Atypical Hemolytic Uremic Syndrome Research Articles

Long-Term Outcomes of Anticomplement Factor H Antibody Positive Versus Negative Atypical Hemolytic Uremic Syndrome

Background Atypical hemolytic uremic syndrome (aHUS) is a severe thrombotic microangiopathy predominantly affecting the kidneys, often associated with complement dysregulation. This study is aimed to analyze the clinical characteristics, treatment outcomes, and long-term implications of aHUS in a resource-limited setting. Materials and Methods A retrospective observational study conducted at an institute between January 2016 and December 2022 included all patients with aHUS, excluding secondary causes and renal transplant recipients. Demographic profiles, clinical features, laboratory parameters, treatment modalities (immunosuppression and plasma exchange), and outcomes were collected. Anticomplement Factor H (anti-CFH) antibody, complement levels, and genetic mutation analysis were performed to ascertain etiological factors. The patient and renal outcomes of anti-CFH positive and negative patients on long-term follow-up were compared. Results Fifty-seven patients (mean age: 12.5 ± 4.9 years; 63% males) were analyzed. Among them, 33 (57.9%) tested positive for anti-CFH antibodies and eight presented postpartum. Initial remission was achieved in 42 (73.6%) patients, with 13 (22.8%) partial and 29 (50.9%) complete remission. The median follow-up duration was 24 months [interquartile range (IQR) 8.5–84]; 12 (21%) patients died, with two deaths during the index admission, six among nonresponders, and 4 among responders. Dialysis-free renal survival was superior in anti-CFH seropositive patients (81.2%) compared to seronegative counterparts (55.9%), while patient survival was statistically similar between the two groups. Elevated anti-CFH titers (>4000 AU/ml), age ≥16 years, female gender, and seizures predicted nonresponsiveness. Conclusion Anti-CFH antibody associated aHUS had better kidney outcomes than the seronegative counterparts. In resource limited settings, a combination of plasma exchange and immunosuppression showed promising results in the short and long term.

Postpartum Renal Cortical Necrosis: A Case Series

Rationale & ObjectivePostpartum renal cortical necrosis (postpartum RCN) is a severe form of obstetric acute kidney injury. This study aimed to identify clinicopathological features in Chinese postpartum RCN cases to determine how pathologic findings may contribute to the treatment and prognosis. Study DesignSingle-center, case series Setting & ParticipantsTwelve patients with postpartum RCN had kidney biopsies at Peking University First Hospital between 2014 and 2021. The diagnosis of postpartum RCN was made according to typical MRI or pathological features. Clinical, laboratory and pathological data were compared between patients with eGFR <30 (poor outcome) and ≥30 ml/min/1.73 m2 after six months. ObservationsAll postpartum RCN patients presented with stage 3 AKI attributed to a probable atypical hemolytic uremic syndrome. Pregnancy terminations occurred at a median gestational age of 35.5 weeks. Kidney biopsy was performed ranging 18 days to 4 months from delivery. Upon biopsy, hemoglobin, platelet count and LDH levels had been restored to 137 g/L, 214 ×109/L and 231.50±65.01 U/L, respectively. Four patients exhibited poor outcome, demonstrating higher schistocyte count, serum creatinine and mean arterial pressure at onset. Pathologically, glomerular segmental sclerosis was prevalent. The NOS variant was the most common type, followed by collapsing variant, cellular variant, and tip variant. Patients with poor kidney outcome had more glomerular coagulative necrosis, capillary thrombosis, extensive cortical coagulative necrosis, and pronounced arteriole/artery lesions including increased interlobular arteriole intimal edema and fibrin thrombosis, but a lower occurrence of segmental sclerosis. LimitationsLimited sample size and retrospective design. ConclusionsOur research has identified key pathological features in postpartum RCN patients with aHUS, highlighting the necessity for more effective therapeutic options. There is a clear demand for non-invasive biomarkers that can accurately track disease progression and inform treatment duration for long-term outcomes improvement.

