Stable Peritoneal Dialysis Patients Research Articles

Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

No Significant Differences in Peritoneal Fluid Handling in Children Using pH-Neutral or Acidic Solutions

Differences in peritoneal fluid handling in the acute setting can be expected if children are converted to pH-neutral dialysis solutions because conventional acidic solutions exert toxic effects on peritoneal mesothelial cells and microcirculation. Peritoneal fluid kinetics was therefore investigated with both types of solutions in a group of children. Peritoneal equilibration tests (PETs) were performed in 12 patients [mean age 70 months, mean time on peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal 3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The results of these PETs were compared to those of a historic group of 12 children (mean age 75 months, mean time on PD 17 months). Pediatric dialysis unit in a tertiary institute. Stable pediatric PD patients. Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. TCUF and lymphatic absorption were not different between the two groups. There was also no significant difference in small solute clearance measured by D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis solutions are applied compared to acidic solutions. An altered TCUF, as is hypothetically possible using an acidic solution, was not established.

Effect of iodinated contrast agents on residual renal function in PD patients

Residual renal function (RRF) is an important predictor of outcome in peritoneal dialysis (PD) patients. Although increasing emphasis has been placed on preserving RRF, the nephrotoxicity associated with contrast medium administration in PD patients remains a controversial issue. In the present prospective study, we evaluated the evolution of RRF 2 weeks after iodinated contrast medium administration (ICMA) in a group of stable PD patients, and compared it with that in a non-treated control group of stable PD subjects. The study was conducted from January 2003 to October 2004. RRF was quantified by the average of 24 h urinary urea and creatinine clearance and peritoneal creatinine clearance (PcrCl) were analyzed, the levels of which were analysed prior to and 2 weeks following ICMA in 36 PD patients and also assessed at the same time points in a group of 36 PD non-ICMA control subjects, matched according to RRF characteristics. Two weeks following ICMA, the values for RRF, daily urine volume and PcrCl were assessed against those at baseline, and the evolution of RRF was compared between the two groups. In the ICMA group, this study was performed with adequate pre-hydration and a minimum dose of contrast medium. Compared with baseline values, RRF, daily urine volume and PcrCl were not found to be significantly different 2 weeks after ICMA (7.0+/-4.3 vs 7.2+/-4.3 ml/min/1.73 m(2), P = 0.12; 1324+/-696 vs 1360+/-755 ml/day, P = 0.5; and 41.1+/-9 vs 40.6+/-9 l/week/1.73 m(2), P = 0.6, respectively). Following ICMA, variations in RRF and daily urine volume were found to be comparable with those of the control group (0.1+/-0.5 vs 0.1+/-0.5 ml/min/1.73 m(2), P = 0.9; 36+/-440 vs 40+/-493 ml/day, P = 0.8, respectively). In this study, 2 weeks following ICMA, no accelerated decline in RRF was determined in stable PD patients with adequate pre-hydration, i.e. subjects treated under optimal circumstances compared with the control group.

The contribution of free water transport and small pore transport to the total fluid removal in peritoneal dialysis

Water transport in peritoneal dialysis (PD) patients is across the small pores and water channels, the latter allowing free water transport. The objective of the study was to investigate the contribution of each transport route on transcapillary ultrafiltration (TCUF). Standard peritoneal permeability analyses of 80 stable PD patients were analyzed. Twenty-nine patients were followed longitudinally. Fluid transport through small pores (SPT) was assessed by the amount of transported sodium. Free water transport (FWT) was calculated by subtracting SPT from TCUF. The contribution of FWT and SPT to the TCUF and water transport rates at any time point was computed. The ultrafiltered volume due to SPT increased gradually during the dwell, while FWT reached its maximum around 3 hours. The rate of FWT decreased continuously during the dwell. SPT decreased during the initial 2 hours and remained stable thereafter. At 60 minutes, the SPT (P < 0.05) and its contribution (P < 0.05) were positively related to the MTAC(creat). The contribution of FWT after 1 hour, but not the absolute amount, showed an inverse relationship. Peritoneal solute transport parameters (P < 0.01) and the contribution of SPT (P= 0.08), but none of the other fluid parameters showed a U-shape with the lowest values in the second year of PD (P < 0.01). The dwell courses of water transport suggest that the activity of water channels is dependent and limited by the crystalloid osmotic pressure gradient, while other determinants are important in SPT. The time-course of SPT paralleled that of peritoneal solute transport parameters.

