Asymmetric Dimethylarginine Plasma Concentration Changes Following Kidney Transplantation: A One Year Prospective Study.

Abstract

Background: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, is positively associated with cardiovascular disease in the general population. Chronic kidney disease is associated with elevated circulating plasma ADMA for a variety of proposed factors including decreased clearance and enhanced vascular dysfunction. We hypothesized that ADMA levels would decrease over time post kidney transplant while accounting for the improvement in kidney function, indicating improved vascular function in the transplanted state. Methods: In a prospective cohort of 141 kidney transplant recipients, we collected medical information and plasma ADMA levels pre-transplant and 1 week, 1 month, 6 months, and 1 year post-transplant. We used a generalized linear regression model to assess the association between ADMA and time, with and without adjustment for creatinine, and to assess the association between creatinine and time. A generalized linear regression model was also used to assess whether clinical covariates selected a priori (gender, race, diabetes, cardiovascular disease, smoking status) were associated with change in ADMA over time. Results: The cohort was 28.4% female and 23.4% African-American. At baseline 37.6% had diabetes and 18.4% had known coronary artery disease. Median ADMA and creatinine levels prior to transplant were 0.38 micromolar and 7.7 mg/dL, respectively. After transplant, ADMA significantly decreased between baseline and post-transplant times (p=0.042) (median change from baseline -0.040, -0.033, -0.010, and -0.012 micromolar at 1 week, 1 month, 6 months and 1 year respectively). Serum creatinine also significantly decreased between baseline and post-transplant times (p<0.001) (median change from baseline -5.6, -6.4, -6.2, and -5.7 mg/dL at 1 week, 1 month, 6 months, and 1 year respectively). There was no significant decrease in ADMA over time after adjusting for creatinine (p=0.25). No covariates were associated with change in ADMA from baseline. Conclusions: ADMA plasma concentration significantly decreased over time post kidney transplant in a prospective cohort of 141 patients, however this decrease was not significant after adjusting for the improvement in renal function. The improvement in ADMA levels via increased clearance could potentially improve vascular function in the transplanted patient and further study is warranted to investigate this relationship. DISCLOSURES:Ikizler, T.: Other, DSI, INC, Baxter Renal Care, SatelliteHealth, Consultancy agreement and research funding, AMGEN, Affymax, Abbott Nutrition, Abbott Renal, Consultancy agreement and research funding, Fresenius - Kabi, Consultancy agreement and research funding.