Recent data on atypical hemolytic uremic syndrome associated with pregnancy, kidney transplantation or hypertensive emergency

Les microangiopathies thrombotiques (MAT) sont un groupe hétérogène de pathologies caractérisées à différents degrés par une anémie hémolytique mécanique, une thrombopénie et une occlusion microvasculaire histologique. Les MAT peuvent se compliquer de multiples atteintes d’organe, principalement neurologiques et néphrologiques (définissant alors le syndrome hémolytique et urémique). La classification fondée sur la physiopathologie de la maladie a mis en évidence l’importance de la dérégulation de la voie alterne du complément dans les SHU atypiques (SHUa) (non-liés aux infections). Cependant, la physiopathologie et le traitement de nombreuses formes de SHUa dans des contextes spécifiques (tels que la grossesse, la transplantation rénale ou l’urgence hypertensive) restent mal caractérisés. Dans cet article, nous reprenons les avancées diagnostiques et thérapeutiques récentes dans ces trois formes de SHUa aux contextes spécifiques. Nous montrons les spécificités de ces formes et décrivons les enjeux actuels et futurs de leur prise en charge.

Генетически-фенотипический профиль детей с атипичным гемолитико-уремическим синдромом

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease caused by dysregulation of the alternative complement pathway as a result of mutations in complement genes or the formation of antibodies (AB) to some of the complement factors. Identification of the gene mutations incidence and the corresponding phenotypic features in pediatric patients with aHUS in Russia is aimed at improving the diagnosis and prognosis of the disease as well as treatment tactics planning for patient management. The purpose of this research was to determine the patterns of progression, prognosis and outcomes of aHUS in children depending on their genetic profile. Materials and methods used: the Article represents data from a retro- and prospective analyses of the characteristics of the course of aHUS in 172 children depending on their genetic profile performed in Jan. 2012-Feb. 2022. The sporadic form of aHUS was diagnosed after exclusion of the other forms of thrombotic microangiopathy (TMA), the familial form (in cases with the familial records), the acquired (CFH-Ab HUS) in cases with AB increase to factor H. AutoAb against factor H was determined by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H). The search for mutations (n=167) was carried out using Next-generation Sequencing (NGS) and Sanger sequencing methods. Results: the sporadic form of aHUS was diagnosed in 96.9% of cases, familial in 3.1% and CFH-Ab HUS in 23.8%. The genetic nature of aHUS was confirmed in 53.4% of cases. Pathogenic mutations were detected in 8.6% of cases, probably pathogenic in 42.8% and those with unclear clinical significance in 46.8%. The complement genes mutations were detected in 88.5% of cases and mutations of genes not related to the complement system (ADAMTS13, DGKE, INF2) in 11.5%. The most frequently identified mutations were in the CFH (17.1%), C3 (12.9%) and CD46 (12.9%) genes and less frequently in CFI (7.1%), THBD (5.7%), CFHR5 (5.7%) and CFB (1.4%). In children with CFH-Ab HUS, the CFHR1/CFHR3 deletion was detected in 87.8% of cases, including in 19.4% in combination with mutations of unknown clinical significance. Multiple organ failure syndrome had developed in 77.8% of cases in children with pathogenic/probably pathogenic mutations, in 85.3% in patients with mutations of unknown clinical significance, in 91.8% in patients without mutations and in 83.3% in patients with CFHR1/CFHR3 deletion. Chronic kidney disease (CKD) stages 3 to 5 in sporadic/familial aHUS, regardless of genetic profile, had counted for 14.5% and 16.7% in CFH-Ab HUS. Lethal outcome occurred in 4.3% of cases in the presence of mutations, in 4.9% in the absence of mutations and in 2.8% in cases of CFHR1/CFHR3 deletion. Relapses of aHUS prior to the Eculizumab treatment had developed more often in the presence of CFHR1/CFHR3 mutations and deletion in comparison with children without mutations (31.4% v. 13.1%, p=0.0313 and 44.4% v. 13.1%, p= 0.004). Relapse of aHUS after discontinuation of the Eculizumab therapy had developed in 16.4% of cases. Risk factors for the relapse of aHUS were as follows: patient’s age above 12 months old at the time of the development of aHUS, severe arterial hypertension in the acute period, the use of Eculizumab at the fourth week after the onset of the disease and/or later, recurrent course of aHUS and the presence of CKD prior to the start of the Eculizumab therapy. Conclusion: The genetic profile of patients does not determine the severity and outcome of aHUS though it does affect the relapse rate. The prognosis and survival of patients with aHUS are determined by the severity of the acute period and the timeliness of the complement blocking therapy management.

