Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms

Abstract

Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms Aims: Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs. Methods and results: The cohort comprised 29 patients (23 men) aged 67 AE 11 years (mean AE standard deviation), diagnosed with chronic myeloid leukaemia (n = 5), polycythaemia vera (n = 9), primary myelofibrosis (n = 5), essential thrombocythaemia (n = 2), or chronic myelomonocytic leukaemia (n = 4), as well as MPNs or MDS/MPNs not otherwise specified (n = 4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double-contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection-related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age-matched and sex-matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable. Conclusions: MPN and MDS/MPN patients show glomerular scarring that exceeds age-related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.

Minimal change disease caused by polycythemia vera: A case report

“…However, the exact mechanisms underlying the pathogenesis of MCD associated with PV remain unclear. In addition to immune dysregulation, kidney injury might also be attributed to hyperviscosity, abnormal function, and/or excessive neoplastic blood cell activation and growth factor production[ 13 ]. Increased blood viscosity and platelet hypersensitivity can induce microcirculatory disturbances, resulting in endothelial damage.…”

“…Many cytokines and growth factors such as interferon-γ, IL-6, and platelet-derived growth factor, which have documented in patients with MPNs, can directly elicit endothelial damage. Growth factors can be generated locally by marginating platelets and cells of extramedullary hematopoiesis, accompanied by hyperviscosity, which exacerbates endothelial damage[ 13 ]. PV can not only result in thrombosis in the main blood vessels[ 14 ], but can also induce thrombotic microangiopathy[ 15 ].…”

Renal post-mortem findings in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

“…It is currently surmised that it may develop as a result of chronic endothelial damage and a combination of fibrosis-inducing factors [8]. The largest recently published study on indication biopsies of patients manifesting with significant proteinuria, hematuria, or impaired kidney function reports a high rate of both acute and chronic TMA-related changes with at least a quarter of cases presenting with renal findings attributed to TMA [5]. Another feature encountered in MPN patients is extramedullary hematopoiesis of the kidney.…”

“…The authors concluded that MPN-related glomerulopathy is a late manifestation of the disease pathway seen in fibrosis of the bone marrow in MPN. Recently, a German group investigated a cohort of indication biopsies of 29 MPN and CMML cases [5]. Renal symptoms were similarly comprised proteinuria, microhematuria, and chronic kidney disease.…”

Modifying the Effects of Cytoreductive Drugs on Kidney Function in Myeloproliferative Neoplasms

“…Specifically, in ET, CKD was associated with an inferior thrombosis-free survival independently of the Revised International Prognostic Score of Thrombosis for Essential Thrombocythemia (R-IPSET), suggesting that CKD may further contribute to the thrombotic risk prognostication [2]. Interestingly, segmental and global glomerular sclerosis, as well as thrombotic microangiopathy, are typical pathological findings in the kidney biopsies of myeloproliferative neoplasm patients, implicating that endothelial damage, microcirculatory disturbances, and the growth factor release from activated blood cells may be the most probable causative mechanisms [7, 8].…”