#5417 EARLY MARKERS AND VASCULAR IMPAIRMENT IN THE PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD)

Abstract

Abstract Background and Aims Soluble Klotho (sKlotho) is thought to decrease early in CKD, but its use as biomarker of the CKD progression is controversial. In addition, the use of newnon-invasive techniques to diagnose incipient vascular damage in CKD would be of clinical interest. The aims of this study were: to assess the utility of serum and urinary sKlotho as a useful biomarker of kidney impairment and; to analyse the value of carotid adventitial neovascularization and aortic stiffness in the course of CKD. Method Forty-three CKD patients were classified according to their estimated glomerular filtration rate (eGFR) into 4 groups (CKD-2/3a, CKD-3b, CKD-4 and CKD-5) and 38 sex and age matched controls were studied. Carotid and femoral adventitial neovascularization was assessed by ultrasensitive ultrasonography without contrast (Superb microvascular image, SMI). Aortic pulse wave velocity (PWV) was measured to determine stiffness. Results No differences in age and body mass index between control group and the four CKD stages were observed. The eGFR showed a significant and progressive decrease (Table 1). Serum PTH, FGF23 and proteinuria were significantly higher and serum calcitriol lower in CKD stages 3b to 5 (Table 1). No changes were observed in serum Ca and serum P increased only in CKD-5 (Table 1). Serum sKlotho displayed a progressive decrease from CKD-2/3a to CKD-5, before other CKD parameters, such as FGF23 and PTH changed. A significant correlation between serum sKlotho and serum creatinine was observed (r = -0.394, p = 0.0003). Urinary sKlotho increased in CKD-2/3a stage and remained similar up to CKD-5 (Table 1). The carotid artery of CKD patients stages 4 and 5 showed a higher number of adventitial vasa vasorum (CKD-4 = 2.09±2.26, p = 0.002; CKD-5 = 1.56±1.67, control = 0.90±2.37, p = 0.019) and a greater area of adventitial neovascularization (CKD-4 = 3.52±3.49, p = 0.0008; CKD-5 = 4.51±7.75, control = 0.84±2.18, p = 0.009) compared to controls. No differences in femoral neovascularization were found. PWV was significantly higher only in CKD-5 (CKD-5 = 12.91, control = 10.81, p = 0.045). A significant correlation was observed between PWV and the area of adventitial neovascularization (r = 0.360, p = 0.001) and the number of adventitial vasa vasorum in the carotid artery (r = 0.246, p = 0.028). Conclusion Serum sKlotho decreased before FGF23 levels begun to rise, indicating the sKlotho decrease as the earliest marker of CKD-MBD, although it remains with no changes throughout the CKD progression. Carotid adventitial neovascularization by SMI and PWV increased in advanced CKD stages, suggesting that they have a limited clinical utility as early markers of vascular damage in CKD.