Diabetic Kidney Disease in a Patient without Diabetes? A Case of Myeloproliferative Neoplasm (MPN)-Associated Glomerulopathy

Introduction: Myeloproliferative neoplasms (MPNs) are now recognized to cause a wide spectrum of renal disease, including thrombotic complications, extramedullary hematopoiesis, vascular nephrosclerosis, and glomerulopathy. The biological basis for vascular nephrosclerosis and glomerulopathy in MPNs remains to be elucidated, although has been presumed to result from increased cytokine levels. Case Description: A 66-year-old man recently diagnosed with primary myelofibrosis (PMF) was referred to onconephrology clinic for acute kidney injury. He had initially presented 4 months prior with several weeks of night sweats and weight loss. Bone marrow biopsy was performed for evaluation of severe anemia and revealed JAK2 V617F and exon 12 mutated PMF. At the time of ruxolitinib initiation, his creatinine was noted to have risen to 2.06 mg/dL from 1.5 mg/dL, prompting nephrology referral. In onconephrology clinic, vital signs were remarkable for hypertension to 185/96 with no abnormalities on physical exam. Creatinine was 1.9 mg/dL with albumin of 3.9 g/dL and 9.5 g/g proteinuria with spot urine albumin to creatinine ratio 7123 mg/g. SPEP and UPEP revealed no M spike. Renal biopsy was performed and revealed glomerular, tubulointerstitial and vascular changes compatible with diabetic nephropathy, including mesangial matrical increase and mild thickening of the glomerular basement membrane, as well as fibrotic and hyaline changes of the arterioles. The patient denied any history of diabetes. Fructosamine test was sent to evaluate for diabetes mellitus in the setting of frequent blood transfusions and was normal at 257 umol/L. In the absence of the appropriate clinical context for diabetes, his biopsy findings were ultimately attributed to MPN-associated glomerulopathy, which closely resembles the glomerular changes of diabetes. Discussion: This report adds to a growing literature describing cases of MPN-associated glomerulopathy, an entity whose pathologic description resembles that of diabetic glomerulosclerosis. Given the lack of clinical association between diabetes and MPN, the close pathologic parallels between diabetic nephropathy and MPN-associated glomerulopathy could suggest common causal mechanisms for both diseases and a possible role for cytokine-mediated glomerular damage in diabetic kidney disease.