Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children.

The ability to predict the course in children with newly diagnosed minimal change nephrotic syndrome (MCNS) may have significant therapeutic implications. Previous attempts based on data available at disease onset have not been successful. Therefore, it was investigated whether characterization of the initial response to adrenocortical steroids and the course during the early months of disease are predictive of the subsequent outcome. Three hundred-eighty-nine children with MCNS, diagnosed at onset, were treated with standard prednisone regimens and monitored for up to 17 yr (mean, 9.4 yr). They were classified, after 8 wk of therapy, as initial responders (complete remission) or initial nonresponders (continued proteinuria). Subsequent classifications included nonrelapsers, infrequent relapsers, and frequent relapsers. At 8 yr of follow-up, 80% of patients were in remission. Three-fourths of initial responders who remained in remission during the first 6-month period after initial therapy (nonrelapsers; 40% of the entire series) either continued in remission during their entire course or relapsed rarely. In contrast, initial relapsers, both frequent and infrequent, achieved a nonrelapsing course only after an average of 3 yr. Unremitting proteinuria during the initial 8 wk of treatment was followed by progression to ESRD in 21%. When proteinuria during the initial 8 wk continued through the subsequent 6 months, progression to renal failure occurred for 35%. Although 95% of children with MCNS do well, 4 to 5% die from complications or undergo progression to ESRD. Documentation of the early course aids in identifying those at increased risk for a poor outcome. More aggressive therapy may be indicated for these individuals.

Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children.

Sixty children, with biopsy diagnosed focal segmental glomerulosclerosis (FSGS) and with unremitting nephrotic syndrome despite intensive therapy with adrenocortical steroids, were randomly allocated into a clinical trial comparing prednisone, 40 mg/m2 on alternate days for a period of 12 months (control group), with the same prednisone regimen plus a 90-day course of daily cyclophosphamide, 2.5 mg/kg in a single morning dose (experimental group). One-quarter of the children in each group had complete resolution of proteinuria. The proportions of children with increased, unchanged, and decreased proteinuria by the end of the study were the same in the two groups. Treatment failure was defined as an increase in serum creatinine of 30% or more or greater than 0.4 mg/dl, or onset of renal failure. Treatment failure occurred in 36% of the control group and 57% of the experimental group (P > 0.1). Five patients died during the trial, 3 in the experimental group and 2 in the control group. A Kaplan-Meier survival analysis revealed no significant differences between the two groups. Cyclophosphamide therapy for children with steroid-resistant FSGS is not recommended.

Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone--a report of the International Study of Kidney Disease in Children.

It has been claimed that long-term prednisone treatment ameliorates the course of children with mesangiocapillary glomerulonephritis (MCGN). The International Study of Kidney Disease in Children conducted a randomized, double-blinded, placebo-controlled clinical trial in 80 children with idiopathic MCGN, including 42 patients with type I disease, 14 with type II disease, 17 with type III disease, and 7 with nontypable disease. Criteria for admission included heavy proteinuria and a glomerular filtration rate of greater than or equal to 70 ml/min per 1.73 m2. Prednisone or lactose, 40 mg/m2, was given every other day as a single morning dose. The mean duration of treatment was 41 months, renal failure being the most common reason for termination of therapy. Treatment failure was defined as an increase from baseline of 30% or more in serum creatinine, or more than 35 mumol/l. Overall, treatment failure occurred in 55% of patients treated with lactose, compared with 40% in the prednisone group. Life-table analysis showed a renal survival rate (i.e., stable renal function) at 130 months of 61% among patients receiving prednisone and 12% among patients receiving lactose (P = 0.07). Of patients with type I or III MCGN, 33% treated with prednisone were treatment failures, compared with 58% in the lactose group. Long-term treatment with prednisone appears to improve the outcome of children with MCGN.