Hemoglobinuria-associated acute kidney injury in hemolytic uremic syndrome without renal thrombotic microangiopathy

Abstract Background Hemolytic uremic syndrome (HUS) is classically defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is most often associated with renal thrombotic microangiopathy (TMA). However, the clinical triad may rarely occur in the absence of histologically demonstrable renal TMA. Case presentation A 64-year-old woman with hypertension treated with an ACE inhibitor presented with asthenia, nausea, dark urine, and oliguria. Laboratory evaluation revealed AKI (serum creatinine 4.5 mg/dL), thrombocytopenia (46 × 10⁹/L), and intravascular hemolysis (LDH > 1,800 U/L, schistocytes, haptoglobin < 10 mg/dL). Procalcitonin was markedly elevated, while complement levels and ADAMTS13 activity were within the normal range. Anti–factor H antibodies and complement genetic testing were negative; however, these findings do not exclude complement-mediated atypical HUS, which remains a diagnosis of exclusion. A positive direct Coombs test was documented at presentation. Paroxysmal nocturnal hemoglobinuria could not be definitively excluded, as flow cytometry was not performed. Mild, self-limited gastrointestinal symptoms preceded admission and may have acted as a triggering event. The patient was initially treated for suspected STEC-HUS with plasma exchange (subsequently discontinued), supportive therapy, and hemodialysis from day 3. Hematologic abnormalities resolved, whereas renal function worsened, with serum creatinine peaking at 10 mg/dL. Kidney biopsy performed on day 7 revealed acute tubular injury with hemoglobin pigment casts and no evidence of renal TMA. Dialysis was withdrawn, and renal recovery followed. Conclusions This case illustrates that in patients fulfilling the clinical triad classically associated with HUS, AKI does not invariably result from renal thrombotic microangiopathy. Hemoglobinuria-induced tubular injury may represent an alternative mechanism of renal injury. When hematologic recovery contrasts with persistent renal dysfunction, pigment nephropathy should be considered and kidney biopsy performed when feasible.