Correction: Terminal complement inhibition in atypical haemolytic uremic syndrome: a single-centre experience

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aHUS is an extremely rare and often underdiagnosed condition, with an annual incidence estimated at 0.5-2 cases per million people (Liu and Qi, 2023). Timely diagnosis and intervention are crucial, as the disease carries a poor prognosis: up to 50% of patients progress to end-stage kidney disease (ESKD) within 10 years (Nester et al., 2015), and mortality ranges from 1% to 7% in the first year after onset (Fremeaux-Bacchi et al., 2013). aHUS affects all age groups, with equal sex distribution in children and a predominance in adult females (Goodship et al., 2017;Schaefer et al., 2018).aHUS is a severe form of TMA, driven by uncontrolled activation of the alternative complement pathway. Diagnosis is based on the triad of AKI, microangiopathic anemia and thrombocytopenia, but requires exclusion of other TMAs-such as typical HUS and thrombotic thrombocytopenic purpura (TTP)via stool cultures and ADAMTS13 activity testing (Goodship et al., 2017;Brocklebank et al., 2023;Brocklebank et al., 2018).Extra-renal involvement occurs in 10%-30% of patients and may affect the neurological, cardiovascular, or gastrointestinal systems, often worsening prognosis. The disease course typically involves relapsing acute episodes that lead to progressive kidney damage (Schaefer et al., 2018;Loirat and Frémeaux-Bacchi, 2011).Complement dysregulation results from genetic abnormalities in complement regulators-CFH, CFI, CFB, CD46, and C3-identified in 40%-60% of cases, with notable geographic variation. Autoantibodies against CFH, frequently associated with CFHR1/CFHR3 deletions, are also found in 6%-20% of patients (Schaefer et al., 2018;Brocklebank et al., 2018;Blanc et al., 2012;Józsi et al., 2008). The genetic burden is additive and is inversely corelated with the intervention of environmental trigger factors of acute aHUS events, which could unmask deficiency in alternative pathway regulation and explain the variable penetrance with age of genetic factors (Rodríguez de Córdoba, 2023).Eculizumab, a monoclonal antibody anti-C5 improved aHUS prognosis to end stage kidney disease (ESKD) with over 70% and about 50% ESKD-free free survival at 1 and 5 years (Schaefer et al., 2018;Brocklebank et al., 2023;Legendre et al., 2013).Given the rarity of aHUS and the potential for regional variability in genetic and environmental risk factors, national data are essential. Moreover, information on aHUS in Southeast Europe, including Romania, remains limited. Accordingly, this study aims to retrospectively analyse the clinical presentation, genetics and outcome in aHUS patients treated in a tertiary Romanian nephrology centre.We conducted a retrospective observational cohort study in all 27 patients with aHUS starting therapy with complement inhibitors (Eculizumab or Ravulizumab) between January 2017 and January 2025, in the nephrology (pediatric and adult) and transplant departments of the "Fundeni" Clinical Institute, Bucharest, Romania. Patients followed for less than 90 days were excluded.TMA was suspected in case of association of AKI with thrombocytopenia and microangiopathic hemolytic anaemia. The diagnosis was confirmed by complement profiling, genetic analysis and, when possible, kidney biopsy. Secondary forms of TMA were excluded through relevant investigations, including ADAMTS13 activity (to rule out TTP), stool cultures for Shigalike toxin-producing bacteria, and screening for autoimmune diseases, vasculitis, pregnancy, transplantation, and drug exposure.Demographic data, family history, suspected triggers, clinical presentation, laboratory parameters (including complement, genetic and pathology findings) and treatment information were extracted from electronic medical records. Delays in diagnosis and treatment were assessed as follows: time from the most recent presumed aHUS-related event to hospital admission (diagnostic delay), and time from clinical suspicion to initiation