Acute kidney injury induced by thrombotic microangiopathy in a patient with hemophagocytic lymphohistiocytosis

Abstract

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome characterized by excessive immune activation and inflammation. It is frequently complicated by acute kidney injury (AKI) that often develops as acute tubular necrosis (ATN). Meanwhile, renal thrombotic microangiopathy (TMA) is a rare pathologic finding that mostly occurs in hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. There are only few reports on TMA developing in patients with HLH. We present here a rare case of TMA associated HLH.Case presentationA 60-year-old woman was admitted for a fever of unknown origin that had persisted for several weeks. She presented with AKI and pancytopenia. Clinical, laboratory and bone marrow biopsy findings met the criteria of HLH. Kidney biopsy showed TMA and minimal ATN, which suggested that the primary cause of AKI was TMA in this case. Because of sustained oliguria, we initiated hemodialysis (HD) and also decided to use chemotherapy composed of dexamethasone, etoposide and cyclosporine for treatment of HLH. Six months after the initiation of chemotherapy, pancytopenia was completely resolved, indicating the resolution of HLH. At the same time, serum creatinine decreased to a normal range without the need for HD, suggesting the resolution of TMA.ConclusionWe report a case of renal TMA associated HLH. This case suggests that renal TMA should be considered as a primary cause of AKI in patients with underlying HLH.

Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy

“…We observed a high incidence of clinically significant complement-mediated thrombotic microangiopathy (TMA) associated with multi-organ injury in children and young adults with a diagnosis of HLH. TMA has not been previously associated with interferon gamma-driven diseases like HLH [26], but TMA has been reported as an iatrogenic therapylimiting side effect in patients receiving interferon alpha and beta therapy [27][28][29][30][31]. We hypothesized that high levels of interferon gamma in HLH might contribute directly to endothelial damage or injure endothelium through complement system activation.…”

Thrombotic microangiopathy led to acute kidney injury in an infant with hemophagocytic lymphohistiocytosis: A case report

“…There were three cases of clinically-diagnosed HLH complicated TMA which did not undergo biopsy (33,34). Bae et al (30) reported that TMA in HLH may occur with greater frequency than previously known, since diagnostic biopsies have rarely been performed in patients with HLH. If AKI occurred in patients with HLH, it is recommended that clinicians should also observe whether TMA is present in the patients as well.…”

“…In TMA pathogenesis, endothelial injury is a key factor in the initiation of microemboli formation (35,36). The mononuclear-macrophage system is activated under the action of cytokines, releasing free radicals and proteolytic enzymes, resulting in endothelial cell damage and inflammatory reactions, thereby triggering TMA (30,33). Similarly, systemically-activated lymphocytes and macrophages and overproduction of highly elevated proinflammatory cytokines in the circulation such as IFN, TNF, IL-6 and macrophage-colony stimulating factor are pathogenetic characteristics of HLH (6,37).…”

Suspected thrombotic microangiopathy in a child with Epstein–Barr virus‐induced hemophagocytic lymphohistiocytosis

“…To the Editor: Thrombotic microangiopathy (TMA) is a form of endothelial injury that has been reported as a complication of hemophagocytic lymphohistiocytosis (HLH) in adults . We report a case of Epstein–Barr virus (EBV)‐induced HLH and suspected TMA in a child.…”