Systemic Arterial Hemodynamics and the “Renal Resistive Index:” What is in a Name?

The RRI was initially proposed for the diagnosis of various forms of renal disease. One of the earliest prospective uses of the RRI was in the prediction of kidney function outcomes following intervention for renal artery stenosis. In this study, an RRI >80 was associated with poorer outcomes, whether surgery or angioplasty was used to correct renal artery stenosis. However, accumulating evidence indicates that the RRI provides important information about the systemic vasculature as well. In this issue of The Journal of Clinical Hypertension, Calabia and colleagues add to our existing knowledge about the relationship between RRI and systemic arterial properties. The authors studied 202 hypertensive and 16 healthy adults and assessed the relationship between the RRI and various systemic arterial phenotypes, including carotid-femoral pulse wave velocity (a measure of large artery stiffness), pulse pressure, the aortic augmentation index (a surrogate of arterial wave reflections), 24-hour blood pressure (BP) measurements, ankle-brachial index, carotid intima-media thickness, and the presence of carotid plaques. They also assessed the relationship between RRI, classic cardiovascular risk factors, and circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) that is independently associated with the presence of carotid atherosclerosis in the general population. The authors found that RRI increases with age, serum creatinine, albuminuria, and diabetes mellitus and with increasing serum levels of ADMA. In multivariable analysis, greater RRI values were independently associated with increasing age, increasing hemoglobin A1c, lower 24-hour diastolic BP, lower glomerular filtration rate, and greater carotid-femoral pulse wave velocity (or ambulatory arterial stiffness index). These findings add to the growing literature that demonstrates that the RRI is associated with aging, large artery stiffness, BP variability, and left ventricular remodeling and diastolic dysfunction. The RRI is also associated with carotid atherosclerosis, although whether this association is independent of large artery stiffness is unclear. In order to interpret existing literature about RRI, it is essential to assess its hemodynamic determinants. This is a highly relevant issue, since it is often assumed that the RRI reflects properties predominantly of the renal vasculature, in particular, intra-renal vascular resistance, as its name would indicate. Indeed, in many papers, the terms resistive index and renal vascular resistance are used interchangeably. Under the assumption that RRI is indeed a measure of intra-renal vascular resistance, associations reported by Calabia and coworkers and others could be interpreted as supportive of a relationship between the large arteries and the small renal vessels. However, strong evidence exists demonstrating that the RRI has hemodynamic determinants different from intra-renal vascular resistance, and that the latter has little influence on the RRI within physiologic ranges. In vitro experiments showed that the RRI is dependent on vascular compliance and resistance, becoming less and less dependent on resistance as compliance decreases, and being completely independent of vascular resistance when compliance is zero. In a different set of experiments, rabbit kidneys were perfused ex vivo using a pulsatile perfusion system in which renal vascular resistance and systolic, diastolic, and pulse pressure were controlled. In these experiments, the RRI increased only with marked, likely nonphysiologic, increases in renal vascular resistance. Indeed, changes in the RRI in response to marked renal vasoconstriction were only marginally greater than RRI measurement variability. However, the RRI was markedly affected by changes in pulse pressure. These in vitro and ex vivo experiments above are supported by in vivo experiments and human observations. Using an infusion of L-NGmonomethyl arginine (L-NMMA), which, like ADMA, is an inhibitor of endothelial NOS, Raff and colleagues showed that neither baseline nor the changes in RRI were correlated with renal vascular resistance or renal perfusion, assessed with para-aminohippuric acid and inulin clearance. In contrast, RRI correlated with central pulse pressure at baseline and during L-NMMA infusion, whereas renal vascular resistance did not correlate with central pulse pressure. Studies in kidney transplant recipients in which a consistent relationship Address for correspondence: Julio A. Chirinos, MD, PhD, Rm-8B111, University & Woodland Avenue, Philadelphia, PA 19104 E-mail: julio.chirinos@uphs.upenn. edu