The changing trends of peritoneal dialysis related peritonitis and novel risk factors.

AIM: Continuous ambulatory peritoneal dialysis (PD) has become a treatment modality for end stage renal disease with a peak of its use in 1990 s. The aim of this study was to examine the peritonitis rates, causative organisms and the risk factors of peritonitis in a large group of patients in our center. METHODS: The study was conducted in the Nephrology Department of a University Hospital in Turkey. Patients in the PD programme between January 2000 and January 2006 were included. Cohort-specific and subject specific peritonitis incidence, and peritonitis-free survival were calculated. Causative organisms and risk factors were evaluated. RESULTS: Totally 620 episodes of peritonitis occurred in 440 patients over the six years period. Peritonitis rates showed a decreasing trend through the years (0.79 episodes/patient-year 2000-2003 and 0.46 episodes/patient-year 2003-2006). Cohort-specific peritonitis incidence was 0.62 episodes/patient-years and median subject-specific peritonitis incidence was 0.44 episodes/patient-years. The median peritonitis-free survival was 15.25 months (%95 CI, 9.45-21.06 months). The proportion of gram-negative organisms has increased from 9.8% to 17.3%. There was a significant difference in the percentage of culture negative peritonitis between the first three and the last three years (53.1% vs. 43.2%, respectively). Peritonitis incidence was higher in patients who had been transferred from HD, who had catheter related infection and who had HCV infection without cirrhosis. CONCLUSIONS: Our study showed significant trends in the peritonitis rates, causative organisms and antibiotic resistance. Prior HD therapy, catheter related infections and HCV infection were found to be risk factors for peritonitis.

Free triiodothyronine in hemodialysis patients: link with malnutrition and inflammation.

INTRODUCTION: Free triiodothyronine (FT3) is a marker of comorbidity in end-stage renal disease and in many acute and chronic diseases. There is lack of data about the link between FT3 levels and malnutrition and inflammation in hemodialysis patients. The objective of the present study was to investigate the link between FT3 and malnutrition and inflammation in hemodialysis patients. MATERIALS AND METHODS: A total of 84 patients were included in the study (38 men and 46 women; mean age, 56.2 +/- 14.8 years; hemodialysis duration, 95.72 +/- 10.35 months). Serum FT3, free thyroxin, and thyroid-stimulating hormone concentrations were determined. Demographic data and laboratory values were evaluated. Patients' comorbidity status was determined using the Charlson Comorbidity Index (CCI), and malnutrition-inflammation status was determined by Malnutrition-Inflammation Score (MIS). RESULTS: Serum FT3 concentration inversely correlated with age (r = -0.328, P = .002), CCI (r = -0.591, P = .001), C-reactive protein (r = -0.299, P = .01), and MIS (r = -0.671, P = .001), and positively correlated with serum albumin (r = 0.389, P = .001). In multivariate linear regression analysis, FT3 was independently associated with MIS (beta;, -0.14; 95% confidence interval, -0.175 to 0.063, P = .003), adjusted for CCI, C-reactive protein level, serum albumin level, and MIS. CONCLUSIONS: The results of this study indicate that FT3 is negatively correlated with inflammatory markers, namely C-reactive protein, and it is independently related with MIS in hemodialysis patients. Therefore, we suggest that FT3 can be accepted as an inflammatory marker in hemodialysis patients.

Clinicopathologic study of kidney biopsies in patients before or after liver transplant.

OBJECTIVES: The purpose of this study was to evaluate the causes of kidney impairment associated with liver transplant in patients who had kidney biopsy before or after liver transplant. MATERIALS AND METHODS: In 408 patients who had liver transplant from January 1990 to December 2012, there were 10 patients who had kidney biopsy (total, 19 kidney biopsies) for evaluation of kidney dysfunction. A retrospective review of clinical records and kidney biopsies was performed. RESULTS: There were 7 male and 3 female patients (median age at liver transplant, 43 y; range, 10 to 62 y). The most frequent reason for liver transplant were hepatitis B virus cirrhosis (4 patients). There were 3 patients who had a kidney transplant before or concurrent with liver transplant. Increased serum creatinine level was the most common clinical finding at the time of kidney biopsy. The median interval from liver transplant to kidney biopsy was 495 days (mean, 1025 d; range, 10-4980 d). The most common pathology in the kidney biopsies was immune complex glomerulonephritis (total, 7 patients: IgA nephropathy, 4 patients; lupus nephritis, 2 patients; membranoproliferative glomerulonephritis, 1 patient). There were 4 patients who had allergic tubulointerstitial nephritis, 2 patients who had chronic calcineurin inhibitor nephrotoxicity, and 1 patient who had karyomegalic nephropathy. There were 7 patients who died at mean 34 months (range, 1-70 mo) after liver transplant. The other 3 patients were alive at mean 128 months (range, 67-193 mo) after liver transplant and had a functioning liver graft and chronic kidney disease. CONCLUSIONS: Chronic kidney disease after liver transplant has a major effect on mortality. The frequency of immune complex glomerulonephritis associated with liver transplant may be greater than previously recognized.

Endothelial nitric oxide synthase polymorphism influences renal allograft outcome.

BACKGROUND: Atherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three- and five-yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism. METHODS: Seventy-one male and 35 female patients (age: 34.9 ± 11.2 yr) who underwent living-related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre- and post-transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated. RESULTS: Patients with the bb allele of eNOS gene had a lower prevalence of post-transplant third year (12.6% and 38.5%, p = 0.005) and fifth year IF/TA (46.6% and 82.3%, p = 0.02) and a lower incidence of five-yr graft failure (35.4% and 55.6%, p < 0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p = 0.01, RR: 29.72, and p = 0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered. CONCLUSIONS: We concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.

Nondipping phenomenon and quality of life: are they related in essential hypertensive patients?

Hypertensive patients report lower general well-being, more severe psychological distress, poorer perceived health status, more physical symptoms, and functional disability when compared to normotensive patients. Nondipping of blood pressure (BP) is related to increased target organ damage in essential hypertension. However, the specific relationship between nocturnal nondipping and quality of life has not been extensively investigated. Patients with essential hypertension underwent the following procedures: anamnesis, office BP measurement, physical examination, routine biochemistry, and 24-hour ambulatory BP monitoring. To determine renal function, 24-hour urine specimens were collected. Quality of life was assessed by a short form of medical outcomes study (SF-36). Totally, 132 patients (male/female: 55/75) were included. Fifty-five of the patients were nondippers. The dippers and nondippers were not statistically different in terms of socio-demographic parameters. Dippers had higher physical functioning (P- 0.004), bodily pain (P- 0.008), and PCS (P - 0.003) than nondippers. PCS of SF-36 was independently associated with age (P - 0.029), body mass index (P - 0.022), presence of coronary artery disease (P - 0.01), gender (P - 0.009), and dipping phenomenon (P - 0.006). A mental component summary score of SF-36 was not associated with dipping phenomenon. Nocturnal nondipping, apart from having important prognostic implications for cardiovascular complications in essential hypertensive patients, is also related to quality of life, especially in its physical aspects.

Insulin resistance is associated with increased renal resistive index independent of other factors in newly diagnosed type 2 diabetes mellitus and hypertensive patients.

Renal resistive index (RRI) is increased in subjects with diabetes. We analyzed whether insulin resistance is independently related with RRI. Medical history, physical examination, laboratory analysis, Doppler ultrasonography, and 24-hour urinary albumin excretion were analyzed. The threshold for an increased RRI was at least 0.70, which has been previously shown to be discriminatory of increased RRI level. Eighty newly diagnosed essential hypertensive and type 2 diabetes mellitus patients were included. Sixty-one patients had low RRI (<0.70). When compared with low-RRI patients, those with high RRI were older and had higher pulse pressure, serum creatinine, and homeostasis model assessment (HOMA) index. The HOMA index and RRI were positively correlated (r = +0.371, P = .001). In multivariate logistic regression analysis, age (odds ratio [OR] = 1.164, 95% confidence interval [CI] = 1.040-1.303, P = .008), pulse pressure (OR = 1.188, 95% CI = 1.020-1.384, P = .027), and HOMA index (OR = 1.422, 95% CI = 1.085-1.862, P = .011) were independently associated with high RRI. Increased insulin resistance is independently related with increased RRI.

