Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry

Abstract

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.

Clonal haematopoiesis of indeterminate potential and impaired kidney function—A Danish general population study with 11 years follow‐up

“…Also, it may indicate that not only do aberrant blood cell counts precede the MPN‐diagnosis 43 but also that the development of MPN‐related nephropathy could be facilitated through a chronic inflammatory state as reflected by an increased NLR, which is negatively associated with eGFR, in our analysis. This is in part supported by the proportion of moderate to severe CKD among MPN patients at the time of diagnosis, 16 but also by the observation that neutrophilia associate with kidney dysfunction 20 …”

“…14,15 MPN is associated with several chronic inflammatory-mediated diseases 16,17 and a progressive reduction in estimated glomerular filtration rate (eGFR). 18 In addition, in patients with MPN, moderate to severe chronic kidney disease (CKD) is associated with thrombosis, 19,20 disease severity 20 and reduced survival. 21 CKD in MPN may be caused by an underlying glomerulonephritis 22 such as focal segmental glomerulosclerosis, mesangial sclerosis and hypercellularity and renal interstitial extramedullary haematopoiesis.…”

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

“…Interestingly, in a recent analysis of 1420 patients from the German Study Group for MPN, there was a strong association of impaired kidney function with the incidence of thrombosis. A total of 29% of the patients had a history of thrombosis [ 99 ].…”

Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives

“…Comorbidities can affect the rate of thrombotic and hemorrhagic complications in MPN patients. For example, kidney dysfunction has been associated with an increased risk of thrombosis in MPN [ 9 , 57 , 58 ]. However, whether comorbidities also affect the rate of progression in MPN patients is largely unknown.…”

“…In particular, the latter contribute to inflammation by (a) the excess production of fibrotic tissue through activation of so-called myofibroblasts which leads to suppression of normal hematopoiesis, (b) enhanced cytokine production that favors the malignant clone (e.g., TNF-alpha), and (c) abnormal expression of thrombogenic surface molecules on endothelial cells which increase the risk of thrombosis (e.g., P-selectin) [ 5 , 6 , 7 , 8 ]. Finally, systemic conditions such as chronic inflammation, cardiovascular diseases, and pro-fibrotic processes in other organs (kidney fibrosis) may augment the risk of MPN progression [ 9 ].…”