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Myeloproliferative neoplasms (MPNs) are hematopoietic cell disorders that have a rare association with glomerular disease. CKD in patients with MPNs has been associated with inferior outcomes. MPN-associated nephropathy is a relatively new entity with a growing spectrum of renal pathology described.
We present the case of a patient with myelodysplastic syndrome (MDS) and kidney disease due to a combination of thrombotic microangiopathy (TMA) and membranous nephropathy (MN).
77 yo female with MDS previously on Lenalidomide (LLM) came to a nephrology clinic for evaluation of 4 months of renal decline. Her Cr was elevated to 1.5 mg/dL with a known baseline of 1.0. Five months prior to presentation the patient was diagnosed with MDS and started treatment with LLM. Two weeks after LLM initiation she developed severe anemia with Hb 3.8 g/dL, associated with undetectable haptoglobin, consistent with hemolytic anemia, and thrombocytopenia with a nadir 68 k/uL, attributed to the medication side effect. LLM was restarted later at a lower dose after Hb stabilization. During an acute episode, her Cr went up to 1.1-1.3 but continued to uptrend further afterward. The patient remained anemic with Hb 9.5, and platelets ~125, which seemed to be her baseline prior to treatment initiation. However, LLM was stopped several days prior to presentation due to concern for persistent anemia.
Upon initial assessment, the patient was found to have proteinuria with PCR 1.3 and microscopic hematuria. Serologic workup was unrevealing except for prominently depressed and undetectable complement C4. This triggered further evaluation, and she then underwent a kidney biopsy showing a combination of subacute to chronic TMA and secondary MDS-related MN with mild subendothelial immune complex deposition. TMA was the cause of the patient’s Cr elevation as MN was thought to be an unlikely reason for that given the low level of deposition. The etiology of TMA was not clear: both MDS and the use of LLM have reported association with TMA. Since the patient was already taken off LLM, the decision was made to monitor, provide supportive management, and consider targeted MDS therapy resumption should kidney function decline further. Four months later her kidney function remained stable with Cr 1.3, along with stable blood indices.
Renal disease in MPNs is rare and when seen it is commonly attributed to the neoplasm itself. At the same time, it is important to remember that furthermore it may be associated with malignancy treatment. Although most seen in solid cancers, TMA can result from the endothelial barrier disruption in the bone marrow by any aggressive bone marrow malignancy. MDS has a known association with TMA, it is in fact a part of MPN-nephropathy described in the literature, but there are a few case reports of LLM-induced TMA. The presence of secondary MN along with TMA in our case would lend further credence to malignancy itself inciting both pathologies. However, the development of acute symptomatic hemolytic anemia associated with kidney decline shortly after LLM initiation raises a concern about their association with the treatment. This duality adds additional challenges to the management, as may lead to the discontinuation of effective drugs to prevent further renal decline. Decision-making in such cases requires deep provider expertise and close patient monitoring.