Baseline carotid intima-media thickness is associated with cardiovascular morbidity and mortality in peritoneal dialysis patients.

Carotid intima-media thickness (CIMT) is an early marker of atherosclerosis and is increased in peritoneal dialysis (PD) patients. Association of CIMT with cardiovascular disease (CVD) or mortality is less clear. Fibroblast growth factor-23 (FGF-23) is a hormone associated with vascular calcification, atherosclerosis, and mortality in the hemodialysis population. We investigated whether baseline CIMT and FGF-23 are associated with CVD and mortality in PD patients. Fifty-five PD patients were included. CVD was defined as ischemic heart disease, stroke, or peripheral artery disease. Intact FGF-23 was measured in plasma. CIMT was measured by ultrasonography. Twenty-one patients developed CVD and 12 died over 47.1 ± 33.8 months. Patients with CVD were older (55.9 ± 10.5 vs. 42.5 ± 12.9 years, P < .01), had lower albumin (3.8 ± 0.5 vs. 4.2 ± 0.3 g/dL, P < .01) and higher CIMT (0.87 ± 0.22 vs. 0.61 ± 0.11 mm, P < .01). Patients with mortality were also older (53.5 ± 11.5 vs. 45.8 ± 13.8 years, P = .05), had lower albumin (3.7 ± 0.6 vs. 4.1 ± 0.3 g/dL, P < .01), higher CRP (15.0 ± 8.5 vs. 7.6 ± 8.4 mg/L, P < .01) and CIMT (0.9 ± 0.3 vs. 0.6 ± 0.1 mm, P < .01). Albumin and CIMT were associated with CVD and CIMT > 0.75 mm was associated with cardiovascular mortality. FGF-23 did not show any correlations. CIMT at baseline is associated with CVD and mortality in PD patients.

Late Pulmonary Toxicity Associated With Everolimus in a Renal Transplant Patient and Review of the Literature.

The use of inhibitors of mammalian target of rapamycin is associated with adverse pulmonary effects. Although sirolimus-related pneumonitis has been well described, reports on pneumonitis with everolimus are scarce. We report a case of everolimus-induced pneumonitis in a renal transplant recipient 5 years after initiation of everolimus treatment, and we also review the literature regarding everolimus-induced pneumonitis in renal transplant patients.

Prevention of peritonitis in newly-placed peritoneal dialysis catheters: efficacy of oral prophylaxis with cefuroxime axetil - a preliminary study.

BACKGROUND: Peritonitis is one of the causes of early peritoneal dialysis (PD) failure in newly-placed catheters. Antibiotic prophylaxis has been recommended to decrease the risk of infection after PD catheter placement. In this study, we compared the efficacy of parenteral versus oral prophylactic cefuroxime axetil for preventing peritonitis after placed PD catheters. METHODS: In total, 67 patients (F/M: 32/35; mean age: 46.6±13.2 years) undergoing 70 percutaneous PD catheter placement procedures were included (in three patients, placement was repeated). In 37 patients (parenteral group), we administered a single intravenous (IV) 750-mg dose of cefuroxime axetil, approximately 30 min before placement. In the oral group, 33 patients received a 500-mg dose of oral cefuroxime axetil 1 hour before the procedure and the patients continued that twice daily for 3 days. Patients were evaluated for peritonitis over the following 14 days. The costs of both oral and parenteral forms of cefuroxime axetil were calculated. RESULTS: The two groups were similar regarding age and gender. Three patients (9%) in the oral group and three (8.1%) in the parenteral group developed peritonitis (P=0.578). All were responded to therapy for peritonitis. The cost of parenteral prophylaxis was $US 7.58, while that of the oral form was $US 3.92. CONCLUSION: For patients undergoing percutaneous PD catheter insertion, a 3-day regimen of oral cefuroxime axetil for preventing early peritonitis was safe, equally effective, and had lower cost comparing with single intravenous dose of the same agent.

Determinants of hemoglobin variability in stable peritoneal dialysis patients.

