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Low plasma homoarginine concentration is associated with high rates of all-cause mortality in renal transplant recipients

Kayacelebi, A. A., Minovic, I., Hanff, E., Frenay, A-R. S., de Borst, M. H., Feelisch, M., van Goor, H., Bakker, S. J. L. & Tsikas, D., Jul-2017, In : Amino Acids. 49, 7, p. 1193-1202 10 p.

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  • Low plasma homoarginine concentration is associated with high rates of all‑cause mortality in renal transplant recipients

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DOI

In renal transplant recipients (RTR), we recently found that low urinary excretion of homoarginine (hArg) is associated with mortality and graft failure. However, it is not known whether such prospective associations also hold true for plasma concentrations of hArg. In the present study, we therefore determined plasma concentrations of hArg in the same cohort, i.e. in 687 RTR (functioning graft ae1 year), and in 140 healthy donors, before and after kidney donation. Plasma hArg concentrations were significantly lower in RTR compared to healthy controls [1.24 (0.95-1.63) A mu M vs. 1.58 (1.31-2.03) A mu M, P <0.001], and kidney donation resulted in a decrease in plasma hArg concentration to 1.41 (1.10-1.81) A mu M (P <0.001). In RTR, multivariable linear regression analysis revealed BMI (beta = 0.124), heart rate (beta = -0.091), pre-emptive transplantation (beta = 0.078), antidiabetic medication (beta = -0.091), eGFR (beta = 0.272), plasma PTH (beta = -0.098), uric acid (beta = 0.137), alkaline phosphatase (beta = -0.100), HDL (beta = -0.111), NT-pro-BNP (beta = -0.166), and urinary urea excretion (beta = 0.139) as main determinants of plasma hArg (all P <0.05). In RTR, plasma hArg concentration was inversely associated with all-cause [hazard ratio (HR) 0.59 (95% CI 0.50-0.70), P <0.001] and cardiovascular mortality [HR 0.50 (0.39-0.66), P <0.001], both expressed per standard deviation change in log-transformed hArg, independent of potential confounders. To conclude, our results suggest that the kidney is a major hArg production site and an important modulator of hArg homeostasis in the renal and cardiovascular systems. Moreover, low plasma hArg is independently associated with increased risk of cardiovascular mortality in RTR, which corroborates the cardiovascular importance of preserving kidney function after transplantation.

Original languageEnglish
Pages (from-to)1193-1202
Number of pages10
JournalAmino Acids
Volume49
Issue number7
Early online date20-Apr-2017
Publication statusPublished - Jul-2017

    Keywords

  • Cardiovascular risk, Transplantation, Graft survival, Kidney, NITRIC-OXIDE SYNTHASE, GLOMERULAR-FILTRATION-RATE, CARDIOVASCULAR RISK, L-ARGININE, SUBSTRATE-SPECIFICITY, GUANIDINO COMPOUNDS, OXIDATIVE STRESS, BLOOD-PRESSURE, HEART-FAILURE, KIDNEY

ID: 44121981