Abstract

Simple SummaryIn patients with myeloproliferative neoplasms (MPN) and in patients with kidney dysfunction, a higher rate of thrombosis has been reported compared with the general population. Furthermore, MPN patients are more prone to develop kidney dysfunction. In our study, we assessed the importance of specific risk factors for kidney dysfunction and thrombosis in MPN patients. We found that the rate of thrombosis is correlated with the degree of kidney dysfunction, especially in myelofibrosis. Significant associations for kidney dysfunction included arterial hypertension, MPN treatment, and increased inflammation, and those for thrombosis comprised arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The identified risk factor associations varied between MPN subtypes. Our data suggest that kidney dysfunction in MPN patients is associated with an increased risk of thrombosis, mandating closer monitoring, and, possibly, early thromboprophylaxis.Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60–89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

Highlights

  • Patients with myeloproliferative neoplasms (MPNs) are at increased risk of developing myelofibrosis as well as vascular complications such as thrombosis or severe hemorrhage [1,2,3,4,5,6], all of which are associated with inferior survival

  • At the time of kidney function assessment, 40% of the patients were treated with hydroxyurea treatment (HU), 19% with RUX, and 21% of the patients were treated with anagrelide, IMIDs, or interferon, respectively, with expected differences among the MPN subtypes, reflecting the drug approval; 19%, 12%, and 4% had a history of arterial thrombosis, venous thrombosis, or severe hemorrhage, respectively

  • Our data revealed a higher prevalence of kidney dysfunction in MF patients compared with ET or polycythemia vera (PV), indicating that MF has a higher impact on kidney function and that this was not due to a higher age or diabetes prevalence

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Summary

Introduction

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of developing myelofibrosis as well as vascular complications such as thrombosis or severe hemorrhage [1,2,3,4,5,6], all of which are associated with inferior survival. CKD occurs significantly more frequently in MPN patients than in the general population, as documented by renal involvement in several case studies [21,22,23] as well as larger monocenter [24,25] or oligocentric studies [26,27] These studies have shown that CKD is associated with thrombosis in MPN patients [26] and that kidney function declines with. MPN duration beyond the expected age-related decline, suggesting that the MPN itself has a deteriorating impact on kidney function [2,24,26] These studies suggested that inflammatory factors are involved in kidney dysfunction in these patients [24,25], providing a potential functional link between MPN and CKD pathogenesis. Whether cytoreductive therapy for MPN improves renal dysfunction overall remains a matter of current debate: while one study showed an increase in the estimated glomerular filtration rate (eGFR) during hydroxyurea treatment (HU) in polycythemia vera (PV)

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