Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome

Abstract

Background: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common.

Methods: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks.

Results: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study.

Conclusion: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

Keywords: Glucocorticoids; Proteinuria; Remission; Steroids.

Figure 1.. Proteinuria at baseline, EOS, and Last evaluation

Shown are the mean 24 hour protein excretion rates at baseline, at end-of-study and at last evaluation. Baseline and EOS outcomes for 21 subjects, 1 subject was withdrawn from study. At last follow-up evaluation 1 subject was lost to follow-up and 1 died from pancreatitis 8 years after completion of study.

Figure 2.. Results of Survey instruments for general health and psychological health.

Presented are the scores, as mean ± SD. A. Short Form Health Survey (SF-36), B. Beck Depression Inventory II (BDI-II), C. Young Mania Rating Scale, and D. Delirium rating scale at baseline, 4 weeks (for the mania scale) and end-of-study (EOS).