• Frequent relapses/ steroid - dependent cases
 
• Steroid resistant cases

These 2 types of nephrotic syndrome are designated as "difficult nephrotics " because of need to use alternative therapy, repeated and prolonged steroid therapy causing serious side effects, increased risk of life, threatening infections, thrombosis,hypertension, drug toxicity and possibility of chronic renal failure in steroid - resistant cases. Difficult nephrotics should be managed by pediatric nephrologists, who are experienced in treating such cases.

Frequent relapsing/steroid dependent NS requires individualized approach. Regular examination of urine for heavy/nephrotic range proteinuria is the only method of diagnosing relapses and treatment should start when three consecutive urine samples show 2+ or more proteinuria, which is defined as a relapse. First, 2-3 relapses are treated with short courses of oral prednisolone i.e. 2 mg/kg/day till remission occurs followed by alternative days single dose for 4 weeks. Since repeated courses of high dose steroids cause more steroid toxicity than alternative day regimes given for 6-12 months, after the 3rd relapse within 6 months i.e. frequent relapser or steroid - dependent case is subsequently treated with oral prednisolone used in as low dose as possible on alternate days to maintain sustained remission without major side-effects. Most children tolerate 0.5 mg/kg of prednisolone on alternate days without side-effects and maintain protein-free urine.

Along with regular urine examination, side effects of steroids should be looked for, namely cushingoid facies, obesity, striae, hirsutism, acne, hypertension, susceptibility to infections, pancreatitis and if used for more than a year, post subcapsular cataract, growth retardation, myopathy and rarely, peptic ulceration and avascular necrosis of bone. Pubertal growth spurt may be delayed in boys.

Alternative drug therapy is indicated in a steroid responsive NS if:

Drugs used for alternative therapy are introduced after inducing remission with oral prednisolone therapy whilst tapering steroids. The details for dosage, duration and side- effects of these drugs is given in Table I.

Table I Drugs used for alternative therapy in steroid - dependent or frequently relapsing NS

Drug dosage and duration	Side Effects	Monitoring
Cyclophosphamide 2.5 - 3 mg/kg/day PO x 8 - 12 weeks MAX 168 mg/kg.	Reversible - alopecia, Hemorrhagic cystitis, Bone Marrow suppression, Infections. Long term - gonadal toxicity, sterility and malignancy.	Clinical: CBC, Urinalysis (every two weeks). Sperm count after puberty.
Chlorambucil 0.2 mg/kg/day PO X 8 - 12 weeks Max 12 mg/kg	Same as above Focal seizures	After puberty EEG.
Levamisole 2.5 mg/kg/alternate day x 6 - 24 months	Skin rash, abdominal pain, vomiting and neutropenia.	CBC monthly.
Cyclosporin A 4-5 mg/kg/day BD for 6 - 24 months.	Hypertension, gingival hyperplasia, hirsutism, hyperkalemia, infections, nephrotoxicity.	Drug monitoring monthly (Trough Level 100 - 150 ng/ml), S. Creatinine monthly. Kidney biopsy yearly.

Last created on 04-06-2001
Last updated on 01-07-2006