Current and future challenges in anaemia management

The introduction of recombinant human erythropoietin (rhEPO; epoetin) nearly 20 years ago revolutionized the management of renal anaemia. The correction of anaemia with epoetin is associated with improvements in the quality of life of patients with chronic kidney disease (CKD), and reductions in morbidity and mortality. In this supplement, the authors present an overview of pertinent issues in renal anaemia management that were tackled during two satellite symposia held on June 9 and 10, 2003 at the World Congress of Nephrology in Berlin, Germany: ‘Current and future challenges in anaemia management’ and ‘Who wants to defeat anaemia? An interactive insight into anaemia management today’. All recombinant human proteins can potentially induce an immune response, especially when administered repeatedly over prolonged periods. A multitude of factors, including structural properties, storage and handling, contaminants and impurities, administration and formulation, may affect immunogenicity. In recent years, a peak was noted in the number of cases of pure red cell aplasia (PRCA) associated primarily with one particular epoetin-a product available outside of the USA, Eprex /Erypo . As a result, regulatory authorities in Europe restricted the administration of this product to the intravenous (i.v.) route. Currently there is no evidence for an increasing trend in antibody-mediated PRCA for this or other epoetin formulations. The optimal route of epoetin administration has been explored in numerous studies. Current European Best Practice Guidelines and K/DOQI Guidelines on renal anaemia management recommend subcutaneous (s.c.) administration as the preferred route for epoetin in CKD patients not on dialysis, in haemodialysis, peritoneal dialysis and transplanted patients, when not contraindicated. These recommendations take into account the efficacy, frequency of dosing, cost and convenience of epoetin treatment, alongside the safety and tolerability of specific products. Target haemoglobin (Hb) levels can be maintained with much lower doses of epoetin when administered by the s.c. route. Clearly, therefore, s.c. administration of epoetin is associated with economic advantages in terms of direct drug cost and may also provide cost benefits by relieving the burden on health care services. In the case of epoetin-b, s.c. administration allows for reduced dosing frequencies at once weekly and even once every 2 week intervals during the maintenance phase of treatment in stable peritoneal dialysis patients, without compromising safety or efficacy. Reduced dosing frequency and the availability of a pen device, specifically designed for the self-administration of s.c. epoetin-b, should increase patients’ readiness to self-administer treatment and should facilitate the early initiation of anaemia treatment in patients with CKD not yet requiring dialysis. Anaemia contributes to the progression of cardiovascular disease. Detrimental effects begin at an early stage of CKD, well before kidney function deteriorates to the point when dialysis is required. Indeed, low Hb is an independent risk factor for left ventricular (LV) growth in CKD patients not needing dialysis, as well as in patients receiving dialysis, and in those who have undergone renal transplantation. Data suggest that management of anaemia can significantly reduce the cardiovascular risks associated with CKD; early correction of anaemia may be especially important in improving patient outcomes. The ability of epoetin to reverse changes in LV geometry may be limited in patients with advanced renal and cardiac disease. In this regard, the ongoing Cardiovascular risk Reduction by Early Anaemia Treatment with Epoetin b (CREATE) study, which is investigating the benefits of early, complete anaemia correction with epoetin-b on cardiovascular events in patients with CKD not receiving renal replacement therapy, will provide important information. The risk of developing cardiovascular disease is even higher in patients with CKD who also have diabetes. Diabetes is now the most common primary diagnosis associated with end-stage renal disease (ESRD), and a Correspondence and offprint requests to: Professor Eberhard Ritz, Department of Internal Medicine, Bergheimer Str. 56a, D-69115 Heidelberg, Germany. Email: Prof.E.Ritz@t-online.de

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.

The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin β in peritoneal dialysis patients with chronic renal anaemia

Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.

2 Renal Anemia Treatment In Peritoneal Dialysis Patients: A Multicenter Slovenian Study

Objectives The aim of our study was to: (i) assess the number of patients who need epoetin treatment and the adequacy of iron treatment, (ii) assess the influence of presence of diabetes mellitus, polycystic kidney disease and the influence of therapy with aluminum phosphate binders and angiotensin system antagonists on the epoetin requirements, (iii) assess the role of other factors possibly influencing epoetin resistance – secondary hyperparathyroidism, inflammation, dialysis dose and residual renal function.Design and Methods Fifty‐one stable peritoneal dialysis (PD) patients (mean age ± SD was 52 ± 13 years, 20 women) without recent bleeding, surgery, bone marrow disease, malignancy, or hypothyroidism were recruited in four Slovenian centers. The dose of epoetin was adjusted to maintain a target hemoglobin of above 110 g/L. At the time of inclusion (median 36 months of PD, range 3–124 months) the PET test results and relevant clinical and laboratory parameters were recorded. Index of epoetin resistance (IRE) was expressed as weekly epoetin dose/body weight/hemoglobin concentration.Results Twenty four percent of patients did not need epoetin treatment, the rest were treated with Epoetin‐beta at a dose of 70 ± 56 U/kg/week s.c.; hemoglobin concentration was 124 ± 15 g/L; 14% had hemoglobin below 110 g/L. Iron adequacy parameters (ferritin &gt; 100 µg/L and TSAT &gt; 20%) were fulfilled by 63% of patients, and their IRE was lower (0.43 ± 0.5 U/kg/week/g/L vs. 0.6 ± 0.72 U/kg/week/g/L), but not significantly (P = 0.502). Patients with polycystic kidneys had lower IRE (0.13 ± 0.3 vs. 0.52 ± 0.55 U/kg/week/g/L, P = 0.011) and majority of them (71%) did not need epoetin treatment (P = 0.006). No difference was found for diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, is associated with increased IRE (0.56 ± 0.59 vs. 0.3 ± 0.4 U/kg/week/g/L, P = 0.038). A statistically significant correlation was found for IRE and CRP (r = 0.48, P = 0.001) and iPTH (r = 0.46, P = 0.001). No correlation between IRE and residual renal function was found (r = −0.2, P = 0.173). Stepwise linear regression analysis for multiple variables (residual renal glomerular filtration rate, total weekly creatinine clearance, CRP, iPTH, iron adequacy, angiotensin system antagonist treatment, presence of polycystic kidneys) showed CRP and treatment with angiotensin system antagonists to be the most significant variables influencing IRE.Conclusion Our results show that systemic inflammation and angiotensin system antagonist treatment are the most important parameters affecting epoetin requirements in stable peritoneal dialysis patients.

Changes in common carotid artery intima-media thickness over 1 year in patients on peritoneal dialysis

Accelerated atherosclerosis and vascular calcifications increase cardiovascular morbidity and mortality in patients on dialysis. Common carotid artery (CCA) intima-media thickness (IMT) is considered useful for imaging atherosclerosis non-invasively. Since chronic inflammation may accelerate atherosclerosis in end-stage renal disease patients, the aim of this 1 year study was to assess changes in CCA-IMT in stable peritoneal dialysis (PD) patients, and to search for possible associations between these changes and selected cytokines, acute phase proteins and other risk factors of atherosclerosis. Of the original cohort of 61 stable patients on PD-28 female, 33 male; mean age 50.4+/-13.6 years; dialyse for a median of 17.5 months at inclusion (range 1-96 months)-47 patients survived the 1 year period on PD. CCA-IMT was assessed at baseline and after 12 months. Pro-inflammatory cytokines (IL-6, TNFalpha), acute phase proteins (CRP, fibrinogen), calcium-phosphate balance and lipid profile were assessed at baseline and after 6 and 12 months. Anthropometric parameters (age, weight, BMI, waist-to-hip ratio) were measured at baseline. The mean CCA-IMT at baseline, 0.66+/- 0.19 mm, increased by a mean of 0.098+/-0.17 to 0.76+/-0.21 mm (P<0.001) in 1 year. In 14 patients (29.8%) at least one plaque was found in the CCAs examined. At the end of follow-up: 28 patients (59.6%) had increases in CCA-IMT (from 0.63+/-0.2 to 0.83+/- 0.21 mm; P = 0.03), and 19 (40.4%) remained stable or even showed slight, but non-significant, decreases of CCA-IMT (from 0.72+/-0.17 to 0.66+/-0.17 mm, P = NS). The 'progressors' had significantly higher initial BMI (P<0.05), and mean concentrations of calcium (P = 0.005), IL-6 (P = 0.05), TNFalpha (P = 0.05), CRP (P = 0.005) and lower HDL-cholesterol than 'non-progressors'. In univariate analysis, DeltaCCA-IMT correlated positively with age (R = 0.32, P = 0.03), BMI (R = 0.29, P = 0.05) and mean concentrations of CRP (R = 0.37, P = 0.01), TNFalpha (0.52, P = 0.0002), but inversely with HDL-cholesterol (R = -0.37, P = 0.01). In multiple regression analysis, however, only age appeared to be independently associated with increase in CCA-IMT (beta = 0.37, P<0.01; R(2) for the model 0.14). Our results suggest a possible role of non-specific inflammation in the progression of atherosclerosis in patients treated with PD, in addition to age.

Trends and dynamics of changes in calcification score over the 1-year observation period in patients on peritoneal dialysis

