The quality of evidence is downgraded by study limitations (unclear allocation concealment and lack of blinding), and by imprecise results (few patients and outcome events).
A Cochrane review [Abstract] 1 included 25 studies with a total of 1 063 children with idiopathic steroid resistant nephrotic syndrome (SRNS). Cyclosporine significantly increased the number of children who achieved complete remission (RR 3.50, 95% CI 1.09 to 11.20; 4 studies, n=74) or complete or partial remission (RR 3.15, 95% CI 1.04 to 9.57; 4 studies, n=74) by 6 months compared with placebo or no treatment.
Calcineurin inhibitors (cyclosporin or tacrolimus) significantly increased the number with complete or partial remission at 3 to 6 months (RR 1.98, 95% CI 1.25 to 3.13; 2 studies, n=156), and reduced the number with treatment failure (non response, serious infection, persistently elevated creatinine)(RR 0.32, 95% CI 0.18 to 0.58; 1 study, n=124) with little or no increase in serious infections (RR 0.49, 95% CI 0.16 to 1.56; 1 study, n=131) compared with IV cyclophosphamide. There was no significant differences in the number who achieved complete or partial remission (RR 1.05, 95% CI 0.87 to 1.25; 2 studies, n=58), or in the number with worsening hypertension (RR 0.41, 95% CI 0.08 to 2.15; 2 studies, n=58) between tacrolimus and cyclosporin.
There was no significant difference in the number achieving complete or partial remission (RR 2.14, 95% CI 0.87 to 5.24; 1 study, n=138), in the number dying (RR 2.14, 95% CI 0.87 to 5.24; 1 study, n=138) or with 50% reduction in glomerular filtration rate (GFR) (RR 2.29, 95% CI 0.46 to 11.41; 1 study, n=138) between cyclosporin and mycophenolate mofetil (MMF) plus dexamethasone.
Among children, who had achieved complete remission, tacrolimus increased the number of children who maintain complete or partial response for 12 months (RR 2.01, 95% CI 1.32 to 3.07; 1 study, n=60) compared with MMF.There was no difference in the number achieving complete remission between oral cyclophosphamide with prednisone compared with prednisone alone (RR 1.06, 95% CI 0.61 to 1.87; 2 studies, n=84).There was no difference in complete remission between IV cyclophosphamide compared with oral cyclophosphamide (RR 1.58, 95% CI 0.65 to 3.85; 2 studies, n=61) and IV compared with oral cyclophosphamide plus IV dexamethasone (RR 1.13, 95% CI 0.65 to 1.96; 1 study, n=49).It was uncertain whether rituximab and cyclosporin compared with cyclosporin, or adalimumab or galactose compared with conservative therapy increased the likelihood of remission.Two studies reported that ACEi reduced proteinuria in children with SRNS. One study reported that the dual angiotensin II and endothelin Type A receptor antagonist, sparsentan, reduced proteinuria more effectively than the angiotensin receptor blocker, irbesartan.
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