Long-term outcome of kidney transplantation from elderly living and expanded criteria deceased donors.

The imbalance between organ demand and supply causes the increasing use of suboptimal donors. The aim of this study is to investigate the survival and allograft function of kidney transplantation from standard (SLD) and elderly living (ELD), standard criteria (SCDD) and expanded criteria deceased (ECDD) donors. All patients transplanted from 1997 to 2005 were investigated according to the donor characteristics. Data were collected retrospectively during the 83.4±43.1 months of follow-up period. ELD was defined as donor age≥60 years. ECDD was defined as UNOS criteria. A total of 458 patients were divided into four groups: SLD (n:191), ELD (n:67), SCDD (n:154), and ECDD (n:46). Seven-year death-censored graft survival in SLD, ELD, SCDD, and ECDD were 81.6%, 64.8%, 84.7%, and 68.3%, respectively (p=0.003). The death-censored graft survival in ELD group was lower than in SLD (p=0.007) and SCDD (p=0.007) groups, while in ECDD group it was lower than in SCDD group (p=0.026). Patient survival was similar. In ECDD group, 83% of total deaths occurred within the first 3 years, mainly due to infections (66.6%) (p<0.05). Estimated glomerular filtration rate (eGFR) was lower in ELD (compared with SLD and SCDD); and ECDD (compared with SCDD) at last visit. In multivariate analysis, ELD, experience of an acute rejection episode and presence of delayed graft function were the independent predictors for death censored graft loss. Transplantation of a suboptimal kidney provides inferior graft survival and function. A higher number of deaths due to infection in the early post-transplant period in the ECDD group are noteworthy.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS: Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS: HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS: Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION: Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

[Meningoencephalitis caused by West Nile virus in a renal transplant recipient]. / Böbrek nakli alicisinda Bati Nil virusuna bagli meningoensefaliti.

West Nile virus (WNV) infection which is asymptomatic or mild in normal population, it may cause serious clinical conditions leading to death in eldery and immunosupressed patients. The virus is mainly transmitted by mosquito bites, however transfusion, transplantation, transplasental and nosocomial ways have also been reported to be responsible for viral transmission. It is known that WNV may cause life-threatining conditions such as central nervous system (CNS) infections especially in bone marrow and solid organ transplant recipients. In this report, the first case of WNV encephalitis in an immunosuppressed patient with renal transplant in Turkey was presented. A 25-year-old male patient admitted to our hospital with the complaints of generalized myalgia, nausea and vomiting, after the 24. day of renal transplantation from a live donor. Since he developed diffuse tonic clonic seizures during his follow up, he was diagnosed as meningoencephalitis with the results of cranial magnetic resonance imaging (MR) and cerebrospinal fluid (CSF) biochemistry. Bacterial and fungal cultures of blood and CSF yielded negative results. CMV antigenemia test and CMV IgM in blood, and nucleic acid tests for CMV, EBV, HSV-1/2, VZV, HHV-6, enterovirus and parvovirus in CSF were also negative. However, WNV RNA was detected in CSF by an in-house reverse transcriptase (RT) nested PCR method. The sequence analysis (GenBank BLAST) of the virus showed that it had 99% similarity with Lineage-1 WNV strains. To define the transmission way of the virus to the recipient, WNV-RNA was searched in the renal biopsy sample and found negative by RT nested PCR. The clinical condition of the patient was improved with supportive therapy and by the de-escalation of immunosuppressive drugs [Mycophenolate mofetil (MMF; 1 g/day), cyclosporin (1 mg/kg/day)]. However WNV meningoencephalitis recurred one month later. The patient presented with fever, myalgia, confusions, leukocytosis, anemia, and repeating WNV-RNA positivity in CSF. This time cyclosporin was stopped, MMF was given in low dose (1 g/day), and high dose parenteral acyclovir and intravenous immunoglobulin (400 mg/kg/day, 7 days) were initiated. The patient recovered completely after 10 days without any neurological abnormalities. In conclusion, especially in endemic areas, WNV should be considered in the differential diagnosis of CNS infections develop in solid organ transplant cases and patients with other immunodeficiencies who present with fever, generalized myalgia, gastrointestinal symptoms and/or neurological disorders.

Evaluation of choroidal and retinal thickness measurements using optical coherence tomography in non-diabetic haemodialysis patients.

