Short-term effects of bicarbonate/lactate-buffered and conventional lactate-buffered dialysis solutions on peritoneal ultrafiltration: a comparative crossover study.

BACKGROUND: This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. METHODS: Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. RESULTS: Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 +/- 602 ml and 881 +/- 633 ml with P (P < 0.001) and this lower daily UF of 443 ml (95% CI 275-610 ml) with P was associated with a similarly lower daily total fluid removal of 394 ml (95% CI 210-577 ml), as urine volume did not differ between D and P. The decrement in UF with the P solution was reversible. There were no significant differences in other peritoneal membrane indices (D/P creatinine, D/D0 glucose, 4-h UF at PET, weekly creatinine clearance, weekly urea Kt/V) or blood pressure and body weight between the solutions whereas calculated peritoneal fluid absorption rate was significantly higher with the P than with the D solution. CONCLUSION: This study shows that the daily UF with the P solution may be lower than with the D solution. The mechanism for this short-term and reversible effect that conceivably reflects differences in biocompatibility is not clear although our results implicate that the peritoneal fluid absorption rate may differ between the two solutions.

Short-term effects of a new bicarbonate/lactate-buffered and conventional peritoneal dialysis fluid on peritoneal and systemic inflammation in CAPD patients: a randomized controlled study.

OBJECTIVES: This study was designed to compare the local peritoneal and systemic inflammatory effects of a conventional lactate-based (Lac) peritoneal dialysis (PD) solution and a new biocompatible bicarbonate/lactate-based (Bic/Lac) solution having low concentration of glucose degradation products. METHODS: 26 stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the Lac solution and 3 months with the Bic/Lac solution in a randomized order. Flow cytometry was used to measure the expression of inflammatory molecules on peritoneal cells in overnight effluent collected at the end of each study period. RESULTS: 21 patients successfully completed the study. Mean fluorescence intensity of human leukocyte antigen (HLA)-DR and CD14 expression by macrophages were not different between Lac and Bic/Lac. The peritoneal appearance rate of cancer antigen 125 (kU/minute) was 68 +/- 37 with Lac and 133 +/- 66 with Bic/Lac (p < 0.001), and of interleukin (IL)-6 (ng/minute), 0.28 +/- 0.2 with Lac and 0.18 +/- 0.16 with Bic/Lac (p = 0.014). HLA-DR macrophage expression and IL-6 peritoneal appearance rates did not correlate. Serum concentrations with Lac and Bic/Lac were, for IL-6, 3.49 +/- 2.28 and 3.72 +/- 2.46 ng/L (p = 0.17), and for high-sensitivity C-reactive protein, 2.31 +/- 2.98 and 2.71 +/- 3.31 mg/L (p = 0.32) respectively. The concentration of effluent macrophages (x10(6)/L) with Lac was 1.6 +/- 1.6 and with Bic/Lac 2.6 +/- 3.3 (p = 0.07). CONCLUSIONS: We conclude that, although there was a significant reduction in peritoneal IL-6 in patients using Bic/Lac solution, systemic levels of inflammatory markers did not differ between the two solutions and no changes were present in macrophage surface activation markers, suggesting perhaps a less important role of peritoneal macrophages in the intraperitoneal chronic inflammatory process. The number of effluent macrophages tended to be higher in patients using the Bic/Lac solution, possibly contributing to improved intraperitoneal defense.

Impact of dialysis duration and glucose absorption on nutritional indices in stable continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The presence of comorbidity is a risk factor for both poor nutrition and poor outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In CAPD specifically, peritoneal glucose load is associated with a possible suppression of appetite, contributing to protein malnutrition. This study sought to explore the factors associated with malnutrition indices in stable peritoneal dialysis patients without significant comorbidity, and to assess the impact of peritoneal glucose absorption on nutrition parameters. DESIGN: This was a cross-sectional observational study. SETTING: This study took place in the peritoneal dialysis department of a university hospital, and involved outpatients. PATIENTS: There were 23 stable, comorbidity-free CAPD patients (9 women), aged 54 +/- 12 years, with a CAPD duration of 28 +/- 25 months (values are mean +/- SD unless otherwise noted). METHODS: Nutritional status was evaluated by means of anthropometric and serum measurements. A peritoneal equilibration test was performed, and daily glucose absorption was measured. Lean body mass (LBM) was assessed through creatinine kinetics. RESULTS: A significant impact of CAPD duration was found. Patients in the upper quartile of CAPD duration had worse nutritional parameters compared with the rest of the group: their mid-upper-arm surface area and fat surface area were lower (65 +/- 9 cm(2) vs. 78 +/- 6.2 cm(2) and 16 +/- 5.3 cm(2) vs. 26 +/- 9.5 cm(2), respectively, P < .05), their albumin concentration was lower (36 +/- 0.5 g/L vs. 42 +/- 4 g/L, P < .05), and their cholesterol and triglycerides were lower (3.5 +/- 0.5 vs. 5.2 +/- 1 mmol/L and 1.3 +/- 0.6 vs. 2.3 +/- 1.1 mmol/L, respectively, P < .05). No significant correlations between peritoneal glucose absorption and these indices were found. CONCLUSION: The duration of dialysis treatment, but not peritoneal glucose absorption, is a predictor of malnutrition in stable, comorbidity-free CAPD patients.

