Turgay Arinsoy

A population-based survey of Chronic REnal Disease In Turkey—the CREDIT study

Background. Chronic kidney disease (CKD) is a growing health problem worldwide that leads to end-stage kidney failure and cardiovascular complications. We aimed to determine the prevalence of CKD in Turkey, and to evaluate relationships between CKD and cardiovascular risk factors in a population-based survey. Methods. Medical data were collected through home visits and interviews. Serum creatinine, blood glucose, total cholesterol, triglycerides, HDL, LDL and uric acid were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation. Results. A total of 10 872 participants were included in the study. The final analysis was performed on 10 748 subjects (mean age 40.5 ± 16.3 years; 55.7% women) and excluded 124 pregnant women. A low glomerular filtration rate (GFR) (< 60 mL/min/1.73 m2) was present in 5.2% of the subjects who were evaluated for GFR, while microalbuminuria and macroalbuminuria were observed in 10.2% and 2% of the subjects, respectively. The presence of CKD was assessed in subjects who gave consent for urinary albumin excretion measurement (n = 8765). The overall prevalence of CKD was 15.7%; it was higher in women than men (18.4% vs. 12.8%, P < 0.001) and increased with increasing age of the subjects. The prevalence of hypertension (32.7% in the general population), diabetes (12.7%), dyslipidaemia (76.3%), obesity (20.1%) and metabolic syndrome (31.3%) was significantly higher in subjects with CKD than subjects without CKD (P < 0.001 for all). Conclusions. The prevalence of CKD in Turkey is 15.7%. Cardiovascular risk factors were significantly more prevalent in CKD patients.

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO4 had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.

Phosphorus control in peritoneal dialysis patients

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Prevalence, awareness, treatment and control of hypertension in adults with chronic kidney disease in Turkey: results from the CREDIT study.

Background: In the Chronic REnal Disease In Turkey -CREDIT Study, a large populationbased study on 10,748 adults, the prevalence of chronic kidney disease (CKD) and relationship between CKD and other cardiovascular risk factors had been studied. Methods: This report presents the results of CREDIT study on the prevalence, awareness, treatment, and control of hypertension among CKD patients. Results: The prevalence and awareness of hypertension in CREDIT population was 32.7% and 48.6%, respectively. Of the patients with hypertension, 31.5.% were under treatment, and 16.4% had hypertension under control. Prevalence of CKD was 25.3% in patients with hypertension. Among CKD patients (15.7% of the CREDIT study population), 56.3% had hypertension. The prevalence of hypertension was 34.8% at stage 1, 79.8% at stage 3, and 92.3% at stage 5 CKD. Only 13.4% of patients with CKD have optimal blood pressure. Among CKD patients, 61.9% were aware of hypertension, and 44.2% were under treatment. Overall control rate of hypertension in subjects with CKD was 16.3% with the lowest rate at stage 1 (12.3%) and highest rate at stage 4 (40%). The control rate increased to 28.8% for CKD patients under treatment for hypertension. Conclusion: As a conclusion, hypertension is highly prevalent in subjects with CKD in Turkey with suboptimal awareness, treatment, and control rates. Appropriate health strategies should be implicated to improve prevention, early diagnosis, and treatment of hypertension, which is one of the leading causes of CKD.

Nonrelated Living-Donor Kidney Transplantation: Medical and Ethical Aspects

Several patients with end-stage renal disease went to Bombay for renal transplantation from nonrelated living donors and then returned to Turkey for posttransplantation follow-up. The aims of this study are to evaluate the long-term results of renal transplantation from nonrelated living donors in Turkish patients with end-stage renal disease and to discuss the ethical and social aspects of nonrelated kidney donation. One hundred and twenty-seven patients (89 males, 38 females; mean age 38.1, range 17–63 years) were investigated retrospectively. None of the patients went to Bombay on our advice. All transplantations were performed between 1991 and 1995. The mean follow-up period after transplantation was 34.2 (range 1–68) months. Graft survival rates were 85, 83, and 57% after 3 months and 1 and 5 years, respectively. Patient survival rates were 94, 93, and 92% after 3 months and 1 and 5 years, respectively. Seven patients died within the first 3 months after the transplantation. Surgical problems, infections, acute rejection, ciclosporin nephrotoxicity, and hepatic problems were common complications. We conclude that medical and surgical complications occur frequently in paid kidney transplantation, but most of these complications can be prevented by adequate preoperative management, and precautionary measures should be taken to prevent commercialization of renal transplantation before the spread of emotionally related living kidney donation.