The aim of this study is to evaluate the effects of haemodialysis with a high ultrafiltration rate on the choroidal and retinal thickness of non-diabetic end-stage chronic renal failure (CRF) patients using optical coherence tomography (OCT). Twenty-one eyes of 21 male CRF patients aged between 46 and 80 years were included in this prospective study. Retinal and choroidal thicknesses of the patients were measured using high-resolution OCT line scans with the activated enhanced depth imaging mode before and shortly after haemodialysis. Retinal and choroidal thickness measurements were taken at the fovea and at two points that were 1,500 µm nasal and temporal to the fovea. The relationships between the haemodynamic changes, intraocular pressure (IOP) and central corneal thickness (CCT) were also evaluated. The mean choroidal thicknesses before haemodialysis at the subfoveal, temporal and nasal locations were 232.81 ± 71.92, 212.43 ± 70.50 and 182.14 ± 68.88 µm, respectively. The mean choroidal thicknesses after haemodialysis at the subfoveal, temporal and nasal locations were 210.90 ± 65.53, 195.38 ± 66.48 and 165.19 ± 66.73 µm, respectively. There were significant differences between the choroidal thicknesses before and after haemodialysis (p < 0.001 for all). The mean retinal thicknesses before haemodialysis at the foveal, temporal and nasal locations were 215.86 ± 41.06, 308.86 ± 37.73 and 338.00 ± 33.32 µm, respectively. The mean retinal thicknesses after haemodialysis at the foveal, temporal and nasal locations were 216.90 ± 39.70, 313.86 ± 32.89 and 335.29 ± 36.85 µm, respectively. There was no significant difference between the retinal thicknesses before and after haemodialysis (p > 0.05 for all). The mean CCT decreased insignificantly from 550.48 ± 17.46 to 548.10 ± 21.12 µm (p = 0.411). The mean IOP decreased significantly from 14.09 ± 2.58 to 12.54 ± 2.23 mmHg (p = 0.003), which did not correlate with the CCT [r = (-)0.134, p = 0.562]. Haemodialysis with a high ultrafiltration volume did not alter the retinal thickness but caused a significant choroidal thinning and an IOP decrease in non-diabetic end-stage CRF patients.

Octreotide lessens peritoneal injury in experimental encapsulated peritoneal sclerosis model.

AIM: Encapsulated peritoneal sclerosis is characterized by neoangiogenesis and fibrosis. Octreotide, a somatostatin analogue is a well-known antifibrotic, antiproliferative and anti-angiogenic agent. The aim of the study is to evaluate the effects of octreotide in encapsulated peritoneal sclerosis-induced neoangiogenesis and fibrosis and compare the results with resting. METHODS: Non-uraemic Wistar-Albino male rats (n = 35) were divided into four groups. Group I, control rats, received 2 mL isotonic saline i.p. daily for 3 weeks. Group II, received daily i.p. 2 mL/200 g injection of chlorhexidine gluconate (0.1%) and ethanol (%15) dissolved in saline for 3 weeks. Group III, chlorhexidine gluconate for 3 weeks plus an additional 3 weeks without any treatment (rest), to a total of 6 weeks. Group IV, chlorhexidine gluconate for 3 weeks plus an additional 3 weeks octreotide, 50 mcg/kg bodyweight s.c., for a total of 6 weeks. RESULTS: Octreotide significantly reversed ultrafiltration capacity of peritoneum with decreasing inflammation, neoangiogenesis and fibrosis compared to the resting group. Octreotide also caused inhibition of dialysate transforming growth factor-ß1, vascular endothelial growth factor and monocyte chemotactic protein-1 activity and improved mesothelial cell cytokeratin expression. Peritoneal resting has no beneficial effects on peritoneum. CONCLUSION: In conclusion, octreotide may have a therapeutic value in peritoneal dialysis patients who suffer from encapsulated peritoneal sclerosis.

What does the dialysate level of matrix metalloproteinase 2 tell us?