Epoetin responsiveness in peritoneal dialysis patients: a multi-center Slovenian study.

The objective of our study was to assess the influence of residual renal function and other factors on epoetin requirements in chronic peritoneal dialysis patients. Fifty-one stable patients (mean age +/- SD: 52 +/- 13 years; 20 women) without recent bleeding, bone marrow disease or malignancy were recruited in four Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal equilibration test results and relevant clinical and laboratory parameters were recorded. The epoetin resistance index was expressed as a weekly epoetin dose/body weight/hemoglobin concentration. Twenty-four percent of the patients did not need epoetin treatment, the rest were treated with epoetin-beta in a dose of 70 +/- 56 U/kg per week s.c.; the hemoglobin concentration was 124 +/- 15 g/L. Ferritin >100 microg/L and transferrin saturation >20% fulfilled 63% of patients whose epoetin resistance index was not significantly lower (0.43 +/- 0.5 U/kg per week per g/L vs 0.6 +/- 0.72 U/kg per week per g/L, P = 0.502). No difference was found between diabetic and non-diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, was associated with increased epoetin resistance index (0.56 +/- 0.59 vs 0.3 +/- 0.4 U/kg per week per g/L, P = 0.038). No correlation between epoetin resistance index and residual glomerular filtration rate was found (r = -0.2, P = 0.173). A multiple linear regression analysis showed C-reactive protein, intact parathormone level, female sex and treatment with angiotensin system antagonists to be the independent predictors influencing epoetin resistance index. Our results show that systemic inflammation, secondary hyperparathyroidism and angiotensin system antagonist treatment are the most important modifiable parameters affecting epoetin requirements in stable peritoneal dialysis patients.

Influence of renin-angiotensin-aldosterone system-blocking drugs on peritoneal membrane in peritoneal dialysis patients.

Therapy with renin-angiotensin-aldosterone system (RAAS)-blocking drugs prevents the development of fibrosis and angiogenesis in animal models and humans. In our study we have evaluated the systemic effect of RAAS blockade and the effect on peritoneal growth factors, cytokine production and membrane transport characteristics in patients on peritoneal dialysis. Thirty-seven peritoneal dialysis (PD) patients were enrolled in our cross-sectional study. Aldosterone and angiotensin II concentrations were measured in serum to determine the RAAS activity. The inflammatory and profibrotic activity was evaluated by measuring the concentration of C-reactive protein (CRP), serum albumin, and peritoneal concentration of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-ß (TGF-ß) and cancer antigen-125 (CA-125). The transport characteristics of the peritoneal membrane were analyzed with a peritoneal equilibration test (PET). Results were compared between the group with RAAS-blocking drugs (RAAS group) and the group without them (non-RAAS group). Mean serum aldosterone concentration was significantly lower in patients treated with ARB-blocking drugs (P = 0.001) and serum angiotensin II concentration was lower in patients treated with ACE inhibitors (P = 0.009). RAAS blockade resulted in lower peritoneal PAI-1 levels (748.1 to 1222.7 ng/L; P = 0.07) without any influence on CRP, peritoneal concentrations of IL-6, VEGF, TGF-ß and CA-125, or alteration in peritoneal membrane characteristics tested by PET. RAAS-blocking drugs could be effective in preventing peritoneal fibrosis due to possible reduction of peritoneal PAI-1 concentrations that have already been etiologically linked with fibrin deposition in the pathogenesis of encapsulating peritoneal sclerosis.

Renal replacement therapy in Slovenia: excerpts from 2011 data.

This report provides a summary of the 2011 Slovenian renal replacement therapy (RRT) data. Data were obtained from 24 renal centers: 23 dialysis and one transplant center, referred as of 31 December 2011, with 100% response rate to individual patient questionnaires. Slovenia has a population of approximately 2 million (2 052 496 in 2011). The total number of patients treated by RRT was 2011,that is, 980 per million of population (pmp); 0.4% decrease compared to 2010. 1347 (67.0%) were treated by hemodialysis, 60 (3.0%) by peritoneal dialysis, and 604 (30.0%) had a functioning kidney graft. A total of 236 incident patients, 115 pmp (at day one), started RRT, their median age was 68 years, 64.8% were men, 36.4% were diabetics. Regarding hemodialysis patients, 59.3% were treated with on-line hemodiafiltration, 86% with ultrapure dialysis fluid. Median weekly duration of hemodialysis was 12.5 h, median dry body weight 70 kg, mean blood flow 275 ± 46 mL/min, 7.1% were dialyzed in a single-needle mode. Vascular accesses were native arteriovenous fistula in 79%, polytetrafluoroethylene graft in 6%, and catheter in 15%. The crude death rate was 15.9% in dialysis patients, 1.9% in transplant recipients, and 12.0% in all RRT patients (both dialysis and transplant, incident patients at day 1 included). Slovenia has been a member of Eurotransplant since 2000. Forty-six kidney transplantations were performed in 2011, all from deceased donors. A slight decrease in prevalent number of RRT patients was observed in 2011, for the first time in 40 years. The number and proportion of patients with functioning kidney grafts is increasing, reaching 30% in 2011.

