Elimination of dimethylarginines in hypertensive patients with mild to moderate renal insufficiency: pp.9.344

Objective: Even minor impairment of renal function has been recognized as an important cardiovascular risk factor in hypertensive patients. Moreover, plasma dimethylarginines are often increased in this population. Whereas the kidneys play a crucial role in the regulation of plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in more severe renal insufficiency, we questioned whether the accumulation of these dimethylarginines in hypertensive patients with mild to moderate impaired renal function is due to a decreased renal elimination. Design and Methods: We selected 127 essential hypertensive therapy resistant patients, who underwent diagnostic renal angiography for exclusion of renal artery stenosis. All antihypertensive medication was discontinued for 3 weeks and 24-hour urine was collected. Prior to contrast infusion, blood samples were drawn selectively from the aorta and both renal veins for determination of ADMA and SDMA. Subsequently, side-selective mean renal plasma flow was determined using 133Xenon washout. Subjects were divided in three groups; normal renal function, mild renal insufficiency (RI) and moderate RI (table). Renal elimination % was calculated according the formula: [(total renal delivery – total renal efflux)/ total renal delivery] x 100%. Results: Arterial ADMA concentrations were significantly higher in the moderate RI group compared to the others, whereas arterial SDMA levels were already significantly elevated in the mild RI group (table). Arteriovenous concentration differences across the kidney and renal elimination percentages of both dimethylarginines did not differ significantly between all groups, in contrast to the creatinine elimination. After adjustment for confounders, both arterial SDMA and ADMA showed an independent inverse correlation to the Glomerular Filtration Rate (GFR), (r = −0.553, p < 0.01 and r = −0.371, p < 0.01 respectively). Conclusion: In hypertensives with mild to moderate RI, arterial ADMA and SDMA concentrations accumulate significantly with decreasing GFR. However, this increase in concentration is apparently not due to a decreased renal elimination at this stage of RI, but probably reflects systemic endothelial dysfunction.