JAK Inhibitor-Induced Improvement of IgA Nephropathy in a Patient With Polycythemia Vera: A Case Report.
Key claim: Ruxolitinib treatment in a PV patient with concurrent IgA nephropathy led to reduction in proteinuria and stabilization of renal function, suggesting JAK inhibition may suppress glomerular inflammation via IL-6/IL-11-mediated mesangial proliferation and aberrant hematopoietic IgA production.
Abstract
Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by the clonal expansion of hematopoietic stem cells, commonly caused by pathogenic variants in Janus kinase 2 (JAK2). Although PV primarily affects the hematologic system, various renal manifestations have been reported, including rare cases of glomerulopathies. We describe a 73-year-old woman with PV harboring amutation who developed hematuria, proteinuria, and renal dysfunction. Kidney biopsy revealed IgA nephropathy (IgAN) with cellular crescents. Because corticosteroid therapy was initially avoided due to concern for exacerbating PV, treatment was initiated with a JAK inhibitor, ruxolitinib. Over the following year, urinary protein levels decreased and serum creatinine stabilized, suggesting that JAK inhibition may have contributed to an improvement in IgAN activity. Two years of tapering corticosteroid therapy later resulted in clinical remission. To our knowledge, this is the first reported case of IgAN showing improvement after JAK inhibitor therapy in a patient with PV. Proposed mechanisms include suppression of IL-6/IL-11-driven platelet-derived growth factor production leading to reduced mesangial proliferation, and modulation of aberrant hematopoietic IgA production. This case suggests that JAK inhibition may not only normalize hematopoiesis in PV but also modify glomerular inflammation in IgAN, particularly in patients with hematologic comorbid conditions.
Why this matters
Renal complications in MPN are underrecognized, and this case suggests that JAK inhibitor therapy — beyond its cytoreductive and symptom-control roles — may directly modulate MPN-associated glomerular inflammation via IL-6/IL-11 suppression. If confirmed in additional cases, ruxolitinib could serve dual purposes in PV patients with concurrent IgA nephropathy, offering symptom management for MPN alongside renal disease stabilization. It also strengthens the emerging pattern of ruxolitinib-responsive nephropathies in MPN.