Abstract:
Pulmonary hypertension (PH) in chronic kidney
disease (CKD) is a multifactorial cardiopulmonary syndrome in which endothelial
dysfunction (ED) plays a central pathogenetic role. The relationship between
validated markers of ED — flow-mediated dilation (FMD) and endothelin-1 (ET-1)
— and health-related quality of life (HRQoL) assessed by the disease-specific
CAMPHOR questionnaire has not been systematically characterised in this
population. Objective: To evaluate the correlation between FMD, ET-1, and
CAMPHOR domain scores in CKD patients with verified PH, and to assess the
impact of six-month bosentan therapy on these associations. Methods: Prospective
cohort study; 184 CKD patients with echocardiographically verified PH (sPAP >= 30
mmHg) and 20 healthy volunteers. Four groups: CKD stages 3-4 (Group I, n=63),
CKD stage 5 / incident haemodialysis (Group II, n=50), long-term programmed HD
>3 years (Group III, n=71). FMD by reactive-hyperaemia ultrasonography; ET-1 by
ELISA; HRQoL by CAMPHOR (0-65 pts; higher = worse). Spearman correlation
with Benjamini-Hochberg FDR correction (n=190-204). Results: FMD decreased
from 7.69+/-4.09% (Group I) to 4.53+/-1.88% in dialysis groups (p<0.01); ET-1 rose
to 3.13+/-0.69 fmol/mL. CAMPHOR total scores: 36.7+/-14.4, 48.6+/-5.6, 47.6+/-6.0
(p<0.001). FMD correlated with CAMPHOR total (r=-0.432) and QoL subscale (r=- 0.457); ET-1 with Activity subscale (r=0.394; all p<0.001). Creatinine was the
strongest HRQoL predictor (r=0.625, p<0.001). After bosentan, CAMPHOR
improved by 2.5-3.5 points (p<0.01); FMD improvement was significant only in
Group I. Conclusion: ED is an independent determinant of impaired HRQoL in
CKD-associated PH, with FMD preferentially linked to the psychosocial QoL domain
and ET-1 to physical activity. Endothelin receptor antagonism improves HRQoL
across all groups but restores FMD only in pre-dialysis patients.