Severe peritonitis in patients treated with peritoneal dialysis: a case series study.

Severe peritonitis causing death and/or technique termination (catheter explanted) is one of the most devastating complications of peritoneal dialysis (PD). The aim of this case series study was to reveal the predictors of risk and clinical characteristics of these cases. We included 38 patients with either peritonitis causing death (18 patients, 47%) or catheter removal (20 patients, 53%) in the period 1996-2006. Their last clinical, laboratory and peritoneal equilibration test data before the peritonitis episode and hospitalization data after the start of peritonitis were reviewed. Their median (range) age was 66 (25-85) years, 61% were male, and the median PD duration was 60 (1-144) months. Baseline C-reactive protein (17.5 ± 19.1 mg/L) was substantially higher than in contemporary stable controls from our unit (3.5 ± 4.2 mg/L, P = 0.002). For 14 patients (37%), this was their first episode, with a significantly lower mortality of 14% as opposed to 47% across the whole group (P = 0.002). Almost half the patients (42%) had a causative abdominal condition identified, such as diverticulitis or cholecystitis. Clinical and laboratory data at presentation were variable and not different according to survival. Non-surviving cases had a significantly larger proportion of fast transporters (83 vs. 45%, P = 0.03), a significantly lower estimate of daily protein intake (0.72 vs. 0.88 g/kg/day, P = 0.007), and a significantly higher proportion of non-Gram-positive causative microorganisms (72 vs. 40%, P = 0.019). The patients with severe peritonitis were characterized as older with a longer PD duration, and a higher baseline C-reactive protein. Fast peritoneal transport, lower normalized protein catabolic rate, and non-Gram-positive causative bacteria were associated with mortality.

Cell-free DNA in the peritoneal effluent of peritoneal dialysis solutions.

The beneficial effects of novel peritoneal dialysis solutions low in glucose degradation products regarding peritoneal cell apoptosis and necrosis are well established in vitro, however in vivo data is lacking. Cell-free DNA quantification is a possible method to determine cell damage through apoptosis and necrosis in vivo. We performed a prospective, cross-over study on 26 stable continuous ambulatory peritoneal dialysis (CAPD) patients, treating each patient for 3 months in a randomized order with a conventional, lactate-buffered, acidic solution (solution D) and a novel, bicarbonate/lactate-buffered neutral solution (solution P). The timed overnight peritoneal effluent was sampled for cell-free DNA quantification using a fluorometric assay. The effluent samples of eighteen patients were finally available for DNA quantification. The concentration range of cell-free DNA in the peritoneal effluents was 1.8-9.5 microg/L. The coefficient of intrapatient variation in overnight effluent cell-free DNA appearance was 15.6 +/- 12.4%. Cell-free DNA peritoneal appearance using solutions D and P was 14.9 +/- 6.8 microg and 11.8 +/- 3.4 microg, respectively (P = 0.02), with the average difference of 3.1 microg (95% CI, 0.7-5.6 microg). Our results show that cell-free DNA is present in the overnight peritoneal effluent of stable CAPD patients. A significant decrease in the cell-free DNA appearance with solution P was found; however, before accepting this as an indicator of a more biocompatible profile causing less peritoneal membrane cell necrosis and apoptosis, confirmatory data on larger patient samples are needed. Our results indicate the potential future role of cell-free DNA in the diagnosis and prognosis of therapy-related peritoneal membrane degeneration.

Encapsulating peritoneal sclerosis in patients on peritoneal dialysis in Slovenia.

Encapsulating peritoneal sclerosis (EPS) is a rare complication in patients on peritoneal dialysis (PD), the prevalence of which increases with the time spent on PD. Various causative factors have been proposed, but the pathogenesis still remains unclear. The aim of our retrospective study was to analyze the basic clinical characteristics and outcomes of five patients diagnosed with EPS out of 423 patients treated with PD between January 1983 and December 2003. One patient was admitted due to ultrafiltration failure of the peritoneal membrane, and four patients were admitted for acute peritonitis. All of our patients presented with clinical symptoms suggestive of obstructive ileus. We confirmed the diagnosis of EPS with a computer tomography scan, a diagnostic laparotomy or laparoscopy, and a biopsy of the parietal peritoneum. We treated all of our patients with catheter removal, transferal to hemodialysis, antibiotics, complete parenteral nutrition, methylprednisolone, and tamoxifen for 6 months. One patient was treated with surgical enterolysis and died of septic complications, another patient died of sudden cardiac death during treatment. Three patients were doing well for 4-7 months after the treatment was started. The incidence of EPS was 1.2% and the mortality rate was 40%. EPS is a rare complication in longstanding PD patients in our institution. Despite treatment with hemodialysis, complete parenteral nutrition, steroids, tamoxifen and surgical intervention, the mortality rate is high and comparable to other reports.