MPN-409 Associations of JAK2 Mutant Allele Burden With Occurrence of CKD (Chronic Kidney Disease) and Dynamics of Kidney Function Over Time in Patients With Chronic Myeloproliferative Neoplasms

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 23; p. S394
• Main Authors: Lucijanic, Marko, Veic, Petra, Aric, Ivona, Marija, Katarina, Soric, Ena, Sabljic, Anica, Glasnovic, Josipa Vlasac, Stoos-Veic, Tajana, Krecak, Ivan, Kusec, Rajko
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2023
• Subjects: chronic kidney disease; JAK2; MPN; JAK2; chronic kidney disease; MPN
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/S2152-2650(23)01241-7

CKD is common in patients with chronic myeloproliferative neoplasms (MPNs). The two diseases may be causally related through development of MPN-related glomerulopathy. To evaluate associations of JAK2-V617F mutant-allele-burden (MAB) with occurrence of CKD and dynamics of kidney function over time. Retrospective cohort study Tertiary hematology referral center 230 patients with JAK2-V617F-mutated MPN (98 polycythemia vera, 94 essential thrombocythemia, 20 primary myelofibrosis, 18 other) were evaluated from 2006 to 2022. MAB was determined using the quantitative real-time polymerase chain reaction (Applied Biosystems, California, USA). Occurrence of CKD defined by CKDEPI formula as estimated glomerular filtration rate <60 ml/min/1.73 m2 present for >3 months. Increase or decrease in serum-creatinine values at 6- and 12-months in comparison to baseline. Median age was 67 years; 50.2% females; median MAB, 26.3%. A total of 24.9% patients had CKD, which did not significantly differ between MPN subsets (P=0.140). Patients presenting with higher MAB stratified at the median had a higher frequency of CKD at baseline (32.6% vs 16.7%, P=0.012). In the multivariate logistic-regression model adjusted for clinically meaningful variables higher MAB stratified at the median remained significantly associated with CKD (OR 2.81, P=0.024) independently of older age (OR 1.11, P<0.001) and arterial hypertension (OR 2.96, P=0.015). Patients with higher MAB rather than lower significantly differed regarding the dynamics of kidney function at 6-months (mean 2% worsening vs 7% improvement, P=0.032) and 12-months (mean 11% worsening vs 8% improvement, P=0.007). In the multivariate logistic-regression model adjusted for clinically meaningful variables higher MAB remained significantly associated with worsening of kidney function at 6-months (OR 3.37, P=0.038) independently of older age (OR 1.05, P=0.024) and ACE inhibitor use (OR 0.21, P=0.024). In the similar model evaluating kidney-function dynamics at 12 months higher MAB remained the only significantly associated factor (OR 9.79, P=0.026). MPN patients with higher MAB seem to have a higher occurrence of concomitant CKD and demonstrate unfavorable dynamics of kidney function over time. Although causal relationship cannot be inferred due to limitations of the study design, our observations support the view that biology of MPN and CKD might be intertwined.