Decreased peripheral vascular function in patients with stage 3 and 4 chronic kidney disease who have elevated symmetric dimethylarginine but not asymmetric dimethylarginine
Authors: Grotle Ann-Katrin , Kaur Jasdeep , Skow Rachel , Young Benjamin , Nandadeva Damsara , Stephens Brandi , Mohan Ponnaiah , Fadel Paul 
Published: May 2023

Cardiovascular disease is a leading cause of death in chronic kidney disease (CKD), yet the mechanisms remain unclear. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous nitric oxide synthase inhibitors shown to be independent risk markers for cardiovascular disease. Previous research has predominantly focused on ADMA as a primary risk marker of reduced vascular function and increased cardiovascular mortality in end-stage (stage 5) CKD. However, limited research has explored the potential roles of ADMA and SDMA in relation to vascular function in the middle stages (stages 3 and 4) of CKD. Therefore, we tested the hypothesis that patients with stage 3-4 CKD would have elevated circulating ADMA and SDMA, which would correspond to a reduced vascular function compared to controls. We studied 17 patients with stage 3-4 CKD (age: 66 ± 7 years, 5 males, eGFR: 44 ± 16 ml/min/1.73m2) and 8 controls (age: 59 ± 7 years; 3 males, eGFR: 81 ± 14 ml/min/1.73m2). ADMA and SDMA were assessed in whole blood serum using liquid chromatography/tandem mass spectrometry by a commercial laboratory (Quest diagnostics). Macro- and micro-vascular function were assessed as brachial artery flow-mediated dilation (FMD; %) and peak reactive hyperemia blood velocity, respectively, using duplex Doppler ultrasound. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (cfPWV) using arterial tonometry. Data are expressed as mean ± standard deviation. Interestingly, we found that SDMA (control: 103 ± 14, CKD: 143 ± 42 ng/mL, p=0.01) but not ADMA (control: 109 ± 7; CKD: 111 ± 28 ng/mL, p=0.40) was significantly elevated in patients with CKD compared to controls. FMD was significantly reduced in the CKD group (control: 5.04 ± 2.59.; CKD: 3.18 ± 1.98 %, p=0.03), while peak blood velocity was similar between groups (control: 53.47 ± 10.40, CKD: 59.72 ± 23.99 cm/s, p=0.25). There tended to be a negative relationship between SDMA concentrations and FMD (R= -0.31, p=0.07), whereas there was no relationship between ADMA and FMD (R= 0.22, p=0.14). Arterial stiffness was also significantly greater in the patient with CKD compared to controls (control: 6.74 ± 0.91, CKD: 7.95 ± 1.60 m/s, p=0.034). These data suggest that patients with stage 3-4 CKD who have elevated circulating SDMA but not ADMA exhibit an impaired macro-vascular function. Moreover, an augmented cfPWV also suggests increased arterial stiffness in patients with CKD with elevated SDMA. Collectively, these preliminary findings suggest that SDMA, but not ADMA, may play a more predominant role in mediating impaired vascular function in the middle stages of CKD. This project was supported by the National Heart, Lung, and Blood Institute R01 HL-127071. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.