Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by the classical triad of acute hemolytic anemia, thrombocytopenia, and kidney impairment. We report a 10-year-old boy with acute pancreatitis presenting simultaneously with atypical HUS (aHUS) with two such episodes occurring 1 year apart. The child presented with abdominal pain, vomiting, oliguria, epigastric tenderness, and had a right undescended testis. During the initial episode, anti-factor H antibodies were mildly elevated while they were normal in the subsequent episode with normal complement components. Whole exome sequencing identified a heterozygous pathogenic CFTR variant, predisposing to recurrent pancreatitis and cryptorchidism, as well as a probable heterozygous CFHR1/CFHR3 deletion, the gene responsible for recurrent aHUS. Treatment of pancreatitis, hemodialysis, and plasma infusions led to complete recovery of acute kidney injury (AKI) and HUS on both occasions.

Hemolytic uremic syndrome (HUS) is classically defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is most often associated with renal thrombotic microangiopathy (TMA). However, the clinical triad may rarely occur in the absence of histologically demonstrable renal TMA. A 64-year-old woman with hypertension treated with an ACE inhibitor presented with asthenia, nausea, dark urine, and oliguria. Laboratory evaluation revealed AKI (serum creatinine 4.5 mg/dL), thrombocytopenia (46 × 10⁹/L), and intravascular hemolysis (LDH > 1,800 U/L, schistocytes, haptoglobin < 10 mg/dL). Procalcitonin was markedly elevated, while complement levels and ADAMTS13 activity were within the normal range. Anti-factor H antibodies and complement genetic testing were negative; however, these findings do not exclude complement-mediated atypical HUS, which remains a diagnosis of exclusion. A positive direct Coombs test was documented at presentation. Paroxysmal nocturnal hemoglobinuria could not be definitively excluded, as flow cytometry was not performed. Mild, self-limited gastrointestinal symptoms preceded admission and may have acted as a triggering event. The patient was initially treated for suspected STEC-HUS with plasma exchange (subsequently discontinued), supportive therapy, and hemodialysis from day 3. Hematologic abnormalities resolved, whereas renal function worsened, with serum creatinine peaking at 10 mg/dL. Kidney biopsy performed on day 7 revealed acute tubular injury with hemoglobin pigment casts and no evidence of renal TMA. Dialysis was withdrawn, and renal recovery followed. This case illustrates that in patients fulfilling the clinical triad classically associated with HUS, AKI does not invariably result from renal thrombotic microangiopathy. Hemoglobinuria-induced tubular injury may represent an alternative mechanism of renal injury. When hematologic recovery contrasts with persistent renal dysfunction, pigment nephropathy should be considered and kidney biopsy performed when feasible.

Complement-mediated hemolytic uremic syndrome (CM-HUS), commonly referred to as atypical HUS, is a rare thrombotic microangiopathy caused by uncontrolled activation of the alternative complement pathway, typically triggered by a "two-hit" mechanism. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage, most commonly affecting the kidneys. While our understanding of the complement system has advanced significantly, CM-HUS remains a complex, heterogeneous disorder influenced by a spectrum of genetic variants, risk haplotypes, and acquired factors such as anti-factor H autoantibodies. This review highlights the current knowledge of CM-HUS pathogenesis, focusing on genetic variants in regulatory and activating proteins of the complement system. We also discuss the diagnostic complexity posed by incomplete penetrance, overlapping phenotypes, and limitations of genetic and functional assays. Emerging ex-vivo assays and complement biomarkers are explored as tools for refining diagnosis and risk stratification. The use of complement inhibitors such as eculizumab and ravulizumab has significantly improved renal outcomes and survival. This review provides a comprehensive, clinically grounded update on the genetics, pathophysiology, diagnostics, and therapeutic considerations in CM-HUS, aiming to provide clinicians and researchers with a deeper understanding of this complex, complement-driven disease.

Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end stage kidney disease (ESKD) associated with a high rate of recurrence in kidney transplants causing a post-transplant thrombotic microangiopathy (TMA). Prophylactic eculizumab can prevent disease recurrence in select patients. Treating at the time of post-transplant TMA occurrence is the only option if the diagnosis of aHUS is not established pre-transplant. We report our experience of using eculizumab at the point of post-transplant TMA in those with a diagnosis or suspicion of aHUS. We conducted a case note review of 26 patients treated with eculizumab for post-transplant TMA. Screening for complement pathway defects included testing for variants in genes of the complement pathway and anti-factor H autoantibodies. 34.6% of recipients had an identified complement pathway defect. Median time to presentation with post-transplant TMA was 8.4 months. Death-censored graft survival 12 months after starting eculizumab was 68% for the cohort and was worse in those presenting >12 months post-transplant where this figure was 42.9%. The outcome is poor despite eculizumab treatment for those presenting >12 months after transplantation with TMA.

Background Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare form of thrombotic microangiopathy that results from complement system activation. It represents a significant etiology of acute kidney injury among children. In India, aHUS is predominantly associated with anti-factor H antibodies, presenting unique diagnostic and therapeutic challenges. This study aims to delineate the clinical characteristics, immunological profile, management strategies, and outcomes of pediatric aHUS cases from a tertiary center in Eastern India. Methodology We conducted a retrospective, observational, case series at a tertiary care hospital in Eastern India, including seven pediatric patients diagnosed with aHUS between January 2023 and December 2024. Diagnosis was based on a clinical triad (acute kidney injury, microangiopathic anemia, thrombocytopenia), exclusion of Shiga toxin-associated cases and secondary causes, confirmation with complement/anti-factor H antibody testing, and, where feasible, genetic analysis. Patients received plasma exchange, immunomodulators, and supportive care. Data were analyzed using descriptive statistics. Results A total of seven children (median age = 7 years, six females) were treated for aHUS. CFHR1-CFHR3 deletions and anti-factor H antibodies were each identified in 43% of patients. Plasma exchange and steroids formed the therapeutic mainstay. Hematological remission was achieved in 71% of cases within one week, and 43% attained full renal recovery. However, 29% progressed to chronic kidney disease or remained dialysis-dependent, and the remaining 29% showed only limited renal improvement. Early initiation of plasmapheresis and immunosuppression was associated with better renal outcomes, while lack of access to eculizumab and genetic testing remained significant barriers. Conclusions Pediatric aHUS in Eastern India demonstrates a high burden of anti-factor H antibody-mediated disease and genetic complement abnormalities. Early plasmapheresis and immunomodulator use result in improved hematological and renal outcomes. There is a critical need for enhanced access to complement inhibitors and diagnostic tools to optimize management and prognosis in resource-constrained settings.