Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults

Abstract

BackgroundImpairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria.MethodsWe conducted a cross-sectional study among older hypertensive male veterans with stage 1–4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders.ResultsAmong 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m2; 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= − 0.42, p = 0.009 and β= −0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD.ConclusionsMicrovascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.

Plasma levels of endothelin-1 and renal function among young and healthy adults

“…However, those studies mostly included either elderly individuals or patients with established renal disease, which may influence the described association there [37]. We presume that the earlier shown association between ET-1 and albuminuria might be more important among individuals with advanced renal damage.…”

Dietary Phosphorus Intake and the Kidney

“…High phosphorus intake may also induce endothelial dysfunction, which has been hypothesized to manifest in the kidney as low-grade albuminuria (41, 136, 145, 150, 154, 155). Human studies from two groups (150, 155) have shown that oral phosphorus loading can impair endothelial function as measured by flow-mediated dilatation.…”

“…The vessels from patients with stage 5 CKD relaxed normally when exposed to normal concentrations of phosphorus, suggesting that disruptive effects of chronic hyperphosphatemia on the endothelium may be partially reversible. Thus, a high-phosphorus diet may induce vascular dysfunction, which could theoretically manifest in the kidney as glomerular microvascular dysfunction and albuminuria (136, 145). …”

“…All these factors in combination with inflammation and decreased levels of calcification inhibitors may result in a perfect storm for ectopic calcification in blood vessels and the renal parenchyma. Another potential mechanism leading to kidney injury and albuminuria is endothelial dysfunction, which occurs with phosphorus loading through the nitric oxide pathway (41, 145, 150, 155). Abbreviations: 1,25(OH) 2 D 3 , 1,25-dihydroxyvitamin D 3 ; CKD, chronic kidney disease; FGF23, fibroblast growth factor 23; PTH, parathyroid hormone.…”

The Cardiovascular Burden in End-Stage Renal Disease

“…As we all know, hypertension (HTN) is a bidirectional risk factor; CKD is a key factor in developing HTN and in turn HTN accelerates CKD in both diabetic and non-diabetic patients [17,18] . Albuminuria is a strong and independent risk factor associated with a lot of adverse outcomes, including CKD and CVD as an indicator of endothelial dysfunction [19,20] . In this review, we will highlight only a few aspects concerning some of the most important nontraditional CV risk factors shown in Table 1 .…”