Annual trends in atypical haemolytic uremic syndrome management in Japan and factors influencing early diagnosis and treatment: a retrospective study

Atypical haemolytic uremic syndrome (aHUS) is a rare disorder characterised by complement-mediated thrombotic microangiopathy (TMA). Despite clinical guidelines, the diagnosis and treatment of aHUS in its early stages remains challenging. This study examined the annual trends in aHUS clinical practices in Japan and explored factors influencing early diagnosis and treatment. Using data from the 2011–2020 Diagnosis Procedure Combination database, 3096 cases with the HUS disease code were identified, of which 217 were confirmed as aHUS and treated with eculizumab or plasma exchange. Early initiation, defined as starting eculizumab or plasma exchange within 7 days of admission, was the focus of the study. Our study revealed no significant changes over time in the number of aHUS diagnoses, cases treated with eculizumab, or early initiation cases. Early initiation cases underwent haemodialysis earlier and had ADAMTS13 activity measured earlier, shorter hospital stays, and lower hospitalisation costs than late initiation cases. In conclusion, we found no increase in the number of newly diagnosed aHUS cases or early treatment initiation over time. Early recognition of TMA and differentiation of the causative disease are crucial for identifying potential aHUS cases, which may lead to better patient prognoses.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. A 15-year-old Chinese girl was diagnosed with aHUS at 3.7years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Bronchopleural fistula management in a pediatric patient requiring extracorporeal membrane oxygenation.

Bronchopleural fistula (BPF) is a connection between the bronchus and pleural cavity. It is associated with high morbidity and mortality and management of BPF has not been well described in the pediatric population. We describe a 2-year-old girl who presented with fever and increased work of breathing, found to have atypical hemolytic uremic syndrome and Streptococcus necrotizing pneumonia with development of persistent air leak due to bronchopleural fistulas requiring extracorporeal membrane oxygenation (ECMO). Three endobronchial valves were placed with successful resolution of bronchopleural fistulas. She required tracheostomy for chronic respiratory failure and endobronchial valves were eventually removed. Approximately 3.5 months after discharge to acute care rehabilitation, tracheostomy was successfully decannulated. This case highlights the successful use of endobronchial valves for resolution of BPF while on ECMO as well as the importance of further studies on optimal candidates, timing and duration of intervention in addition to sequelae of endobronchial valve placement.

The potential for therapeutic drug monitoring of belatacept and other biologicals in solid organ transplantation.

In solid organ transplantation (SOT), biologicals such as recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO (blood group) incompatibility, antibody-mediated rejections and atypical haemolytic uremic syndrome. In this paper, we review the medical evidence available for biologicals used in SOT and the potential for improvement by the application of therapeutic drug monitoring (TDM) and model-informed precision dosing. Biologicals are used for off-label indications within the field of SOT, building on the experience from their use on labelled indications. Dosing is currently mostly standard, and experience vs. effect and toxicity is limited. Pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules. Individualization by concentration measurements and modelling has mostly been proof-of-concept or feasibility studies that lack the power to provide evidence for improvement in clinical outcome. For some drugs such as alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept, studies have demonstrated significant interindividual variability in pharmacokinetics. Variability in absorption from subcutaneous administration may increase interindividual variability. There is also an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, but trials of adequate size to document the usefulness of TDM and MIPD are scarce. Collaboration within the TDM community seems mandatory to establish studies of sufficient strength to provide evidence for the use of biologicals that are currently used off-label in SOT and furthermore to identify the settings where TDM may be beneficial.

Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.

