Comparison of Methylprednisolone Plus Prednisolone with Prednisolone Alone as Initial Treatment in Adult-Onset Minimal Change Disease

Abstract

Background and objectives Previous studies suggested that intravenous methylprednisolone possibly accelerates remission of proteinuria in adult-onset minimal change disease; its impact on relapse of proteinuria is unknown.Design, setting, participants, & measurements This multicenter retrospective cohort study included 125 adultonset minimal change disease patients diagnosed by kidney biopsy between 2000 and 2009 and treated initially with corticosteroid in five nephrology centers in Japan participating in the Study of Outcomes and Practice Patterns of Minimal Change Disease. Times to first remission and first relapse of proteinuria after initiating the first immunosuppressive therapy were compared between 65 patients with initial use of intravenous methylprednisolone followed by prednisolone and 60 patients with initial use of prednisolone alone using multivariate Cox proportional hazards models. After calculating the probability of receiving methylprednisolone and prednisolone using a logistic regression model (propensity score), the results were ascertained using propensity score-matched and -stratified models.Results During the median 3.6 years of observation (interquartile range=2.0-6.9), all 65 patients in the methylprednisolone and prednisolone group achieved remission within 11 (8-20) days of the corticosteroid initiation, whereas in the prednisolone group, 58 of 60 patients (96.7%) achieved remission within 19 (12-37) days (P,0.001). After achieving first remission, 32 (49.2%) patients in the methylprednisolone and prednisolone group and 43 (74.1%) patients in the prednisolone group developed at least one relapse. Multivariate Cox proportional hazards models revealed that methylprednisolone and prednisolone use was significantly associated with early remission (multivariate-adjusted hazard ratio, 1.56; 95% confidence interval, 1.06 to 2.30) and lower incidence of relapse (0.50; 95% confidence interval, 0.29 to 0.85) compared with prednisolone use alone. These results were ascertained in propensity score-based models. No significant difference was observed in incidence of adverse events, including infection, aseptic osteonecrosis, cataract, diabetes, and gastrointestinal bleeding.Conclusions Initial use of methylprednisolone was associated with earlier remission and lower incidence of relapse in adult-onset minimal change disease patients. Efficacy of methylprednisolone should be evaluated in randomized controlled trials.

Enhanced Steroid Therapy in Adult Minimal Change Nephrotic Syndrome: A Systematic Review and Meta-analysis

“…Others observed that no correlation between the response time to remission and time to relapse (4, 27). Shinzawa et al reported that earlier induction of remission could decrease the rate of relapse (15). However, according to our meta-analysis, earlier induction after enhanced steroid therapy does not cause earlier relapse, and a decrease in the long-term dosage of steroids is recommended.…”

“…Five studies assessed the effect of mean time to CR in a total of 299 patients with adult MCNS (9,10,12,14,15). Patients were assigned to the enhanced treatment group (n= 141) or the control group (n=158).…”

“…Six of the seven studies, involving 308 patients, published the effect of enhanced steroid therapy on the relapse rate in adult patients with MCNS (9)(10)(11)(12)(13)15). Patients were assigned to the enhanced treatment group (n=144) and the control group (n=164).…”

“…Four studies reported treatment-related adverse events in details (9,11,14,15). We classified adverse events into serious or less serious based on the guidelines by ICH in 1994 which defined a serious adverse event (experience) or reaction as any untoward medical occurrence that (at any dose) resulted in death, life threatening, persistent or significant disability/incapacity, congenital anomaly/birth defects, inpatient hospitalization or prolongation of existing hospitalization (16).…”

Short-Term Steroid Regimen for Adult Steroid-Sensitive Minimal Change Disease

“…A previous observational study investigating adult MCD reported that younger patients had a higher risk of relapse than middle aged and elderly patients [18]. The same authors reported that mPSL pulse therapy may be associated with a lower incidence of MCD relapse [25]. However, it considered to be difficult to determine which factors associated with early relapse and which lead the good-indication for the short-term regimen from our data, because of limited sample size and the study design that did not have strictly regulated protocol.…”