Evidence map›Paper›PMID 39676096›Full record

SynthesisPediatric research2025

Extrarenal manifestations of atypical hemolytic uremic syndrome: a systematic review and meta-analysis.

Kush Doshi, Abdel Yusuf, Christoph Licht, Olivia Boyer, Carla Nester, Ali Murra, Pranjal Sharma, Sidharth Sethi, Rupesh Raina

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Observational
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kush DoshiAkron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA.
Abdel YusufNortheast Ohio Medical University, Rootstown, OH, USA.
Christoph LichtDepartment of Paediatrics, Division of Nephrology, University of Toronto, Toronto, ON, Canada.
Olivia BoyerDepartment of Pediatric Nephrology, Dialysis and Transplantation, Necker-Enfants Malades Hospital, Paris Cité University, Paris, France.
Carla NesterDivision of Pediatric Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
Ali MurraNortheast Ohio Medical University, Rootstown, OH, USA.
Pranjal SharmaNephrology, Northeast Ohio Medical University, Rootstown, OH, USA.
Sidharth SethiDivision of Pediatric Nephrology, Kidney Institute, Gurgaon, Haryana, India.
Rupesh RainaAkron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA. raina@akronnephrology.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtypical Hemolytic Uremic Syndrome (aHUS) is categorized as a thrombotic microangiopathy (TMA), which arises due to abnormal or unregulated complement pathway activation. While the disease frequently affects renal blood vessels, it can also involve multiple other organ systems. This review examines the prevalence and clinical outcomes of aHUS patients with extrarenal involvement.

methodsA comprehensive literature search was performed using PubMed/Medline, Embase, the Web of Science Core Collection, and CINAHL. Search terms included 'aHUS', 'extrarenal', and specific organ systems such as neurological, gastrointestinal, and cardiovascular. Patient data was collected on clinical characteristics, including extrarenal symptoms, lab findings, genetic mutations, and adverse events. Meta-analysis was conducted using R software, version 3.1.0.

resultsA total of 47 studies were reviewed, comprising 890 aHUS patients, ranging in age from 3 months to 66 years. Common genetic abnormalities included factor H (CFH) mutations, seen in 12% (84/700 patients) across 19 studies, and anti-FH IgG autoantibodies, identified in 27.1% (102/376 patients) from 10 studies. The central nervous system was the most frequently involved extrarenal site [28% (240/858 patients) from 32 studies], with seizures as the predominant CNS symptom. Gastrointestinal symptoms were next most common [31% (230/741 patients) from 25 studies], followed by cardiovascular involvement [16% (97/607) from 23 studies]. Kidney failure was reported in 13.2% (61/463 patients) from 11 studies, with an overall mortality rate of 8.9% (56/632 patients) reported across 27 studies.

conclusionsAround 20-30% of aHUS patients experience extrarenal manifestations, with neurologic symptoms occurring most frequently. Due to the high costs and limited availability, genetic data is rarely reported, and studies are often small, underscoring the need for larger, multi-center cohort studies. PROSPERO REGISTRATION: 466915. IMPACT: Approximately 20-30% of patients with atypical Hemolytic Uremic Syndrome (aHUS) experienced extrarenal manifestations, with neurologic involvement being the most common. Current studies in aHUS patients are heterogeneous and inconsistent in reporting complement mutations with extrarenal manifestations. This systematic review highlights the significance of multi-system assessment in aHUS patients and the need for larger, multi-centered cohort studies.

Indexed as

Atypical Hemolytic Uremic SyndromeAdolescentAdultChildChild, PreschoolComplement Factor HHumansInfantMutationPrevalenceComplement Factor H

Identifiers

PMID39676096

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.