Telomere shortening in patients on long-term hemodialysis

Abstract

Background: Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification.

Methods: A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis.

Results: The leukocyte telomere length was negatively associated with age (rho = -0.306, P＜0.01); it was shorter in middle-aged patients than in young patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P < 0.01). The telomere length was significantly different among patients aged 52-74 years in groups with different HD vintages. Additionally, the telomere length was positively associated with serum hemoglobin (Hb) levels in all patients (rho = 0.290, P < 0.01). There was a significant difference among patients divided into three groups according to the degree of anemia (17.09 ± 5.64 vs. 14.40 ± 4.07 vs. 13.99 ± 3.95, P < 0.01). Further, a significant difference was observed in the telomere length among patients with different degrees of vascular calcification (16.79 ± 4.91 vs. 13.61 ± 2.82 vs. 14.62 ± 3.63 vs. 10.71 ± 3.74, P < 0.01). The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant than in the surgical patients (8.12 ± 1.83 vs. 14.33 ± 4.63, P < 0.01).

Conclusion: This study demonstrated that the telomere length was significantly correlated with HD vintage in patients of a certain age group. The telomere length was shorter in patients on hemodialysis who matched for age and dialysis vintage with kidney transplant patients. It was also associated with vascular calcification and serum Hb levels in all patients undergoing HD.

Keywords: Cardiovascular disease; Chronic kidney disease; Hemodialysis; Hemoglobin; Telomere length.

Fig. 1

The leukocyte telomere length was negatively associated with age in 144 patients (rho = −0.306, P＜0.01) (A). In young patients, the leukocyte telomere lengths were longer than those in middle-old-aged patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P < 0.01) (B).

Fig. 2

A total of 18 patients aged 52–74 years who underwent a longer period of HD had shorter telomere lengths than those with hemodialysis vintage <24 months (15.58 ± 3.89 vs. 10.54 ± 3.30, P < 0.05) (A). A total of 144 patients were classified into four groups according to the degree of their vascular calcification; there was a significant difference in telomere length among the groups (16.79 ± 4.91 vs. 13.61 ± 2.82 vs. 14.62 ± 3.63 vs. 10.71 ± 3.74, P＜0.01) (B). The classification criteria were as follows: 0, no calcification; 1, focal calcification spots; 2, partial calcification covering 20%–80% of the arterial circumference; and 3, circumferential calcification. m: months.

Fig. 3

The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant when matched for sex, age, and dialysis vintage with our 144 patients on hemodialysis and who received kidney transplant (8.12 ± 1.83 vs. 14.33 ± 4.63, P < 0.01).

Fig. 4

The telomere length was positively associated with serum hemoglobin levels in all patients (rho = 0.290, P＜0.01) (A). A significant difference was observed among patients divided into three groups according to the degree of anemia (17.09 ± 5.64 vs. 14.40 ± 4.07 vs. 13.99 ± 3.95, P < 0.01) (B).