Israel Medical Association Journal

Background: Several studies link the pathogenesis of nephrotic syndrome to tumor necrosis factor-alpha (TNFα). However, data on the serum TNFα level in children with nephrotic syndrome are sparse. 

Objective: To investigate serum TNFα levels and the effect of steroid therapy in children with nephrotic syndrome. 

Methods: A prospective cohort pilot study of children with nephrotic syndrome and controls was conducted during a 1 year period. Serum TNFα levels were measured at presentation and at remission, or after a minimum of 80 days if remission was not achieved.

Results: Thirteen patients aged 2–16 years with nephrotic syndrome were compared with 12 control subjects. Seven patients had steroid-sensitive and six had steroid-resistant nephrotic syndrome. Mean baseline serum TNFα level was significantly higher in the steroid-resistant nephrotic syndrome patients than the controls (6.13 pg/ml vs. 4.36 pg/ml, P = 0.0483). Mean post-treatment TNFα level was significantly higher in the steroid-resistant than in the steroid-sensitive nephrotic syndrome patients (5.67 pg/ml vs. 2.14 pg/ml, P = 0.001). In the steroid-resistant nephrotic syndrome patients, mean serum TNFα levels were similar before and after treatment.

Conclusions: Elevated serum TNFα levels are associated with a lack of response to corticosteroids. Further studies are needed to investigate the role of TNFα in the pathogenesis of nephrotic syndrome.

 

Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies.