THE FIRST IRAQI EXPERIENCE OF MANAGING ATYPICAL UREMIC SYNDROME (aHUS): FROM GENETIC DIAGNOSIS TO THE USE OF ANTI-C5 THERAPY, THE IRAQI aHUS TASKFORCE

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by abnormal activation of the alternative complement pathway. If not diagnosed and treated promptly, it can lead to significant morbidity and mortality due to various renal and extrarenal complications, as well as the long-term effects of CKD and ESKD. Anti-C5 therapies have transformed and changed the natural course of aHUS, turning it from a deadly disease into a more manageable condition. 

Anti-C5 therapy, Ravulizumab, was approved only a few months ago in Iraq. Here, we present the first Iraqi experience in diagnosing and managing patients with aHUS through the collaborative efforts of the Iraqi aHUS Taskforce.

The program started on June 1, 2025. Initially, we launched an aHUS awareness campaign targeting both adult and pediatric nephrologists. We issued a national call to refer previously diagnosed aHUS survivors and new cases. The retrospective cases were reviewed, sent for genetic testing, and some patients had kidney biopsies. The newly identified prospective group underwent comprehensive clinical evaluations, STEC toxin measurement, ADAMTS13 testing, genetic studies, and kidney biopsies when possible. All patients were tested for schistocytes in their peripheral blood, LDH, and immunological markers (ANA, Anti-ds-DNA, C3, C4, CH50). Then, the cases were classified based on etiology. All active cases received treatment, including dialysis, plasma exchange, and appropriate anti-C5 therapy. Before starting anti-C5 therapy, all patients received the recommended vaccination. It is important to note that anti-C5 therapy was initiated before the genetic diagnosis to avoid delays and expedite recovery while waiting for the final genetic results. The flow of the diagnostic process is shown in Figure 1.

By October 20, 2025, fifty-three patients had been tested, with ages ranging from 11 months to 71 years. Ten patients either had survived aHUS attack previously or experienced brief episodes of MAHA. The other forty-three patients had documented MAHA or kidney biopsies indicating TMA. Four patients had secondary TMA caused by pregnancy, scleroderma renal crisis, severe lupus nephritis, and crescentic IgA nephropathy. Serum complement (C3) levels were low in 75% of cases, and kidney biopsies were performed in nine cases. 

Thirty-seven patients from the new cohort (37/43) required acute kidney replacement therapy (KRT) and therapeutic plasma exchange (TPE). Currently, eight patients are on maintenance therapy and are doing well. There was only one event of encephalitis in a two-year-old male, who fortunately recovered.  It is essential to mention that the main barrier to early start of treatment is the delayed referral.

There were 17 confirmed positive cases through genetic diagnosis, 20 negative cases, 3 with inconclusive genetic testing results, and 4 with other diagnoses. The reports for the genetic diagnosis of the remaining nine patients are still pending. The different diagnoses included two cases of C3 glomerulonephritis and two cases of hereditary TTP. Genetic mutations of Factor H accounted for 76% of the positive cases, with the remaining 24% involving CD46 mutations. 

The summary of cases and genetic diagnoses is presented in Figure 2.

This study detailed the Iraqi experience in diagnosing and treating aHUS that developed over a few months. Our collaborative approach resulted in a dataset with the potential to evolve into a robust registry that informs clinical practice. The introduction of Anti-C5 therapy has transformed the care of Iraqi patients with aHUS. However, we still need to improve disease awareness across different disciplines.