Long-term peritoneal dialysis leads to encapsulating peritoneal sclerosis (EPS), which is a rare but often fatal complication. The pathogenesis of EPS is characterized by increased inflammation, neoangiogenesis, epithelial-mesenchymal transition (EMT), and fibrosis. Matrix metalloproteinase 2 (MMP-2), which degrades type IV collagen, plays an important role in pathogenesis. Clinical trials report that dialysate levels of MMP-2 can be used as an early marker of peritoneal sclerosis. We aimed to determine the association of MMP-2 with peritoneal function, histology, and effluent cytokine levels in an experimental EPS model in rats. We evaluated data for 71 rats from our various studies using an experimental EPS model. Functional assessment was performed using a 1-hour peritoneal equilibration test with peritoneal dialysis fluid containing 3.86% glucose. Specimens of parietal peritoneum were examined with light microscopy for histologic evaluation. Parietal peritoneum thickness and submesothelial area were measured. Fibrosis, number of vessels, neovascularization, and cellular infiltration were evaluated by one pathologist. The relationships between MMP-2 and other parameters were analyzed using Pearson correlation analysis. Dialysate levels of MMP-2 reflect both functional and histologic change in peritoneum. Levels of MMP-2 were negatively correlated with net ultrafiltration, effluent protein levels, and end (1-hour)-to-initial dialysate concentration ratio of glucose. Cytokines such as vascular endothelial growth factor transforming growth factor beta, monocyte chemotactic protein 1, and osteopontin-which are known to play important roles in neovascularization, inflammation, and EMT leading to fibrosis-were correlated with MMP-2. In peritoneal dialysis patients, MMP-2 levels may be an early marker of EPS and EMT

Risk factors and consequences of post-transplant diabetes mellitus.

BACKGROUND: The aim of this study is to investigate the clinical course as well as risk factors and prognosis of post-transplant diabetes mellitus (PTDM). METHODS: Five hundred fifty-five kidney transplant recipients were retrospectively evaluated. PTDM was defined as fasting blood glucose ≥140 mg/dL on at least two consecutive measurements or requirement of oral antidiabetic drug or insulin. Patients with PTDM were divided into subgroups according to time of onset (early; <90 d vs. late, ≥90 d) and duration of diabetes (transient, <90 d vs. sustained ≥90 d). RESULTS: The frequency of PTDM was 18.3%. In multivariate analysis age (p < 0.001), hepatitis C virus (HCV) infection (p < 0.05) and tacrolimus use (p < 0.001) were independent risk factors. Among 220 HCV+ patients, liver biopsy was performed in 158, the histological grade (3.3 ± 2.8 vs. 4.4 ± 3.1) and stage (0.9 ± 1.1 vs. 1.4 ± 1.2) were significantly more severe in patients with PTDM than in non-diabetics. Incidence of PTDM in patients with severe fibrosis was 46.7%; 19.2% in nil or mild fibrosis (p < 0.05). Patient and graft survival were significantly worse, and cardiovascular events and life-threatening infection episodes were more frequent in PTDM. Half of the patients had early PTDM, while 30.3% of patients with PTDM showed transient nature. Five- and 10-yr death censored graft survival rates were worse in transient subgroup compared with sustained patients with diabetes (log rank 0.025) whereas there was no difference in outcome between early and late subgroups. CONCLUSIONS: Age, tacrolimus, and HCV are independent risk factors for PTDM. PTDM has a negative impact on both patient and graft survival, irrespective of the time of onset and duration of diabetes.

Prevalence of gastroesophageal reflux disease in patients with asthma and chronic obstructive pulmonary disease.

BACKGROUND AND AIM: It is speculated that the prevalence of gastroesophageal reflux disease (GERD) might increase with asthma or chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the prevalence of GERD in patients with asthma and COPD in an area representative of developing countries. METHODS: A validated GERD questionnaire was conducted face-to-face with 308 consecutive asthma (240 women) and 133 COPD (35 women) patients in the tertiary referral pulmonary outpatient clinic, and 694 controls from the research area. Detailed histories of patients and pulmonary function tests were also recorded. RESULTS: The prevalence of GERD (heartburn/regurgitation once a week or more) was 25.4%, 17.0%, 19.4% and occasional symptoms (less than weekly) were 21.2%, 16.3% and 27.0% of patients with asthma, COPD and controls, respectively. The prevalence was higher in the asthma group compared with the controls and the COPD group. No significant difference was found between the COPD group and the controls. Heartburn started following pulmonary disease in 24.1% of the asthma group, and 26.4% of the COPD group. The majority of additional symptoms were significantly higher in asthmatics compared with the controls. No difference was found in the consumption of pulmonary medications in asthmatic patients in groups with different symptom frequency. Heartburn was increased 13.8% by the consumption of inhaler medications. CONCLUSIONS: These results implicate that the prevalence of GERD in asthma and COPD are lower than in published reports in a tertiary referral center. These differences might be related to the characteristics of developing countries, increased consumption of powerful medications in GERD and pulmonary diseases, or methodological flaws in earlier studies.

