Relationship of Serum Soluble Klotho Levels and Echocardiographic Parameters in Patients on Maintenance Hemodialysis

Abstract

Background: Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients. Uremic cardiomyopathy, characterized by myocardial hypertrophy and fibrosis, has a significant contribution to these adverse cardiac outcomes. The protective effect of soluble Klotho (s-Klotho) on myocardial damage was demonstrated in in vitro and animal experiments. However, data from MHD patients is limited. The present study was designed to identify potential correlations between echocardiographic parameters and serum s-Klotho levels in MHD patients. Methods: This is a cross-sectional study involving 105 MHD patients from the Dialysis Center of Capital Medical University affiliated Beijing Friendship Hospital between March and October 2014. The general information for each patient was recorded. Fasting blood samples were collected prior to hemodialysis during the mid-week session in all patients. The echocardiogram and left lateral lumbar spine radiograph were performed after the same mid-week session. The dialysis records for each session within 3 months before the blood tests were documented. According to the quartiles of s-Klotho levels, patients were divided into four groups (Group 1–4). The demographic and clinical characteristics, echocardiographic parameters, and abdominal aortic calcification scores among the groups were compared. Results: The enrolled 105 patients were predominantly male (54.3%) with an average age of 59.9 ± 11.2 years. Previous hemodialysis durations were 76 (42–133) months. Sixteen (15.2%) patients had diabetes mellitus. Mean serum s-Klotho level was 411.83 ± 152.95 pg/mL, and the 25th percentile, 50th percentile, and 75th percentile values of serum s-Klotho levels were 298.9, 412, and 498.2 pg/mL, respectively. Individuals in the bottom quartile of s-Klotho levels (Group 1) had significantly increased interventricular septal thickness (IVST) compared to those in the other three quartiles of s-Klotho levels (Group 1: 1.12 ± 0.16 cm; vs. Group 2: 1.12 ± 0.16 cm, p = 0.008; vs. Group 3: 0.94 ± 0.13 cm, p < 0.001; vs. Group 4: 1.03 ± 0.1 5 cm, p = 0.022). There were significant differences in the ratios of IVST and posterior wall thickness (PWT) between patients of Group 1 and Group 3 (1.12 ± 0.1 2 vs. 1.00 ± 0.1 4, p = 0.004). No significant differences were found for other parameters among the groups. The univariate correlation analyses showed that gender (r = –0.211, p = 0.030), Kt/V urea (r = –0.240, p = 0.014), hypersensitive C reactive protein (hs-CRP) (r = 0.196, p = 0.045), and serum s-Klotho levels (r = –0.260, p = 0.007) significantly correlated with IVST. Ultimately, only hs-CRP and serum s-Klotho levels were entered into a multiple regression model. Conclusions: The present study showed that patients with lower circulating s-Klotho levels were more often associated with larger IVST and greater ratios of IVST and PWT. There was an independent association between s-Klotho and IVST, and lower s-Klotho levels seem to be a potential risk factor of uremic...

The Protective Role of Klotho in CKD-Associated Cardiovascular Disease

“…Recent data prefer to pay more attention on the role of Klotho in CKD-induced LVH. It has been reported that maintenance hemodialysis patients with lower circulating sKlotho levels were more often associated with larger interventricular septal thickness and greater ratios of interventricular septal thickness and posterior wall thickness, which are typical indicators of LVH in patients [64]. Consistently, in a survey of 86 patients with CKD, we found that increased left ventricular mass was more apparent in patients with low Klotho level [6].…”

The relationship of soluble klotho level with uremic cardiomyopathy and ecocardiographic parameters in hemodialysis patients

“…In the same study, LVEF, LVMI, and LA were not associated with sKlotho. Other echocardiographic parameters do not seem to support IVST elevation in their study 13 …”

“…In a study conducted with 105 hemodialysis patients, a significant relationship was found between low sKlotho and high IVST and IVST/LVPWT. Zhang et al divided the patients into four groups according to sKlotho values in their study and found an independent relation and negative correlation between low sKlotho and IVST, but they did not find a significant relationship between sKlotho and LVEF, LVMI, and LA 13 …”

“…sKlotho acts as a co‐receptor for bone‐derived FGF‐23 protein 10 . sKlotho has many systemic biological effects in remote organs, suppresses apoptosis, and also protects cells against hypoxia, hyperoxy, oxidative stress, and cytotoxic agents 11‐13 . There are studies reporting that sKlotho deficiency plays a role in cardiovascular disease in addition to traditional risk factors such as diabetes, hypertension (HT), anemia, smoking, and excessive volume burden.…”

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

“…Klotho is also expressed in vascular tissue, and Klotho deficiency in mice caused severe calcification in vascular and soft tissues [ 31 ]. In clinical studies, lower sKlotho levels were shown to be closely linked to increased artery calcification, coronary artery calcification, and valve calcification in dialysis patients [ 32 – 34 ]. Calcification in vascular or soft tissue can most certainly greatly increase detrimental outcomes in MHD patients.…”