Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 26, Issue 10, Pages 2545-2558Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014070640
Keywords
-
Categories
Funding
- European Research Council [ERC-2012-ADG_20120314, 322947]
- Agence Nationale pour la Recherche Programme Blanc SVSE1 [ANR-12-BSE1-0002-01]
- Fondation pour la Recherche Medicale Equipe FRM grant
- European Research Council (ERC) [322947] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A(2) receptor (anti-PLA(2)R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituxinnab (375 mg/m2) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA(2)R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA(2)R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA(2)R antibody depletion. On average, 50% anti-PLA(2)R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% Cl, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% Cl, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA(2)R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating antiPLA(2)R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available