Presentations

Abstract

Introduction:

Atypical hemolytic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) secondary to a genetic cause. Due to the high morbidity and mortality of aHUS, prompt diagnosis and treatment are paramount. Diagnosis may be complicated by testing limitations and clinical prominence of acute kidney injury over thrombotic symptoms. We report a case of aHUS that was initially thought to be progression of chronic kidney disease (CKD).

Case Information:

A 73-year-old female with chronic kidney disease (CKD) stage V due to ANCA vasculitis, lupus, hypertension, and chronic combined heart failure presented to the emergency department with oliguria, intractable nausea, dysgeusia, and unintentional weight loss of 20 lbs over 2 months. On exam she had 2+ bilateral pretibial edema, generalized fine crackles, benign cardiovascular exam, and conserved distal pulses. On admission she had creatinine of 6.1 up from her baseline of 3. Hemodialysis was initiated due to fluid overload and uremia with mild initial symptoms improvement. Progression of chronic kidney disease was suspected, and she was discharged home on hemodialysis.

Despite dialysis adherence she declined, was readmitted after four weeks, and was found to have new thrombocytopenia to 53 K/uL. Additional investigation revealed a haptoglobin <1 mg/dL, immature platelet fraction of 22.5%, elevated LDH to 211 U/L, normal coagulation panel, negative ADAMTS-13 testing, and schistocytes and decreased platelets seen on peripheral blood smear suggestive of TMA. Daily plasmapheresis (PLEX) was initiated with marked platelet count improvement and modest symptom improvement. Her genetic work up returned negative for known genetic markers of aHUS. Considering her clinical picture and improvement with PLEX, she was diagnosed with aHUS. Eculizumab was initiated and she achieved complete resolution of symptoms. On further follow up, her cell counts normalized after four cycles of eculizumab.

Discussion/Clinical Findings:

aHUS is one of several subsets of TMA and represents a significant diagnostic challenge. aHUS is characterized by thrombocytopenia, microangiopathic hemolytic anemia( MAHA), and acute renal failure. Unlike other types of TMA, aHUS often presents as intrarenal pathology rather than with impressive systemic or coagulopathy findings. The exact cause of aHUS is not well characterized. Current theories suppose an underlying genetic origin that encodes individual susceptibility paired with some external insult such as drugs, pregnancy, or systemic disease.

Treatment with isolated plasmapheresis (PLEX) has a high rate of end stage renal failure. Eculizumab, a recombinant humanized monoclonal Ab to the C5 complement protein, is safe and effective for use in aHUS except in cases of specific genetic C5 polymorphisms. Eculizumab positively influences long term renal function as measured by eGFR. Due to the high morbidity and mortality of untreated aHUS, current best treatment guidelines are genetic testing, empiric PLEX, and eculizumab in cases of poor or absent response to PLEX.

Diagnosis of aHUS is difficult to establish early in care. aHUS lab findings are nonspecific, initial complement studies appear normal in majority of patients, and the primary renal etiology may further delay diagnosis. Additionally, only 40-60% of patients diagnosed with aHUS have a clear genetic association and only 10% have an isolatable complement auto-antibody. The remainder of cases are diagnoses of exclusion.

Our case demonstrates the two challenges to timely diagnosis of aHUS - renal predominant symptoms and imperfect genetic testing. Our patient had a history of complex and chronic renal disease, signs suggestive of AKI, and was found to have negative genetic testing for known aHUS variants. Her recovery with PLEX and early initiation of eculizumab supports standard practice and existing literature consensus. Her case demonstrates the importance of including aHUS on the differential of intrarenal disease and monitoring for coagulopathy development especially if symptoms are refractory to dialysis.

Conclusion:

This case highlights a challenging diagnosis of aHUS in setting of advanced CKD. In our patient acute worsening of CKD V led to initiation of hemodialysis. Lack of symptom resolution prompted further work up revealing aHUS. This case also highlights current limitations of testing for aHUS. In cases with high clinical suspicion treatment directed towards presumptive diagnosis of aHUS may be lifesaving.