Reviewed by Dr. Lauren Smith
Lv J, et al. JAMA 2017 Aug 1 318(5):432-442

SUMMARY
This article describes a multi-center, double-blind, randomized control trial to assess the clinical and physiologic effects of steroid use in patients with IgA nephropathy. The study planned to include 750 participants that met the following inclusion criteria: proteinuria >1g/day and estimated glomerular filtration rate (eGFR) between 20-120 mL/min/1.73m2, with adequate blood pressure control. However, after about 2 years of follow up, study enrollment was discontinued because of numerous adverse events in the methylprednisolone arm of the trial. A total of 262 participants had been enrolled. The methylprednisolone group was comprised of 136 patients that received a weight-based dose with a maximum dose of 48mg/day. The remaining 126 participants received placebo. Treatment was given at full dose for 2 months and tapered over 4-6 months. The primary outcome was a composite measure defined by the development of end-stage renal disease (ESRD), a decrease in eGFR by 50%, or death due to kidney disease, over a median follow-up duration of 2.1 years. Safety outcomes were also studied including: development of diabetes, gastrointestinal hemorrhage, infection, cardiovascular event, new fracture or development of osteonecrosis.

The primary study outcome was seen in 8 (5.9%) in the methylprednisolone group and 20 (15.9%) participants in the placebo group (p=0.02), driven primarily by an improvement in the risk of 50% eGFR decline in the steroid arm. Four participants (2.9%) in the methylprednisolone arm progressed to ESRD, as compared to 10 (7.9%) in the placebo arm (p=0.10). With regards to proteinuria at 6 months: the rate of complete remission and partial remission were much higher in the methylprednisolone group compared to placebo at 7.8% vs 1.1% (p=0.04) and 45.1% vs 13.7% (p<0.001), respectively. Finally, 20 patients (14.7%) in the methylprednisolone arm experienced adverse events, as compared to 4 patients (3.2%) in the placebo arm (p=0.001). The majority of adverse events in the methylprednisolone group were serious infections, of which two resulted in death. No serious infections occurred in the placebo group.

COMMENTARY
Current guidelines recommend a 6-month course of corticosteroids as treatment of IgA nephropathy in patients with persistent proteinuria after initial supportive care.1 However, the evidence for this is not definitive. Prior studies hint at clinical improvements in renal function but adverse effects of steroid use are reported inconsistently.2

Strengths of this study include multi-center enrollment and larger sample size compared to previous work. However, early enrollment termination and thus decreased study power may have overestimated the risks and benefits of steroid therapy. Another limitation of the generalizability of the study derives from the almost exclusively East Asian ethnicity of the study population. Despite the improvement in proteinuria and modest improvement in eGFR, increased adverse events make it challenging to recommend steroid therapy in IgA nephropathy based on these data.

REFERENCES
1. Cattran DC, Feehally J, Cook HT, et al. Kidney disease: Improving Global Outcomes (KDIGO) glomerulonephritis work group: KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl. 2012;2(2):139-274.
2. Lv J, Xu D, Perkovic V, et al. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012;23(6):1108-1116.

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