Background Accelerated vascular calcification is an important cause of excess mortality in patients on dialysis therapy. The aim of the study was to evaluate the trends in coronary artery calcification (CAC) score (CaSc) during a 1-year period in a group of stable peritoneal dialysis (PD) patients and identify factors that may be associated with CaSc changes. Methods Sixty-one stable patients (28 women, 33 men) on PD therapy with a mean age of 50.4 ± 13.6 years were included. Forty-seven patients survived the entire study period on PD therapy and were suitable for the final analysis. CaSc was assessed at baseline and after 12 months by using multislice spiral computed tomography. Proinflammatory cytokines (interleukin-6, tumor necrosis factor-α [TNF-α]), acute-phase proteins (C-reactive protein [CRP], fibrinogen), calcium-phosphate balance, and lipid profile were assessed at baseline and after 6 and 12 months. Results Median CaSc was 22.6 Agatston units (range, 0 to 5,502.8 Agatston units) at baseline and increased to 84 Agatston units (range, 0 to 5,001.3 Agatston units) at a 1-year follow-up (P < 0.05). In the entire group of patients, 3 subgroups were identified: patients with progression (n = 21; P = 0.02 for the difference between initial versus follow-up CaSc), patients with regression (n = 12; P = 0.05), and subjects without change in CaSc after 1 year (n = 14). Patients without progression showed no calcifications at baseline and follow-up and were younger, less overweight, and characterized by significantly lower mean TNF-α, leptin, and CRP levels during 1 year compared with both progressors and regressors. Mean serum phosphate and calcium × phosphate product (Ca × P) values were gradually increasing from regressors through the no-calcification group to progressors (P < 0.01 for phosphate levels, P < 0.02 for Ca × P product). Significant correlations were found between changes in CaScs and mean values for phosphate (R = 0.44; P < 0.0005) and Ca × P product (R = 0.38; P < 0.005). Conclusion Chronic nonspecific inflammation does not directly attribute to progression in CaScs. Calcium-phosphate balance abnormalities appear to be the only important factors promoting CAC, although a permissive or promoting role of inflammation cannot be ruled out. Background Accelerated vascular calcification is an important cause of excess mortality in patients on dialysis therapy. The aim of the study was to evaluate the trends in coronary artery calcification (CAC) score (CaSc) during a 1-year period in a group of stable peritoneal dialysis (PD) patients and identify factors that may be associated with CaSc changes. Methods Sixty-one stable patients (28 women, 33 men) on PD therapy with a mean age of 50.4 ± 13.6 years were included. Forty-seven patients survived the entire study period on PD therapy and were suitable for the final analysis. CaSc was assessed at baseline and after 12 months by using multislice spiral computed tomography. Proinflammatory cytokines (interleukin-6, tumor necrosis factor-α [TNF-α]), acute-phase proteins (C-reactive protein [CRP], fibrinogen), calcium-phosphate balance, and lipid profile were assessed at baseline and after 6 and 12 months. Results Median CaSc was 22.6 Agatston units (range, 0 to 5,502.8 Agatston units) at baseline and increased to 84 Agatston units (range, 0 to 5,001.3 Agatston units) at a 1-year follow-up (P < 0.05). In the entire group of patients, 3 subgroups were identified: patients with progression (n = 21; P = 0.02 for the difference between initial versus follow-up CaSc), patients with regression (n = 12; P = 0.05), and subjects without change in CaSc after 1 year (n = 14). Patients without progression showed no calcifications at baseline and follow-up and were younger, less overweight, and characterized by significantly lower mean TNF-α, leptin, and CRP levels during 1 year compared with both progressors and regressors. Mean serum phosphate and calcium × phosphate product (Ca × P) values were gradually increasing from regressors through the no-calcification group to progressors (P < 0.01 for phosphate levels, P < 0.02 for Ca × P product). Significant correlations were found between changes in CaScs and mean values for phosphate (R = 0.44; P < 0.0005) and Ca × P product (R = 0.38; P < 0.005). Conclusion Chronic nonspecific inflammation does not directly attribute to progression in CaScs. Calcium-phosphate balance abnormalities appear to be the only important factors promoting CAC, although a permissive or promoting role of inflammation cannot be ruled out.

Trends and dynamics of changes in calcification score over the 1-year observation period in patients on peritoneal dialysis

Accelerated vascular calcification is an important cause of excess mortality in patients on dialysis therapy. The aim of the study was to evaluate the trends in coronary artery calcification (CAC) score (CaSc) during a 1-year period in a group of stable peritoneal dialysis (PD) patients and identify factors that may be associated with CaSc changes. Sixty-one stable patients (28 women, 33 men) on PD therapy with a mean age of 50.4 +/- 13.6 years were included. Forty-seven patients survived the entire study period on PD therapy and were suitable for the final analysis. CaSc was assessed at baseline and after 12 months by using multislice spiral computed tomography. Proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha [TNF-alpha]), acute-phase proteins (C-reactive protein [CRP], fibrinogen), calcium-phosphate balance, and lipid profile were assessed at baseline and after 6 and 12 months. Median CaSc was 22.6 Agatston units (range, 0 to 5,502.8 Agatston units) at baseline and increased to 84 Agatston units (range, 0 to 5,001.3 Agatston units) at a 1-year follow-up (P < 0.05). In the entire group of patients, 3 subgroups were identified: patients with progression (n = 21; P = 0.02 for the difference between initial versus follow-up CaSc), patients with regression (n = 12; P = 0.05), and subjects without change in CaSc after 1 year (n = 14). Patients without progression showed no calcifications at baseline and follow-up and were younger, less overweight, and characterized by significantly lower mean TNF-alpha, leptin, and CRP levels during 1 year compared with both progressors and regressors. Mean serum phosphate and calcium x phosphate product (Ca x P) values were gradually increasing from regressors through the no-calcification group to progressors (P < 0.01 for phosphate levels, P < 0.02 for Ca x P product). Significant correlations were found between changes in CaScs and mean values for phosphate (R = 0.44; P < 0.0005) and Ca x P product (R = 0.38; P < 0.005). Chronic nonspecific inflammation does not directly attribute to progression in CaScs. Calcium-phosphate balance abnormalities appear to be the only important factors promoting CAC, although a permissive or promoting role of inflammation cannot be ruled out.