PURPOSE: Significant within-patient hemoglobin (Hb) level variability is well recognized in particularly hemodialysis patients. Several factors such as hospitalizations, intercurrent diseases and IV iron therapy are found to be related to Hb variability (Hb-var). In this observational study, we aimed to identify predictors and outcome of Hb-var in peritoneal dialysis (PD) patients without hospitalization, intercurrent disease and IV iron therapy during the study period. METHODS: All patients were in the maintenance phase of short-acting erythropoiesis-stimulating agents (ESAs) therapy. The target range of Hb was 11-12 g/dL according to KDOQI Guidelines in 2007. The desired range of Hb was 11-12.5 g/dL. Patients' demographic and laboratory data were collected at baseline. Atherosclerotic disease was assessed using carotid intima-media thickness (CIMT). We assessed Hb variability with various methods using SD Hbmean, SD Hbrange and the velocity of Hb change. Hb deflectpositive, Hb deflectnegative, Hb values and ESA dosing were recorded monthly for 6 months. RESULTS: This study included 50 prevalent PD patients (mean age 46.9 ± 13.7 years, 25 women). The mean velocity of Hb change was negatively correlated with age and positively correlated with frequent ESA dose changes. Higher albumin and residual renal function (RRF) were also positively correlated with Hb deflectpositive. Patients with CIMT ≥0.7 cm had lower SD Hb range compared to CIMT <0.7 cm. Cumulative survival was better in patients with Hb levels consistently ≥10 g/dL compared to patients who had Hb <10 g/dL for at least 1 month. However, Hb-var was not associated with mortality. CONCLUSIONS: In PD patients without hospitalization, intercurrent disease(s) or IV iron therapy, young age, higher albumin or RRF and lower CIMT were associated with greater oscillations in response to ESA therapy. Careful and appropriate ESA dose changes considering these parameters could minimize Hb variability in these patients.

The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study.

PURPOSE: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. METHODS: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. RESULTS: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p < 0.001). On Kaplan-Meier analysis, patient survival was significantly lower in DM patients with the 2-, 3- and 5-year patient survival rates of 90.8%, 87.8% and 78.2% in non-diabetics and 80.9%, 70.4% and 61.2% in diabetics, respectively. On Cox regression analysis, DM (HR 1.5, p = 0.022), age (HR 1.03, p < 0.001), baseline serum albumin (HR 0.39, p < 0.001), heart failure (HR 0.038, p = 0.038), peripheral artery disease (HR 1.83, p = 0.025) and amputation (HR 4.1, p = 0.009) at baseline were significant predictors of overall mortality. CONCLUSIONS: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality.

Cysteinyl 1 receptor antagonist montelukast, does not prevent peritoneal membrane damage in experimental chronic peritoneal dialysis model in rats.

BACKGROUND/AIMS: Continuous ambulatory peritoneal dialysis (CAPD) induces structural changes in the peritoneal membrane such as fibrosis, vasculopathy and angioneogenesis with a reduction in ultrafiltration capacity. Leukotriene (LT) receptor antagonists have been found to be effective to prevent fibrosis in some nonperitoneal tissues. The aim of this study is to investigate the possible beneficial effect of montelukast, a LT receptor antagonist, on peritoneal membrane exposed to hypertonic peritoneal dialysis in uremic rats. METHODS: Of the 48 male, 5/6 nephrectomized Wistar rats 29 remained alive and were included in the study. These studied rats were divided into 3 groups: Group I (n=7) was the control group, Group II (n=8) was treated with 20 ml hypertonic PDF intraperitoneally daily and Group III was treated with montelukast and similar PDF treatment protocol. The morphological and functional changes in the peritoneal membrane as well as cytokine expression were compared between groups. RESULTS: Submesothelial thickness and the severity of the degree of hyaline vasculapathy were more prominent in group III when compared to group I. There were no significant differences between group II and other groups in terms of submesothelial thickness and the severity of the degree of hyaline vasculapathy. Increased expressions of TGF-ß and VEGF in parietal peritoneal membrane were found in group II and group III when compared to group I. The amount of TGF-ß and VEGF expression were similar in group II and group III. CONCLUSION: This study suggests that montelukast treatment does not prevent the peritoneal membrane from deleterious effects of hyperosmolar PDF in the uremic environment.

Fibroblast growth factor-23 levels are associated with vascular calcifications in peritoneal dialysis patients.

