Management of steroid sensitive nephrotic syndrome: revised guidelines

1. ISKDC. Primary nephrotic syndrome in children: Clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. Ref: Kidney Int 1981; 20: 765–771.  • The pioneering studies of the International Study of Kidney Diseases in Children (ISKDC) settled on a regimen of 60 mg/m2/day prednisone, to a maximum of 80 mg/day for four weeks, followed by intermittent prednisone (40 mg/m2/day) on three consecutive days out of seven days for the next four weeks

2. The European collaborative group, Arbeitsgemeinschaft fur Padiatrische Nephrologie (APN), suggested that in the second four weeks of treatment, prednisone given every second day might be more effective in preventing relapses. • These two regimens were compared in a randomized controlled study in a group of 48 frequently relapsing patients • Patients receiving alternate-day prednisone had an approximate 50% reduction in relapse rate compared with the controls receiving prednisone three days out of seven • This difference occurred during only the six months of the trial, whereas the later relapse rate was similar • The investigators concluded that the alternate-day regimen was superior for the second four weeks of therapy and have recommended it even for the first attack of minimal lesion disease • Ref: Lancet 1979; 1: 401–403 : Klin Padiatr 1982; 194: 162–165.

3. Management of steroid sensitive nephrotic syndrome: revised guidelines • JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated guidelines for management of patients with steroid sensitive nephrotic syndrome. In view of emerging scientific evidence, it was felt necessary to review the existing recommendations. • PROCESS: Following a preliminary meeting in March 2007, a draft statement was prepared and circulated among pediatric nephrologists in the country to arrive at a consensus on the evaluation and management of these patients • Ref: Indian Pediatr. 2008 Mar;45(3):203-14.

4. Management of steroid sensitive nephrotic syndrome: revised guidelines – contd. • The need for adequate cortico-steroid therapy at the initial episode is emphasized • Guidelines regarding the initial evaluation, indications for renal biopsy and referral to a pediatric nephrologist are updated • It is proposed that patients with frequently relapsing nephrotic syndrome should, at the first instance, be treated with long-term, alternate-day prednisolone • Ref: Indian Pediatr. 2008 Mar;45(3):203-14.

5. Management of steroid sensitive nephrotic syndrome: revised guidelines – contd. • The indications for use of alternative immunosuppressive agents, including levamisole, cyclophosphamide, mycophenolate mofetil and cyclosporin are outlined • The principles of dietary therapy, management of edema, and prevention and management of complications related to nephrotic syndrome are described • Ref: Indian Pediatr. 2008 Mar;45(3):203-14.

6. Management of steroid sensitive nephrotic syndrome: revised guidelines – contd. • These guidelines, formulated on basis of current best practice, are aimed to familiarize physicians regarding management of children with steroid sensitive nephrotic syndrome • Ref: Indian Pediatr. 2008 Mar;45(3):203-14.

7. Management of steroid resistant nephrotic syndrome • JUSTIFICATION: There is a lack of evidence based guidelines for management of children with steroid resistant nephrotic syndrome (SRNS). • PROCESS: Experts of the Indian Society of Pediatric Nephrology were involved in a two-stage process, the Delphi method followed by a structured face to face meeting, to formulate guidelines, based on current practices and available evidence, on management of these children • Ref: Indian Pediatr. 2009 Jan;46(1):35-47

8. Management of steroid resistant nephrotic syndrome – contd. • The Expert Group emphasized that while all patients with SRNS should initially be referred to a pediatric nephrologist for evaluation, the subsequent care might be collaborative involving the primary pediatrician and the nephrologist • Following the diagnosis of SRNS (lack of remission despite treatment with prednisolone at 2 mg/kg/day for 4 weeks), all patients (with initial or late resistance) should undergo a renal biopsy, before instituting specific treatment • Ref: Indian Pediatr. 2009 Jan;46(1):35-47

9. Management of steroid resistant nephrotic syndrome – contd. • Patients with idiopathic SRNS secondary to minimal change disease or focal segmental glomerulosclerosis should receive similar therapy • Effective regimens include treatment with calcineurin inhibitors (tacrolimus, cyclosporine), intra-venous cyclophosphamide or a combination of pulse corticosteroids with oral cyclophosphamide, and tapering doses of alternate day corticosteroids • Ref: Indian Pediatr. 2009 Jan;46(1):35-47

10. Management of steroid resistant nephrotic syndrome – contd. • Supportive management comprises of, when indicated, therapy with angiotensin converting enzyme inhibitors and statins • It is expected that these guidelines shall enable standardization of care for patients with SRNS in the country • Ref: Indian Pediatr. 2009 Jan;46(1):35-47