Nephrotic Syndrome in a Multiple Sclerosis Patient Treated with Interferon β1a

Abstract

Europe and the Middle East. Interferon β1a is available worldwide as Avonex, given weekly as an intramuscular injection, and Rebif, which is given three times a week subcutaneously.The drugs are generally well-tolerated but side effects are common and include injection site reactions and flu-like symptoms. 4 Laboratory abnormalities are described and most commonly are lymphopenia, neutropenia, and raised liver transaminases.More recently there have been reports of more serious complications arising in the context of interferon therapy. It was ABSTRACT: Background: Interferon β has become standard therapy for reducing relapse frequency in relapsing/remitting Multiple Sclerosis (RRMS). Several different preparations are available including interferon β1a (Avonex, Rebif) and interferon β1b (Betaferon/Betaseron). For the most part these preparations have been considered safe. Recently there have been concerns relating to liver 1 and now kidney toxicity. Case Report: We present a case of a 28-yr old male who developed a severe case of nephrotic syndrome while being treated for relapsing/remitting Multiple Sclerosis (RRMS) with weekly injections of interferon β1a. Subsequent course: The nephrosis resolved almost completely once the interferon was stopped and after immunosuppressive treatment. At its peak the daily protein loss was 35.82 g. Kidney biopsy demonstrated membranous glomerulonephritis. Discussion: Two other case reports of nephrotic syndrome have been reported in the literature. This latest (third) report suggests that the safety profile should be reexamined and at least raises the question of potential renal toxicity of interferons in MS.RÉSUMÉ: Syndrome néphritique chez un patient atteint de sclérose en plaques traité par l'interféron β β1a. Introduction: L'interféron b est devenu le traitement standard pour diminuer la fréquence des récidives dans la sclérose en plaques récurrente/rémittente (SEPRR). Plusieurs préparations différentes sont disponibles dont l'interféron β1a (Avonex, Rebif) et l'interféron β1b (Betaferon/Betaseron). En général, on considérait que ces préparations étaient sûres. Depuis peu, on s'inquiète de leur toxicité hépatique et maintenant de leur toxicité rénale. Observation: Nous rapportons le cas d'un patient de 28 ans, originaire des Émirats arabes unis, qui a développé un syndrome néphritique aigu au cours du traitement de sa SEPRR au moyen d'injections hebdomadaires d'interféron b1a. Suivi: La néphrose a presque complètement disparu suite à l'arrêt du traitement et à un traitement immunosuppresseur. En phase aiguë, la perte quotidienne de protéines était de 35,82 g. La biopsie rénale a montré qu'il s'agissait d'une glomérulonéphrite membraneuse. Discussion: Deux autres cas de syndrome néphritique ont été rapportés dans la littérature. Ce troisième cas indique que le profil de sécurité des interférons devrait être réexaminé et soulève des questions concernant leur toxicité rénale chez les patients atteints de la SEP.

Thrombotic microangiopathy associated with use of interferon-beta

“…Kidney complications have not been directly attributed to multiple sclerosis. 2 Renal side effects including minimal change disease, 2-5 collapsing focal segmental glomerulosclerosis, [6][7][8] membranous nephropathy, 9 lupus nephritis, 10,11 acute renal failure, 12 and thrombotic microangiopathy, [13][14][15][16][17][18][19][20][21][22][23] are most often associated with interferon therapy rather than with interferon-beta. The incidence of transient proteinuria during interferon-beta therapy is around 20%.…”

“…Interferons are well established agents for standard therapy in several malignancies, hepatitis C, idiopathic pulmonary fibrosis, and multiple sclerosis. 1,2 Despite this, adverse autoimmune effects associated with their use have been reported, including minimal change disease in the kidney, [2][3][4][5] collapsing focal segmental glomerulosclerosis, 6,7 membranous glomerulonephritis, 8 acute renal failure, 9 lupus nephritis, 10,11 acute renal failure, 12 and thrombotic microangiopathy. [13][14][15][16][17][18] These side effects are most often associated with interferon-alpha therapy, rather than interferon-beta.…”

Broad spectrum of interferon-related nephropathies-glomerulonephritis, systemic lupus erythematosus-like syndrome and thrombotic microangiopathy: A case report and review of literature

“…Cases of nephritic or nephrotic syndrome have been reported during treatment with IFN associated with different underling nephropathies, such as focal segmental glomerulosclerosis[31-34], minimal change disease[35,36], IgA nephropathy[37], and membranoproliferative glomerulonephritis[38,39]. Among these, MN is an uncommon but important and previously described pattern[40,41]. Different clinical features at onset have been described, varying from a full-blown nephritic or nephrotic syndrome, to a severe oligoanuria requiring dialysis[42,43].…”

Nephrotic syndrome associated with interferon-β-1b therapy for multiple sclerosis

“…8,9 The common adverse effects of IFN-β-1b are flu-like symptom complex, lymphopenia, injection-site reactions, and depression. Although there have been several reports of proteinuria and nephrotic syndrome associated with natural IFN-β and IFN-β-1a, [10][11][12][13] there have been no previous reports of nephrotic syndrome associated with IFN-β-1b. (Table 1).…”