Angiopoietin 2 and Cardiovascular Disease in Dialysis and Kidney Transplantation

Background

Accelerated atherosclerosis in patients with chronic kidney disease (CKD) is still incompletely understood. Angiopoietin 1 (Ang-1) and Ang-2 are 55-kDa antagonistic nonredundant gatekeepers of endothelial activation and thus are potential important factors in accelerated atherosclerosis. We aimed to study: (1) angiopoietin levels in patients treated by means of dialysis and kidney transplantation, (2) the association of altered angiopoietin levels with atherosclerosis, and (3) changes in altered levels after renal transplantation.

Study Design

Cross-sectional and longitudinal observational study.

Setting & Participants

117 patients with CKD (61 hemodialysis [HD] patients, 24 peritoneal dialysis [PD] patients, and 32 renal transplant recipients) and 22 healthy controls.

Predictor

Treatment by means of HD or PD or renal transplantation versus healthy controls.

Outcome

Serum Ang-1 and Ang-2 levels and ratio and changes in levels before and 3 months after transplantation. Correlations of angiopoietin levels with the presence and severity of coronary heart disease and peripheral arterial disease.

Measurements

Ang-1 and Ang-2 were measured in sera by using an immunoradiometric sandwich assay and enzyme-linked immunosorbent assay, respectively. Coronary heart disease was scored by using coronary angiography, and peripheral arterial disease, by using ultrasonography.

Results

Ang-1 level was decreased in HD patients compared with controls (29.1 ± 12 versus 45.3 ± 11.5 ng/mL; P < 0.001). In contrast, Ang-2 level was increased (HD, 8.7 ± 0.64; PD, 6.48 ± 8.1 ng/mL versus controls, 0.88 ± 0.43 ng/mL; P < 0.001). Ang levels in renal transplant recipients were not different from healthy controls. Longitudinally, individual Ang-2 levels decreased after kidney transplantation (P = 0.01). In addition, in patients with CKD, Ang-2 level correlated significantly with scores of coronary heart disease (r = 0.486; P < 0.001) and peripheral arterial disease (r = 0.648; P < 0.001).

Limitations

Cross-sectional study design.

Conclusions

Circulating Ang-2 level was increased in patients treated with dialysis, although the mechanism is unknown. Kidney transplantation normalized circulating Ang-2 levels after 3 months. In addition, Ang-2 might be a mediator (and thus a marker) that accounts for accelerated atherosclerosis in dialysis patients.

Index Words: Angiopoietin, Ang-1, Ang-2, atherosclerosis, cardiovascular disease (CVD), coronary heart disease (CHD), peripheral arterial disease (PAD), hemodialysis, dialysis, renal transplantation, kidney