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

Background: The spectrum of interferon-ß (IFN-ß)-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-ß treatment administered for at least 6 months. Results: Eighteen patients (13 women, median age 48 years) with biopsy-proven renal disease occurring during IFN-ß therapy were included. The median exposure to IFN-ß (14 patients were treated with IFN-ß1a and 4 patients with IFN-ß1b) 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-ß-associated TMA was significantly associated with Rebif, with a weekly dose >50 µg and with multiple weekly injections. In all cases, IFN-ß 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 <60 mL/min/1.73 m2 was present in 61% of patients. Conclusions: IFN-ß-associated nephropathy must be sought in the case of HT and/or protU onset during treatment. When TMA and/or FSGS are observed on renal biopsy, early discontinuation of IFN-ß is essential.