Urinary Transforming Growth Factor Beta-1 in Children With Nephrotics Syndrome and End-Stage Renal Disease

Background: Nephrotics Syndrome is one of the most important disorder in childhood and it may end with chronic renal failure. Transforming growth factor- beta1 (TGF-β1) is a multifunctional cytokine that plays an important role in glomerulosclerosis that leads to resistance to steroid therapy and chronic renal failure.
Objectives: This study aimed to evaluating the role of estimation of TGF-β1 in urine of nephrotic children as a parameter of progression of the disease and a predictor of response to steroid therapy.
Methods: Forty-four children attending the Nephrology Unit of Ain Shams University Children′s Hospital were enrolled in the study, 30 with idiopathic syndrome and 14 with end-stage renal disease under regular hemodialysis and were compared to 30 normal; age and sex matched controls. The nephrotic children were divided according to their response to steroid therapy into 13 dependent and 10 resistant cases. In addition to 7 newly diagnosed nephrotic children who were sampled at presentation and after one month of steroid therapy. All patients were subjected to history taking and complete clinical examination. Laboratory investigations included, serum albumin and creatinine, random urinary protein and creatinine and urine protein to creatinine (uPr/Cr) ratio was calculated. In addition to determination of TGF-β1 in the random urine sample by ELISA technique and its expression as a ratio to urinary creatinine.
Results: UTGF-β1/Cr was highly significantly elevated in all nephrotic groups when compared to controls and a significant difference was found between steroid dependent and steroid resistant groups (14.46 ± 5.13 and 48.4 ± 23.13 pg/mg Cr respectively). In the newly diagnosis group the mean uTGF-β1/Cr ratio at presentation was significantly higher than after one month and both were higher than the control (57.28 ± 66.18, 25.66 ± 29.6 and 4.76 ± 3.3 pg/mg Cr respectively). The lowest uTGF-β1/Cr values were among patients who turned to be steroid responsive and the highest values among steroid resistant patients. A significant positive correlation was found between uTGF-β1/Cr ratio in all studied nephrotic groups, while no correlation could be elicited between uTGF-β1/Cr and age, sex, blood pressure, duration of illness or dose of steroid. In the end stage renal disease (ESRD) group, the highest mean value of uTGF-β1/Cr ratio among the studied group was found (219.86 ± 19.79 pg/mg Cr), but it could not be correlated with age, sex, duration of dialysis, type of dialyzer membrane, type of dialysate, blood pressure, serum albumin or serum creatinine. Patients with uTGF-β1/Cr ratio lower than a cut-off value of 11.9 pg/mg Cr (mean ± 2.5 SD) have a higher chance to be steroid responsive or dependent while those with values above the cut-off are mostly steroid resistant.
Conclusions: uTGF-β1/Cr is a good diagnostic and prognostic marker in patients with nephrotic syndrome. It is a simple and easy marker for predication of response to steroid therapy in nephrotic patients, in addition to its value in monitoring progression of glomerulosclerosis among nephrotic patients that ends in chronic renal insufficiency.