BACKGROUND: The aim of the study was to assess the relationship between fibroblast growth factor-23 (FGF-23) and vascular calcifications (VC) in peritoneal dialysis (PD) patients. METHODS: A cross-sectional study was performed in 55 PD patients who underwent pelvic X-ray to assess for VC. Patients with and without linear calcifications were recorded. RESULTS: Fifteen patients (27.3%) had linear calcifications on pelvic X-ray. FGF-23 levels were higher in patients with VC (299.5 (30.4-2,410.0) vs. 74.4 (14.8-1,030) pg/ml, p < 0.01). Diabetic patients had lower FGF-23 values (43.2 (14.9-134.0) vs. 103.5 (14.8-2,410) pg/ml, p < 0.01). Patients with residual renal function (RRF) had lower FGF-23 levels (70.6 (14.8-513) vs. 179.5 (30.4-2,410) pg/ml, p = 0.06); however, this did not reach statistical significance. FGF-23 levels, age, creatinine, Ca, dialysis duration and HbA1c were positively correlated with VC, whereas RRF, Ca intake and ALP were negatively associated. Multivariate logistic analysis confirmed FGF-23 levels, age, dialysis duration and RRF to be associated with VC. CONCLUSIONS: FGF-23 levels are associated with VC in PD patients. Further studies are needed to clarify whether it is simply a marker or a potential factor. It may prove to be an important therapeutic target for VC management.

Waist circumference is associated with carotid intima media thickness in peritoneal dialysis patients.

PURPOSE: Atherosclerosis is responsible for the high mortality rate in end-stage renal disease patients. Defining risk factors for atherosclerosis may lead to reduction in cardiovascular disease through modification of these factors. Peritoneal dialysis (PD) patients are subjected to high glucose loads on a daily basis, which results in considerable weight gain and an increase in waist circumference (WC). WC as an indicator of abdominal obesity is a risk factor for atherosclerosis in the general population. Carotid artery intima media thickness (CIMT) measurement is a reliable method for the detection of early atherosclerosis. The aim of this study was to investigate the relationship between WC and CIMT and to define risk factors associated with CIMT in PD patients. METHODS: Fifty-five PD patients and 40 healthy controls were included. Atherosclerosis was assessed using measurement of CIMT. Fasting blood was collected for analysis. Anthropometric parameters (age, weight, BMI, and WC) were measured. RESULTS: Peritoneal dialysis patients had higher WC (93.9 ± 1.7 vs. 87.3 ± 1.2 cm, p < 0.05) and CIMT (0.70 ± 0.02 vs. 0.57 ± 0.01 mm, p < 0.01) than the control group. On univariate analysis, age, WC, plaque formation, and D/P creatinine were positively correlated with CIMT, whereas residual renal function, albumin, ultrafiltration volume, and D/D0 glucose were negatively correlated. On multivariate analysis, only age, WC, and plaque formation showed correlation (p < 0.001). CONCLUSIONS: Carotid artery intima media thickness is associated with age, plaque formation, and WC in PD patients. WC measurement is a simple, inexpensive, reproducible, and reliable method of evaluating atherosclerosis risk in PD patients and should be assessed at every visit. Appropriate counsel should be provided to patients with greater WC who are deemed to be at risk for atherosclerosis.

Role of tyrosine kinase inhibition with imatinib in an encapsulating peritoneal sclerosis rat model.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model. METHODS: We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0-3 followed by a peritoneal rest period between weeks 3-6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0-3 followed by 50 mg/kg imatinib mesylate through weeks 3-6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-ß1 (TGF-ß1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry. RESULTS: An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-ß1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-ß1-positivity on immunohistochemistry between the groups. CONCLUSIONS: Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.

Arm circumference: its importance for dialysis patients in the obesity era.

PURPOSE: The purposes of this study were to investigate the association between arm circumference and body mass index (BMI) and to discuss problems, mainly arm circumference and cuff size mismatch, that could affect the reliability of home blood pressure monitoring (HBPM) among peritoneal dialysis (PD) and hemodialysis (HD) patients. METHODS: 525 PD and 502 HD patients from 16 centers were included in the study. A two-part questionnaire was used to gather information from the participants. Arm circumferences were categorized into four groups according to the British Hypertension Society cuff size recommendations. RESULTS: Mean BMI and arm circumference of all participants were 25.0 kg/m(2) and 27.6 cm, respectively. There was a significant correlation between BMI and arm circumference. The mean BMI and arm circumference values were higher in PD patients than in HD patients. Requirement of a large-sized adult cuff was more common among PD patients compared to HD patients (14 % vs 8 %, p = 0.002). CONCLUSIONS: Since HBPM is a useful tool for clinicians to improve BP control, nephrologists should be aware of the problems related to HBPM in dialysis patients and take an active role to increase the reliability of HBPM.