Does immunosuppressive treatment ameliorate morphology changes in encapsulating peritoneal sclerosis?

Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with ileus symptoms and irreversible sclerosis of the peritoneal membrane. Inflammation, fibrosis, and neoangiogenesis are the main features of the pathophysiology. No evidence-based therapy is currently available for EPS. In recent years, anti-inflammatory and immunosuppressive (IS) treatment modalities have become more popular. The aim of the present study was to investigate the effects of various IS treatment strategies-glucocorticosteroid (GC), azathiopurine (AZT), and cyclosporin (CsA)- on regression of EPS. We divided 52 nonuremic Wistar albino rats into six groups: Control group-2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group-2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for 3 weeks; Resting group-CG (weeks 1 - 3), plus peritoneal rest (weeks 4 - 6); Corticosteroid (GC) group-CG (weeks 1 - 3), plus 10 mg/L prednisolone in drinking water (weeks 4 - 6); AZT group- CG (weeks 1 - 3), plus 100 mg/L azathioprine in drinking water (weeks 4 - 6); and CsA group-CG (weeks 1 - 3), plus cyclosporin 7.5 mg/kg by subcutaneous injection daily (weeks 4 - 6). At the end of the study, under ketamine HCl anesthesia, the rats were humanely killed by bleeding. Parietal peritoneal samples were then taken from same location (away from the injection site) and changes of parietal peritoneum morphology were examined by a single pathologist. The CG severely disturbed parameters of peritoneal morphology, increasing peritoneal thickness, inflammatory activity, vascularity, and fibrosis score as compared with the Control group (p < 0.05). No benefit was observed for any parameter in the Resting group as compared withthose parameters in the CG group (p < 0.05). We observed a lower fibrosis score and less peritoneal thickness in the GC group as compared with the Resting group (p < 0.05). No beneficial effects of AZT on peritoneal morphology were observed as compared with the effects of peritoneal rest or corticosteroid therapy. Treatment with cyclosporin resulted in more fibrosis, vascularity, and inflammation than was seen with corticosteroid therapy (p < 0.05). Immunosuppressive therapies, especially those that are corticosteroid-based, may have therapeutic value in the management of EPS. Patients treated with cyclosporin may have a risk for developing EPS.

[Tuberculin skin test reactivity in patients with chronic renal failure]. / Kronik böbrek yetmezligi olan olgularda tüberkülin cilt testi yaniti.

The aim of this study was to evaluate the response of tuberculin skin test (TST) and the parameters that affect the response in patients with chronic renal failure (CRF) on different treatment regimens. The study population consisted of 150 patients (78 females, mean age 48.1 + or - 16.7 years, the mean disease duration 6.6 + or - 6.1 years). Of these patients, 50 were on haemodialysis (HD), 50 were renal transplant patients, 26 were on peritoneal dialysis (PD) and 24 were treated medically. TST was performed to all patients, an induration with a diameter of 10 mm or more was accepted as positive response in HD, PD, medical treatment groups, whereas 5 mm or more was considered as positive in transplant group. TST was positive in 52% of the study population (56% in HD group, 54% in PD group, 44% in transplant group, 58% in medical treatment group, p> 0.05). There was a positive correlation between TST and age in patients older than 60 of transplant and medical treatment groups (p= 0.008). In HD patients with negative TST, the number of female patients was higher (p= 0.02). In transplant patients with positive TST, duration of HD was shorter (p= 0.01), the blood urea level was lower (p= 0.04), hemoglobin level was higher (p= 0.04). The ratio of negative TST was higher (p< 0.05), TST reactivity was smaller (p= 0.01) in only transplant patients with no BCG scar. The number of BCG scar was correlated positively with TST (p= 0.04). In the medical treatment group, patients with positive TST response were older (p= 0.02) and in PD group the tuberculin reactivity was not affected by any of the patient-related parameters. It must be considered that the response to TST is low in young patients with uncontrolled CRF and under immunosuppressive therapy.

