Erhan Tatar

Endogenous Testosterone and Mortality in Male Hemodialysis Patients: Is It the Result of Aging?

BACKGROUND AND OBJECTIVES Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile. RESULTS Mean testosterone level was 8.69 ± 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P = 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P = 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses. CONCLUSIONS Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

Nutritional State Alters the Association between Free Triiodothyronine Levels and Mortality in Hemodialysis Patients

Background: Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. Methods: A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. Results: Baseline fT3 was 1.47 ± 0.43 (0.01–2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. Conclusions: Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.

Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

BACKGROUND AND OBJECTIVES End-stage renal disease is linked to alterations in thyroid hormone levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low triiodothyronine (T3) levels. These alterations are involved in endothelial damage, cardiac abnormalities, and inflammation, but the exact mechanisms are unclear. In this study, we investigated the relationship between serum free-T3 (fT3) and carotid artery atherosclerosis, arterial stiffness, and vascular calcification in prevalent patients on conventional hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 137 patients were included. Thyroid-hormone levels were determined by chemiluminescent immunoassay, carotid artery-intima media thickness (CA-IMT) by Doppler ultrasonography, carotid-femoral pulse wave velocity (c-f PWV), and augmentation index by Sphygmocor device, and coronary artery calcification (CAC) scores by multi-slice computerized tomography. RESULTS Mean fT3 level was 3.70 ± 1.23 pmol/L. Across decreasing fT3 tertiles, c-f PWV and CA-IMT values were incrementally higher, whereas CACs were not different. In adjusted ordinal logistic regression analysis, fT3 level (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97), age, and interdialytic weight gain were significantly associated with CA-IMT. fT3 level was associated with c-f PWV in nondiabetics but not in diabetics. In nondiabetics (n = 113), c-f PWV was positively associated with age and systolic BP but negatively with fT3 levels (odds ratio = 0.57, 95% confidence interval 0.39 to 0.83). CONCLUSIONS fT3 levels are inversely associated with carotid atherosclerosis but not with CAC in hemodialysis patients. Also, fT3 levels are inversely associated with surrogates of arterial stiffness in nondiabetics.

Soluble TWEAK level: is it a marker for cardiovascular disease in long-term hemodialysis patients?

BACKGROUND Reduced soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) levels follow declining renal function, are strongly associated with endothelial dysfunction and predict cardiovascular events in nondialyzed chronic kidney disease patients. In contrast, elevated levels of sTWEAK predict poor survival in hemodialysis (HD) patients. Recent evidence suggests a role for sTWEAK in the pathophysiology of vascular calcification. The aim of the study was to investigate plausible links between sTWEAK, atherosclerosis, arterial stiffness and vascular calcification in HD patients. METHODS Coronary artery calcification score (CACs) determined by multislice computed tomography, arterial stiffness by pulse wave velocity (PWV) and carotid artery intima-media thickness (CA-IMT) by carotid Doppler ultrasonography were assessed in 131 long-term prevalent HD patients. sTWEAK levels were measured by ELISA (Bender MedSystems, Vienna, Austria). RESULTS Mean serum sTWEAK level was 237.0 ± 147.5 pg/mL (range 78-937). sTWEAK level was inversely correlated with CA-IMT at a borderline significance (r=-0.168, p=0.05). Neither carotid-radial PWV nor carotid-femoral PWV values correlated with sTWEAK. sTWEAK level was higher in patients with severe vascular calcification (CACs ≥400) compared to patients with CACs <400 (264.5 ± 146.8 pg/mL vs. 205.04 ± 122.4 pg/mL, p=0.02).The association between sTWEAK and vascular calcification persisted after multivariate adjustment. CONCLUSIONS There exists a weak inverse correlation between sTWEAK and carotid atherosclerosis and a positive correlation with coronary artery calcification in long-term HD patients. Our data give support for a role for sTWEAK in the pathogenesis of vascular injury in HD patients.

Impact of mean arterial pressure on progression of arterial stiffness in peritoneal dialysis patients under strict volume control strategy

INTRODUCTION Arterial stiffness is an important contributor to the increased cardiovascular burden of uremia. The aim of the study was to identify determinants of arterial stiffness progression in peritoneal dialysis (PD) patients with strict volume control. PATIENTS AND METHODS 89 prevalent PD patients were enrolled. Assessment of arterial stiffness was performed at baseline and after nine months on average (range 8 - 12 months) by carotid-femoral pulse wave velocity (cf-PWV). RESULTS Mean age was 51 ± 13 y; preceeding time on PD was 40 ± 34 months. 57% of the patients were men and 9% were diabetic. At baseline, mean cf- PWV was 8.7 ± 2.7 m/s and was significantly higher in patients with diabetes and on automated PD therapy. Cf-PWV was positively correlated with age, history of cardiovascular disease, mean arterial pressure (MAP), blood glucose, left atrium diameter and left ventricular mass index. Sixty patients underwent a second cf-PWV measurement. 36% had progression of arterial stiffness. Delta cf- PWV value was 2.08 ± 1.89 m/s for progressors and -1.25 ± 1.43 m/s; p < 0.01 for nonprogressors (p < 0.01). In logistic regression analysis, the change in MAP was the only predictor for progression of arterial stiffness. CONCLUSIONS MAP is the main determinant of arterial stiffness progression. Our results suggest that efficient blood pressure control may contribute to preserved or reduced arterial stiffness in PD patients.

