2308, P ≤ 0.0001). Table 3 Stepwise regression analysis for soluble α-Klotho levels in the total study population Variables α-Klotho β F P eGFR 0.604 70.725 <0.0001 Log FGF23 0.166 5.93 <0.05 Hb −0.102 2.649 0.1 Total R 2 = 0.2308, P < 0.0001 Stepwise multiple
regression analysis was performed in all subjects (n = 292) The dependent variable is soluble α-Klotho levels F values for the inclusion and exclusion of variables were set at 4.0 at each step Discussion The findings of this study demonstrate that serum soluble α-Klotho level is positively associated with eGFR and inversely associated with age and serum FGF23 level. Serum soluble α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1, and not only in the advanced stages selleck chemical of the disease. Our data thus demonstrate that serum soluble α-Klotho may represent a useful biomarker for detecting early stage CKD. To our knowledge, check details this is the first report showing that serum soluble α-Klotho level is decreased in stage 2 CKD compared with stage 1. Early diagnosis of CKD is critical to prevent CKD progression and associated complications, including cardiovascular events. Most CKD biomarkers currently in clinical use are not sensitive enough and cannot accurately detect early stage disease [4–6]. In addition to being decreased in stage 2 versus
stage 1 disease, we found that serum soluble α-Klotho level was associated positively with eGFR and inversely with serum creatinine level.
Particularly in the early stages of CKD (stage 1–3), serum soluble α-Klotho level showed a highly positive association with eGFR. Our data thus indicate that serum α-Klotho may represent a new sensitive biomarker for CKD, especially in the early stages of the disease. The following mechanisms may underlie the early decrease in α-Klotho levels we observed. Secreted α-Klotho results from the shedding of membrane α-Klotho, which is expressed in renal distal tubules. A decrease in soluble α-Klotho therefore reflects a decrease in the amount of membrane α-Klotho. A subtle decrease in nephron number may already occur in the early stages of CKD. Membrane α-Klotho is a co-factor for FGF23, and a decrease in membrane α-Klotho may prevent the actions of FGF23 in CKD. A recent study revealed that activation of the renin–angiotensinogen–aldosterone Smoothened system (RAAS) reduces renal expression of α-Klotho [25]. Further, activation of the RAAS has been reported to occur in CKD [25]. Thus, activation of the RAAS may be responsible for the reduction in secreted α-Klotho levels in the early stages of CKD observed in our study. Previous studies have reported that expression of α-Klotho is reduced in the kidney in animal CKD models and patients with CKD [26–28] and that a decrease in urinary α-Klotho levels is evident in the early stages of CKD in a relatively small number of patients [29]. Our data are in accordance with these previous studies.
No related posts.