of anti-complement therapy (treatment delay). Data were compared between admission and last follow-up.Anemia was defined using WHO thresholds: Hb < 13 g/dL in men, <12 g/dL in women, <11 g/dL in women during pregnancy and in children. In cases of advanced CKD (eGFR <30 mL/min/1.73 m2) or kidney failure we accepted patients with a target Hb of 10.5-11.5 g/dL, if the blood smear was without schistocytes and there weren't signs of hemolysis (normal LDH <250 U/mL and haptoglobin >0.3 g/dL). Thrombocytopenia was defined as platelet count <150.000*10 3 /L or a ≥25% drop from baseline. eGFR was calculated using the 2021 CKD-EPI equation. Complement components (C3 and soluble C5b-9) were measured by ELISA. Reference values were 90-180 mg/dL for C3 and 110-252 ng/mL for sC5b-9.Kidney biopsies were performed in 10 patients and evaluated by light microscopy (toluidine blue), immunofluorescence (IgM, IgG, IgA, C3, C1q, κ/λ light chains, fibrinogen), and electron microscopy.Genetic testing, performed in 23 patients, was conducted in collaboration with the Department of Internal Medicine and Haematology, Semmelweis University (Hungary). The protocol includes multiplex ligation-dependent probe amplification (MLPA) using the P236-A3 probe mix from MRC-Holland to identify deletions or duplications in the CFH, CFHR1, CFHR2, CFHR3, CFHR4, and CFHR5 genes. Additionally, direct DNA sequencing of PCR-amplified products from total genomic DNA was used to analyse the entire coding regions of several complement-related genes, including CFH, CFI, CD46, C3, CFB, THBD, and CFHR5.Eculizumab was started empirically in suspected cases, with a switch to Ravulizumab when aHUS diagnosis was confirmed. Dosing followed protocols used in clinical trials, with weightbased adjustments (Legendre et al., 2013;Ariceta et al., 2021;10.3389/fphar.2025.1683188 Frontiers in Pharmacology 03 frontiersin.org Barbour et al., 2021). Adjuvant corticosteroids were administered when appropriate. All patients were vaccinated against Neisseria meningitidis and received antibiotic prophylaxis if treatment preceded immunization.Descriptive statistics for categorical variables were presented as frequencies and percentages. Continuous variables were summarized as medians and quartiles (q1; q3 The study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of"Fundeni" Clinical Institute (No. 15386).The median age was 30 years (range, 0-70); aHUS debuted in childhood in 44% of patients. There was a female predominance (59%). No patient had a family history of aHUS.Infections were the predominant identified triggers, observed in two-thirds of patients, equally divided between respiratory and gastrointestinal causes (Table 1).The median time from the most recent acute aHUS event to referral was 30 days (range, 9-92.5), although about one-third of patients experienced multiple TMA events before admission. The median time from admission to anti-complement therapy initiation was 8 days (range, 0.25-83.5) (Table 1). The median time for eculizumab treatment was 9 months (range, 6-22) and ravulizumab was 4 months (range, 3-5).At admission, all patients had proteinuria (median 1.95 g/day) and hematuria occurred in 96%. Serum creatinine was 3.41 mg/dL, corresponding to an eGFR 22 mL/min/1.73 m 2 . Acute nephritic syndrome (77%) was the main presentation, followed by chronic nephritic (15%) and nephrotic syndrome (7%) (Tables 1,2).AKI was seen in 89% of cases, and was severe, stage III in 66%, imposed dialysis in 59% of patients. Microangiopathic anemia was present in 92% and thrombocytopenia in 80%. However, all three cardinal elements for TMA diagnosis were concomitantly present in 76% of cases. Median C3 was low (73.2 mg/dL) and was lower than the laboratory inferior limit in 72% of patients, as well as sC5b-9 was higher than the laboratory upper limit in 75% in patients with a median of 363 mg/dL (Tables 1,2).All patients experienced at least one extrarenal manifestation, 26% had two and 11% had three extrarenal manifestation

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