Relationship between renal resistive index and inflammation in untreated hypertensive patients.

The aim of this study was to evaluate the relationship between renal resistive index and inflammation in untreated hypertensive patients. Sixty-one hypertensive patients (male/female: 38/23, aged 45.8 +/- 8.3 years, and mean hypertension duration 28.2 +/- 35.6 months) and 40 (male/female: 23/17, aged 42.7 +/- 8.5 years) healthy control subjects were included in the study. Renal resistive index was positively correlated with age (P = 0.016, r = 0.308), pulse pressure (P = 0.022, r = 0.294), C-reactive protein (P = 0.00, r = 0.757), urinary albumin excretion (P = 0.003, r = 0.371) and negatively correlated with creatinine clearance (P = 0.042, r = -0.262) in the hypertensive group. The hypertensive group was further divided in two groups according to the renal resistive index; < 0.60 and > 0.60. In the > 0.60 group, age (48.0 +/- 7.3 versus 42.8 +/- 8.9 years, P = 0.01) and C-reactive protein levels (7.4 +/- 1.5 versus 4.0 +/- 1.6 mg/L, P = 0.01) were higher, and creatinine clearance (95.5 +/- 22.1 versus 109.1 +/- 25.3 mL/min, P = 0.04) was lower than the < 0.60 group. Renal resistive index was higher in the nondippers than the dippers (0.61 +/- 0.04 versus 0.58 +/- 0.03, P = 0.003). Renal resistive index is associated with inflammation and may be a useful marker, together with albuminuria, in hypertensive patients when evaluating hypertensive renal damage.

Factors related to silent myocardial damage in hemodialysis patients.

BACKGROUND: Both traditional and non-traditional risk factors play a role for the development of cardiovascular disease in hemodialysis patients. However, a specific relationship between these risk factors and silent myocardial damage is unknown. METHODS: Demographic, anthropometric, clinical, and laboratory data were collected. Silent myocardial damage was defined by elevated cardiac troponin I values above cutoff values. RESULTS: In total, 113 hemodialysis patients were included. Cardiac troponin I concentrations were below cutoff value (<2.3 ng/mL) in 103 (91.2%) patients (Group 1), whereas 10 (8.8%) patients had elevated concentrations (Group 2). Group 1 patients had higher levels of hemoglobin (p = 0.002) and high-density lipoprotein cholesterol (p = 0.002) and lower C-reactive protein (p = 0.003) and tumor necrosis factor-alpha (p = 0.005) levels, as well as less incidence of left ventricular hypertrophy (p = 0.045), when compared to Group 2 patients. Diabetes mellitus (Beta = +0.160, p = 0.021), left ventricular hypertrophy (Beta = +0.247, p < 0.0001), uncontrolled blood pressure (Beta = +0.170, p = 0.016), normalized protein equivalent of total nitrogen appearance (Beta = -0.230, p = 0.001), hemoglobin (Beta = -0.302, p < 0.0001), and tumor necrosis factor-alpha (Beta = +0.506, p < 0.0001) were found to be independently associated with cardiac troponin I levels in multiple linear regression analysis. CONCLUSIONS: Both traditional and non-traditional risk factors are related with silent myocardial damage, which is considered to an antecedent of major cardiovascular events. Hemodialysis patients, even when asymptomatic, must be closely followed up for the presence of these risk factors.

Early assessment of renal resistance index and long-term renal function in renal transplant recipients.

BACKGROUND: The effect of the intrarenal arterial resistance index (RI) on long-term renal functions is not well known. We examined the predictive value of intrarenal RI on long-term allograft outcomes. METHODS: We retrospectively investigated 121 stable renal transplant recipients, followed for a mean of 63.21 +/- 19.9 months after renal transplant. Patients with complications during the first six months after transplant were not included. Color Doppler ultrasonography was done to calculate the intrarenal RI within the first four weeks after transplant. RESULTS: Older recipient age, high pulse pressure, active smoking, and proteinuria were associated with a higher intrarenal RI. Multivariate analyses revealed that renal RI and donor age were independent predictors of allograft outcome. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had an RI of 0.7 or more than they were in patients who had an RI of less than 0.7 (p = .005). Development of chronic allograft nephropathy (CAN) was significantly higher in patients who had an RI of 0.7 or more (p = .02). CONCLUSIONS: Renal RI determined within the first month after renal transplant predicts long-term allograft function and development of CAN in renal transplant recipients.

