Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study
Angelica Rodriguez-Niño,
Diego O. Pastene,
Adrian Post,
M. Yusof Said,
Antonio W. Gomes-Neto,
Lyanne M. Kieneker,
M. Rebecca Heiner-Fokkema,
Tuba Esatbeyoglu,
Gerald Rimbach,
Peter Schnuelle,
Benito A. Yard,
Stephan J. L. Bakker
Affiliations
Angelica Rodriguez-Niño
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Diego O. Pastene
Department of Nephrology, Endocrinology and Rheumatology (Fifth Department of Medicine), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
Adrian Post
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
M. Yusof Said
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Antonio W. Gomes-Neto
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Lyanne M. Kieneker
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
M. Rebecca Heiner-Fokkema
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
Tuba Esatbeyoglu
Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, 30167 Hannover, Germany
Gerald Rimbach
Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany
Peter Schnuelle
Department of Nephrology, Endocrinology and Rheumatology (Fifth Department of Medicine), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
Benito A. Yard
Department of Nephrology, Endocrinology and Rheumatology (Fifth Department of Medicine), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
Stephan J. L. Bakker
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.
