The role of MDR-1 mRNA gene expression determining steroid treatment response in children with nephrotic syndrome

ABSTRACT THE ROLE OF MDR-1 mRNA GENE EXPRESSION DETERMINING STEROID TREATMENT RESPONSE IN CHILDREN WITH NEPHROTIC SYNDROME Nephrotic syndrome is a chronic disease of childhood which is characterized by protein loss with the urine that causes hypoalbuminemia, hyperlipidemia and edema. Nephrotic syndrome is classified as clinically according to the response to steroid treatment. Many factors are effective in the development of steroid resistance, one of them is a membrane protein which is named p-glycoprotein (p-gp) that is responsible for excretion of intracellular steroid. P-gp is the MDR–1 gene's final product which is responsible for drug elimination. Therefore, there have been many studies to investigate the effect of p-gp in steroid resistance. Measurement of MDR–1 gene mRNA is reported to be more sensitive than measurement of p-gp protein. The aim of this study is to evaluate whether MDR–1 gene which is responsible for drug elimination is an effective factor for determining the response to steroid therapy in children with nephrotic syndrome. A total of 40 children diagnosed with nephrotic syndrome by the Pediatric nephrology division of Fırat University Medical Faculty and 22 healthy children who have neither chronic nor renal disease were included in this study. Demographic characteristics, clinical states, laboratory values and information about treatment regimens of the patients were recorded. mRNA expression levels of MDR-1 gene in whole patients with NS were determined at the time of diagnosis. MDR-1 gene mRNA levels were measured again for patients with SSNS (Steroid Sensitive Nephrotic Syndrome) at the end of treatment and fourth week of treatment. There wasn't any as statistically significant difference between the patients with nephrotic syndrome and control group in terms of age and gender (p>0,05). mRNA level of the control group was 4.78±2.54 copies/µg RNA. mRNA level at the time of diagnosis was 3.03±4.23 copies/µg RNA in patients with NS. There was no statistically significant difference between the two groups (p>0.05). Furthermore, there was no statistically significant difference for mRNA levels between the two groups (SSNS and SRNS) at the time of diagnosis (p>0.05). Serum creatinine levels of patients with SRNS were higher than patients with SSNS, as well as the incidence of hematuria in patients with SRNS was higher as statistically (p<0.05). mRNA levels were 3.65±3.79 copies/µg RNA at the time of diagnosis, 3.15±4.46 copies/µg RNA at the end of fourth week of treatment and 2.97±3.01 mRNA copies/µg RNA at the end of treatment in patients with steroid responsive. Althoug mRNA levels decrease gradually in patients with SSNS who were used steroid, there was no as statistically significant difference (p>0.05). As a conclusion; MDR–1 gene mRNA expression which is responsible for drug elimination was determined to be ineffective for the development of steroid resistance. We show that more studies related to pathogenesis will be needed for developing appropriate treatment modality. Because the unresponsiveness of treatment is multifactorial. Key Words: Nephrotic syndrome, steroid, MDR–1, mRNA, p-glycoprotein