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Atypical Hemolytic Uremic Syndrome (aHUS) is a rare and potentially life-threatening condition characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal involvement. It is typically associated with complement mutations or other conditions like infections, autoimmune diseases, or neoplasms.
We present the case of a patient who presented with thrombotic microangiopathy (TMA) suggestive of aHUS, and her clinical course, along with an extensive study, revealed a less frequently described secondary cause.
A 46 y/o woman with a history of intracranial hemorrhage in 2011 due to a ruptured aneurysm, sought medical attention in June 2022. She presented with generalized edema, abdominal and back pain, associated with KDIGO stage I acute kidney injury (AKI), mild anemia, thrombocytopenia, proteinuria, and dysmorphic hematuria. A CT scan revealed renal infarction in the upper right and lower left posterior poles. She developed rapidly progressive AKI, MAHA, and thrombocytopenia. Simultaneously, she began receiving methylprednisolone pulses, hemodialysis, and plasma exchange. Laboratory studies showed a 19% ADAMTS13 activity before plasma exchange, low C3, negative ANA, ENA, ANCA P and C antibodies, and normal C4 levels. A renal biopsy confirmed TMA with moderate glomerular and vascular involvement, mild chronic tubulointerstitial changes, and signs of acute tubular injury. After the biopsy, she experienced retroperitoneal bleeding requiring embolization of the left renal artery. She recovered well and was discharged with antihypertensive treatment.
Twenty days later, she returned with clinical and MRI findings consistent with Posterior Reversible Encephalopathy Syndrome, without evidence of TMA. A follow-up abdominal CT angiography revealed residual dense material in the distal left renal artery and a residual hematoma, while the right renal artery showed no stenosis. There was a 60% occlusion of the celiac trunk and multisegmental stenosis of the superior mesenteric artery. A targeted mutational analysis of 13 genes related to aHUS and TMA identified a heterozygous variant in CFH c.1315A>G (p.Thr439Ala), classified as a Variant of Uncertain Significance (VUS). Her condition improved with intensified antihypertensive therapy, and she was discharged for outpatient follow-up.
She remained clinically stable for eight months but returned with abdominal and back pain, along with KDIGO I AKI. An angiographic examination revealed irregular parietal changes with a "rosary bead" appearance, affecting the celiac trunk and the splenic artery, with a 50% reduction in caliber. The single renal arteries were patent but showed parietal irregularities, with 50% and 70% stenosis in the right and left arteries, respectively. Angiography confirmed these findings, and a stent was placed in the left hepatic artery from the celiac trunk, followed by the recanalization of the left renal artery. Due to a high suspicion of polyarteritis nodosa, prednisone was initiated at 1 mg/kg. She responded with improved renal function and blood pressure control.
In the context of malignant or accelerated hypertension, endothelial damage can lead to aHUS. This case demonstrates that a medium-vessel vasculitis affecting the renal artery and causing severe hypertension can trigger TMA, particularly in the presence of a CFH variant that remains classified as a VUS.