Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease

Marie-Camille Lafargue; Mickaël Bobot; Helmut G Rennke; Marie Essig; Martin Carre; Lucile Mercadal; Jonathan Farhi; Hamza Sakhi; Thibault Comont; Léonard Golbin; Pierre Isnard; Jonathan Chemouny; Nathalie Cambier; Kamel Laribi; Umut Selamet; Leonardo V Riella; Olivier Fain; Lionel Adès; Pierre Fenaux; Camille Cohen; Arsène Mekinian; MINHEMON, GFM and French VEXAS group

doi:10.1016/j.ekir.2023.09.005

Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease

Kidney Int Rep. 2023 Sep 7;8(12):2733-2741. doi: 10.1016/j.ekir.2023.09.005. eCollection 2023 Dec.

Authors

Marie-Camille Lafargue¹, Mickaël Bobot², Helmut G Rennke³, Marie Essig⁴, Martin Carre⁵, Lucile Mercadal⁶, Jonathan Farhi⁷, Hamza Sakhi⁸, Thibault Comont⁹, Léonard Golbin¹⁰, Pierre Isnard¹¹, Jonathan Chemouny¹², Nathalie Cambier¹³, Kamel Laribi¹⁴, Umut Selamet¹⁵, Leonardo V Riella¹⁶, Olivier Fain¹⁷, Lionel Adès¹⁸, Pierre Fenaux¹⁸, Camille Cohen¹⁹, Arsène Mekinian¹⁷; MINHEMON, GFM and French VEXAS group

Collaborators

MINHEMON, GFM and French VEXAS group:
Marie-Camille Lafargue, Mickaël Bobot, Thibault Comont, Nathalie Cambier, Kamel Laribi, Olivier Fain, Lionel Adès, Pierre Fenaux, Arsène Mekinian, Thibault Comont, Nathalie Cambier, Kamel Laribi, Olivier Fain, Lionel Adès, Pierre Fenaux, Arsène Mekinian, Thibault Comont, Olivier Fain, Lionel Adès, Pierre Fenaux, Arsène Mekinian

Affiliations

¹ Department of Nephrology, Tenon's Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
² Centre de Néphrologie et Transplantation Rénale, AP-HM, Hôpital de la Conception, CHU de la Conception, 13005, Marseille, France.
³ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Paré, Boulogne-Billancourt, Université Paris-Saclay, Paris, France.
⁵ Service d'Hématologie, Centre Hospitalier Universitaire, Grenoble, France.
⁶ Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital de La Pitié Salpêtrière, Paris, France.
⁷ Maladies du Sang, CHU d'Angers, 49000 Angers, France.
⁸ Department of Nephrology and renal transplantation, Necker's Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
⁹ Department of Internal Medicine, Institut universitaire du cancer de Toulouse, Centre Hospitalier Universitaire de Toulouse, Université Toulouse III - Paul Sabatier, Toulouse, France.
¹⁰ Service de Néphrologie, Dialyse et Transplantation Rénale, CHU Rennes, Hôpital Pontchaillou, Rennes, France.
¹¹ Department of Pathology, Université Paris Cité, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹² Hématologie Clinique, Centre Hospitalier de Valenciennes, Valenciennes, France.
¹³ Department of Haematology, Centre Hospitalier Le Mans, France.
¹⁴ Centre Hospitalier Le Mans, Le Mans, France.
¹⁵ Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁶ Center of Transplantation Sciences, Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
¹⁷ Hôpital Saint-Antoine, Service de Médecine Interne et de l'Inflammation-(DHU i2B), F-75012, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹⁸ Hématologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Paris, France.
¹⁹ INSERM U1151 « mechanisms and therapeutic strategies of chronic kidney diseases », Hôpital Necker, Université Paris Cité, Paris, France; Service de Néphrologie et Transplantation rénale, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France.

Abstract

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes.

Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities.

Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978).

Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Keywords: acute kidney injury; chronic myelomonocytic leukemia.