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

Abstract

Background The spectrum of Interferon-beta-associated nephropathy (IFN-β) remains poorly described and the potential features of this uncommon association remain to be determined. Methods In this study, we retrospectively analyzed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-β treatment administered since 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 by IFN-β1a and four patients by IFN-β1b) was 67 months (ranged from 23 to 165 months). The clinical presentation consists in hypertension (HT) (83%), malignant HT (44%), proteinuria >1g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA) (61%), edematous 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 two cases, and five 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 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 consequently discontinued. Patients with TMA lesions received other therapies included corticosteroids (44%), eculizumab (13%) or plasmatic exchanges (25%). At the end of a 36-month median follow-up, persistent hypertension and persistent proteinuria were observed in 61% and 22% of patients. Estimated glomerular filtration rate <60 ml/min/1.73m2 was present in 61% of patients. Conclusion IFN-β-associated nephropathy must be sought in the case of hypertension and/or proteinuria onset during treatment. When TMA and/or FSGS are observed on renal biopsy, early discontinuation of IFN-β is essential.

Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

“…All the patients were treated with IFN-β at the usual dosage administered in MS, albeit being under a higher cumulative IFN-β dosage than recommended in the nephrological guidelines. A high IFN-β dosage for weight might be suspected as a potential risk factor for TMA, especially in patients with a long-tolerated administration of doses exceeding 50 µg per week and a low body mass index [15,28].…”

“…Interferon-β (IFN-β) is one of the most-used disease-modifying therapies (DMTs) in relapsing-remitting (RR) MS. IFN-β has also been proven safe and effective in a long-term follow-up, and the collateral effects are usually mild and often transitory. However, in recent years, growing evidence about a relationship between the use of IFN-β and thrombotic microangiopathy (TMA) development has been described through several case series [12][13][14][15]. TMA consists of the triad of consumptive thrombocytopenia, microangiopathic hemolytic anemia, and signs of ischemic damage in different organs (and, particularly, acute kidney injury).…”

Crosstalk between TBK1/IKKε and the type I interferon pathway contributes to tubulointerstitial inflammation and kidney tubular injury

“…Nephrotoxicity, such as acute tubular necrosis and rejection, has also been observed following antiviral treatment with TI-IFNs in several conditions, as in kidney transplant recipients ( Fabrizi et al, 2013 ). Recently, biopsy-proven thrombotic microangiopathy and focal glomerulosclerosis were reported in patients with IFNβ-associated nephropathy ( Dauvergne et al, 2021 ). Although not reflected in the abstract, acute tubular necrosis was observed in 69% of the cases, being more frequent than glomerulosclerosis ( Dauvergne et al, 2021 ).…”

“…Recently, biopsy-proven thrombotic microangiopathy and focal glomerulosclerosis were reported in patients with IFNβ-associated nephropathy ( Dauvergne et al, 2021 ). Although not reflected in the abstract, acute tubular necrosis was observed in 69% of the cases, being more frequent than glomerulosclerosis ( Dauvergne et al, 2021 ). Data presented in the present manuscript suggest that tubular injury may be a primary event and not necessarily secondary to injury in other kidney structures.…”

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management

“…In our review, we have noticed that some drugs may lead to a more distinctive clinical scenario. For instance, IFN-related DITMA is generally characterized by a fulminant presentation with classical TMA clinical manifestations accompanied by severe headache and severe/malignant hypertension in most of the patients, or may alternatively describe progressive worsening of hypertension, proteinuria, and headache ( Hunt et al, 2014 ; Dauvergne et al, 2021 ). A new or exacerbated hypertension was a prominent feature also in gemcitabine-induced DITMA, together with signs/symptoms of severe fluid overload (rarely resembling capillary leak syndrome) ( Walter et al, 2002 ; Humphreys et al, 2005 ).…”