Childhood nephrotic syndrome is a disease with relapses and remissions. Only a small number of children, not more than 20%, have a single attack and never relapse again. Most children will have relapses for several years following the diagnosis of nephrotic syndrome. Over half the children will have frequent relapses

Relapse is diagnosed when urine albumin is 3+ or 4+ for three consecutive early morning specimens, having been in remission previously.

The trigger for relapses is not known. Some relapses are triggered by infections, usually a viral upper respiratory tract infection (URTI). Infections should be treated before starting steroids. Resolution of infection might result in spontaneous remission in some cases, thereby avoiding the need for treatment with corticosteroids. Persistence of proteinuria after resolution of infections requires steroid therapy.

There is no rationale for the routine use of antibiotics in patients with nephrotic syndrome for prevention of relapse. Most URTIs are viral and do not need antibiotics. Antibiotics are only indicated for complications of URTI such as acute suppurative otitis media, streptococcal pharyngitis and sinusitis

A child who relapses not more than three times in a year is said to have an infrequent relapsing nephrotic syndrome. (IFRNS)

Prednisolone is administered at a dose of 2 mg/kg/day (single or divided doses) until urine protein is trace or nil for three consecutive days. Subsequently, prednisolone is given as a single morning dose of 1.5 mg/kg on alternate days for 4 weeks, and then discontinued

Children who have 4 or more relapses in a year are considered to have frequently relapsing nephrotic syndrome. (FRNS)

The initial treatment for a relapse would be to give oral prednisolone at 2mk/kg/day until remission is achieved followed by alternate day prednisolone at 1.5 mg/kg with gradual tapering of Prednisolone to maintain the patient in remission on alternate day dose of 0.5 mg/kg. This low dose can be given for for 9-18 months with close monitoring for steroid toxicity

Children with SDNS are those frequent relapsers who relapse while on tapering doses of steroids or within 2-weeks of steroid omission on two consecutive occasions

Second line treatment is started for 1. All SDNS. 2. For frequent relapsers who need prednisolone doses higher than 0.5 mg/kg on alternate days to maintain remission. 3. In those who have features of corticosteroid toxicity.

Levamisole is the most common second line drug used. It is administered at a dose of 2-2.5 mg/kg on alternate days for 12-24 months. Prednisolone is continued at a dose of 0.5 mg/kg/AD and then gradually tapered over a period of several months under cover of Levamisole.

The drugs available are Cyclophosphamide, Calcineurin inhibitors such as Cyclosporin or Tacrolimus; and Mycophenolate Mofetil. Rituximab is a third line drug used in severe cases who are steroid dependent despite the above therapies.

These drugs should be used only on the advice and close supervision of a pediatric nephrologist.

 Children with frequently relapsing NS or SDNS do not routinely need a renal biopsy. Kidney biopsy is needed in these children prior to starting cyclosporine or tacrolimus.

Urine albumin 3+ or 4+ (or proteinuria >40 mg/m2/h) for 3 consecutive early morning specimens, having been in remission previously

Infrequent relapses

Three or less relapses a year

Frequent relapses

Two or more relapses in initial six months or four or more relapses in any twelve months

Steroid dependence

Two consecutive relapses when on alternate day steroids or within 14 days of its discontinuation.

Steroid resistance

Absence of remission despite therapy with daily prednisolone at a dose of 2 mg/kg per day for 4 weeks.

All children with SDNS

Children with steroid toxicity

Children who continue to relapse despite Levamisole for 6 months

 All children who need additional immunosuppressive medication such as cyclophosphamide, mycophenolate, cyclosporine, tacrolimus or Rituximab