Hemophagocytic Lymphohistiocytosis (HLH)-Associated AKI: A Hyperacute Presentation in a Critically Ill Patient

Introduction: HLH is a life-threatening hyperinflammatory syndrome marked by unchecked activation of inflammatory cytokines. AKI is a well-documented complication of HLH, occurring in up to 50% of HLH cases. Its mechanism includes acute tubular necrosis (ATN), cytokine-induced endothelial injury, glomerulopathies or rarely, direct infiltration of hemophagocytosis. Case Description: A 35-year-old woman with Ehlers-Danlos syndrome, pulmonary hypertension, and chronic gastrojejunostomy tube presented with worsening abdominal pain, nausea and vomiting. On admission, she was tachycardic (HR 110bpm) and hypertensive (BP 176/110 mmHg). Physical examination was unremarkable. Initial labs revealed a leukocytosis of 12.7K/uL and normal complete metabolic panel. On hospital day 2, she acutely decompensated with hypotension (BP 90/56 mmHg) and hypoxemia prompting a medical rapid response. Labs were consistent with multi-organ dysfunction and impending shock including leukocytosis of 19K/uL, platelets 16K/uL, serum bicarbonate < 7mmol/L, serum creatine 2.44mg/dL, AST 6112U/L and ALT 1375U/L, LDH 7051U/L, INR > 9, fibrinogen 73mg/dL and lactate of 13.5mmol/L. She was transferred to the ICU with distributive shock, coagulopathy and suspected sepsis from a urinary tract infection. By day 4, she developed AKI, became anuric and was initiated on continuous renal replacement therapy (CRRT). Urinalysis revealed leukocyte esterase, proteinuria (100mg/dL) and no hematuria. Further renal workup revealed depressed complement levels, mildly elevated free light chain ratio (2.9) without monoclonal proteins. Given persistently hemodynamic instability, systemic hyperinflammatory syndromes were considered. Labs showed ferritin 51,000 ng/mL, IL-2 receptor 11876 pg/mL and triglycerides of 270mg/dL. Bone marrow biopsy confirmed hemophagocytic lymphohistiocytosis (HLH). High dose dexamethasone was initiated, resulting in gradual improvement of hepatic function and coagulopathy, however the patient remained anuric. Renal biopsy was deferred due to critical illness and bleeding risk. Discussion: HLH should be considered with a presentation of rapid deterioration along with severe sepsis features, pancytopenia, and AKI. Prompt initiation of empiric therapy may improve outcomes in this otherwise fatal condition as biopsy is often not feasible.