Determination of the impact of hepatitis C virus on insulin resistance and arterial stiffness in hemodialysis patients.

AIM: It has been shown that Hepatitis C virus (HCV) seropositivity and carotis artery plaque formation are independently correlated in the general population. Insulin resistance is also a risk factor for atherosclerosis. The association between HCV and type 2 diabetes mellitus is known. Determination of the impact of HCV on insulin resistance and arterial stiffness in hemodialysis patients would help to prevent related cardiovascular complications. METHODS: Thirty-seven HCV(+) and 30 HCV(-) HD patients were enrolled in this study. All patients were non-diabetic. Insulin resistance was assessed by "HOMA-IR." Arterial stiffness was measured by "stiffness index b" and "elastic modulus." RESULTS: In the HCV(+) group, there were 20 males and 17 females, while the HCV(-) group had 19 males and 11 females. The mean age was 43.4 +/- 16.7 years and 44.5 +/- 16.8 years, respectively. The HOMA-IR was 1.50 in HCV(+) group and 1.31 in HCV(-) group (p > 0.05). Stiffness index b and elastic modulus measurements revealed no difference between groups. In the HCV(+) group, arterial stiffness parameters were correlated with age, white blood cell, thrombocyte, total and LDL cholesterol, uric acid, mean arterial pressure, diastolic blood pressure, and HOMA-IR. There was no association between arterial stiffness and the above-mentioned parameters in the HCV(-) group. CONCLUSION: We found that there was no association of arterial stiffness in HCV(+) patients with insulin resistance. Further studies with larger patient groups and more sensitive methods of detecting HCV are needed. This study is the first in literature on this issue.

The relationship between obesity and transforming growth factor beta on renal damage in essential hypertension.

The aim of this study was to evaluate the effect of obesity on renal functions and the possible relationship between TGF-beta1 and obesity in hypertensive patients. Seventy newly diagnosed, hypertensive patients (male/female 36/34, aged 45.0 +/- 8.0 years) and 30 (male/female 17/13, aged 41.8 +/- 7.7 years) normotensive controls were included. Patients in both groups were analyzed for serum levels of glucose, creatinine, uric acid, lipids, and TGF-beta1. A 24-hour urine sample was also obtained; creatinine clearance rate and urinary albumin excretion (UEA) were investigated. TGF-beta1 levels were significantly higher (40.7 +/- 13.6 versus 34.2 +/- 12.1 pg/mL, P = 0.02), and creatinine clearance was significantly lower in patients compared with controls (98.9 +/- 25.5 versus 124.5 +/- 23.1 mL/min. per. 1.73 m(2), P = 0.001). Serum TGF-beta1 levels (45.2 +/- 14 versis 38.0 +/- 12.8 pg/mL, P = 0.03), creatinine clearance rates (109.8 29.9 versus 93.0 +/- 20.8 mL/min. per. 1.73 m(2), P = 0.001), and urinary albumin excretion (55.7 +/- 62.0 versus 12.7 +/- 12.6 mg/24 h, P = 0.002) were higher in obese hypertensive patients than in nonobese patients. In hypertensive patients, TGF-beta1 levels correlated with body mass index (r = 0.296, P = 0.01) and creatinine clearance (r = 0.238, P = 0.04). The results suggest that increased body mass index is associated with increased creatinine clearance, urinary albumin excretion, and TGF-beta1 levels in essential hypertension. In addition, TGF-beta1 is positively correlated with body mass index and creatinine clearance in patients with essential hypertension.

Influence of pretransplant IFN-alpha therapy on interstitial fibrosis in renal allografts with hepatitis C virus infection.

