Association of Kidney Graft Long-term Outcome With Recipient Cystathionine Gamma-lyase Polymorphisms and Hydrogen Sulfide Levels: A Cohort Study

Matthieu Halfon, MD; Raffaella Emsley; Thomas Agius, PhD; Arnaud Lyon; Sébastien Déglise, MD; Manuel Pascual, MD; Korkut Uygun, PhD; Heidi Yeh, MD; Leonardo V. Riella, MD, PhD; James F. Markmann, MD, PhD; Pierre-Yves Bochud, MD; Dela Golshayan, MD, PhD; Alban Longchamp, MD, PhD; the Swiss Transplant Cohort Study

doi:10.1097/txd.0000000000001779

Transplantation Direct (May 2025)

Association of Kidney Graft Long-term Outcome With Recipient Cystathionine Gamma-lyase Polymorphisms and Hydrogen Sulfide Levels: A Cohort Study

Matthieu Halfon, MD,
Raffaella Emsley,
Thomas Agius, PhD,
Arnaud Lyon,
Sébastien Déglise, MD,
Manuel Pascual, MD,
Korkut Uygun, PhD,
Heidi Yeh, MD,
Leonardo V. Riella, MD, PhD,
James F. Markmann, MD, PhD,
Pierre-Yves Bochud, MD,
Dela Golshayan, MD, PhD,
Alban Longchamp, MD, PhD,
the Swiss Transplant Cohort Study

Affiliations

Matthieu Halfon, MD: 1 Department of Medicine and Surgery, Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Raffaella Emsley: 2 Service of Vascular Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Thomas Agius, PhD: 2 Service of Vascular Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Arnaud Lyon: 1 Department of Medicine and Surgery, Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Sébastien Déglise, MD: 2 Service of Vascular Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Manuel Pascual, MD: 1 Department of Medicine and Surgery, Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Korkut Uygun, PhD: 3 Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
Heidi Yeh, MD: 3 Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
Leonardo V. Riella, MD, PhD: 3 Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
James F. Markmann, MD, PhD: 3 Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA.
Pierre-Yves Bochud, MD: 4 Department of Medicine, Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Dela Golshayan, MD, PhD: 1 Department of Medicine and Surgery, Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Alban Longchamp, MD, PhD: 2 Service of Vascular Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
the Swiss Transplant Cohort Study

DOI: https://doi.org/10.1097/txd.0000000000001779
Journal volume & issue: Vol. 11, no. 5
p. e1779

Abstract

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Background. Hydrogen sulfide (H2S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia–reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H2S serum levels influence kidney graft outcomes after transplantation. Methods. We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H2S levels. The primary endpoint was graft loss during follow-up. Results. CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9–9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection (P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection (P = 0.01). Finally, in patients with delayed graft function, serum H2S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m2) (P = 0.05). Conclusions. Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H2S serum levels. Further research is needed to define the underlying protective mechanisms.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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