which are responsible for drug elimination, whether or not the effect factor of steroid response in children with nephrotic syndrome. A total of 53 children diagnosed with nephrotic syndrome by the Pediatric nephrology department of Fırat University Medical Facutlty and 22 healthy children who have neither chronic nor renal disease were enrolled in this study. Demographic characteristics, clinical states, laboratory values and information about treatment regimens of the patients were recorded. Podocin and nephrin mutations, MDR-1, CYP3A4 and CYP3A5 polymorphisms, treatment regimens and response to these regimes, number of relapses, presence of renal failure, and biopsy results were evaluated in all patients. There wasn?t as statistically significant difference between the patients with nephrotic syndrome and control group in terms of age and gender (p>0,05). Considering the distribution of gender, female gender was more frequent in the steroid-resistant group (p <0.05). Serum urea and creatinine values were significantly higher in steroid-resistant group than steroid-responsive group. While podocin mutation was detected in all patients with steroid-resistant group, 40 patients had mutations in the steroid-responsive group (88,9%). Similarly, nephrin mutations were detected in all patients in the steroid-resistant group, and 38 patients had mutations in the steroid-responsive group (84,4%) (p> 0.05). However, we found that podocin and nephrin mutations have not a statistically significant effect in the steroid resistance (p> 0.05). In addition, there wasn?t as statistically significant relationship between MDR-1, CYP3A5 and CYP3A4 gene polymorphisms and steroid responsiveness. As a result, both gene of glomerular capillary wall proteins and genes which are responsible for drug elimination was determined to be ineffective in the development of resistance to steroids in nephrotic syndrome treatment. We thought that resistance to treatments in nephrotic syndrome was multifactorial and it will be required more studies which are elucidated pathogenesis of the disease for a constitution of convenient treatment models.