The aim of this study is to identify the influence of chronic HCV infection on development of interstitial fibrosis (IF) in renal allografts and evaluate if pretransplant interferon-alpha (IFN-alpha) therapy has an effect on IF. The development of IF and graft outcome were compared between anti-HCV positive (n = 28) and anti-HCV negative (n = 30) recipients. The influence of IFN-alpha therapy on IF and graft survival was compared between anti-HCV positive recipients who received pre-transplant IFN-alpha therapy (n = 15, group 1) and anti-HCV positive recipients who did not receive IFN-alpha therapy (n = 13, group 2). Recipients with anti-HCV antibodies had higher incidences of IF and shorter graft survival than did recipients without anti-HCV antibodies (p < 0.05 for both). Development of IF was higher in group 2 recipients, and patients in group 1 had longer graft survivals (p < 0.05 for both). Patients with positive HCV-RNA had higher grades of tubular TGF-beta1 expression than did patients with negative HCV-RNA (p < 0.05). Expression of tubular TGF-beta1 was lower in group 1 patients when compared with group 2 patients (p < 0.001). In conclusion, we suggested that HCV infection may have a triggering effect on the development of IF in renal allografts by augmenting renal expression of TGF-beta1.

Is HOMA index a predictor of nocturnal nondipping in hypertensives with newly diagnosed type 2 diabetes mellitus?

OBJECTIVE: Insulin resistance is involved in glucose intolerance, type 2 diabetes mellitus and hypertension. We aimed to analyze relationship between insulin resistance and nocturnal nondipping. METHODS: Patients underwent physical and biochemical evaluation, clinic and ambulatory blood pressure measurements. The homeostasis model assessment (HOMA) index was calculated. RESULTS: Ninety-six essential hypertensive patients, of whom 42 were dippers, with newly diagnosed type 2 diabetes mellitus were included. Nighttime average heart rate and mean arterial pressure of nondippers were higher than dippers (P<0.0001 and 0.001). Nondippers had higher fasting plasma glucose, serum insulin levels and HOMA indices than dipper patients (P=0.006, <0.0001 and <0.0001). Ten dippers and 36 nondippers were insulin resistant (P<0.0001). Clinic (r=+0.22, P=0.031), daytime average (r=+0.27, P=0.007), nighttime average (r=+0.33, P=0.001), 24-h average systolic (r=+0.25, P=0.015) and nighttime average diastolic blood pressures (r=+0.31, P=0.002) were positively correlated with homeostasis model assessment index. Nighttime mean arterial pressure and heart rates (daytime, nighttime, 24-h average) showed positive correlation with homeostasis model assessment index. In multivariate analysis, high homeostasis model assessment index was associated with increased nondipping risk (odds ratio: 1.85, confidence interval: 1.24-2.76, P=0.003). After adjustment of several factors, average nighttime systolic (P<0.0001), diastolic (P<0.0001) and 24-h diastolic blood pressure (P=0.029) and heart rate (P=0.001) measurements of insulin resistant patients were higher than nonresistant patients. CONCLUSIONS: Insulin resistance is related with diurnal blood pressure variation. The HOMA index may be a predictor of nocturnal nondipping in patients with essential hypertension and newly diagnosed type 2 diabetes mellitus.

Adherence, depression and quality of life in patients on a renal transplantation waiting list.

To study nonadherence, and its relationship with depression and quality of life (QOL) in patients on a cadaveric renal transplantation waiting list (RTWL). In 86 RTWL patients (56 men/30 women), there were 49 nonadherent patients (age, 46.8 +/- 21.8 years) and 37 adherent patients (age, 42.8 +/- 12.1 years). Clinical nonadherence was defined as skipping or shortening dialysis sessions, interdialytic weight gain (IDWG) of >5.7% body weight, a predialysis potassium level of >6 mEq/l and a predialysis phosphate level of >7.5 mg/dl. For each study subject, marital status, level of education duration of dialysis, prior renal transplantation, IDWG, predialysis blood urea nitrogen (BUN) value and creatinine, potassium, phosphate levels were recorded as were scores from the short form-36 and Beck depression inventory (BDI). A high IDWG (33.7% of the subjects) was the most common nonadherence pattern noted. Age, sex, marital status, duration of dialysis, prior transplantation, comorbid conditions the predialysis BUN values, the levels of creatinine, potassium, and phosphate were not significantly different between the two groups (P > 0.05). The level of education was higher in adherent group (P = 0.018). QOL and BDI scores were negatively correlated (P = 0.001, r = -0.561). Nonadherent patients had lower QOL (P = 0.04) and higher depression scores (P = 0.01) than did adherent patients. Of the depressed patients, 77.8% had a comorbid condition. Nonadherence was only associated with BDI scores (OR, 2.146; CI, 2.052-2.350; P = 0.002). In dialysis patients, close monitoring of adherence, early diagnosis of depression, and the treatment of disease may further enhance QOL during the waiting period for a cadaveric renal transplant.

