JAK2 Mutant Allele Burden Linked with Chronic Kidney Disease in MPN

Patients with chronic myeloproliferative neoplasms (MPN) who present with a higher JAK2 mutant allele burden have “higher occurrence” of chronic kidney disease and “unfavorable dynamics of kidney function over time,” according to a recent study.

Marko Lucijanić, MD PhD, of the Clinical Hospital Dubrava and the University of Zagreb, and colleagues conducted the research and presented their findings during the 2023 European Hematology Association Congress.

Dr. Lucijanić and colleagues investigated the relationship because an “accumulating pool of evidence suggests MPN might be causally related” to chronic kidney disease, but 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.”

They retrospectively analyzed a cohort that included 230 patients with MPN who had the JAK2 V617F mutation. All patients received treatment between 2006 and 2022 at a single center in Zagreb, Croatia. The study included 98 patients with polycythemia vera (PV), 94 patients with essential thrombocytopenia (ET), 20 with primary myelofibrosis, and 18 with other JAK2-mutated MPNs. The median patient age was 67 years.

All patients in the study had available data on the JAK2 V617F allele burden. The researchers determined the JAK2 mutant allele burden using quantitative real-time PCR and compared it with baseline clinical data, including serum creatinine levels. In a subset of patients, they repeatedly assessed allele burden and serum creatinine over a six-month period and a 12-month period.

The median JAK2 mutant allele burden was 26.3% at baseline. It significantly differed among MPN subsets, with a median of 47.5% in PV, 21.6% in primary myelofibrosis, 21.6% in other MPNs, and 16.5% in ET (P>.05 for all analyses). However, 32.6% of patients who had a higher mutant allele burden had chronic kidney disease, nearly double that of those with a lower mutant allele burden (16.7%; P=.012).

Patients who had a lower baseline mutant allele burden showed significant improvement in kidney function at six and 12 months, but those with a higher baseline mutant allele burden did not show this improvement, according to the study’s authors. Furthermore, age also impacted dynamics of kidney function over time (P>.05 for difference at both timepoints).

“MPN patients presenting with higher JAK2 mutant allele burden have higher occurrence of [chronic kidney disease] and unfavorable dynamics of kidney function over time,” Dr. Lucijanić and colleagues concluded. “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.”

Reference

Lucijanic M, Veic P, Aric I, et al. Higher JAK2 allele burden in patients with chronic myeloproliferative neoplasms is associated with higher prevalence of chronic kidney disease and unfavorable dynamics of kidney function over time. Abstract PB2194. Presented at the 2023 European Hematology Association Congress. June 8-15, 2023; Frankfurt, Germany.