Renal diseases secondary to interferon-β treatment: a multicentre clinico-pathological study and systematic literature review

Background The spectrum of interferon-β (IFN-β)-associated nephropathy remains poorly described and the potential features of this uncommon association remain to be determined. Methods In this study we retrospectively analysed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-β treatment administered for at least 6 months. Results Eighteen patients (13 women, median age 48 years) with biopsy-proven renal disease occurring during IFN-β therapy were included. The median exposure to IFN-β (14 patients were treated with IFN-β1a and 4 patients with IFN-β1b) was 67 months (range 23–165 months). The clinical presentation consists in hypertension (HT; 83%), malignant HT (44%), proteinuria (protU) >1 g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA; 61%), oedematous syndrome (17%) or nephritic syndrome (11%). The pathological findings included typical features of isolated TMAs in 11 cases, isolated focal segmental glomerulosclerosis (FSGS) lesions in 2 cases and 5 cases with concomitant TMA and FSGS lesions. An exploration of the alternative complement pathway performed in 10 cases (63%) did not identify mutations in genes that regulate the complement system. The statistical analysis highlighted that the occurrence of IFN-β-associated TMA was significantly associated with Rebif, with a weekly dose >50 µg and with multiple weekly injections. In all cases, IFN-β therapy was discontinued. Patients with TMA lesions received other therapies, including corticosteroids (44%), eculizumab (13%) and plasma exchanges (25%). At the end of a 36-month median follow-up, persistent HT and persistent protU were observed in 61% and 22% of patients, respectively. Estimated glomerular filtration rate
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