Alaattin Yildiz

Quality of Life in Male Hemodialysis Patients

Background: Health-related quality of life (QOL) is affected in hemodialysis patients (HD). A number of factors such as age, anemia, and comorbidity had been implicated in decreased QOL. Erectile dysfunction (ED) is a frequent and potentially treatable complication in HD patients. In this cross-sectional study, we aimed to evaluate the possible relation between the QOL and ED in HD patients. Patients and Methods: Among the 511 chronic HD patients dialyzed in 11 outpatient HD centers, 148 male patients (mean age: 46 ± 9 years) were included. The mean time on dialysis was 41 ± 35 months (range: 3–203 months). Biochemical parameters such as BUN, creatinine, hemoglobin, serum albumin and Kt/V were measured. The QOL of the patients were measured with the short form of Medical Outcomes Study (SF-36), physical component scores (PCS) and mental component scores (MCS) were calculated. The ED was evaluated by the International Index of Erectile Function (IIEF). Results: One hundred and four of the 148 patients (70%) had ED. Hemoglobin levels were correlated with PCS (r = 0.197, p = 0.02) and MCS (r = 0.20, p = 0.019). Patients with ED had lower scores in nearly all the components related to PCS and MCS as compared to patients without ED. IIEF score was correlated with PCS (r = 0.369, p < 0.001) and MCS (r = 0.308, p < 0.001). In linear regression analysis, IIEF score and hemoglobin levels were the independent variables that predicted both PCM and MCS. Conclusion: ED, a frequent complication in HD patients, was related to QOL together with anemia. Successful treatment of ED and anemia may lead to improvement in QOL in HD patients.

Improvement of Uremic Autonomic Dysfunction after Renal Transplantation: A Heart Rate Variability Study

Autonomic dysfunction in hemodialysis patients is one of the components of uremic neuropathy. In this prospective study, we investigated the effect of renal transplantation on uremic autonomic dysfunction with long-term time-domain and frequency-domain heart rate variability. Fourteen hemodialysis patients (10 male, 4 female; mean age 33 ± 11 (range 16–50) years) were examined before and at the early after transplantation period (mean 4.6 ± 1.5 (range 3–7.5) months). The mean time spent on hemodialysis was 16.7 ± 15.6 (range 6–65) months. In time-domain analysis, significant increases in all parameters except pNN50 (SD, SDANN, SDNN, rMSSD) were observed after renal transplantation (p < 0.01). In frequency-domain analysis, low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) spectral power were found to be significantly increased after renal transplantation (4.54 ± 1.04 vs. 12.58 ± 8.69 for LF (p = 0.005), 2.80 ± 1.0 vs. 6.50 ± 3.55 for HF (p = 0.005)), but the LF/HF ratio was not different from a pretransplant period (1.71 ± 0.349 vs. 1.85 ± 0.49, p = 0.26). It was concluded that autonomic dysfunction in hemodialysis patients is reversible and renal transplantation reverses the sympathetic and parasympathetic autonomic dysfunction simultaneously and at a relatively early stage.

Association between hepatitis C virus infection and development of posttransplantation diabetes mellitus in renal transplant recipients.

BACKGROUND Posttransplantation diabetes mellitus (PTDM) is a metabolic complication of renal transplantation. A high prevalence of DM has been recently reported in patients with chronic hepatitis C virus (HCV) infection in the nontransplant population. The aim of this study was to investigate possible factors that may have a role in the development of DM, including HCV infection in renal transplant recipients. PATIENTS AND METHODS This case-control study included 43 patients with PTDM (36 men, 7 women; mean age, 44+/-10 years) and 43 consecutive transplant patients who did not develop PTDM (30 men, 13 women; mean age, 37+/-11 years). Age, body mass index, high-dose steroid use, family history for DM and HCV, and presence of HLA-DR2, -DR3, and -DR4 were considered as possible factors for predicting PTDM. RESULTS Patients with PTDM were older (P=0.002) and had a higher prevalence of family history of DM (61% vs. 9%, P<0.001) and a higher rate of HCV seropositivity (72% vs. 37%, P=0.002; odds ratio = 1.94; 95% confidence interval = 1.26-2.98). The prevalence of pancreatic autoantibodies (anti-glutamic acid decarboxylase, islet cell antibody) was similar between patients with and without PTDM. In logistic regression analysis (r = 0.61, P<0.001), age, family history, and HCV infection were independent variables for predicting development of PTDM. CONCLUSION HCV infection was associated with the development of PTDM, in addition to family history and increased age. The rate of autoantibodies against pancreatic cells was not increased in patients with HCV, which suggested that nonimmunologic mechanisms were likely to have a role in the pathogenesis of PTDM.

Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease.

BACKGROUND Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the nonuremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. METHODS In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. RESULTS Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001). CONCLUSION Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.

Treatment with antidepressive drugs improved quality of life in chronic hemodialysis patients.

BACKGROUND Despite some improvements in dialysis therapies, depression still remains an important problem in chronic hemodialysis (HD) patients. In this study, we aimed to investigate the association of depression and its treatment with quality of life (QOL) in HD patients. PATIENTS AND METHODS 97 HD patients (52 male, 45 female, mean age 55 +/- 16 years) were enrolled. All patients had been dialyzed for more than 6 months. In order to evaluate QOL of the patients, a short form of Medical Outcomes Study (SF-36) was used. Depression was assessed by using Beck Depression Inventory (BDI). Patients who had BDI score > or = 15 were diagnosed as to have depression. Patients with depression received antidepressive treatment (sertralin HCl, 50 mg/day) for an 8-week period. After 8-week antidepressive treatment, all biochemical analysis, SF-36 and BDI were performed again. RESULTS 40 patients (20 male, 20 female, mean age 56 +/- 14 years) had depression. All parameters related to QOL were significantly decreased in patients with depression as compared to patients without depression. Severity of depression was correlated with QOL parameters. After 8 weeks of treatment, as parallel to changes in BDI, QOL parameters improved in patients with depression. CONCLUSION Decrease in QOL, associated with depression and antidepressive treatment, improves QOL in HD patients. Hemodialysis patients should be followed-up closely for presence of depression. Treatment of depression with antidepressive drug regimen would lead to relieve the symptoms related to depression and improvement of QOL in these patients. Antidepressive treatment should be required more often than we prescribe in routine clinical practice now.

Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine

Background: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients. Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients; however, a diminished immune response and loss of protective antibodies have been observed.Patients and methods: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients. A total of 21 patients (6 female, 15 male) with well‐functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study. The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppresive agents. After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur–Merieux, lot No: K 1131).Results: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies. Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one. These titers did not show any statistically significant difference between double and triple therapies. There was no significant difference between the 12th and 6th wk postvaccination antibody titers. No systemic or local adverse effects were observed.Conclusion: Pneumococcal vaccination is safe and effective in patients with well‐functioning renal allografts, at least in the short term. This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.

Osteoprotegerin/RANKL Axis and Progression of Coronary Artery Calcification in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive. RESULTS Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model. CONCLUSIONS Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

Comparison of the effects of enalapril and losartan on posttransplantation erythrocytosis in renal transplant recipients: prospective randomized study.

Background. The aim of this prospective randomized study was to compare the safety and efficacy of enalapril (E) and losartan (L) in the treatment of posttransplantation erythrocytosis and the effect of the ACE genotype on response to therapy. Methods. Twenty-seven (24 male and 3 female, mean age 34±8 years) renal transplant recipients with erythrocytosis were treated either with E (15 patients) (10 mg/day) or L (12 patients) (50 mg/day) for 8 weeks. Results. The hemoglobin levels were significantly decreased in the L (17.1±0.7 to 15.9±1.3 g/dl, P =0.01) and E groups (17.4±1.1 to 14.9±2.2 g/dl, P =0.001). Among the responders who discontinued treatment, there was a trend for longer time to relapse in the L group (7.38±3.75 months; 95% confidence interval: 0.03–14.7) compared with the E group (2.75±0.70 (95% confidence interval: 1.37–4.13) (P =0.11). Decrease in hemoglobin was more prominent with E compared with L (−3.26±0.65 vs. −1.70±0.39 g/dl, P =0.05). Decrease in hemoglobin levels between DD and non-DD genotype groups was similar (−2.0±1.5 vs. −1.7±2.3 g/dl, P =0.69). Conclusions. Enalapril caused a greater decrease but faster relapse in hemoglobin levels compared with losartan in patients with posttransplantation erythrocytosis. The DD type polymorphism had no effect on response.