Does Lymphatic Absorption Change with the Duration of Peritoneal Dialysis?

Ultrafiltration failure is an important complication of long-term peritoneal dialysis (PD). A high effective lymphatic absorption rate (ELAR) can contribute to impaired ultrafiltration. It is unknown whether the ELAR increases with time on PD. The relationship between the ELAR and duration of PD was analyzed, as well as the correlation between the ELAR and other transport parameters. We also studied the relation between the ELAR and cancer antigen 125 (CA125) a marker for mesothelial cell mass. Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. Cross-sectional and longitudinal studies of standard peritoneal permeability analyses (SPAs; 4-hour dwells, dextran 70 as a volume marker) with glucose 3.86% in 130 PD patients. SPAs were analyzed in 130 stable PD patients (77 males). Median duration of PD was 25 months (range 1-214) in a cross-sectional study. The last SPA from each patient was analyzed. The longitudinal analysis included 24 patients (12 males) from whom at least 3 SPAs were available with a minimum interval of 8 months. Dextran 70, 1 g/L, was administered intraperitoneally at the initiation of the test. Lymphatic absorption was calculated from the disappearance rate of dextran 70 during the 4-hour dwell. Therefore, the ELAR included both transmesothelial and subdiaphragmatic uptake of dextran 70. Median ELAR was 1.43 mL/minute (range 0.17- 6.59 mL/minute). No relationship was found between the ELAR and duration of PD in the cross-sectional analysis, nor was there a trend in time for 20 of the 24 patients studied longitudinally. In 4 patients, a negative trend was found. None of these had ultrafiltration failure and all 4 patients had a different cause for end-stage renal failure. The ELAR was correlated with parameters of peritoneal solute transport, but not with CA125 when investigated in a cross-sectional analysis. Only after 48 months of PD treatment was a significant relationship between the ELAR and CA125 seen (r = 0.46, p < 0.05). No time trend is present for the effective peritoneal lymphatic absorption rate, and it is not associated with patient or technique survival. Although increased lymphatic absorption is one of the causes of ultrafiltration failure, it is unlikely to contribute to the development of ultrafiltration failure in long-term PD patients with well-maintained transcapillary ultrafiltration.

A Randomized Clinical Trial with a 0.6% Amino Acid/1.4% Glycerol Peritoneal Dialysis Solution

Glucose is an accepted osmotic agent for peritoneal dialysis (PD) although it has several drawbacks. Some of these drawbacks have been addressed by the introduction of solutions with low glucose degradation products and physiological pH in dual-chambered bags. Despite this achievement, there is a need for alternative osmotic agents.This randomized clinical trial analyzes 3-month's clinical experience with a mixture of 0.6% amino acids and 1.4% glycerol. The study was performed at the renal units of the University Hospitals Ghent, Belgium, and Utrecht, The Netherlands. Stable PD patients were randomized for either protocol A (test solution, n = 5) or protocol B (control regimen, n = 5). In both protocols, there was a run-in phase of 1 month with a dialysis regimen of 2 x 2 L 2.27% glucose solution (Dianeal; Baxter, Nivelles, Belgium), 1 x 2 L Extraneal (Baxter), and 1 x 2 L glucose solution (Dianeal). After this month-long run-in period, patients in group A received during 3 months 2 x 2 L amino acid/glycerol solution, 1 x 2 L Extraneal, and at least 1 x 2 L of a classic glucose solution. Glucose absorption decreased in the test group during the test phase (from 84.2 +/- 8.7 to 11.7 +/- 11.6 g/24 hours, p = 0.001). Dialysate levels of cancer antigen 125 (CA125) increased in the test group, from 17.5 +/- 11.0 to 32.4 +/- 4.6 units/L (p = 0.04), whereas, in the control group, the levels remained stable (15.5 +/- 8.7 and 14.9 +/- 9.8 units/L respectively, p = 0.4). There were no differences in serum urea, serum bicarbonate, serum osmolarity, serum albumin, or parameters related to skin-fold thickness or serum glycerol levels between control and test solutions. No differences were observed in obtained ultrafiltration after a 4-hour dwell with 2.27% glucose or the test solution, both measured at week 4 of the run-in period and week 12 of the test period. This study demonstrated that the use of a new 0.6% amino acid/1.4% glycerol-containing dialysis solution is safe and well tolerated. Glucose load was reduced significantly and dialysate CA125 levels improved significantly. Ultrafiltration was comparable with that of a 2.27% glucose solution. All these factors, in combination with the potential nutritional benefits, can contribute to a beneficial impact on the success of the PD technique. Further long-term studies in larger patient groups are warranted to explore the potential of this promising new solution.

