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.
6 affiliations
- 1Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
- 2Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan.
- 3Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. [email protected].
- 4Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan.
- 5Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
- 6Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
Abstract
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.
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BibTeX
@article{kobayashi2026longterm,
title = {{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.}},
author = {Shizuka Kobayashi and Tomokazu Shimizu and Shun Manabe and Momoko Seki and Yusuke Ushio and Rina Takahashi and Shiho Makabe and Naoko Ito and Kohei Unagami and Hiroshi Kataoka and Sekiko Taneda and Toshihiro Hirai and Kazuho Honda and Kosaku Nitta and Toshio Takagi and Hideki Ishida and Junichi Hoshino},
journal = {BMC nephrology},
year = {2026},
month = jul,
doi = {10.1186/s12882-026-05236-x},
url = {https://europepmc.org/article/MED/42928182},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Shizuka Kobayashi
AU - Tomokazu Shimizu
AU - Shun Manabe
AU - Momoko Seki
AU - Yusuke Ushio
AU - Rina Takahashi
AU - Shiho Makabe
AU - Naoko Ito
AU - Kohei Unagami
AU - Hiroshi Kataoka
AU - Sekiko Taneda
AU - Toshihiro Hirai
AU - Kazuho Honda
AU - Kosaku Nitta
AU - Toshio Takagi
AU - Hideki Ishida
AU - Junichi Hoshino
PY - 2026
DA - 2026/07/01
JO - BMC nephrology
DO - 10.1186/s12882-026-05236-x
UR - https://europepmc.org/article/MED/42928182
AB - 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.
SN - 1471-2369
ER -