Pulse cyclophosphamide therapy in frequently relapsing nephrotic syndrome.

BACKGROUND: The treatment of frequently relapsing (FR) and steroid-dependent (SD) idiopathic nephrotic syndrome (INS) with oral cyclophosphamide (OCP) poses problems of compliance, side-effects and infections. METHODS: We prospectively evaluated the usefulness of intravenous cyclophosphamide (IVCP) in children with steroid sensitive INS who were frequent relapsers or steroid dependent. Fifty-one children were included in the study of whom 22 were FR and 29 were SD. IVCP was administered in a dose of 500 mg/m(2)/month for 6 months after achieving a steroid-induced remission. The response to IVCP was evaluated in terms of remission, change in the steroid response status of the patient, duration of remission (i.e. proteinuria-free days), side effects and compliance with therapy. RESULTS: The proteinuria-free days (mean 19.9+/-3.5 before IVCP therapy vs 1256+/-167 days after IVCP therapy) (P<0.00001), and serum albumin levels (23+/-1.6 g/l before IVCP therapy vs 34+/-2 g/l after IVCP therapy) (P<0.001) were significantly higher following IVCP therapy. The cumulative remission rate in the study group was 49% at 5 years and was comparable to that achieved with oral cyclophosphamide at a 40% lower cumulative dose. CONCLUSIONS: We conclude that IVCP is a safe and effective therapeutic modality in children with INS who are FR and SD. Its efficacy is comparable to the results obtained with oral cyclophosphamide based on historical comparisons with previous studies.

Early versus late-onset idiopathic focal segmental glomerulosclerosis.

Glomerular diseases in children, although similar in histological appearance to those in adults, may have a better prognosis. There is much controversy regarding the prognostic factors in idiopathic focal segmental glomerulosclerosis (FSGS), especially the comparative prognosis of children and adults. A comparative analysis was carried out of 36 consecutive biopsy-proven cases of idiopathic FSGS presenting early in life ['early onset' as seen in children < or =12 years (group I)] and 36 cases presenting later ['late-onset' as seen in older children >12 years and adults (group II)]. Patients were compared for clinical, biochemical, and histopathological features, as well as disease outcome. A significantly higher prevalence of hypertension (P=0.002) and microscopic hematuria was seen in group II (P=0.02). There were no differences between the two groups in glomerular filtration rates corrected for body surface area at initial presentation (92+/-11 ml/min/1.73 m2 vs. 94+/-14 ml/min/1.73 m2). Patients with 'late-onset' FSGS had a significantly higher number of glomeruli with segmental sclerosis (P=0.007), more mesangial matrix expansion (P=0.009), greater mesangial cellularity (P=0.003), and significantly higher blood vessel involvement (P=0.03) than those with 'early onset' FSGS. There was a significantly higher response to steroids in group I (82.3%) than group II (36.4%) (P<0.02). At the end of the study period, 2 patients in group I and 11 in group II had developed persistent renal failure (P=0.01). Thus 'early onset' FSGS is more common in males, has significantly lower prevalence of hypertension and microscopic hematuria, with less-severe histopathological involvement, is more often steroid responsive, and has a better prognosis than 'late-onset' FSGS.

Treatment of nephrotic syndrome.

There are well defined therapeutic protocols for childhood nephrotic syndrome. Appropriate therapy helps in minimizing side effects besides decreasing referrals to tertiary care centres. We have analysed the appropriateness of therapy of primary care physicians in 111 children with nephrotic syndrome referred to our Institute from January 1989 to December 1991. Prednisone was administered in adequate doses in 51 (52.6%), and for adequate duration in 41 children (42.2%). Adjunctive cyclophosphamide therapy was administered in the recommended doses and duration in 33% of the cases. On evaluation of the therapy it was observed that inappropriate treatment had been administered by 39.4% of the pediatricians, 59% of internists and 80% of general practitioners. This study highlights the lacunae in the current state of knowledge amongst the primary physicians and highlights the need for creating greater awareness regarding the therapy of children with nephrotic syndrome.

Intravenous pulse cyclophosphamide--a new regime for steroid-resistant minimal change nephrotic syndrome.

The treatment of steroid-resistant minimal change nephrotic syndrome (MCNS) continues to pose a therapeutic challenge. We conducted a randomised prospective controlled trial to evaluate the efficacy of i.v. cyclophosphamide compared with oral cyclophosphamide in 13 children with biopsy-proven steroid-resistant MCNS. All 7 patients receiving i.v. cyclophosphamide achieved remission; this was sustained in 4 patients, while 3 relapsed. However, even these 3 patients subsequently became steroid sensitive. Of the 6 patients who received oral cyclophosphamide, 2 dropped out, 1 responded and 3 children continued to remain steroid resistant. The children who received IV cyclophosphamide had more sustained remissions, longer periods without proteinuria and fewer significant side effects; this was achieved at a lower cumulative dose.