Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients

Abstract

Klotho is a single-pass transmembrane protein predominantly expressed in the kidney. The extracellular domain of Klotho is subject to ectodomain shedding and is released into the circulation as a soluble form. Soluble Klotho is also generated from alternative splicing of the Klotho gene. In mice, defects in Klotho expression lead to complex phenotypes resembling those observed in dialysis patients. However, the relationship between the level of serum soluble Klotho and overall survival in hemodialysis patients, who exhibit a state of Klotho deficiency, remains to be delineated. Here we prospectively followed a cohort of 63 patients with a mean duration of chronic hemodialysis of 6.7 ± 5.4 years for a median of 65 months. Serum soluble Klotho was detectable in all patients (median 371 pg/mL, interquartile range 309–449). Patients with serum soluble Klotho levels below the lower quartile (<309 pg/mL) had significantly higher cardiovascular and all-cause mortality rates. Furthermore, the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29–13.48). We conclude that there may be a threshold for the serum soluble Klotho level associated with a higher risk of mortality.

Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease

“…In older community-dwelling adults, serum Klotho is an independent predictor of all-cause mortality; this study showed that participants in the lowest quartile of plasma Klotho (< 575 pg/mL) had an increased risk of death compared to participants in the highest quartile of plasma Klotho (> 763 pg/mL) [36]. For dialysis patients, several studies have indicated that plasma Klotho is associated with allcause mortality [22,23]. However, in CKD patients without dialysis, there is nearly no research reporting on the association between serum Klotho and mortality in CKD patients.…”

“…Moreover, the risk of CVD mortality among CKD patients between the ages of 25 and 34 years is 100-150 times higher than that of other age groups and, even in CKD patients over 60 years of age, the CVD mortality rate is 5 times higher than that in the general population [20,21]. In chronic hemo- [22] demonstrated that patients with serum Klotho levels below the lower quartile (< 309 pg/mL) had a significantly higher CVD mortality rate. In a study by Marçais et al [23], the serum Klotho level was markedly reduced compared to that of nondialysis CKD patients or healthy volunteers, and patients with a serum Klotho level above 280 ng/L had a significantly reduced occurrence of an outcome combining CVD and CVD-related death.…”

Uremic Cardiomyopathy: A New Piece in the Chronic Kidney Disease-Mineral and Bone Disorder Puzzle

“…The role of CKD-MBD in the pathophysiology of uremic cardiomyopathy, owing to its strong correlation with cardiovascular events and mortality, was recognized following the advances in dialysis treatment and correction of major uremia-related abnormalities (Figure 2 ) ( 12 , 34 , 35 ).…”

Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: A prospective single-center cohort study

“…Alpha-klotho and FGF-23 have been widely reported to play important roles in a number of complications caused by hemodialysis, particularly in disorders of calcium and phosphorus metabolism 22 , 23 . Alpha-klotho, an anti-ageing protein, has been widely reported to be down-regulated in Alzheimer’s disease, an ageing-related disease characterized by cognitive decline 24 , 25 .…”