Transplantation of a kidney with a heterozygous mutation in the SLC22A12 (URAT1) gene causing renal hypouricemia: a case report

• Main Authors: Kiyokazu Tsuji, Mineaki Kitamura, Kumiko Muta, Yasushi Mochizuki, Takayasu Mori, Eisei Sohara, Shinichi Uchida, Hideki Sakai, Hiroshi Mukae, Tomoya Nishino
• Format: Article
• Language: English
• Published: BMC 2020-07-01
• Series: BMC Nephrology
• Subjects: SLC22A12; Renal hypouricemia; Chimerism; Renal allografts; Fluorescence in situ hybridization
• Online Access: http://link.springer.com/article/10.1186/s12882-020-01940-4

Abstract Background Renal hypouricemia (RHUC) is a genetic disorder caused by mutations in the SLC22A12 gene, which encodes the major uric acid (UA) transporter, URAT1. The clinical course of related, living donor-derived RHUC in patients undergoing kidney transplantation is poorly understood. Here, we report a case of kidney transplantation from a living relative who had an SLC22A12 mutation. After the transplantation, the recipient’s fractional excretion of UA (FEUA) decreased, and chimeric tubular epithelium was observed. Case presentation A 40-year-old man underwent kidney transplantation. His sister was the kidney donor. Three weeks after the transplantation, he had low serum-UA, 148.7 μmol/L, and elevated FEUA, 20.8% (normal: < 10%). The patient’s sister had low serum-UA (101.1 μmol/L) and high FEUA (15.8%) before transplant. Suspecting RHUC, we performed next-generation sequencing on a gene panel containing RHUC-associated genes. A heterozygous missense mutation in the SLC22A12 gene was detected in the donor, but not in the recipient. The recipient’s serum-UA level increased from 148.7 μmol/L to 231.9 μmol/L 3 months after transplantation and was 226.0 μmol/L 1 year after transplantation. His FEUA decreased from 20.8 to 11.7% 3 months after transplantation and was 12.4% 1 year after transplantation. Fluorescence in situ hybridization of allograft biopsies performed 3 months and 1 year after transplantation showed the presence of Y chromosomes in the tubular epithelial cells, suggesting the recipient’s elevated serum-UA levels were owing to a chimeric tubular epithelium. Conclusions We reported on a kidney transplant recipient that developed RHUC owing to his donor possessing a heterozygous mutation in the SLC22A12 (URAT1) gene. Despite this mutation, the clinical course was not problematic. Thus, the presence of donor-recipient chimerism in the tubular epithelium might positively affect the clinical course, at least in the short-term.