Low dose intradermal vaccination is superior to high dose intramuscular vaccination for hepatitis B in unresponsive hemodialysis patients.

After two intramuscular (IM) vaccination protocols (40 microg at 0, 1, 2, and 6 months), patients who were unresponsive to hepatitis B vaccination were collected from three HD centers. The aim of this study was to compare the effectiveness of intradermal (ID) and repeated IM vaccination protocols. Thirty-three of 639 HD patients were found to be unresponsive. Patients were randomly assigned into two groups: one to receive 80 microg ID and the other 160 microg IM vaccination protocol. Both ID (p = 0.000) and IM (p = 0.03) groups disclosed statistically significant seroconversion rates six months after the last vaccination dose. The seroconversion rate was 94.1% in the ID and 50% in the IM groups - showing a significant improvement in the ID group (p = 0.011). A low-dose ID is superior to standard IM vaccination protocol and also more cost-effective in unresponsive HD patients.

Increased body mass index is not a reliable marker of good nutrition in hemodialysis patients.

OBJECTIVE: The aim of the study was to assess the body fat (BF) composition in hemodialysis (HD) patients using anthropometry and bioelectrical impedance analysis (BIA) and investigate relationships between BIA-determined BF composition and nutritional parameters in different weight groupings. DESIGN: Cross-sectional study. SETTING: A tertiary-care university hospital. METHODS: 164 HD patients (M/F: 89/75, mean age: 48.4 +/- 15.8 years, mean HD duration: 58.2 +/- 42.6 months) were divided into three groups according to body mass index (BMI): normal weight (NW: BMI 18.5-24.9), overweight (OW: BMI 25-29.9), obese (OB, BMI > or = 30). Biochemical parameters and BF composition using anthropometry and foot-to-foot BIA were compared between three groups. RESULTS: Ninety-six (59%) patients were NW, 40 (24%) were OW, and 28 (17%) were OB. Average mean skinfold thickness (p = 0.005), mid-arm circumference (p = 0.001), BF% (p = 0.001), and fat-free mass (FFM) (p = 0.03) were all significantly greater in the OB group than in the NW group. Compared to the NW patients, the OB group had significantly higher serum levels of glucose (p = 0.03), total cholesterol (p = 0.02), and triglycerides (p = 0.02), but significantly lower serum albumin (p = 0.05) and blood urea nitrogen (p = 0.05). The OB group also had significantly higher white blood cell count (p = 0.002) and serum CRP (p = 0.001) than the NW group. CONCLUSIONS: The results suggest that BIA-determined BF composition is correlated with body mass index. In addition, obesity is associated with elevated CRP and white blood cell count and lower serum albumin level in HD patients.

Effect of protein-energy malnutrition on erythropoietin requirement in maintenance hemodialysis patients.

