ニッタ　コウサク   NITTA Kousaku   新田　孝作    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Long-term donor and graft safety despite subclinical mitochondrial abnormalities: mechanistic insights from a 22-year follow-up of a carrier-to-MELAS kidney transplant.
掲載誌名	正式名：BMC nephrology 略　 称：BMC Nephrol ISSNコード：14712369/14712369
掲載区分	国外
巻・号・頁	27(1),pp.630
著者・共著者	Kobayashi Shizuka, Shimizu Tomokazu, Manabe Shun, Seki Momoko, Ushio Yusuke, Takahashi Rina, Makabe Shiho, Ito Naoko, Unagami Kohei, Kataoka Hiroshi, Taneda Sekiko, Hirai Toshihiro, Honda Kazuho, Nitta Kosaku, Takagi Toshio, Ishida Hideki, Hoshino Junichi
発行年月	2026/07/28
概要	BACKGROUND:Ideally, deceased donor kidney transplantation is preferred for patients with mitochondrial nephropathy caused by the m.3243 A > G mutation to avoid genetic risks. However, in regions where deceased donation is limited and living donation predominates, such as Japan, family members are often the only available donors. The safety of using maternal relatives, who are obligate carriers of the mutation, remains highly controversial due to the risk of unmasking renal failure in both the donor and the allograft.CASE PRESENTATION:We report a 22-year follow-up of an inadvertent living kidney transplant from a 55-year-old mother to her 26-year-old daughter. The recipient presented with MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) and end-stage kidney disease due to focal segmental glomerulosclerosis (FSGS), with the m.3243 A > G mutation confirmed prior to transplantation. Conversely, the donor mother was phenotypically normal regarding renal function without diabetes, and conventional genetic testing at the time failed to detect the mutation. Consequently, the recipient's mutation was presumed to be de novo, allowing the donation to proceed. Notably, the donor's zero-hour allograft biopsy revealed ultrastructural mitochondrial abnormalities but no overt light microscopic damage (i.e., no FSGS). At 22 years post-transplant, both the recipient's graft function (serum creatinine 1.16 mg/dL, albuminuria 5.0 mg/gCr) and the donor's remaining kidney function (serum creatinine 0.98 mg/dL, albuminuria 10.4 mg/gCr) remain excellent. Current highly sensitive genetic analysis revealed an extremely low blood heteroplasmy in the donor (0.1%) compared to 20% in the recipient, demonstrating a severe "genetic bottleneck" effect. Furthermore, the recipient's older sister was found to have a 4% mutational load, definitively confirming maternal inheritance rather than a de novo mutation.CONCLUSIONS:This case represents the longest reported follow-up of a living kidney transplant from an m.3243 A > G carrier. It demonstrates that maternal carriers with extremely low heteroplasmy and no light microscopic evidence of overt renal damage on biopsy can be safe donors and provide excellent long-term graft outcomes. Precise risk stratification based on genotype and biopsy findings, rather than uniform exclusion, may expand transplant options.
DOI	10.1186/s12882-026-05236-x
PMID	42928182