Relationship of Demographic, Dietary, and Clinical Factors to the Hydration Status of Patients on Peritoneal Dialysis

To establish which clinical factors are associated with an increased proportion of extracellular fluid (ECF) in peritoneal dialysis (PD) patients. A single-center, cross-sectional analysis of 68 stable PD patients. Bioelectrical impedance measurements (RJL, single frequency; RJL Systems, Clinton, Michigan, USA) of resistance and reactance were used to determine the proportion of ECF comprising total body water (TBW) in 68 stable PD patients attending for routine clearance and membrane studies. All patients underwent detailed dietetic, adequacy, and membrane function tests. Blood pressure and antihypertensive requirements were also documented. Significant gender differences in body composition were observed, such that women had lower absolute TBW and fat-free mass per kilogram body weight, but proportionately more ECF for a given TBW, mean ECF:TBW 0.5 +/- 0.03 versus 0.44 +/- 0.05, p < 0.005. In view of this, patients were split into two groups, defined as "over-" or "normally" hydrated, either by using the single discriminator (median ECF:TBW = 0.47) for the whole population, which resulted in groups distorted by gender, or by using different discriminators according to gender (women: 0.49, men 0.45). In both analyses, overhydrated patients were older, had significantly lower plasma albumin, less total fluid removal per kilogram body weight, and higher peritoneal solute transport. When split by a single discriminator, the overhydrated patients had lower sodium removal and significantly less intracellular fluid volume due to an excess of women in this group who also had less residual function and had been on dialysis longer. Using gender-specific discrimination, overhydrated patients were heavier due to expansion of the ECF volume: 20 +/- 4.1 L versus 16 +/- 3.3 L, p < 0.001. Stepwise multivariate analysis found age (p = 0.001), albumin (p = 0.009), and fluid losses per kilogram body weight (p = 0.025) to be independent predictors of gender-adjusted hydration status. Sodium intake did not vary according to hydration status. Gender influences the assessment of hydration status of PD patients when employing bioimpedance, such that women tend to have more ECF. Taking this into account, age, albumin, and achieved fluid removal appear to be independently associated with hydration status, whereas peritoneal solute transport is not. Advice on dietary sodium should take account of hydration status and achievable losses.

Nepsilon-(carboxymethyl)lysine, Nepsilon-(carboxyethyl)lysine and vascular cell adhesion molecule-1 (VCAM-1) in relation to peritoneal glucose prescription and residual renal function; a study in peritoneal dialysis patients.

Advanced glycation end products (AGEs) may contribute to peritoneal and cardiovascular damage in peritoneal dialysis (PD) patients, possibly in part by over-expression of vascular cell adhesion molecule-1 (VCAM-1). It has been suggested that peritoneal glucose load, oxidative stress, as well as the uraemic state itself may lead to an increased formation of AGEs. Aims of the present study were first to investigate the relation between residual glomerular filtration rate (rGFR), malondialdehyde (MDA) as a marker of lipid peroxidation, and peritoneal glucose prescription and absorption with serum levels of VCAM-1 and with the well characterized AGEs N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), as well as with CML and CEL in peritoneal effluent. CML and CEL were measured by tandem mass spectroscopy, MDA by HPLC, and VCAM-1 by ELISA in 37 stable PD patients (age 54 +/- 12 years; time on PD 25 +/- 18 months). CML and CEL were also measured after a 4-month interval. rGFR was independently related to CML both in serum (r = -0.66; P<0.001) and effluent (r = -0.62; P<0.001), whereas peritoneal glucose prescription and absorption were, respectively, related to CML in serum and effluent (r = 0.49; P<0.001 and r = 0.44; P<0.01). Relationships were comparable when assessed after the follow-up period. Peritoneal glucose absorption (r = 0.37; P<0.05), but not rGFR, was related to CEL in serum. The relation between peritoneal glucose prescription and CML in effluent lost significance when rGFR was added to the multi-regression model. Both rGFR (r = -0.40; P<0.05) and peritoneal glucose absorption (r = 0.37; P<0.05) were associated with VCAM-1 expression, which was itself weakly related only to CML in effluent (r = 0.38; P<0.05). MDA was not related to any parameter. Peritoneal glucose prescription and absorption, as well as rGFR are related to serum and effluent levels of CML and to VCAM-1 expression in serum, whereas peritoneal glucose absorption was related to serum levels of CEL. Still, the effect of rGFR, which does not appear to be mediated through lipid peroxidation pathways, on effluent levels of CML appears to outweigh the effect of the PD treatment. Even small differences in residual renal function in patients already on dialysis therapy are related to large variations of CML in serum and the peritoneal cavity.

Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities

Background:Malnutrition is frequent in peritoneal dialysis (PD) patients, but the contribution of gastrointestinal (GI) dysfunction has not been well established. Methods:We studied GI function in 49 stable PD patients to ascertain its relationship with malnutrition. After an overload fat diet, fecal fat, sugar, starch and nitrogen, intestinal protein permeability (α1-antitrypsin fecal clearance [C-α1-AT]), fecal chymotrypsin (CT), GI hormones and gastrin, pepsinogen I and II, cholecystokinin (CCK), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) were measured. Vasoactive intestinal polypeptide (VIP), substance P (SP), and tumor necrosis factor (TNF-α) and biochemical nutritional markers were evaluated. Results:All patients showed high fecal sugar. Elevated fecal nitrogen was found in 21 patients, 6 with high C-α1-AT. High fecal starch levels appeared in 21, fat in 20, and low fecal CT in 39 patients. These determinations showed inverse relation with nutritional markers. Increased fecal C-α1-AT values were associated with lower serum albumin. Fecal CT values showed a negative linear correlation with serum albumin and were inversely associated with retinol-binding protein, normalized protein nitrogen appearance, and serum iron. High plasma levels of pancreatic stimulating hormones were found: gastrin, CCK, and VIP. These levels were higher in patients with a worse pancreatic exocrine function. Higher values of other GI hormones, gastrin, pepsinogen I and II, CCK, GRP, and TNF-α. Normal concentrations of NPY, VIP, and PS were observed. Conclusion:GI abnormalities (malabsorption, maldigestion, pancreatic dysfunction, and protein losing enteropathy) are present in an important number of PD patients. These features are negatively associated to nutrition.

Lean Mass Estimation by Creatinine Kinetics and Dual-Energy X-Ray Absorptiometry in Peritoneal Dialysis

Background: Malnutrition is widely prevalent in dialysis. Malnourished patients present depletion of somatic protein stores and a decrease in lean body mass (LBM) that can be measured by different techniques. Aims: (1) To assess the reliability of lean mass measurements obtained by creatinine kinetics (CrK) in a group of stable peritoneal dialysis (PD) patients, using dual-energy x-ray absorptiometry (DEXA) measurements as the reference method; (2) to establish the reproducibility of LBM estimated by CrK in individual patients analyzing repeated measurement in the short term, and (3) to correlate measurements of LBM with laboratory determinations that assess nutritional status. Methods: We performed a cross-sectional evaluation of LBM by DEXA and CrK in 39 PD patients. In 14 patients we performed repeated measurements of LBM by CrK in the short term. Results: No significant difference was found in mean lean mass values estimated by both methods: mean DEXA LBM was 41.7 kg, 36.1 ± 4.5 kg in females and 52.7 ± 6.4 kg in males and mean CrK LBM was 41.08 kg, 37.5 ± 6.1 kg in females and 48.1 ± 8.4 kg in males. A good correlation was found between both techniques (r = 0.71; p < 0.003). The mean difference between the two methods was 0.638 ± 6.95 kg (95% confidence limits: –12.98 and +14.26). A wide scatter of the differences between both methods was seen throughout the range of measurements of LBM. When LBM by CrK was repeatedly (2–3 times) measured in a period of 3–4 months in 14 patients, it had a coefficient of variation (CV) of 15.39% (range 2.89–42.88%), while body weight CV in the same period was 0.69% (range 0–1.9%). Conclusions: CrK is an unsatisfactory method for the assessment of LBM in PD patients.

Peritoneal Function and Assessment of Reference Values Using a 3.86% Glucose Solution

