Kidney Involvement in Patients With Chronic Myelomonocytic Leukemia or BCR-ABL–Negative Myeloproliferative Neoplasms

Abstract

Introduction The identification of specific molecular signatures and the development of new targeted drugs have changed the paradigm of onco-nephrology, now allowing a multiscale approach of kidney involvement related to hematologic malignancies relying on combined hematologic and molecular assessments. In this study, we aimed to refine the spectrum of kidney disorders associated with chronic myelomonocytic leukemia (CMML) or BCR-ABL–negative myeloproliferative neoplasms (MPNs), 2 very rare conditions scarcely described. Methods Case series. Patients with myeloid neoplasms who were referred to Toulouse University Hospital Nephrology Unit and were diagnosed with acute kidney injury (AKI), chronic kidney disease (CKD), or urine abnormalities were retrospectively included. Results Eighteen patients (males n =13, CMML n =8, essential thrombocytosis [ET] n =7, polycythemia vera [PV] n =1, and myelofibrosis n =2) developed kidney disease 7.7±2 years after the diagnosis of the malignancy. Twelve patients had AKI at presentation. Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy ( n =14) showed various patterns, including pauci-immune glomerulosclerosis ( n =5), extramedullary hematopoiesis ( n =6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation ( n =8). Immunostaining of CD61 confirmed the infiltration of megakaryocytes within glomeruli or interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy n =2, AA amyloidosis n =1). Massive kidney infiltration by CMML was identified in 1 patient. After a mean follow-up of 24±6 months, malignancy was considered as stable in 11 patients (61%), but 22% of patients had progressed to end-stage renal failure. The remaining had persistently reduced kidney function. No correlation between the malignancy and the renal presentation and outcomes could be identified. Conclusions Kidney complications of CMML/MPN are heterogenous, and kidney biopsy may help to identify new molecular targets to prevent the development of kidney fibrosis.

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

“…However, Belliere et al. 13 identified a delay of 7.7 ± 2 years for CMML or BCR-ABL-negative myeloproliferative neoplasms patients. We found that lysozyme nephropathy and an infiltration by the CMML were by far the most frequent kidney diseases associated with CMML.…”

“…Kidney injuries related to CMML were described in small cohorts, generally associated with myeloproliferative neoplasms. 13 , 14 There is a higher incidence of AKI (34.9%) and CKD (7.6%) among patients with myeloproliferative form of CMML. 8 Main findings revealed that tubulointerstitial compartment was the first kidney injury in a study of 8 CMML cases, with chronic tubulointerstitial nephropathy, and acute interstitial nephropathy.…”

“… 8 Main findings revealed that tubulointerstitial compartment was the first kidney injury in a study of 8 CMML cases, with chronic tubulointerstitial nephropathy, and acute interstitial nephropathy. 13 An interstitial infiltration can be seen, by T cells, or a massive infiltration by the CMML. Another histologic study of 4 patients showed glomerular injuries such as endothelial damage, mesangiolysis, double contours, and rare lesions of podocytopathy and thrombotic microangiopathy.…”

Clinical characterization of polycythemia vera associated with IgA nephropathy in a single Chinese center: A case series

“…Based on the present literatures, the other possible pathogenesis of PV associated with renal disease also include changing blood volume and viscosity which resulted in mesangial hypercellularity and matrix proliferation, vascular microthrombi, interstitium ischemia, and more rapid progression of renal failure. [ 27 , 28 ] However, according to the literature, the coexistence of the 2 diseases might be simply coincidental and no causative relationship is presented.…”

Significance of reduced renal function in patients with chronic myelomonocytic leukemia

“…The cause of impaired kidney function in our study remains unclear for most patients, but there are some indications in the literature which provide some possible explanations. In one study, 18 patients with myeloid neoplasms who were referred to a nephrology unit because of reduced renal function were retrospectively studied [ 28 ]. The study included 8 patients with CMML, 7 patients with essential thrombocytosis, 1 patient with polycythemia vera, and 2 patients with myelofibrosis.…”