Effect of Renal Function on Asymmetric Dimethylarginine (ADMA) Homeostasis in Kidney Donors and Recipients

M. Y. Said¹, R. M. Douwes¹, M. van Londen¹, I. Minović¹, A. Frenay², M. H. de Borst¹, E. van den Berg¹, M. R. Heiner-Fokkema³, A. A. Kayacelebi⁴, A. Bollenbach⁴, H. van Goor⁵, G. J. Navis¹, D. Tsikas⁴, S. J. Bakker¹

¹Internal medicine, University Medical Center Groningen, Groningen, Netherlands, ²Gynecology and Obstetrics, Amsterdam University Medical Center, Amsterdam, Netherlands, ³Laboratory Medicine, University Medical Center Groningen, Groningen, Netherlands, ⁴Inst. of Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany, ⁵Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands

Meeting: 2019 American Transplant Congress

Abstract number: C175

Keywords: Donation, Kidney transplantation, Oxidant stress, Renal function

Session Information

Session Name: Poster Session C: Kidney: Cardiovascular and Metabolic

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: ADMA is a methylated form of arginine and an endogenous nitric oxide synthase inhibitor. Plasma ADMA (pADMA) is known as a strong cardiovascular risk factor. Renal function decline is associated with increase of pADMA in chronic kidney disease. It is yet unknown how isolated renal function impairment affects ADMA homeostasis in healthy humans.

*Methods: We measured pADMA and urinary excretion of ADMA (uADMA) 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), 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 ¹²⁵I-iothalamate. To study enzymatic metabolism of ADMA, we also measured plasma L-citrulline as primary metabolite.

*Results: Mean age was 52±10 years in donors and 54±12 years in RTR. Renal function significantly decreased from pre- to post-donation (mGFR: 104±17 vs. 66±10 ml/min/1.73m² BSA, -36±7%, P<0.001). uADMA strongly and significantly decreased from pre- to post-donation (61±16 vs. 41±12 µmol/24 h, -32±22%, P<0.001), while pADMA increased only slightly (0.53±0.08 vs. 0.58±0.09 µM, 11.1±20.1%, P<0.001). RTR had significantly worse renal function than donors post-donation (mGFR: 49±18 ml/min/1.73 m², -25±2%, P<0.001) and lower uADMA (30.9±12.4 µmol/24 h, -23.9±3.4%, P<0.001). pADMA 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).

*Conclusions: In both groups, the response of uADMA to renal function loss was much larger than that of pADMA. Also, our study shows increased ADMA metabolism to citrulline with lower GFR. These data indicate that with renal function impairment, a decrease in uADMA does not lead to a corresponding proportional increase in pADMA, likely due to enhanced metabolism, thus allowing for lower renal excretion of ADMA. These data suggest that renal function decline may lead to increased cardiovascular risk for subjects with insufficient ADMA metabolism.

To cite this abstract in AMA style:

Said MY, Douwes RM, Londen Mvan, Minović I, Frenay A, Borst MHde, Berg Evanden, Heiner-Fokkema MR, Kayacelebi AA, Bollenbach A, Goor Hvan, Navis GJ, Tsikas D, Bakker SJ. Effect of Renal Function on Asymmetric Dimethylarginine (ADMA) Homeostasis in Kidney Donors and Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/effect-of-renal-function-on-asymmetric-dimethylarginine-adma-homeostasis-in-kidney-donors-and-recipients/. Accessed May 31, 2025.

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