Guidelines advise eculizumab prophylaxis for most kidney transplant recipients with atypical hemolytic uremic syndrome (aHUS). However, recurrence rates may be overestimated, and starting eculizumab at relapse ("rescue therapy") may prevent graft loss. Randomized controlled trials have not compared the efficacy, safety, and costs of different treatment strategies. We performed a comparative study, including a previously described Dutch cohort treated with rescue therapy and a UK cohort using eculizumab prophylaxis. In the Netherlands, we selected all adult patients with aHUS who received a kidney transplant between 2010 and 2021 in the Radboud University Medical Center (n = 30) and enriched this cohort with 8 patients who received rescue therapy in other centers. The UK cohort included all adult patients with aHUS at moderate or high risk of recurrence, transplanted between 2013 and 2017 with prophylactic eculizumab. We included 38 Dutch patients and 35 UK patients. Characteristics were comparable, although the UK cohort included more patients with a complement factor H SCR20 mutation or hybrid gene (31% versus 5%; P < 0.01), and more Dutch patients received living donor kidneys (66% versus 20%; P < 0.001). Follow-up was comparable (the Dutch patients 70.8 mo, range, 10-134; UK patients 55.4 mo, range, 2-95). Eighteen (47%) Dutch patients received rescue therapy. Death-censored graft survival was not significantly different (the Dutch patients 1 y, 3 y, and 6 y: 97.4%, 91.2%, and 87.1%, respectively; UK patients 1 y, 3 y, and 6 y: 97.1%, 88.2%, and 65.6%, respectively, log-rank P = 0.189). In a population characterized by low prevalence of "very high risk" genes, who were predominantly transplanted using an endothelial protective regime, death-censored graft survival with eculizumab rescue therapy was not inferior to prophylaxis.

Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report

BackgroundNo reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies.Case presentationA 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening.ConclusionsThis is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Cancer Related Atypical Hemolytic Uremic Syndrome with Cepacia Syndrome

Cancer Related Atypical Hemolytic Uremic Syndrome with Cepacia Syndrome

Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia

BackgroundThe etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare.Case PresentationWe describe a 7-month-old male patient presenting with fatigue and edema. His initial laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria. Further examinations reveals hemolysis in peripheral blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported a diagnosis of nephrotic syndrome. The patient’s condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement.Discussion/ConclusionThis case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

Kidney involvement in rare hereditary diseases

Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant and benign tumors. Genetic nephropathy should be always considered in children, adolescents and young patients with the kidneys or urinary tract disorders and/or patients with positive family anamnesis. Extrarenal manifestations can be a valuable clue for diagnosis of certain hereditary diseases, e.g. neurosensory deafness in Alport syndrome or photofobia in nephropathic cystinosis. Diagnosis of monogenic inherited diseases should be verified by genetic testing. Specific drugs are available for treatment of certain hereditary diseases involving kidney, e.g. Fabry disease, cystinosis, primary hyperoxaluria I type and atypical hemolytic uremic syndrome.

Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension

The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy. To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH. 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome - exome) by next-generation sequencing technology (NGS). GD of CS were detected in a quarter of patients. Rare genetic variants classified as "likely pathogenic" including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3). Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy.

Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H(CFH) gene mutation, currently classified as a variant of uncertain significance (VUS). Now he is in disease remission after successful complement blockade therapy, thus highlighting a unique presentation of aHUS in a patient with newly diagnosed NB.

Recurrent Atypical Hemolytic Uremic Syndrome: A Masquerade of Antibody-Mediated Rejection?

Abstract Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy (TMA) resulting from uncontrolled activation of the alternate complement pathway. It is necessary to distinguish a recurrent aHUS posttransplant from de novo aHUS, as the former is usually associated with complement abnormalities and has a poorer prognosis. Furthermore, COVID-19 is believed to unmask underlying complement defects triggering a relapse of aHUS. In this report, we present one such unique histologic presentation of recurrent TMA following a COVID-19 infection, which was not just a diagnostic challenge but could easily have been misdiagnosed as an antibody-mediated rejection.