Chronic renal disease in children aged 5–18 years: a population-based survey in Turkey, the CREDIT-C study

BACKGROUND Data on the epidemiology of chronic kidney disease (CKD), which is a serious health problem and refers to a condition related to irreversible kidney damage that further progress to end-stage renal disease in children, are insufficient and data that are available were based on hospital records. The aim of this nationwide, population-based field study was to determine the prevalence of CKD in children in Turkey and to evaluate the association between CKD and possible risk factors such as obesity and hypertension. METHODS The study was the paediatric stratum (3622 children aged 5-18 years) of the previously published population-based survey of Chronic REnal Disease In Turkey (CREDIT study). Medical data were collected through home visits and interviews between November 2007 and July 2008; height, weight and blood pressure were also measured. Serum creatinine, total cholesterol, uric acid and complete blood count were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation. RESULTS Following adjustment according to gender, residence, age groups and geographical regions, the prevalence of children with estimated glomerular filtration rate (eGFR) <75 mL/min/1.73 m(2) was 0.94 [95% confidence interval (CI): 0.63-1.35], and the prevalence of children with CKD Stages 3-5 [National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI)] was 2600 (95% CI 1100-5100) per million age related population. The mean eGFR was found to increase with age; the ratios of children with eGFR <90 and <75 mL/min/1.73 m(2) were higher in younger age groups. The frequencies of overweight and obese children were 9.3 and 8.9%, respectively, and the mean eGFR was lower in patients with higher body mass index. The prevalence of hypertension and hypercholesterolaemia was 6.1 and 5.8%, respectively; the mean eGFR was lower in children with hypercholesterolaemia. CONCLUSIONS This is the first population-based CKD study performed in children aged 5-18 years. The prevalence of CKD in our study was 25-100 times greater than that found in previous hospital-based studies. Our data suggest that approaches focusing on patients in tertiary centres are likely to lead to patients being missed at early stages of CKD and that a vast majority of these children will never develop symptomatic CKD during childhood.

Predictive markers of asymptomatic atherosclerosis in end-stage renal disease patients

Objective: Uremia is associated with accelerated atherosclerosis and increased cardiovascular mortality in patients with end-stage renal disease (ESRD). Cardiac injury markers, such as myoglobin, creatine kinase-MB (CK-MB), or troponins, frequently used to recognize acute coronary events, may be falsely elevated in this patient group. In this study, our aim was to (i) test serum levels of myoglobin, CK-MB, and troponin I (cTnI) in ESRD patients without coronary artery disease (CAD) and compare the results with healthy controls and (ii) to investigate the association between these markers and carotid artery intima–media thickness (CA–IMT), high-sensitive C-reactive protein (hs-CRP), and serum uric acid (SUA) levels in ESRD patients. Materials and methods: Fifty-two ESRD patients (25 hemodialysis and 27 peritoneal dialysis) and 17 healthy controls were included in the study. Serum levels of myoglobin, CK-MB, and cTnI were measured and ultrasonographic CA–IMT was determined in all participants. SUA and hs-CRP levels were only measured in the ESRD group. Results: Serum myoglobin, CK-MB levels, and the mean CA–IMT were significantly higher in ESRD group (p < 0.01), whereas cTnI levels were not different compared to healthy controls (p = 0.70). There was also a positive correlation between CA–IMT and cTnI levels (p = 0.003, r = 0.35) and CA–IMT and hs-CRP (p = 0.03, r = 0.30) or SUA levels (p = 0.003, r = 0.43). Conclusion: cTnI may serve as a more sensitive marker in detecting cardiovascular events in patients with renal failure. Besides the traditional risk factors of atherosclerosis, cTnI, hs-CRP, and SUA may have a predictive role in recognizing premature atherosclerosis in ESRD patients.

The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-α, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-α levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 ± 387.86 ng/mL) than hemodialysis (97.68 ± 244.96 ng/mL,) and control (41.33 ± 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-α (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = −0.305, p = 0.01), (r = −0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (β = 0.369, p = 0.001) and IL-6 (β = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-α. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.

Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction

Abstract:  Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long‐term, and current immunologic strategies have little effect on this condition. The renin‐angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor‐1 (PAI‐1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI‐1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI‐1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence‐specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI‐1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction.