{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:42:46Z","timestamp":1788547366813,"version":"build-2803163510"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate kidney transplantation outcomes in genetically confirmed primary mitochondrial diseases with multi-organ involvement and provide clinical insights from systematic literature review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>We systematically searched PubMed, MEDLINE, EMBASE and Google Scholar from inception to 10 June 2025 using keywords and MeSH terms related to \u201cmitochondrial disease\u201d, \u201ctransplantation\u201d and \u201coutcome\u201d.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study eligibility criteria<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants and interventions<\/jats:title>\n                    <jats:p>Participants included paediatric or adult patients diagnosed with genetically confirmed primary mitochondrial diseases who received isolated kidney transplant from living or deceased donor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study appraisal and synthesis methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty-six patients (15 paediatric, 31 adult) were included from 18 eligible studies. Ten patients had\n                      <jats:italic>RMND1<\/jats:italic>\n                      -related disease. All harboured either homozygous or compound heterozygous\n                      <jats:italic>c.713A<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>G<\/jats:italic>\n                      variants in\n                      <jats:italic>RMND1<\/jats:italic>\n                      . Thirty patients carried the\n                      <jats:italic>m.3243A<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>G<\/jats:italic>\n                      mtDNA point mutation variant in\n                      <jats:italic>MT-TL1<\/jats:italic>\n                      . The remaining six patients harboured an\n                      <jats:italic>m.3271\u00a0T<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>C<\/jats:italic>\n                      variant in\n                      <jats:italic>MT-TL1<\/jats:italic>\n                      , single mtDNA deletions,\n                      <jats:italic>m.8618dup<\/jats:italic>\n                      in\n                      <jats:italic>MT-ATP6<\/jats:italic>\n                      ,\n                      <jats:italic>m.12418delA<\/jats:italic>\n                      in\n                      <jats:italic>MT-ATP6<\/jats:italic>\n                      and\n                      <jats:italic>m.13513G<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>A<\/jats:italic>\n                      in\n                      <jats:italic>MT-ND5<\/jats:italic>\n                      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\u00a0years. 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\n                      <jats:italic>m.3243A<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>G<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications of key findings<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration number<\/jats:title>\n                    <jats:p>CRD420251086889.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00467-025-07034-3","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:50:38Z","timestamp":1764226238000},"page":"2443-2455","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Kidney transplantation in mitochondrial diseases: a systematic review"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7265-9798","authenticated-orcid":false,"given":"Sze Wa","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheuk Wing","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Tomlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-9081","authenticated-orcid":false,"given":"Jelena","family":"Stojanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"7034_CR1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000597","volume":"7","author":"P Forny","year":"2021","unstructured":"Forny P, Footitt E, Davison JE, Lam A, Woodward CE, Batzios S, Bhate S, Chakrapani A, Cleary M, Gissen P, Grunewald S, Hurst JA, Scott R, Heales S, Jacques TS, Cullup T, Rahman S (2021) Diagnosing mitochondrial disorders remains challenging in the omics era. 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