Abstract Topic: 16. Myeloproliferative neoplasms - Clinical
Background: Chronic myeloproliferative neoplasms (MPN) may be associated with the presence of chronic kidney disease (CKD) in up to one quarter of patients at the time of presentation which is higher than in general population. Accumulating pool of evidence suggests MPN might be causally related to CKD due to inflammatory and thrombotic manifestations of MPN at the level of glomeruli, termed MPN related glomerulopathy, and kidney function may improve over time with institution of MPN specific therapies. Nevertheless, it is unknown at the moment whether higher JAK2 mutant allele burden at the time of presentation might be associated with higher occurrence or worsening of kidney function over time in JAK2 V617F mutated MPN patients.
Aims: To evaluate associations of JAK2 mutant allele burden with baseline and dynamic kidney function over time.
Methods: We retrospectively analyzed a cohort of 230 JAK2 V617F mutated MPN patients treated in the University hospital Dubrava, Zagreb, Croatia in period from 2006 to 2022 who had available data on JAK2 V617F allele burden. JAK2 mutant allele burden was determined using the quantitative real-time PCR (7300 RealTime PCR System (Applied Biosystems, Foster City, California, USA) and was compared with baseline clinical data including serum creatinine levels. Allele burden and serum creatinine were repeatedly assessed over time in the 6 months and 12 months period in a subset of patients. Chronic kidney disease was defined as estimated glomerular filtration rate defined by CKD-EPI formula of less than 60 ml/min/1.73 m2 present for at least 3 months. Study was approved by the Institutional review board.
Results: A total of 230 MPN patients were analyzed, 98 with PV, 94 with ET, 20 with PMF and 18 with other JAK2 mutated MPNs. Median age was 67 years. There were 115 (50.2%) females. Median JAK2 mutant allele burden at baseline was 26.3% and significantly differed between MPN subsets (median 47.5% in PV, 21.6% in PMF, 21.6% in other MPN and 16.5% in ET patients, P<0.001). Median serum creatinine level was 84 mcmol/L with 46 (24.9%) of patients having CKD which did not significantly differ between MPN subsets (P=0.140). Patients presenting with higher mutant allele burden stratified at median had higher frequency of CKD (32.6% vs 16.7%, P=0.012).
Neither JAK2 mutant allele burden nor serum creatinine levels showed significant dynamics at 6- and 12-months time points in comparison to baseline values in an entire cohort (P>0.05 for all analyses). Nevertheless, patients with higher in comparison to lower baseline mutant allele burden significantly differed regarding 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) as shown in a Figure. Patients with lower baseline mutant allele burden experienced significant improvement in kidney function whereas same was absent in those with higher baseline mutant allele burden at both timepoints. Age similarly affected dynamics of kidney function over time (P<0.05 for difference at both timepoints). Baseline CKD, MPN subtype and sex did not significantly affect dynamics of the kidney function over time (P>0.05 for all analyses).
Summary/Conclusion: MPN patients presenting with higher JAK2 mutant allele burden have higher occurrence of CKD and unfavorable dynamics of kidney function over time. These observations support the view that MPN disease biology might participate in deteriorated kidney function observed in a high number of MPN patients. Future studies are warranted.
Figure: Relative changes in serum creatinine at 6 and 12 months time points regarding baseline JAK2 mutant allele burden.
Keywords: Renal impairment, Chronic renal failure, Myeloproliferative disorder