Abstract
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 < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; 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.
Highlights
Introduction distributed under the terms andKidney transplantation is the treatment of choice in patients with end stage renal disease
Urinary Carnosine is Reduced in kidney transplant recipients (KTRs) Compared to Healthy Donors
Urinary CN1 concentrations are inversely associated with urinary carnosine in the KTR population, this inverse association appears to be mediated by renal function
Summary
Kidney transplantation is the treatment of choice in patients with end stage renal disease. Compared to treatment by dialysis, it reduces mortality, is cost effective, and increases quality-adjusted life years [1,2,3,4]. Despite significant progress in immunosuppression and supportive treatment, half of kidney recipients still experience graft conditions of the Creative Commons. Antioxidants 2021, 10, 1102 failure or die within a decade after transplantation [5]. Identification of patients at risk of early graft failure is decisive in improving graft survival rate. Even though a kidney biopsy is the gold standard for the diagnosis of graft rejection, identification of potentially modifiable risk factors for predicting risk of graft failure might help to improve long-term graft survival
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