The unusual suspects: a curious case of acute kidney injury—Answers

Figure 1a, b shows red supernatant suggestive of hemoglobinuria or myoglobinuria accompanied by muddy brown cast, many tubular epithelial cells, and few erythrocytes on microscopy, consistent with rhabdomyolysis. In Fig. 2, we can see necrotic fibers with minimal presence of lymphocytes or histiocytes (marked by arrows). Ancillary staining showed moderate diffuse MHC-1 consistent with inflammatory or autoimmune-mediated process, as well as scattered C5b-9 deposition in some myofibers and capillaries.

While the differential diagnoses associated with the initial presentation included prerenal acute kidney injury (AKI), and pigment nephropathy associated with rhabdomyolysis, the development of worsening anemia and thrombocytopenia suggested a burgeoning thrombotic microangiopathy (TMA). The differential diagnoses for TMA is as follows:

Initial management in a patient with rhabdomyolysis should focus on hydration and prevention of pigment deposition. With the development of TMA, evaluation and management of the potential etiologies is key [1]. Since STEC-HUS occurs even in the absence of diarrheal illness in about 5% of cases, all patients with HUS should be assessed for the presence of STEC. For possible sepsis management, blood cultures and relevant viral serologies should be obtained early and consideration given to empiric antibiotic therapy until results are available. Coordination with oncology colleagues to discuss the utility of bone marrow biopsy or other investigation for possible malignancy is important to consider prior to initiation of immunosuppressive medications given that the risk of masking malignancy with treatment and that immunosuppressive therapy is the mainstay of management for autoimmune causes of TMA. Screening should be conducted for TMA-associated medications, including those detailed above. Early pheresis is appropriate, as TTP is a possibility, ensuring that an ADAMTS-13 level has been obtained prior to therapy. Macrophage activation syndrome is treated with anakinra (IL-1 antagonist), and inflammatory markers are tracked to determine response to treatment. Other autoimmune etiologies for TMA may be elicited by testing for autoantibodies, to include ANA, anti-dsDNA, antiphospholipid, anti-Scl70, ACA, and RNA polymerase III. Screening for cobalamin deficiency would include homocysteine, methionine, and methylmalonic acid levels.