Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Abstract

Plasma concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) increase already in the early stages of renal insufficiency. There is no agreement as to whether reduced renal plasma clearance (RPCL) contributes to this increase. Therefore, we investigated the relationship between estimated glomerular filtration rate (eGFR), RPCL, and plasma ADMA and SDMA in essential hypertensive patients with mild to moderate renal insufficiency. In 171 patients who underwent renal angiography, we drew blood samples from the aorta and both renal veins and measured mean renal blood flow (MRBF) using the (133)Xe washout technique. RPCL was calculated using arteriovenous concentration differences and MRBF. After correction for potential confounders, reduced eGFR was associated with higher plasma ADMA and SDMA [standardized regression coefficient (β) = -0.22 (95% confidence intervals: -0.41, -0.04) and β = -0.66 (95% confidence intervals: -0.83, -0.49), respectively]. However, eGFR was not independently associated with RPCL of ADMA. Moreover, reduced RPCL of ADMA was not associated with higher plasma ADMA. Contrary to ADMA, reduced eGFR was indeed associated with lower RPCL of SDMA [β = 0.21 (95% confidence intervals: 0.02, 0.40)]. In conclusion, our findings indicate that RPCL of ADMA is independent of renal function in hypertensive patients with mild to moderate renal insufficiency. Unlike the case for SDMA, reduced RPCL of ADMA is of minor importance for the increase in plasma ADMA in these patients, which indicates that increased plasma ADMA in this population is not a direct consequence of the kidneys failing as a plasma ADMA-regulating organ.