Primary myelofibrosis associated glomerulopathy: significant improvement after therapy with ruxolitinib

Abstract

BackgroundPrimary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the predominant proliferation of megakaryocytes and granulocytes in the bone marrow, leading to the deposition of fibrous tissue, and by a propensity toward extramedullary hematopoiesis. Renal involvement in PMF is rare, but kidney tissue samples from these patients reveal MPN-related glomerulopathy, a recently discovered condition, in the late stages of the disease.Case presentationWe present the first case described in the medical literature of a patient with early renal glomerular involvement in PMF/MPN. A 60-year-old man with stage 4 chronic kidney disease and a recent diagnosis of PMF (within 4 weeks of presentation at our renal division) presented with generalized body swelling, acute kidney injury, and massive nephrotic-range proteinuria. Kidney biopsy was performed to determine the etiology of the patient’s renal dysfunction and revealed early renal glomerular involvement that was histologically characteristic of MPN-related glomerulopathy. Early diagnosis and prompt medical management returned the patient’s kidney functionality to the levels seen on initial presentation at our hospital.ConclusionLarge studies with long follow-up durations are necessary to identify and categorize the risk factors for the development of MPN-related glomerulopathy, to standardize therapeutic regimens, and to determine whether aggressive management of the myelofibrosis slows the progression of kidney disease.

Focal segmental glomerulosclerosis in a patient with prefibrotic primary myelofibrosis

“…A similar case was earlier described by Rajasekaran et al with early MPN-related glomerulopathy in a 60-year-old man 8. The pathogenesis of glomerulopathy in MPN is still unclear.…”

Kidney Involvement in Patients With Chronic Myelomonocytic Leukemia or BCR-ABL–Negative Myeloproliferative Neoplasms

“…In this study, most patients had slowly progressive chronic kidney disease whereas patients included in ours frequently had AKI that may be triggered by different pathophysiological mechanisms. Thus, which patients with renal complications of MPN may beneficiate from specific drugs (for instance, ruxolitinib for PMF) remains to be determined 33 . Furthermore, azacytidine (n=4) and decitabine (n=1) were used as second line treatment after the identification of kidney injury with closed monitoring J o u r n a l P r e -p r o o f of potential additional renal impairment, as they are known to be sometimes nephrotoxic, especially for tubules 34 35 .…”

Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era

“…The histopathological findings in kidney biopsy allow excluding ruxolitinib as the cause of renal disease. No benefit in nephrotic syndrome from ruxolitinib therapy is reported in the literature [ 14 ]. This might correlate with the progression of hematological disease rather than with the inflammatory state [ 16 ], leaving the best therapeutic strategy for PMF still uncertain [ 17 ].…”

“…Table 1 and Table 2 show the main studies of the last two decades. Table 1 shows the clinical data, and Table 2 describes the glomerular and interstitial lesions, EMH location exclusively in patients with PMF, and performed renal biopsy [ 3 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Of the 38 patients with MPN, 26 (68%) had PMF, 21 (81%) were male, and median age was 66.5 years (range 49 – 87).…”