Helicobacter pylori antibodies in hemodialysis patients and renal transplant recipients

In this cross‐sectional, controlled study, Helicobacter pylori (H. pylori) infection, a probable factor in the development of gastrointestinal problems, was investigated in dialysis patients and renal transplant recipients. Forty‐seven dialysis patients (22 male, 25 female, mean age of 36.6±15 yr (range 18–83 yr)), 57 renal transplant recipients (39 male, 18 female, mean age of 36.8±10 yr (range 19–60 yr)) and 55 healthy individuals (34 male, 21 female, mean age of 33.4±9.6 yr (range 21–58 yr)) were included and no significant difference was found in the study groups. The mean time spent on dialysis in the hemodialysis group was 32.5±27.7 months (range 1–100 months). H. pylori antibodies were detected in 22 of 57 (38.6%) patients in the transplantation group, 31 of 47 (65.9%) patients in the dialysis group and 39 of 55 (72.5%) in the control group. No correlation was found between H. pylori infection and age, sex, primary disease, frequency of dialysis, duration and type of transplantation and the immunosuppressive therapy. However, patients with H. pylori antibodies spent a shorter time on dialysis compared to patients without the antibodies (26.6±23.5 vs 44.1±32.1 months, p=0.038). The frequency of H. pylori infection in the transplantation group was significantly lower than the control and dialysis groups (p<0.01). This finding may be explained on the basis of decreased humoral antibody response to H. pylori infection, secondary to immunosuppressive therapy rather than decreased incidence of infection in the transplantation group. Finally, we concluded that the value of the serological test for diagnosis of H. pylori infection should be interpreted cautiously in these patient groups.

Endothelial dysfunction in patients with asthma: the role of polymorphisms of ACE and endothelial NOS genes.

Objectives. Polymorphisms of the angiotensin converting enzyme (ACE) and endothelial nitric oxide (eNOS) genes have been implicated in asthma pathogenesis. Angiotensin II and NO have important roles in maintaining vascular tone. In this study, the relationship between endothelial dysfunction and ACE and eNOS gene polymorphisms was investigated in patients with asthma. Methods. This cross‐sectional, controlled study was conducted at the Yedikule Chest Disease Hospital and Cardiology Center in a University Hospital. Forty‐nine patients with asthma (18 male, 31 female; mean age: 33 ± 12 years) and 49 age‐ and sex‐matched healthy controls (20 male, 29 female; mean age: 30 ± 8 years) were included. Pulmonary function tests and flow‐mediated dilatation of the brachial artery [endothelium dependent dilatation (EDD)] were examined by high‐resolution ultrasonography. The ACE and eNOS genotypes were determined by PCR. Results. Asthma patients showed lower EDD (12 ± 6% vs. 22 ± 6%, p < 0.001) as compared to controls. The EDD was correlated with both predicted value of FEV1 (r = 0.31, p = 0.04) and predicted value of FVC (r = 0.37, p = 0.013). Conversely, EDD values in patients with moderate asthma were significantly lower than those in patients with mild asthma (10.1 ± 5.2% vs. 14.1 ± 5.7%, p = 0.017). However, the ACE and eNOS genotype distribution was not significantly different between controls and asthma groups. Furthermore, EDD was not associated with both gene polymorphism of ACE and eNOS. Conclusion. Patients with asthma have decreased vasodilatatory response to shear stress (EDD). Decreased EDD is correlated with the severity of asthma, but not with the distribution of ACE and eNOS genotypes.