Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jul;40(7):2177-2188.
doi: 10.1007/s00467-024-06547-7. Epub 2024 Nov 11.

Inborn errors of metabolism in neonates and pediatrics on varying dialysis modalities: a systematic review and meta-analysis

Manan Raina  1 , Kush Doshi  2 , Archana Myneni  2 , Abhishek Tibrewal  2 , Matthew Gillen  3 , Jieji Hu  4 , Timothy E Bunchman  5
Affiliations
Meta-Analysis

Inborn errors of metabolism in neonates and pediatrics on varying dialysis modalities: a systematic review and meta-analysis

Manan Raina et al. Pediatr Nephrol. 2025 Jul.

Abstract

Background: Some inborn errors of metabolism (IEMs) resulting in aberrations to blood leucine and ammonia levels are commonly treated with kidney replacement therapy (KRT). Children with IEMs require prompt treatment, as delayed treatment results in increased neurological and developmental morbidity.

Objectives: Our systematic review in neonates and pediatrics evaluates survival rates and reductions in ammonia and leucine levels across different KRT modalities (continuous KRT (CKRT), hemodialysis (HD), peritoneal dialysis (PD)).

Data sources: A literature search was conducted through PubMed, Web of Science, and Embase databases for articles including survival rate and toxic metabolite clearance data in pediatric patients with IEM undergoing KRT.

Study eligibility criteria: Cross-sectional, prospective, and retrospective studies with survival rates reported in patients with IEM with an intervention of CKRT, PD, or HD were included. Studies with patients receiving unclear or multiple KRT modalities were excluded.

Study appraisal and synthesis methods: Analysis variables included efficacy outcomes [% reduction in ammonia (RIA) from pre- to post-dialysis and time to 50% RIA] and mortality. The Newcastle Ottawa Risk of Bias quality assessment was used to assess bias. All statistical analyses were performed with MedCalc Statistical Software version 19.2.6.

Results: A total of 37 studies (n = 642) were included. The pooled proportion (95% CI) of mortality on CKRT was 24.84% (20.93-29.08), PD was 34.42% (26.24-43.33), and HD 34.14% (24.19-45.23). A lower trend of pooled (95% CI) time to 50% RIA was observed with CKRT [6.5 (5.1-7.8)] vs. PD [14.4 (13.3-15.5)]. A higher mortality was observed with greater plasma ammonia level before CKRT (31.94% for ≥ 1000 µmol/L vs. 15.04% for < 1000 µmol/L).

Conclusions and implications of key findings: Despite the limitations in sample size, trends emerged suggesting that CKRT may be associated with lower mortality rates compared to HD or PD, with potential benefits including prevention of rebound hyperammonemia and improved hemodynamic control. While HD showed a trend towards faster achievement of 50% RIA, all modalities demonstrated comparable efficacy in reducing ammonia and leucine levels.

Prospero registration: CRD42023418842.

Keywords: CKRT; IEM; Neonates; Pediatrics.

PubMed Disclaimer

Conflict of interest statement

Declarations. Statement of ethics: Not applicable. Consent for publication: Not applicable. Conflict of interest: The authors presented no conflicts of interest.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
A Forest plot of the meta-analysis of mortality among neonates and pediatrics with inborn errors of metabolism who received continuous kidney replacement therapy across different studies. The lower diamond in the graph represents the pooled estimate. B Funnel plot for showing publication bias
Fig. 2
Fig. 2
A Forest plot of the meta-analysis of mortality among neonates and pediatrics with inborn errors of metabolism who received peritoneal dialysis across different studies. The lower diamond in the graph represents the pooled estimate. B Funnel plot for showing publication bias
Fig. 3
Fig. 3
A Forest plot of the meta-analysis of mortality among neonates and pediatrics with inborn errors of metabolism who received hemodialysis across different studies. The lower diamond in the graph represents the pooled estimate. B Funnel plot for showing publication bias
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jeanmonod R, Asuka E, Jeanmonod D (2024) Inborn errors of metabolism. In: StatPearls. StatPearls Publishing, Treasure Island - PubMed
    1. Cho H (2019) Renal replacement therapy in neonates with an inborn error of metabolism. Korean J Pediatr 62:43–47. 10.3345/kjp.2018.07143 - PMC - PubMed
    1. Amaral AU, Wajner M (2022) Pathophysiology of maple syrup urine disease: focus on the neurotoxic role of the accumulated branched-chain amino acids and branched-chain α-keto acids. Neurochem Int 157:105360. 10.1016/j.neuint.2022.105360 - PubMed
    1. Raina R, Bedoyan JK, Lichter-Konecki U et al (2020) Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy. Nat Rev Nephrol 16:471–482. 10.1038/s41581-020-0267-8 - PMC - PubMed
    1. Spinale JM, Laskin BL, Sondheimer N et al (2013) High-dose continuous renal replacement therapy for neonatal hyperammonemia. Pediatr Nephrol 28:983–986. 10.1007/s00467-013-2441-8 - PMC - PubMed