David Malka, Alexis Mathian, Olivier Lambotte, Hassan Izzedine, Zahir Amoura, Andrea Varga, Sihem Kaaki, Christine Mateus, Alexandra Leary, Jean-Charles Soria, Isabelle Brocheriou, Aurélien Marabelle, Stéphane Champiat, Jean-Michel Goujon, Emilie Routier, Cécile Picard, Nathalie Quellard, Judith Michels, Jean-Marie Michot, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Interdisciplinaire de Soins de Support aux Patients en Onco-hématologie [Gustave Roussy] (DISSPO), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncologie digestive, Oncologie gynécologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de pathologie [CHU Pitié-Salpêtrière]
International audience; Objective : Expanded clinical experience with patients treated by pembrolizumab has accumulated. However, renal toxicities associated with this anti-programmed cell death 1 agent are poorly described because kidney histology is rarely sought. As a nephrology referral centre, we aimed to describe the clinic-biological and histopathological characteristics of pembrolizumab-related nephropathy and its response to treatment.Methods : We conducted a monocentric large case series study, including all pembrolizumab-treated cancer patients presenting a renal toxicity addressed to our centre from 2015 to 2017.Results : A total of 12 patients (7 men) out of 676 pembrolizumab-treated patients (incidence 1.77%) were included (median age 69.75 years). Patients were referred for acute kidney injury (n = 10) and/or proteinuria (n = 2). A kidney biopsy was performed in all patients, with a median duration of use of 9 months (range 1-24 months) after the beginning of treatment. Biopsy showed that four patients had acute interstitial nephritis (AIN), whereas five had acute tubular injury (ATI) alone, one had minimal change disease (MCD) and ATI, and one had MCD alone. Pembrolizumab withdrawal coupled with corticosteroid therapy was the most effective treatment for kidney function recovery. Drug reintroduction resulted in a more severe recurrence of AIN in one patient who required maintenance of pembrolizumab. Two patients died of cancer progression with one of them developing severe renal failure requiring dialysis.Conclusion : In our series, ATI, AIN and MCD are the most frequent forms of kidney involvement under pembrolizumab therapy. Kidney dysfunction is usually isolated but can be severe. Use of corticosteroids in case of AIN improves the glomerular filtration rate.