A case report of atypical haemolytic-uremic syndrome (aHUS) in a patient with type IIB von Willebrand disease (VWD): management and differential diagnosis of thrombotic microangiopathies (TMA) disorders in pregnancy

A case report of atypical haemolytic-uremic syndrome (aHUS) in a patient with type IIB von Willebrand disease (VWD): management and differential diagnosis of thrombotic microangiopathies (TMA) disorders in pregnancy

Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab

Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data in patients with aHUS who switched to ravulizumab from eculizumab are lacking. The Global aHUS Registry is a multicenter study (NCT01522183) collecting data on adult or pediatric patients with an aHUS diagnosis, regardless of treatment. Patient characteristics, genetic data, hematological and renal parameters, clinical events (e.g., dialysis and kidney transplantation), and adverse events (AEs) were extracted from patients who switched to ravulizumab from eculizumab up to July 3,2023. Overall, 60 patients switched to ravulizumab (adult: n= 43; pediatric: n= 17); 11 patients were excluded from effectiveness and genetic analyses (N= 49; adult: n= 40; pediatric: n= 9) because they received<3 months ravulizumab treatment and/or had >1 month between eculizumab discontinuation and ravulizumab initiation. Pathogenic complement variants were identified in 11 of 49 patients (22%); the most common was a complement factor H variant (n= 5/49 [10%]). During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue). No meningococcal infections or deaths were reported. No new events of dialysis, kidney transplantation, or thrombotic microangiopathy were reported. Renal and hematological parameters remained stable after switching to ravulizumab. This is the first real-world cohort analysis of data from patients treated with ravulizumab and reinforces the real-world safety and effectiveness data of ravulizumab in patients with aHUS who switched from eculizumab.

Clinical efficacy and safety of switching from eculizumab to ravulizumab in adult patients with aHUS– real-world data

BackgroundThe complement factor 5 (C5)-inhibitor eculizumab has been established as standard-of-care for the treatment of atypical hemolytic uremic syndrome (aHUS). In 2021, the long-acting C5-inhibitor ravulizumab was approved, extending intervals of intravenous treatment from two to eight weeks resulting in improvement of quality of life for patients and lowering direct and indirect therapy associated costs.MethodsThis multicenter, retrospective data analysis of 32 adult patients with aHUS (including 10 kidney transplant recipients) treated with eculizumab for at least three months and switched to ravulizumab aims to evaluate the safety and efficacy of switching medication in the real-world setting. Hematologic parameters, kidney function, concurrent therapy and aHUS associated events were evaluated three months before and until up to 12 months after switching to ravulizumab.ResultsMean age (range) at ravulizumab initiation was 41 years (19–78 years) and 59% of the patients were female. Genetic analysis was available for all patients with 72% showing a pathogenic variant. Median time (range) on eculizumab before switching was 20 months (3–120 months). No new events of TMA or worsening of renal function were reported during up to 12 months of follow-up during ravulizumab treatment.ConclusionsThis is the largest, non-industry derived, multi-center retrospective analysis of adult patients with aHUS switching C5-inhibitor treatment from eculizumab to ravulizumab in the real-world setting. Switching to ravulizumab was safe and efficient resulting in sustained hematological stability and preservation of renal function.

Idiopathic Atypical Hemolytic Uremic Syndrome: A Case Report

Thrombotic microangiopathies (TMAs) are a spectrum of disorders characterized by hemolytic anemia, thrombocytopenia, and formation of microthrombi in blood vessels, resulting in tissue injury due to compromised blood flow. This classical presentation of TMA is characterized by varying degrees of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemic damage to the brain, kidneys, heart, lungs and GI tract. TMA can be classified into different types based upon the etiology and pathogenesis like thrombotic thrombocytopenic purpura (TTP), Complement mediated TMA (atypical Hemolytic uremic syndrome [aHUS]), infection associated TMA (shiga toxin producing E.coli, streptococcus pneumoniae) secondary to systemic causes like malignancy, autoimmune diseases and medications. In this article, we discuss a case of a female diagnosed with aHUS with acute kidney injury complicated by hypertension and severe anemia. As aHUS is known to be associated with high mortality and morbidity, prompt recognition of aHUS is crucial for efficient treatment. Here we have discussed the clinical presentation, histopathological hallmarks, and the diagnostic approach for TMA.