Typical! Atypical Hemolytic Uremic Syndrome (aHUS) Overlooked in Malignant Hypertension and Thrombotic Microangiopathy: Case Reports and Clinical Implications

Introduction: Thrombotic microangiopathy (TMA) is a clinicopathologic manifestation of atypical HUS (aHUS) and often overlooked in patients with malignant hypertension (MH) leading to a delay in diagnosis. Prompt diagnosis of aHUS can significantly improve patient outcomes, especially in the setting of kidney transplantation where recurrent disease can occur rapidly in the allograft. Here we describe two cases of patients with severe HTN and TMA: one where aHUS was diagnosed and managed with eculizumab prior to kidney transplantation and one where the diagnosis was masked by other clinical features and ultimately resulted in recurrence after transplant. Case Description: Case 1: A 34 y/o woman with CKD due to Class IV lupus nephritis presented with hypertensive emergency with native kidney biopsy also showing features of TMA. Genetic testing for aHUS revealed variants of unknown significance in CD46 (membrane co-factor protein). She later underwent a renal transplant with immediate graft function, but soon after developed allograft dysfunction with hematological features of TMA confirmed by biopsy. Other causes of TMA were ruled out leading to a diagnosis of aHUS. She was treated with eculizumab emergently and had normalization of allograft function. Case 2: A 32 y/o woman presented with hypertensive emergency and cardiomyopathy during the postpartum period and was found on biopsy to have chronic TMA. Genetic testing revealed a homozygous variant in the CFI gene, a variant of unknown significance in the THED gene, and a homozygous deletion of CFHR3-CFHRI. She was treated with eculizumab prior to transplantation and had a stable post-transplant course without recurrent disease. Discussion: It can be challenging to determine whether TMA is due to MH or underlying aHUS caused by derangement in the alternative complement pathway. It has been estimated that 20% of MH patients who require hospital admission have TMA features and 60% of these patients may have underlying aHUS when genetic testing was performed. We believe it is crucial to obtain genetic testing for aHUS in patients with severe HTN and TMA to help distinguish these conditions and improve patient outcomes by making the diagnosis of aHUS, guiding treatment options, facilitating genetic counseling and preventing recurrence of TMA in renal allografts.