BALKAN ENDEMIC NEPHROPATHY, PULSE WAVE VELOCITY AND INCREASED TELOMERE LENGTH-ASSOCIATED CARDIOVASCULAR MORTALITY IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS

Abstract

Objective: Balkan endemic nephropathy (BEN) is characterized with later onset, milder forms of hypertension and lower pulse wave velocity (PWV)). We hypothesized that telomere length (TL) would be longer in BEN patients and associated with lower PWV and less cardiovascular (CV) mortality. Design and method: On total 124 hemodialysed (HD) patients (68 BEN, 56 non-BEN; 48.4% men; 65 ± 14 years) were enrolled and followed-up for 25 months. Blood pressure and PWV were determined before mid-week dialysis. TL was determined by telomere restriction fragment analysis. Results: Age-sex adjusted TL was significantly longer in the BEN group (7.19 vs 6.79; p < 0.001) despite being significantly older. In the BEN group TL was associated with PWV (beta = -0.373, p < 0.05), and in the non-BEN group with age (beta = -0.680, p < 0.01). In the full-adjusted model of multivariate linear regression analyses significant predictors of TL were systolic BP/PWV, and age in the BEN and the non-BEN group, respectively. BEN patients died significantly less frequently from CV events than non-BEN patients (p < 0.001) and lived significantly longer (log-rank p = 0.04). Patients who died had significantly shorter TL than survivors (p < 0.001). In the Cox Regression analysis older age, diagnosis of non-BEN and shorter TL were determinants of shorter survival in the entire cohort. In the BEN group shorter TL was the only determinant of shorter survival (HR 0.11 [95% CI 0.03, 0.35]). To analyze the diagnostic value of TL for CV mortality we used ROC analysis that revealed TL < 6.21 Kb to be useful for prediction of CV mortality in patients undergoing chronic HD. Conclusions: Shorter TL is associated with CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. PWV was significant predictor of TL in BEN patients. This study confirmed our hypothesis that BEN is associated with slower vascular aging.