Impact of body mass index on short-term and long-term survival in prevalent hemodialysis patients.

INTRODUCTION: Numerous studies showed that higher body mass index (BMI) is associated with better survival in hemodialysis (HD) patients. Most of them evaluated short-term mortality. It has been suggested that presence of inflammation may be a key modifier of relationship between BMI and mortality in incident HD patients. We examined whether presence of inflammation modifies the association between BMI and mortality in both short-term and long-term follow-up in a large group of prevalent HD patients. METHODS: A total of 3.252 HD patients from 41 HD centers were enrolled; the patients were divided into quartiles based on time-averaged BMI (Q1 < 21.5, Q2 21.5 to <24.3, Q3 24.3 to <27.4, Q4 ≥ 27.4 kg/m2 ). Inflammation status was defined as present (inflamed) (C-reactive protein (CRP) ≥1.0 mg/dL and/or serum albumin ≤3.5 g/dL) or absent (noninflamed). FINDINGS: During 7 years of follow-up 1386 patients (42.6%) died. Compared to noninflamed patients, inflamed patients in the lowest BMI quartile showed 5-fold increased risk for mortality in the short-term (95% confidence interval [CI] 2.82-9.22, P < 0.001) and 3-fold in the long-term (95%CI 2.42-4.27, P < 0.001) compared to the highest BMI quartile. Whereas, inflamed patients in the highest BMI quartile experienced 2-fold increased risk in short-term (95%CI 1.17-3.74, P = 0.01) and 1.68-fold increased risk in long-term (95%CI 1.30-2.18, P < 0.001) than in noninflamed patients. The protective effect of BMI for overall mortality was present in all age groups, in both genders, in patient with and without diabetes. BMI was not a mortality predictor in patients with HD duration more than 76 months at baseline. The protective effect of BMI was observed in all albumin tertiles. In patients in the lowest CRP tertile, BMI was not associated with mortality. DISCUSSION: Higher BMI is associated with lower short-term and long-term mortality risk, especially in patients with inflammation in a prevalent HD population.

The effects of renin-angiotensin system inhibition on regression of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin-angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. OBJECTIVE: To determine the advantages of RAS blockade in regression of EPS. METHODS: We divided 56 nonuremic albino Wistar rats into 6 groups: control group (n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group (n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group (n = 10), daily IP injection of CG (0 - 3 weeks) plus peritoneal rest (4 - 6 weeks). After 3 weeks of being injected with CG (0 - 3 weeks), a fourth group (n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group (n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group (n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 - 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. RESULTS: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity (p < 0.05), and peritoneal thickness (p > 0.05). Dual blockade of RAS had no additional beneficial effects. CONCLUSION: We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.

The effects of colchicine on the progression and regression of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. OBJECTIVE: To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). METHODS: 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 - 3 weeks) + peritoneal resting (4 - 6 weeks); C-R group, CG (0 - 3 weeks) + 1 mg/L colchicine (4 - 6 weeks); C-P group, CG (0 - 3 weeks) + 1 mg/L colchicine in drinking water (0 - 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. RESULT: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. CONCLUSION: We suggest that colchicine may have therapeutic value in the management of EPS.

Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model.

The most serious complication of peritoneal dialysis is encapsulating peritoneal sclerosis (EPS). The prolonged inflammatory stimuli, fibrogenic cytokine overexpression, and angiogenesis that underlie EPS ultimately result in increased production of fibrous tissue, encapsulating the bowel loops. In recent years, inhibitors of mammalian target of rapamycin (mTOR) as an alternative agent for calcineurin inhibitor toxicity have been widely used in organ transplantation. These agents have also been used since the 1990s in endovascular medicine for drug-eluting stents because of antiproliferative effects on vascular smooth muscle cells and potent anti-inflammatory properties by direct action on human immune cells. Because of the shared characteristics of EPS and other fibrotic processes, we hypothesized that everolimus, an mTOR inhibitor can reverse the process responsible for the eventual development of EPS. We allocated 32 non-uremic albino Wistar rats to 4 groups: control group, 2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group, 2 mL/200 g (0.1%) chlorhexidine gluconate (CG) injected IP daily and ethanol (15%) dissolved in saline, for 3 weeks; resting group, CG (weeks 0 - 3), plus peritoneal rest (weeks 3 - 6); and Evo-R, CG (weeks 0 - 3), plus 0.3 mg/L everolimus in drinking water (weeks 3 - 6). At the end of the study, we performed a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution, and examined the dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell count, ultrafiltration (UF) volume, and morphologic change in the parietal peritoneum. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, p < 0.05). Peritoneal rest has some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However; everolimus was more effective than peritoneal rest with regard to vascularity and peritoneal thickness (p < 0.05). Everolimus has beneficial effects on UF failure, inflammation, and fibrosis. Everolimus may have therapeutic value in the management of EPS.

