Glomerular Filtration and Coronary Flow: Is ADMA the Faucet Regulating Both?

A bout 13% of the US population suffer from any degree of chronic kidney disease (CKD).1 These patients are more likely to die of cardiovascular disease than to develop overt kidney failure. Therefore, CKD has been recognized as a cardiovascular risk factor.2 Despite the overwhelming epidemiological evidence, the pathogenesis of accelerated atherosclerosis even in early stages of renal impairment is only poorly understood. In this issue of American Journal of Hypertension, Fujii et al.3 report an interesting study in which they strengthen the notion that the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) might be the crucial link between renal and cardiovascular disease. They determined coronary flow velocity reserve (CFVR) using adenosine stress Doppler echocardiography in 66 hypertensive patients with and without renal impairment. Aside from classical cardiovascular risk factors, intima-media thickness and pulse wave velocity were also measured. Not only was a decreased glomerular filtration rate (GFR) mirrored by an impaired CFVR, but also was ADMA an “independent” clinical parameter associated with both estimated GFR and CFVR. This has to be interpreted with caution as the authors excluded age from their multivariate analysis. Unfortunately, despite using a high-performance liquid chromatography– based method to measure ADMA, the authors did not provide data on ADMA’s structural isomer symmetric dimethylarginine, which has also been linked to renal and coronary artery disease.4 The concept of coronary flow reserve (CFR) was developed to describe the flow increase available to the heart in response to an increase in oxygen demand. CFR was expressed as the ratio between the maximal hyperemic flow and resting flow. A pressure drop across a stenosis causes compensatory vasodilation at rest, resulting in a diminished capability of the coronary circulation to adapt to an increase in oxygen demand. Therefore, a stenosis within the coronary artery results in a reduction of CFR. CFVR measured by Doppler ultrasound was introduced