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.

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.

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.

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.

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.

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.

Relationship of ENOS and RAS gene polymorphisms to initial peritoneal transport status in peritoneal dialysis patients.

BACKGROUND: Peritoneal membrane permeability is of major importance for adequate dialysis and fluid balance in peritoneal dialysis (PD) therapy. The peritoneal capillary endothelium plays a key role in peritoneal transport. Nitric oxide derived from endothelial cells is related to the maintenance of vascular permeability. We investigated the relationship between the endothelial nitric oxide synthase (ENOS) gene polymorphism, the renin-angiotensin system (RAS) gene polymorphisms, and initial peritoneal transport type in PD patients. METHODS: This study included 74 incident continuous ambulatory PD patients. The ENOS gene polymorphism was identified at the 4a/b variable number of tandem repeats in intron 4. Genetic polymorphisms of the renin-angiotensin system were performed for the angiotensin-converting enzyme I/D, angiotensinogen M235T, and angiotensin II type 1 receptor A1166C and type 2 receptor C3123A by polymerase chain reaction. Patients were divided into two groups according to the initial peritoneal equilibration test results performed within 3 months of PD therapy: group 1 consisted of high/high average transporters (n = 41), and group 2 consisted of low/low average transporters (n = 33). RESULTS: Demographic, clinical, and laboratory data were similar between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of the ENOS b/b genotype than group 2 (78% vs. 48.5%, p < 0.008). In contrast, group 2 had a significantly greater prevalence of the ENOS a/a+a/b genotype than group 1 (51.5% vs. 22%, p < 0.008). Genetic polymorphisms of the renin-angiotensin system were not associated with initial peritoneal transport type (p > 0.05). CONCLUSIONS: Modulation of the nitric oxide activity via the ENOS a/b polymorphism may have a considerable effect on the basal peritoneal permeability.