What does peritoneal thickness in peritoneal dialysis patients tell us?

Loss of peritoneal function is a major factor leading to failure of treatment in peritoneal dialysis (PD). Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. The aim of the present study was to uncover the relationship between functional parameters of peritoneum and peritoneal thickness as measured by ultrasonography. We studied 43 prevalent patients who had been on PD for at least 12 months in the Ege University PD unit. We recorded body weight, height, age, sex, PD duration, episodes of peritonitis, and results of peritoneal equilibration tests. Parietal peritoneal thickness was measured from four abdominal quadrants at the mid-clavicular line. The peritoneal thickness measurement was determined as the mean of the four separate measurements. (In some cases, the measurement at one of the lower quadrants was excluded from the calculation if the peritoneal catheter was present near the area probed.) Mean peritoneal thickness in the patients was 446 +/- 164 microm (range: 250-930 microm), which was significantly correlated with mean body weight (r = 0.31, p < 0.05), height (r = 0.31, p < 0.05), end-to-initial ratio of dialysate glucose (r = -0.44, p < 0. 01), dialysate-to-plasma creatinine (r = 0.51, p < 0.01), and PD duration (r = 0.48, p < 0.01). Peritoneal thickness was positively correlated with time on dialysis, being a median of 370 microm [interquartile range (IQR): 283-400 microm] in patients who had been on PD for less than 24 months up and 660 microm (IQR: 483-733 microm) in patients who had undergone PD for more than 6 years. Ultrasound examination is a simple and noninvasive method of measuring peritoneal thickness in PD patients. It may be useful in the study of peritoneal structure and function. Sequential measurements over time may be useful for early diagnosis of encapsulating peritoneal sclerosis.

Patients with failed renal transplant may be suitable for peritoneal dialysis.

BACKGROUND: It has been claimed that patients with late transplant failure returning to peritoneal dialysis have lower patient and technique survival. PURPOSE: In this retrospective study, we aimed to clarify this issue in a large PD population. METHODS: Thirty-four PD patients with a failed renal transplant (FTx) and 82 PD patients who had never received a kidney transplant (Non-Tx) or HD treatment were investigated. All fTx patients were using only steroids (5-10 mg/day) for first 3 months of peritoneal dialysis. The groups were similar regarding to age, sex, residual renal function and KT/V; none of them was diabetic. RESULTS: Ftx group had a higher number of peritonitis attack than Non-Tx group (2.42 +/- 0.41 v 1.61 +/- 0.15, attack per patient, p = 0.013). PET status was not different. One, 3 and 5 year patient survival calculated with the Kaplan Meier method were 93%; 93%; 93% respectively in Ftx and 97%; 89%; 82% respectively in Non-Tx patients. Technique survival was 83%; 77%; 60% in Ftx and 91%; 64%; 48% in Non-Tx patients respectively. CONCLUSIONS: We conclude that PD appears to be a good option for fTx patients. A previous renal transplantation does not adversely affect patient and technique survival. Although the somewhat higher infection risk is of some concern, we did not observe earlier loss of peritoneal functions (high transporter) in the post transplant patients.

Glycosylated hemoglobin levels are associated with cardiovascular events in nondiabetic peritoneal dialysis patients.

