MO304COMPLEMENT INHIBITION FOR REFRACTORY GLOMERULONEPHRITIS IN SYSTEMIC VASCULITIS. (29th May 2021)

• Record Type: Journal Article
• Authors: Uriol, Miguel; Obrador Mulet, Aina; Arrufat, Gemma; Escriva, Ana; Lado Fuentes, Mario; Garcia, José Luis; Pallares, Lucio
• Is Part Of: Nephrology dialysis transplantation. Volume 36(2021)Supplement 1
• Publication Date: 2021-05-29
• Subjects: Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfab104.0062
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background and Aims: Systemic vasculitis(SV) is a life-threatening disease and, in some cases, refractory to intensive multi-immunosuppressant drugs. Complement hyperactivation has gained interest in the pathogenesis of the SV. We report the efficacy of the short course of C5-inhibitor (eculizumab) in refractory cases of lupus nephritis (r-LN) and refractory ANCA-associated glomerulonephritis (r-AGN). Method: In this retrospective study, eight consecutive patients were assessed (r-LN:n=3 and r-AGN:n=5). All patients were previously treated with three or more drugs included: corticosteroids (n=8), mycophenolate (n=8), rituximab (n=7), immunoglobulins (n=5), therapeutic plasma exchange (n=4), cyclophosphamide (n=1), and belimumab (n=1). Eculizumab was considered for use in off-label indication in patients with progressive renal deterioration (worsening creatinine, protein-to-creatinine ratio) or developing a high-risk lethal complication after the induction immunosuppressive therapy. The histologic lesson observed were: a) r-LN: Type VI (n=1), Type V(n=1), and type IV(n=1), and b) r-AGN: sclerotic (n=3), and malignant hypertension+/-thrombotic microangiopathy (n=1), in one patient who developed pulmonary hemorrhage no renal biopsy was performed. Results: Mean age (SD): 51(17)years. Median (p25-p75) of follow-up: 19(12-28) months. Overall, 2(25%) of the patients needed chronic renal replacement therapy (one r-AGN patient who required urgent haemodialysis at presentation and one r-LN within 12 months after the onset eculizumab). During the follow-up the eGFR(mean(95%CI) changed from 28(16-40) to 30(20-41)mil/min/1.73m2(P = 0.51) and the median(p25-p75) protein-to-creatinine ratio decreased from 2.3(1.5-6.4) to 0.6(0.3-1.7) mg/mg(P= 0.028). The mean eculizumab cycle dose number was 5(95%CI:3-6), four patients required two cycles. Overall, the mean eculizumab dosage required was 7162 mg (95%CI: 2969-11355). No major side effects were recorded. Conclusion: The coadyuvant complement inhibition with eculizumab stabilized renal function and decreased proteinuria in six out of the eight previously refractory patients and represents a promising tool in treating lupus and ANCA vasculitis nephritis.