A child comes with steroid resistant nephrotic syndrome secondary to FSGS. not responsive to methylprednisolone. What next should be given aEUR'
Oral cyclosporine [Ref. Indian society of pediatric nephrology (MIMS) Dr. Arvind Bagga Aicle from Indian Journal of pediatrics volume 46 January 17, 20091 There is a lack of evidence based guidelines for management of children with steroid resistant nephritic syndrome (SRNS). - Expes of the Indian society of peadiatric nephrology were involved in two stage process and gave the following guidelines:? Definitions of coicosteroid resistant nephrotic syndrome A patient is diagnosed to have steroid resistance if there is lack of remission despite treatment with prednisolone at a dose of 2 nig/kg/day (60 mg/m2/day) for 4 weeks. Remission is defined as absence of proteinuria (urine albumin nil or trace for three consecutive days by dipstick or boiling test). - Following treatment with daily prednisolone, 95% patients with steroid sensitive nephrotic syndrome achieve remission by the .first 4 weeks and an additional 3% in additional 4 weeks. Prolonged cources of daily coicosteroids are associated with increased incidence of side effects. Therefore, defining SRNS as lack of remission despite 4 weeks treatment with daily prednisolone is reasonable. - This definition is in conformity with that used by the Cochrane Renal Group. The national Institutes of Health (USA) trial on patients with steroid resistant .focal segmental glomerulosclerosis (FSGS) has accepted a similar definition. All children with SRNS, whether initial or late. should undergo a renal biopsy before instituting specific treatment. Despite absence of evidence based recommendations regarding the role of renal biopsy in patients with SRNS, this procedure provides impoant information on renal histology and outcome. Most patients with steroid sensitive nephritic syndrome (90%) show minimal change nephritic syndrome on renal histology. - The renal histology in SRNS is different, with 30-40% patients each showing minimal change nephritic syndrome and FSGS, and a smaller group with mesangioproliferative glomerulonephritis (8). The response to therapy is determined by renal histology; patients with minimal change nephritic syndrome show satisfactory response to therapy, while presence of FSGS or chronic tubulointerstitial changes is associated with unsatisfactory outcomes. A renal biopsy is also necessary before initiating treatment with potentially nephrotoxic agents, especially cyclospo- rine or tacrolimus. Mutational Analysis Studies for mutations of genes involved in synthesis of podocyte protein are not routinely necessary in children with SRNS. Where facilities exist, mutational analysis may be offered to patients with congenital nephrotic syndrome (onset below 3 months of age), initial steroid resistance and family history of a SRNS). - Mutations in the genes encoding various podocyte proteins, including podocin (NHHS2) and nephrin (NPHS1), have been described in a variable propoion of patients with familial and sporadic SRNS. - The likelihood of detecting a mutation is higher in patients with family history of nephrotic syndrome or its onset in infancy. Patients with mutations involving these genes often do not respond to immunosuppressive medications and show progressive kidney disease. - In view of lack of data in Indian children, routine mutational analysis in patients with initial SRNS is not recommended. Patients with late steroid resistance have not been. found to have genetic mutations. Principles of therapy Patients with idiopathic SRNS secondary to minimal change nephrotic syndrome, FSGS and mesangioproliferative glomerulonephritis should receive similar therapy. Review of the of the literature suggests that patients with steroid resistance secondary to minimal change nephrotic syndrome are more likely to achieve remission and have a better prognosis compared to other histological types. However, a systemic review by the Cochrane Renal Group showed similar outcome in patients with steroid resistant minimal outcome in patients with steroid resistant minimal change nephrotic syndrome and FSGS who were treated with cyclosporine or cyclophosphamide. - There is not clear evidence to suppo that patients with minimal change nephrotic syndrome and FSGS should be treated differently. Specific treatment The aim of therapy is induction of remission while avoiding medication related toxicity. The option for treatment for patients with idiopathic SRNS include :? Cakineurin inhibitors with tapering doses of alternate day steroids : ? Cyclosporine - Tacrolimus Cvclophosphamide oral and I.V. with tapering doses of alternate day steroids. Pulse coicosteroids -high dose intravenous steroids (dexamethasone, methyl- prednisolone) with oral cyclophosphamide and tapering alternate day steroids. There is lack of consensus on the most appropriate first line therapy for children with SRNS, with many of the regimens extrapolated from studies in adults. - The level of evidence on efficacies of available regimens is summarized below. "From these evidences calcineurin inhibitors i.e. cyclosporine and Tacrolimus seems to be the most effective drugs for steroid resistant nephritic syndrome". An impoant point There is still lack of consensus on first line appropriate therapy for steroid resistant nephrotic syndrome.
Oral cyclophosphamide
Oral cyclosporine
Oral mycophenolate
IV cyclophosphamide