BACKGROUND: High glycosylated hemoglobin (HbA1c) levels are recognized as a risk factor for cardiovascular disease in the diabetic dialysis population. However, it is not known whether this also applies to nondiabetic dialysis patients. We prospectively investigated the association between HbA1c levels and new cardiovascular events in nondiabetic patients treated with peritoneal dialysis. METHODS: Eighty nondiabetic patients who had been on peritoneal dialysis treatment were prospectively followed for 5 years. HbA1c levels were measured at baseline and every 3 months. Fatal and nonfatal cardiovascular events were assessed during the follow-up. RESULTS: Mean age was 48.5 ± 15.2 years; 51% were male. Baseline HbA1c level was 5.46% ± 0.41% (range 4.6%-6.3%). Mean HbA1c was 5.44% ± 0.31% (range 4.8%-6.3%) during the study, and positively correlated with age and high-sensitivity C-reactive protein. Twenty fatal and nonfatal cardiovascular events were observed during a mean 41.8 ± 7.1 months of follow-up. Event-free survival was better in patients with HbA1c levels <5.45%, compared with that for those with HbA1c levels =5.45% (p=0.01). In crude Cox regression analysis, an increase in HbA1c level of 0.1% was associated with a 1.22-fold increase in new cardiovascular events (p=0.007). In Cox analyses, HbA1c level was found as a significant predictor of cardiovascular events. CONCLUSION: HbA1c levels predict fatal and nonfatal cardiovascular events in nondiabetic peritoneal dialysis patients.

Neither oxidized nor anti-oxidized low-density lipoprotein level is associated with atherosclerosis or mortality in hemodialysis patients.

It is anticipated that oxidized low-density lipoprotein (oxLDL) and anti-oxLDL are associated with atherosclerosis and mortality. However, data on this issue are controversial and limited. We aimed to investigate the effect of these two markers on the extent and progression of atherosclerosis and mortality in a group of hemodialysis patients. In this prospective observational study with a follow-up of 36 months, 124 hemodialysis patients were studied. Ninety-five patients underwent carotid intima media thickness (CA-IMT) measurement by B-Mode ultrasonography both at baseline and at the end of the study. oxLDL and anti-oxLDL were measured by enzyme-linked immunosorbent assay. The extent and progression of CA-IMT, along with overall and cardiovascular mortality, were assessed. The mean age at baseline was 54.0 ± 14.8 years, 57.3% male and 20% diabetic. The mean oxLDL and anti-oxLDL levels were 8.11 ± 3.16 mU/L and 1.30 ± 0.31, respectively. Baseline mean CA-IMT was 0.82 ± 0.20 mm. Fifteen patients died during a follow-up period of 28.5 ± 6.6 months, 11 from cardiovascular causes. Only oxLDL, not anti-oxLDL, was correlated with the extent of atherosclerosis at baseline. However, both had no role in the progression of atherosclerosis. Also, in unadjusted and adjusted models, both parameters were not associated with overall or cardiovascular mortality. Neither oxLDL nor anti-oxLDL level is associated with the progression of atherosclerosis or mortality in hemodialysis patients.

A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis.

INTRODUCTION: Encapsulated peritoneal sclerosis (EPS) is characterized by neoangiogenesis and fibrosis. Increased inflammation is the leading cause of EPS. In turn, neoangiogenesis is both a consequence of and contributor to inflammation. The effects of sunitinib, a multitargeted receptor tyrosine kinase inhibitor, have been postulated in various antiangiogenesis, antiinflammatory and antifibrotic processes both in vitro and in vivo. This novel angiogenesis inhibitor, Sutent (sunitinib malate), was investigated in our rat EPS model. MATERIALS AND METHODS: Forty nonuremic Wistar albino rats were divided into 4 groups as follows: 2-mL isotonic saline intraperitoneally (i.p.) daily, for 3 weeks (control group); daily 2 ml/200 g injection i.p. of chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline, 3 weeks (CG group); CG + additional 3 weeks without any treatment, total 6 weeks (resting group); and CG + additional 3 weeks 1 mg/kg daily Sutent (SUT) in drinking water, total 6 weeks (SUT group). At the end of the study, 1-hour PET was performed. Functional parameters and morphological changes of peritoneum with dialysate cytokine levels were examined. RESULTS: SUT renewed ultrafiltration failure, D1/D0 glucose levels and dialysate protein loss. Peritoneal thickness, white blood cell count and inflammation of peritoneum were also decreased with SUT treatment. SUT significantly improved overexpression of dialysate transforming growth factor-ß1, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) levels as compared with resting group. CONCLUSION: In conclusion, SUT might preserve membrane viability even at lower dosages. Although this is an experimental study, we believe that SUT after controlled trials may be a therapeutic agent for long-term peritoneal dialysis patients.