The Relationships between Serum sTWEAK, FGF-23 Levels, and Carotid Atherosclerosis in Renal Transplant Patients

Background: Cardiovascular disease is the main cause of mortality after renal transplantation. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and fibroblast growth factor-23 (FGF-23) are two novel molecules that have been associated with atherosclerosis in different populations. In this cross-sectional study, we investigated the associations between sTWEAK, FGF-23, and carotid artery intima-media thickness (CA-IMT) in renal transplant patients. Methods: A total of 117 renal transplant patients were studied. CA-IMT was determined by B-mode Doppler ultrasonography. Serum sTWEAK and FGF-23 were measured by a commercially available enzyme-linked immunosorbent assay (ELISA). Results: Mean age was 39.6 ± 9.6 years and 51% of the patients were male. Mean sTWEAK level was 595 ± 225 pg/mL (158–1140), FGF-23 level was 92 ± 123 RU/mL (9.6–1006), and CA-IMT level was 0.62 ± 0.11 mm (0.40–0.98). sTWEAK level was positively correlated with CA-IMT. There was no association between sTWEAK and FGF-23 levels. FGF-23 was also associated with CA-IMT. In adjusted models using linear regression analysis, only age and serum TWEAK levels were predictors for CA-IMT. Conclusion: There is a positive correlation between CA-IMT and sTWEAK, but not with FGF-23 levels in renal transplant patients.

The contribution of thyroid dysfunction on cardiovascular disease in patients with chronic kidney disease.

Accelerated atherosclerosis and arterial stiffness are the two leading causes of increased cardiovascular disease in patients with chronic kidney disease. Dysfunctional thyroid hormone metabolism has been suggested to play a role in atherosclerosis and arterial stiffness. Changes in cardiac contractility and output, myocardial oxygen demand, systemic and peripheral vascular resistance, blood pressure and lipid profile, increased inflammatory burden and endothelial dysfunction may be responsible for thyroid hormone-related cardiovascular disease. This article focuses on the mechanistic insights of this association and provides a concise review of the current literature.

The relationship between renal volume and histology in obese and nonobese kidney donors

Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity‐related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population.

A mucormycosis case presented with orbital apex syndrome and hemiplegia in a renal transplant patient.

Solid organ transplantation is a risk factor for mucormycosis. Mucormycosis is a necrotizing opportunistic fungal infection with high morbidity and mortality. We report a fatal mucormycosis case with rhino-orbital-cerebral involvement in a renal transplant patient, which presented with orbital apex syndrome and hemiplegia.

Correlation between serum YKL-40 (Chitinase-3-like protein 1) level and proteinuria in renal transplant recipients

BACKGROUND YKL-40 (chitinase-3-like protein 1) is a novel inflammation and endothelial dysfunction biomarker. Although YKL-40 is associated with albuminuria and predicts cardiovascular morbidity and mortality in a non-uremic population, its status is not known in renal transplant recipients. The aim of this study was to investigate plausible links between serum YKL-40 and proteinuria. MATERIAL AND METHODS A total of 110 renal transplant recipients were included in this study. The level of proteinuria was calculated from spot urine using the protein/creatinine ratio. The estimated glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Serum YKL-40 was determined by ELISA (R&D Systems, USA). RESULTS The mean patient age was 40.5 ± 10 years. The mean YKL-40, GFR, and proteinuria levels were 66 ± 46 ng/ml, 49 ± 24 ml/min/1.73 m2, and 0.77 ± 1.15 g/day, respectively. Increases in the YKL-40 tertiles were correlated with increases in proteinuria and C-reactive protein and decreases in the GFR and serum albumin. An adjusted linear regression analysis demonstrated that the YKL-40 level (t=3.28, P=0.001), GFR (t=-3.00, P=0.003), and systolic blood pressure (t=2.51, P=0.01) were independently associated with proteinuria. CONCLUSIONS This is the first study to show that increased serum YKL-40 levels are independently associated with proteinuria in renal transplant recipients. YKL-40 may be responsible for the pathogenesis of cardiovascular injury in this patient population.