Safety and efficacy of sirolimus combined with cyclosporine in primary membranous nephropathy: a randomized controlled trial
In a phase 2 randomized trial in primary membranous nephropathy, adding sirolimus to cyclosporine matched cyclosporine alone for clinical remission while achieving more immunological remission (anti-PLA2R clearance) and significantly better preservation of kidney function.
Background
Calcineurin inhibitors such as cyclosporine are a mainstay for membranous nephropathy but carry nephrotoxicity. Combining sirolimus with cyclosporine was hypothesized to maintain remission while improving kidney-function preservation and antibody clearance.
Study design
Single-center, phase 2 randomized controlled trial in 74 patients with biopsy-proven primary membranous nephropathy and persistent proteinuria >3.5 g/day despite 6 months of supportive care. Patients were randomized 1:1 to sirolimus plus cyclosporine or cyclosporine monotherapy for 12 months; the primary outcome was composite (complete or partial) remission at 12 months, tested for noninferiority.
Key findings
Composite remission at 12 months was 72% (26/36) with combination therapy versus 67% (24/36) with cyclosporine alone, meeting noninferiority. Immunological remission (anti-PLA2R antibody conversion to negative) at 6 months was significantly higher with combination therapy (70% vs 20%; P<0.001), and eGFR decline was markedly attenuated (ΔeGFR −7.1 vs −21.3 ml/min/1.73 m²; P<0.001). One serious adverse event occurred in the combination group versus none with monotherapy.
Clinical implications
Adding sirolimus to cyclosporine offers comparable clinical remission with superior antibody clearance and substantially better kidney-function preservation, suggesting a calcineurin-inhibitor-sparing benefit. As a single-center phase 2 trial, the findings warrant confirmation in larger studies before routine adoption.
Category
Research
Source
BMC Medicine
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