The most widely used peritoneal function test, the peritoneal equilibration test (PET), is performed with a 2.27% glucose solution. Recently, the International Society for Peritoneal Dialysis committee on ultrafiltration failure (UFF) advised performing the test with 3.86% glucose solution because it is more sensitive for detecting clinically significant UFF. Because no reference values for this test were available, we analyzed the results of standard peritoneal permeability analyses (SPAs) using 3.86% glucose. The tests were performed in our center on 154 clinically stable peritoneal dialysis (PD) patients that were free of peritonitis for at least 4 weeks. For the assessment of reference values, we used two approaches. In approach A, patients with UFF, defined as net ultrafiltration (UF) < 400 mL/4 hours, were excluded. In approach B, only patients within their first 2 years of PD treatment were included, regardless of net UF. Means and 95% confidence intervals (95% CI) were calculated for the transport parameters of the PET and SPA. Means of normal distribution with 95% CI in approach A were as follows: for 2.0-L exchanges, mass transfer area coefficient (MTAC) for creatinine 8.8 mL/minute (4.7 - 12.7 mL/min), dialysate/plasma ratio (D/P) creatinine 0.70 (0.52 - 0.88), glucose absorption 58% (44% - 72%), dialysate240/initial dialysate ratio of glucose (Dt/D0) 0.28 (0.18- 0.38), net UF 675 mL (375 - 975 mL), and maximal dip in D/P sodium after correction for diffusion from the circulation 0.110 (0.050 - 0.164); for 1.5-L exchanges, MTAC creatinine 7.4 mL/min (3.8 - 11.0 mL/min), D/P creatinine 0.69 (0.52 - 0.86), glucose absorption 62% (52% - 72%), Dt/D0 glucose 0.25 (0.17- 0.32), net UF 551 mL (430 - 670 mL), and maximal dip D/P sodium 0.120 (0.048 - 0.166). In approach B, most of the transport values were similar; however, values for lymphatic absorption were significantly higher [1.52 mL/min (2-L) and 1.40 mL/min (1.5-L), p < 0.01] and values for the maximum dip in D/P sodium were lower [0.101 (2-L) and 0.112 (1.5-L), p > 0.05]. This was probably the result of including patients with UFF in approach B, since these parameters can be causative factors of UFF. A peritoneal transport function test using 3.86% glucose provides data on various aspects of transport. This study gives normal reference values that can be used for analysis of causes of UFF.

Regulation of apoptosis by lethal cytokines in human mesothelial cells

Dysregulation of peritoneal cell death may contribute to the complications of peritoneal dialysis (PD). Chronic peritoneal dialysis and acute peritonitis are both associated with loss of mesothelial cells. In addition, acute peritonitis is characterized by sudden changes in the number of peritoneal leukocytes. However, the factors regulating peritoneal cell survival are poorly understood. Peritoneal effluent cells and mesothelial cells cultured from peritoneal dialysis patients were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to assess the expression of FasL and Fas mRNA and protein. Western blot was used to assess FasL and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). RT-PCR was used to study TRAIL and TRAIL receptor mRNA. Apoptosis was quantified by flow cytometry of DNA content and confirmed by morphology. Apoptotic cells, including apoptotic mesothelial cells, were present in the peritoneal effluent of stable peritoneal dialysis patients and patients with bacterial peritonitis. The lethal cytokines FasL and TRAIL were expressed by peritoneal effluent cells, while cultured mesothelial cells expressed FasL, Fas, and TRAIL receptors. Cultured mesothelial cells were sensitive to FasL-induced apoptosis. IFNgamma increased the cell surface expression of Fas and the sensitivity of mesothelial cells to FasL-induced apoptosis. In contrast to the effect of FasL, TNFalpha and TRAIL did not induce apoptosis in human mesothelial cells from peritoneal dialysis patients. Lethal cytokines, such as FasL, may contribute to peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. The role of other cytokines, such as TRAIL, remains undefined. Approaches in limiting mesothelial cell injury that interferes with apoptosis should be considered.

Short- and Medium-Term Increase of CA125 in Peritoneal Effluent using a Neutral-pH Solution

♦ Objective To investigate the effects of an alternative peritoneal dialysis (PD) solution composed of a lactate/bicarbonate (Lac/Bic) mixture (35/2 mmol/L), pH 7.0, on the appearance of cancer antigen 125 (CA125) in the peritoneal effluent. ♦ Methods Eight stable PD patients received a conventional solution containing 35 mmol/L lactate (Lac) for 11.9 ± 9.2 months, and then changed to Lac/Bic for 3.1 ± 0.7 months. Each patient acted as his/her own control. ♦ Results We studied 4 males and 4 females with a mean age of 57.4 ± 16.8 years. Higher concentrations (U/mL) ( p &lt; 0.005) and appearance rates (AR) (U/min) ( p &lt; 0.05) of CA125 in the dialysate were observed with Lac/Bic than with Lac, during the sampling times of the peritoneal equilibration test (10, 120, and 240 minutes) and in the overnight effluent: CA125 5.7 versus 0.6, 18.9 versus 1.9, 29.7 versus 3.7, and 43.2 versus 5.5 U/mL; and AR 1177 versus 125, 354 versus 36,297 versus 37, and 194 versus 26 U/min, respectively. Mean CA125 content in the 24-hour dialysate was 34.2 U/min (baseline) and 30.9 U/min (11.9 months) with Lac, and 207.9 U/min and 185 U/min after 1.6 and 3.1 months with Lac/Bic ( p = 0.009). The intraperitoneal pH was more physiological during the dwell with the Lac/Bic solution. ♦ Conclusions The CA125 levels in the peritoneal effluent with Lac/Bic are an effect of the solution's neutral pH, as other factors of the prescription were constant. The Lac/Bic solution is more biocompatible than Lac, reflecting short- and medium-term changes in the mesothelial cells, whose clinical significance has not yet been determined.