Background Primary mitochondrial diseases are a group of rare, heterogeneous, multisystem disorders. While renal involvement is increasingly recognised, especially in paediatric patients, data on kidney transplantation outcomes in this population remain limited. Objectives To evaluate kidney transplantation outcomes in genetically confirmed primary mitochondrial diseases with multi-organ involvement and provide clinical insights from systematic literature review. Data sources We systematically searched PubMed, MEDLINE, EMBASE and Google Scholar from inception to 10 June 2025 using keywords and MeSH terms related to “mitochondrial disease”, “transplantation” and “outcome”. Study eligibility criteria We included studies that reported post-transplant clinical outcomes in patients with genetically confirmed primary mitochondrial diseases. Studies without genetic confirmation or transplant follow-up were excluded. Patients with Co-enzyme Q 10 deficiency were excluded as they mainly manifest as isolated steroid resistant nephrotic syndrome with subtypes that respond well to co-enzyme replacement. Participants and interventions Participants included paediatric or adult patients diagnosed with genetically confirmed primary mitochondrial diseases who received isolated kidney transplant from living or deceased donor. Study appraisal and synthesis methods Data were extracted on demographics, genotypes, renal and extra-renal features, transplant characteristics, complications and outcomes. Risk of bias was assessed qualitatively by two independent reviewers. Discrepancies were resolved through consensus or discussion with third reviewer. Due to clinical and methodological heterogeneity, a narrative synthesis was performed. Results Forty-six patients (15 paediatric, 31 adult) were included from 18 eligible studies. Ten patients had RMND1-related disease. All harboured either homozygous or compound heterozygous c.713A > G variants in RMND1. Thirty patients carried the m.3243A > G mtDNA point mutation variant in MT-TL1. The remaining six patients harboured an m.3271 T > C variant in MT-TL1, single mtDNA deletions, m.8618dup in MT-ATP6, m.12418delA in MT-ATP6 and m.13513G > A in MT-ND5 respectively. At nephrology referral, chronic kidney disease and kidney failure each was present in 26.1% of patients. Median time from renal presentation to kidney failure was 6 years. Graft and patient survival exceeded 90% across different genetic mutations and age groups. Post-transplant deterioration of neurological or metabolic features was reported predominantly in patients with an m.3243A > G variant. Limitations The review is limited by small sample size, selection and reporting bias, heterogeneous follow-up durations and outcome measures. Data were derived mainly from case reports and small case series. Conclusions and implications of key findings Kidney transplantation is a viable option of kidney replacement therapy for patients with mitochondrial diseases. Patients with primary mitochondrial diseases should be considered for kidney transplantation. Further prospective studies are needed to define optimal transplant timing, immunosuppression strategies and long-term systemic outcomes. Systematic review registration number CRD420251086889. Graphical abstract

Kidney transplantation in mitochondrial diseases: a systematic review

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2025年11月27日

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Sze Wa Wong,
Cheuk Wing Fung,
Fred Tomlin,
Jelena Stojanovic

摘要

Background

Primary mitochondrial diseases are a group of rare, heterogeneous, multisystem disorders. While renal involvement is increasingly recognised, especially in paediatric patients, data on kidney transplantation outcomes in this population remain limited.

Objectives

To evaluate kidney transplantation outcomes in genetically confirmed primary mitochondrial diseases with multi-organ involvement and provide clinical insights from systematic literature review.

Data sources

We systematically searched PubMed, MEDLINE, EMBASE and Google Scholar from inception to 10 June 2025 using keywords and MeSH terms related to “mitochondrial disease”, “transplantation” and “outcome”.

Study eligibility criteria

We included studies that reported post-transplant clinical outcomes in patients with genetically confirmed primary mitochondrial diseases. Studies without genetic confirmation or transplant follow-up were excluded. Patients with Co-enzyme Q 10 deficiency were excluded as they mainly manifest as isolated steroid resistant nephrotic syndrome with subtypes that respond well to co-enzyme replacement.

Participants and interventions

Participants included paediatric or adult patients diagnosed with genetically confirmed primary mitochondrial diseases who received isolated kidney transplant from living or deceased donor.

Study appraisal and synthesis methods

Data were extracted on demographics, genotypes, renal and extra-renal features, transplant characteristics, complications and outcomes. Risk of bias was assessed qualitatively by two independent reviewers. Discrepancies were resolved through consensus or discussion with third reviewer. Due to clinical and methodological heterogeneity, a narrative synthesis was performed.

Results

Forty-six patients (15 paediatric, 31 adult) were included from 18 eligible studies. Ten patients had RMND1-related disease. All harboured either homozygous or compound heterozygous c.713A > G variants in RMND1. Thirty patients carried the m.3243A > G mtDNA point mutation variant in MT-TL1. The remaining six patients harboured an m.3271 T > C variant in MT-TL1, single mtDNA deletions, m.8618dup in MT-ATP6, m.12418delA in MT-ATP6 and m.13513G > A in MT-ND5 respectively. At nephrology referral, chronic kidney disease and kidney failure each was present in 26.1% of patients. Median time from renal presentation to kidney failure was 6 years. Graft and patient survival exceeded 90% across different genetic mutations and age groups. Post-transplant deterioration of neurological or metabolic features was reported predominantly in patients with an m.3243A > G variant.

Limitations

The review is limited by small sample size, selection and reporting bias, heterogeneous follow-up durations and outcome measures. Data were derived mainly from case reports and small case series.

Conclusions and implications of key findings

Kidney transplantation is a viable option of kidney replacement therapy for patients with mitochondrial diseases. Patients with primary mitochondrial diseases should be considered for kidney transplantation. Further prospective studies are needed to define optimal transplant timing, immunosuppression strategies and long-term systemic outcomes.

Systematic review registration number

CRD420251086889.

Graphical abstract