Possible interactions between inflammatory and nutritional markers and their impact on recombinant human erythropoietin (rHuEPO) hyporesponsiveness are not well understood. We investigated the role of nutritional status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without evidence of inflammation. This cross-sectional study included 88 MHD patients. The associations between required rHuEPO dose and malnutrition-inflammation score (MIS) and several laboratory values known to be related to nutrition and/or inflammation were analyzed. Anthropometric measures including body mass index, triceps skinfold thickness, and midarm circumferences were also measured. Twenty-three patients with serum C-reactive protein levels >10 mg/L were excluded from the analysis. The remaining 65 patients (male/female, 41/24; age 49.1+/-11.4 years; dialysis duration 99.7+/-63.0 months) were studied. These patients had moderate malnutrition and the average MIS was 7.4 (range 3-17). The average weekly dose of administered rHuEPO was 69.1+/-63.1 U/kg. Malnutrition-inflammation score had a positive correlation with the serum concentration of tumor necrosis factor-alpha, whereas it had a negative correlation with anthropometric measures, total iron-binding capacity, prealbumin, phosphorus, creatinine, and triglyceride. According to Pearson's correlation analysis, significant relationships of increased MIS with increased required rHuEPO dose and rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=-0.326; p=0.017, r=-0.306, respectively). Recombinant human erythropoietin dose requirement is correlated with MIS and adverse nutritional status in MHD patients without evidence of inflammation. Further research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.

Endothelial nitric oxide synthase gene intron 4 (VNTR) polymorphism and vascular access graft thrombosis.

Vascular access thrombosis is a leading cause of vascular access failure in hemodialysis patients. Thrombosis is a multifactorial condition and genetic makeup can affect thrombosis risk. We conducted a study to investigate for possible associations between ecNOS gene intron 4 variable-number tandem repeat (VNTR) polymorphism and thrombosis of polytetrafluoroethylene hemodialysis arteriovenous access grafts (AVG) in Turkish patients. Fifty-five patients with end-stage renal disease who had AVGs implanted between 2000 and 2002 and 167 healthy individuals representing our healthy population were enrolled in this prospective study. Each subject provided a venous blood sample from which DNA was isolated, and polymerase chain reaction analysis was done to identify genotypes (aa, bb, ab) for ecNOS gene intron 4 VNTR polymorphism. All grafts were placed in brachioaxillary position. The subjects were divided into two groups based on duration of graft patency. The thrombosis group (Group I) comprised 26 patients who developed AVG thrombosis in the first 12 months after placement. The no-thrombosis group (Group II) comprised 29 patients whose grafts remained patient for at least 12 months. The frequency of the aa genotype in Group I was significantly higher than that in Group II (p = .005). At 6, 12, and 24 months, the primary patency rates for the AVGs in patients with the aa genotype were significantly lower than the corresponding rates for the bb and ab genotype groupings (p = .01, p = .01 and p = .04 for the three respective time points; Kaplan-Meier). ecNOS gene intron 4 VNTR polymorphism is linked with the pathogenesis of vascular access thrombosis in Turkish patients undergoing hemodialysis.

Effects of ACE gene polymorphism on vitamin D therapy according to parathyroid hormone level in patients on hemodialysis.

Medical management is still far from optimal in secondary hyperparathyroidism. This may be explained, at least in part, by genetic differences. The aim of this study was to evaluate the association of genetic influences of angiotensinconverting enzyme (ACE) gene polymorphisms with response to vitamin D therapy among patients on hemodialysis (HD). Eighty-two patients (female/male, 34/48; mean age, 47.5+/-15.3 y; HD duration time, 76.6+/-33.2 mo) with endstage renal disease who were on maintenance HD were included in the study. Five-year retrospective demographic, clinical, laboratory, and treatment data (5-y cumulative doses of phosphate-binding drugs and oral and intravenous cumulative doses of active vitamin D) were retrieved from patients' hospital records. ACE gene polymorphisms of patients were documented and were used to group patients as follows: The insertion/deletion polymorphism group (I/D) consisted of (1) group non-DD (n=43), who had the DI or II allele, and (2) group DD (n=39), who had the DD allele. Patients with the DD allele (group DD) of ACE gene polymorphism had (1) significantly elevated mean 5-y intact parathyroid hormone levels when compared with the non-DD group (P=.009), and (2) significantly elevated oral and intravenous 5-y cumulative doses of vitamin D. Oral and intravenous 5-y cumulative doses of vitamin D used in group DD patients were significantly higher than those in group I patients (P=.038 and P=.037, respectively). Knowledge of genetic differences among patients on HD may be useful to the clinician in planning treatment strategy. ACE gene polymorphism may have an effect on hyperparathyroidism, as is seen in patients on HD. Patients from this group who have resistant hyperparathyroidism may be candidates for ACE inhibitor therapy.