Effects of rapamycin and tacrolimus on mature endothelial cells and endothelial progenitor cells.

OBJECTIVE: To investigate the effects of the potent immunosuppressive agents tacrolimus and rapamycin on the number of circulating mature endothelial cells and circulating endothelial progenitor cells in an experimental model. METHODS: It was an experimental study performed from December 2007 to January 2008 in which the effects of the immunosuppressive agents tacrolimus and rapamycin on endothelial progenitr cells and circulating mature endothelial cells were analysed on 24 male wistar albino rats in a controlled environment model. Circulating cell populations were measured by flow-cytometric analysis. Maun-Whitney U test and analysis of vartiance were used for statistical purposes. RESULTS: Rapamycin increased the number of circulating mature endothelial cells approximately 2-fold compared to tacrolimus. The number of endothelial progenitor cells also was increased in the peripheral blood of rats treated with rapamycin compared to those treated with tacrolimus. CONCLUSION: The study showed that treatment with rapamycin is associated with an increase in endothelial progenitor cells and circulating mature endothelial cells. This increase may be associated with endothelial cell damage and repair.

Unusual causes of peritonitis in a peritoneal dialysis patient: Alcaligenes faecalis and Pantoea agglomerans.

An 87 -year-old female who was undergoing peritoneal dialysis presented with peritonitis caused by Alcaligenes faecalis and Pantoea agglomerans in consecutive years. With the following report we discuss the importance of these unusual microorganisms in peritoneal dialysis patients.

Protective effect of the vasopressin agonist terlipressin in a rat model of contrast-induced nephropathy.

BACKGROUND/AIMS: Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute renal failure. Terlipressin, a long-acting analog of vasopressin, may improve renal function. This study aimed to investigate the possible protective effect of terlipressin against the development of experimental CIN in rats. METHODS: Wistar albino rats (n = 32) were allocated randomly into four equal groups of 8 each, i.e. control, terlipressin, contrast media (CM), and terlipressin plus contrast media (TCM). CIN was induced by intravenous administration of indomethacin (10 mg/kg), N-nitro L-arginine methyl ester (L-NAME, 10 mg/kg, twice at 15 and 30 min), and high-osmolar contrast media meglumine amidotrizoate 60%. Renal function parameters, kidney histology, and tubular expression of vascular endothelial growth factor (VEGF) were determined. RESULTS: Mean serum creatinine levels were decreased (p < 0.05) and creatinine clearance (p < 0.05) increased in the TCM group compared with the CM group. Notably, rats in the TCM group displayed less tubular necrosis (p < 0.05), medullary congestion (p < 0.05), and a reduced tubular expression of VEGF (p < 0.05) compared with the CM group. CONCLUSION: These results demonstrate that terlipressin can inhibit the development of CIN.

Unusual presentation of peritonitis with persistent clear aspirate: a case report.

INTRODUCTION: Peritonitis is the most frequent complication of peritoneal dialysis. Diagnosis of peritonitis includes symptoms and signs of peritonitis with a cloudy aspirate of more than 100 WBC/ml, as well as positive cultures. Although sterile peritonitis has been reported in the literature, to the best of our knowledge this is the first report of an unusual presentation of peritonitis without any white blood cells in the peritoneal aspirate despite multiple positive peritoneal cultures. CASE PRESENTATION: An 82-year-old Caucasian man who had been on continuous cycling peritoneal dialysis for 12 years was admitted to our hospital with general malaise, loss of appetite, weight loss and somnolence. He did not describe abdominal pain or fever. Even though his peritoneal fluid was consistently negative for leukocytes and clear, he had peritonitis with different organisms consecutively. CONCLUSIONS: Our case report shows that any patient on peritoneal dialysis presenting with evidence of infection (fever, peripheral leukocytosis) without an obvious cause should have aspirate cultures done even if the aspirate is clear and abdominal pain is absent. Our case report may change the initial work-up and management of these patients. We believe this report is of interest to general medicine and emergency room physicians as well as nephrologists.