| Autor: |
Said MY; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands. m.y.said@umcg.nl., Douwes RM; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands., van Londen M; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands., Minović I; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Frenay AR; Department of Gynecology and Obstetrics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands., de Borst MH; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.; Groningen Kidney Center, Groningen, The Netherlands., van den Berg E; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands., Heiner-Fokkema MR; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Kayacelebi AA; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany., Bollenbach A; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany., van Goor H; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Groningen Kidney Center, Groningen, The Netherlands., Navis G; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.; Groningen Kidney Center, Groningen, The Netherlands., Tsikas D; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany., Bakker SJL; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Sector A, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.; Groningen Kidney Center, Groningen, The Netherlands. |
| Abstrakt: |
Asymmetric dimethylarginine (ADMA) is a methylated form of arginine and an endogenous nitric oxide synthase inhibitor. Renal function decline is associated with increase of plasma ADMA in chronic kidney disease populations. It is yet unknown how isolated renal function impairment affects ADMA homeostasis in healthy humans. Here, we measured plasma concentrations and urinary excretion of ADMA using GC-MS/MS in 130 living kidney donors before and at 1.6 (1.6-1.9) months after donation. We additionally analyzed 201 stable renal transplant recipients (RTR) that were included > 1 year after transplantation, as a model for kidney disease in the context of single kidney state. We measured true glomerular filtration rate (mGFR) using 125 I-iothalamate. To study enzymatic metabolism of ADMA, we also measured L-citrulline as primary metabolite. Mean age was 52 ± 10 years in donors and 54 ± 12 years in RTR. Renal function was significantly reduced from pre- to post-donation (mGFR: 104 ± 17 vs. 66 ± 10 ml/min per 1.73 m 2 BSA, - 36 ± 7%, P < 0.001). Urinary ADMA excretion strongly and significantly decreased from pre- to post-donation (60.6 ± 16.0 vs. 40.5 ± 11.5 µmol/24 h, - 31.5 ± 21.5%, P < 0.001), while plasma ADMA increased only slightly (0.53 ± 0.08 vs. 0.58 ± 0.09 µM, 11.1 ± 20.1%, P < 0.001). Compared to donors post-donation, RTR had significantly worse renal function (mGFR: 49 ± 18 ml/min/1.73 m 2 , - 25 ± 2%, P < 0.001) and lower urinary ADMA excretion (30.9 ± 12.4 µmol/24 h, - 23.9 ± 3.4%, P < 0.001). Plasma ADMA in RTR (0.60 ± 0.11 µM) did not significantly differ from donors post-donation (2.9 ± 1.9%, P = 0.13). Plasma citrulline was inversely associated with mGFR (st. β: - 0.23, P < 0.001), consistent with increased ADMA metabolism to citrulline with lower GFR. In both groups, the response of urinary ADMA excretion to renal function loss was much larger than that of plasma ADMA. As citrulline was associated with GFR, our data indicate that with renal function impairment, a decrease in urinary ADMA excretion does not lead to a corresponding increase in plasma ADMA, likely due to enhanced metabolism, thus allowing for lower renal excretion of ADMA. |
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