Evaluation of the relation of NR3C1 gene variants to kidney survival in children with nephrotic syndrome

Nephrotic syndrome (NS) is a chronic health condition that is caused by the disorder of the permeability of the glomerular capillary wall, which is especially important for childhood age. While most of the patients are responsive to steroids and progress with a good prognosis, patients who are resistant to steroids is a clinical problem in which a sufficient and effective treatment should be provided. In steroid-resistant patients, it may progress to end-stage renal disease (ESRD) and a need for kidney transplantation may develop. While clinical features regarding the NS kidney prognosis are well known, genotypes are not completely revealed yet. This study aims to analyse the factors related to kidney survival in children who are followed up with the diagnosis of nephrotic syndrome and to evaluate the relation of NR3C1 (nuclear receptor superfamily 3, group c, member 1) gene variants to kidney survival. Patients followed up with the diagnosis of NS in our clinic were included in the study according to outpatient application order. Demographic characteristics, clinical and laboratory data of the patients were obtained from the medical record system of the hospital; NR3C1 c.-13-6284C>T (rs10052957) and c.2298T>C (rs6196) variants were analysed. The patients were divided clinically as SRNS (steroid-resistant NS), SSNS (steroid-sensitive NS), SDNS (steroid-dependent NS), FRNS (frequently relapsing NS). The patients with SSNS, SDNS, FRNS were grouped as steroid-sensitive, and SRNS patients were grouped as steroid-resistant. 123 patients diagnosed with NS and 45 healthy children were included in the study. Of the patients, 49 (39.8%) were girls, 74 (60.2%) were boys; mean diagnosis age was 5.49±3.76 years; and surveillance period was 6.86±4.54 years. 63 patients were diagnosed with SRNS, 35 with SSNS, 17 with SDNS, and 8 with FRNS; 60 patients were in the steroid-sensitive group and 63 patients were in the steroid-resistant group. In the last polyclinic follow-up, it was observed that more than half of the patients (n=71) were in remission, 15 patients developed CKD, and in the remaining 37 patients, there was a progress to ESRD (35 patients with kidney transplantation and 2 patients with dialysis). Of the 71 cases within the remission, more than half (n=44) were in drug-free total remission while 27 were in remission under medication. In the steroid-resistant group, it was detected that the diagnosis age was higher; the rate of kin marriage in parents was higher; the history of nephrotic syndrome and CKD in the family was more frequent; hypertension rate during diagnosis was higher; complications of dyslipidaemia, chronic kidney damage, growth deficiency, thrombosis, osteopenia, osteoporosis were more frequent (p<0.05). Pathological allele distribution of the rs10052957 and rs6196 variants evaluated were found similar in the patient and control groups; SSNS, SRNS, FRNS, SDNS groups; full-remission, medicated remission, and ESRD groups. Steroid-resistant patients were compared to steroid-sensitive patients; full remitters to non-remitters; patients developing ESRD to patients who did not develop ESRD; steroid-resistant patients who developed ESRD to those who did not develop ESRD; the rs10052957 and rs6196 variants, and pathological allele distribution were similar. In the patients who did not have hypertension in diagnosis, rs10052957-CC natural variant frequency was higher compared to the group with hypertension; in the group with hypertension, rs10052957-T pathological allele frequency was higher compared to the group without hypertension (p<0,05). Study results show that having NR3C1 gene rs10052957 and rs6196 variants is not a condition specific to nephrotic syndrome. No relation was detected between these variants, which are known to affect the expression/function of the glucocorticoid receptor, and kidney survival in children with NS. Clinic characteristics in the diagnosis of the steroid-resistant and steroid-sensitive patients were found to be significantly different, however, no difference was observed in the distribution of the NR3C1 gene variants evaluated. Keywords: Nephrotic Syndrome, prognosis, NR3C1