Children who fail to respond to corticosteroids in the first episode of nephrotic syndrome (initial resistance) or develop resistance after one or more responses to corticosteroids (delayed resistance) may be treated with immunosuppressive agents including calcineurin inhibitors (CNI) (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB).
It has been reported (this issue Pediatric Nephrology) that cyclosporine A (CyA) therapy in combination with corticosteroids, angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker decreased proteinuria in three patients with nephrotic syndrome (NS) due to WT1 mutations.
The results show that ACE I/D polymorphism does not contribute to the steroid resistance, even though this study indicates that the presence of the I/D genotype has a much higher risk--approximately 2.8 times--of having nephrotic syndrome.
Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction.
There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene.