SUCCESSFUL PARENT-TO-CHILD LIVING KIDNEY DONATIONS WITHIN FAMILY MEMBERS AFFECTED WITH COENZYME Q8B NEPHROPATHY: TWO CASE SERIES

Coenzyme Q8B (COQ8B) nephropathy is an autosomal recessive hereditary disorder caused by primary coenzyme Q10 (CoQ10) deficiency. It manifests as a genetic steroid-resistant nephrotic syndrome (SRNS), typically of childhood-onset. CoQ10 supplementation is a treatment option; however, it is not always effective in an entire patient population, leading to end-stage kidney disease. Kidney transplantation (KTx) is an effective treatment option for genetic SRNS; however, living KTx within biologically related members is associated with increased risk of allograft failure in recipients and future kidney dysfunction in donors.

Here, we present two successful cases of living kidney donations from parents to their siblings with COQ8B nephropathy.

Case 1: An 11-year-old girl was diagnosed with proteinuria, but she did not undergo further examination. At 18 years of age, she was referred to our nephrology department with an elevated serum creatinine. A kidney biopsy was not performed because of kidney atrophy. The patient was lost to follow-up, and when she was admitted to our hospital for loss of appetite at 19 years of age, she had progressed to ESKD, demonstrating the need for hemodialysis. She eventually underwent living KTx from her father when she was 20 years old. A zero-time renal biopsy revealed normal findings including podocyte mitochondria. Next-generation and Sanger sequencing analysis was conducted to determine the origin of the kidney disease, which revealed a novel compound heterozygous mutation in the COQ8B gene (c.737G>A in exon 9 and c.1468C>T in exon 15), leading to a diagnosis of COQ8B nephropathy. Five years after the KTx, post-transplant recurrence was not observed in the kidney graft. Kidney function and urinalysis results of the donor were normal.

Case 2: An 8-year-old girl was diagnosed with proteinuria. A kidney biopsy was performed at 11 years of age. Five of 30 glomeruli were sclerotic, and five showed segmental sclerosis, which was consistent with FSGS. Granular swollen epithelial cells were observed in tubular cells. Electronic microscopy revealed foot process effacement and a marked increase in mitochondria of abnormal shape and size in the podocytes, with the presence of microvillus transformation. A diagnosis of COQ8B nephropathy was confirmed based on genetic mutation patterns identical to those of her older sister. CoQ10 supplementation therapy was initiated, although her kidney function continued to deteriorate with an increase in urinary protein and beta-2-microglobulin. The addition of lisinopril was not beneficial, and the patient progressed to ESKD. She underwent living KTx from her mother at 16 years of age, 4 years after initiating treatment. Two years after the KTx, kidney function and urinalysis results were within normal levels in both the recipient and donor without post-transplant disease recurrence.

Although kidney donation from biologically related donors is generally associated with a higher risk of allograft failure in recipients and future kidney dysfunction in donors, living KTx from the parents as heterozygotes of COQ8B mutation to the COQ8B nephropathy siblings was uneventfully performed without post-transplant recurrence in the recipients or kidney dysfunction in the donors. Parent-to-child KTx may be an effective treatment option within family members affected with COQ8B nephropathy.

This work was first presented at Western Regional Meeting of JSN 2025, and re-submission is permitted by JSN