Assessment of microvascular function using a novel technique Flow Mediated Skin Fluorescence (FMSF) in patients with diabetic kidney disease: A preliminary study.

Abstract

Diabetic kidney disease (DKD) plays an important role in morbidity and mortality in patients with diabetes mellitus. The pathogenesis of this microangiopathy is mainly due to impaired vascular endothelial function. The Flow Mediated Skin Fluorescence (FMSF) method is an innovative, non-invasive tool for assessing the microcirculation function (especially microcirculatory response to hypoxia), also in patients with complications of diabetes mellitus (DM). The study was conducted at the Medical University of Lodz, Poland. Total of 84 volunteers including 30 patients with DKD, 33 patients with DM without complications, and 21 healthy subjects underwent microvascular function assessments using FMSF. This technique measures changes in the intensity of nicotinamide adenine dinucleotide (NADH) fluorescence from the skin on the forearm as a function of time, in response to blocking and releasing blood flow in the forearm. In this study we asses two key parameters: Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity [log(HS)] to characterize vascular circulation in patients with DKD and their response to transient ischemia. The patients with low reactive hyperemic response (the RHR parameter) had a significantly higher sCr than patients with moderate and high RHR value (p<0.001, p<0.05, respectively) and a significantly lower eGFR than the patients with moderate and high RHR parameter (p<0.001, p<0.01, respectively). The patients with very low and low log(HS) values had a significantly higher sCr than the patients with high log(HS) (p<0.001, p<0.01, respectively), and a significantly lower eGFR than the patients with high log(HS) parameter (p<0.001, p<0.01, respectively). The patients with very low log(HS) had a significantly higher sCr and a significantly lower eGFR than the patients with moderate (p<0.05, p<0.01, respectively). The mean value of the RHR parameter was significantly lower in DKD patients (18.31±5.06%) compared to both healthy subjects (34.37±8.18%, p<0.001) and DM without complications subgroup (28.75±7.12%, p<0.001). Similar trends were noted with the mean value of log(HS) parameter in DKD subgroup (1.03±0.5) vs. healthy subjects (1.59±0.53, p<0.001), and vs. DM without complications subgroup (1.73±0.52, p<0.001). We observed a significant inverse correlation between the RHR parameter and serum creatinine (sCr) and a significant positive correlations with eGFR (R= -0.3; p<0.05, R=0.61; p<0.001, respectively). We found also a significant negative correlations of the log(HS) measure with sCr and a significant positive correlations with eGFR (R=-0.33; p<0.01, R=0.55; p<0.001, respectively). We observed also a significant inverse correlation between the RHR and log(HS) parameters and advanced glycation end products (AGEs) (R=-0.6; p<0.001, R=-0.32; p<0.01, respectively). The AGEs parameter was also a significantly higher in patients with low RHR parameter than in patients with moderate (p<0.01) and high (p<0.001). The FMSF technique makes it possible to identify impairments of the microvascular function in patients with DKD. This study confirms that the simple two-parametric approach diagnostic tool perfectly characterizes the state of the microvascular system in diabetic patients with impaired renal function. These preliminary results require further validation in a larger patients cohort.