. Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure. Am J Physiol Heart Circ Physiol 287: H2687-H2696, 2004. First published August 5, 2004; doi:10.1152/ajpheart.00287.2004.-Endothelial cell dysfunction (ECD) has been demonstrated in patients with end-stage renal disease (ESRD) who have cardiovascular disease (CD) or diabetes mellitus (DM). While techniques to examine conduit arteries have been adapted to these patients, evaluation of microvascular function has lagged behind. Therefore, we used laser Doppler flowmetry (LDF) and scanned laser Doppler imaging (LDI) to quantify parameters of the postocclusion reactive hyperemia and thermal hyperemic responses (local heating to 43°C) in ESRD patients (n ϭ 63) and healthy individuals (n ϭ 33). Patients with ESRD were partitioned among those with either CD or DM or both (designated CDorDM, n ϭ 30), patients with both CD and DM (designated CDϩDM, n ϭ 12, statistically similar to CDorDM), and patients with neither CD or DM (designated ϳCDorDM, n ϭ 33). LDF during thermal hyperemia showed a decrease in the thermal peaks and plateau as well as a delay in plateau compared with control, consistent with ECD. LDF during reactive hyperemia showed a decrease in the pay-back area under the curve, also consistent with ECD. ϳCDorDM were heterogeneous: almost 50% contained flow abnormalities similar to CDorDM. There was also a reduction in the number of functional arterioles on LDI images. Fourier analysis of LDF oscillations showed that low-frequency oscillations characterizing endothelial function were impaired in CDorDM and in many ϳCDorDM. The data demonstrate that ESRD patients with expected ECD (CDorDM) are characterized by distinct abnormalities in LDF parameters. However, similar abnormalities are found in approximately one-half of ESRD patients without evidence for CD or DM. Postocclusive and thermal interrogation of the microvasculature with laser Doppler-resolved parameters of the microcirculation, followed by Fourier analysis of the very slow oscillations, may provide a valuable adjunct to early noninvasive diagnosis of ECD in ESRD, especially important in a subpopulation of ESRD patients with no known CD or DM, which could be at increased risk of impending clinical manifestations of vasculopathy.laser Doppler flowmetry; imaging; microcirculation; coronary artery disease; diabetes mellitus CARDIOVASCULAR COMPLICATIONS have emerged as the most serious life-threatening accompaniment of end-stage renal disease (ESRD) (23). Widespread macrovascular endothelial cell dysfunction (ECD), diagnosed in large conduit vessels as paradoxical vasoconstriction to acetylcholine occurring before angiographic stigmata of atherosclerosis are detectable, is believed to be ultimately responsible for the development of many cardiovascular complications (24,33,43). Patients with ESRD are at additional risk for ECD because the uniform and concomitant presence of hyperhomocystenemia, accumulation of asymmetric dimethylargi...