Effects of Steady Glucose Concentration Peritoneal Dialysis on Ultrafiltration Volume and Sodium Removal: A Pilot Crossover Trial.

BACKGROUND: Volume overload is common in patients treated with peritoneal dialysis (PD) and is associated with poor clinical outcome. Steady concentration PD is where a continuous glucose infusion maintains the intraperitoneal glucose concentration and as a result provides continuous ultrafiltration throughout the dwell. The primary objective of this study was to investigate the ultrafiltration rate and glucose ultrafiltration efficiency for steady concentration PD in comparison with a standard continuous ambulatory PD (CAPD) dwell, using the novel Carry Life UF device. METHODS: Eight stable patients treated with PD (six fast and two fast average transporters) were investigated four times: a standard 4-hour CAPD dwell with 2 L of 2.5% dextrose solution as control and three 5-hour steady concentration PD treatments (glucose dose 11, 14, 20 g/h, initial fill 1.5 L of 1.5% dextrose solution). All investigations were preceded by an overnight 2 L 7.5% icodextrin dwell. RESULTS: Intraperitoneal glucose concentration increased during the first 1-2 hours of the steady concentration PD treatments and remained stable thereafter. Ultrafiltration rates were significantly higher with steady concentration PD treatments (124±49, 146±63, and 168±78 mL/h with 11, 14, and 20 g/h, respectively, versus 40±60 mL/h with the control dwell). Sodium removal and glucose ultrafiltration efficiency (ultrafiltration volume/gram glucose uptake) were significantly higher with steady concentration PD treatments versus the control dwell, where the 11 g/h glucose dose was most efficient. CONCLUSIONS: Steady concentration PD performed with the Carry Life UF device resulted in higher ultrafiltration rates, more efficient use of glucose (increased ultrafiltration volume/gram glucose absorbed), and greater sodium removal compared with a standard 2.5% dextrose CAPD dwell. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Performance Analysis of the Peritoneal Ultrafiltration (PUF) Achieved With the Carry Life ® UF, NCT03724682 .

Factors associated with time to first dialysis-associated peritonitis episode: Data from the Peritonitis Prevention Study (PEPS).

INTRODUCTION: Peritonitis remains a potentially serious complication of peritoneal dialysis (PD) treatment. It is therefore important to identify risk factors in order to reduce the incidence of peritonitis. The aim of the present analysis was to identify factors associated with time to first peritonitis episode. METHODS: Incident PD patients from 57 centres in Europe participated in the prospective randomised controlled Peritonitis Prevention Study (PEPS) from 2010 to 2015. Peritonitis-free, self-care PD patients ≥18 years were randomised to a retraining or a control group and followed for 1-36 months after PD initiation. The association of biochemical, clinical and prescription data with time to first peritonitis episode was studied. RESULTS: A first peritonitis episode was experienced by 33% (223/671) of participants. Univariable Cox proportional hazard regression showed a strong association between the time-updated number of PD bags connected per 24 h (PD bags/24 h) and time to first peritonitis episode (HR 1.35; 95% confidence interval (CI) 1.17-1.57), even after inclusion of PD modalities in the same model. Multivariable Cox regression revealed that the factors independently associated with time to first peritonitis episode included age (HR 1.16 per 10 years; 95% CI 1.05-1.28), PD bags/24 h (HR 1.32; 95% CI 1.13-1.54), serum albumin <35 versus >35 g/L (HR 1.39; 95% CI 1.06-1.82) and body weight per 10 kg (HR 1.10; 95% CI 1.01-1.19). CONCLUSION: This study of incident PD patients indicates that older age, greater number of PD bags connected/24 h, higher body weight and hypoalbuminaemia are independently associated with a shorter time to first peritonitis episode.

Retraining for prevention of peritonitis in peritoneal dialysis patients: A randomized controlled trial.

BACKGROUND: Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients. METHODS: This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved. RESULTS: In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65-1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75-1.16). CONCLUSIONS: In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.

Bacteria on catheters in patients undergoing peritoneal dialysis.

BACKGROUND: Peritonitis is the leading cause of morbidity for peritoneal dialysis (PD) patients, and microbial biofilms have previously been identified on catheters from infected patients. However, few studies of catheters from patients without clinical signs of infection have been undertaken. The aim of the present study was to investigate the extent to which bacteria are present on catheters from PD patients with no symptoms of infection. METHODS: Microbiologic culturing under aerobic and anaerobic conditions and confocal laser scanning microscopy were used to determine the distribution of bacteria on PD catheters from 15 patients without clinical signs of infection and on catheters from 2 infected patients. The 16S rRNA gene sequencing technique was used to identify cultured bacteria. RESULTS: Bacteria were detected on 12 of the 15 catheters from patients without signs of infection and on the 2 catheters from infected patients. Single-species and mixed-microbial communities containing up to 5 species were present on both the inside and the outside along the whole length of the colonized catheters. The bacterial species most commonly found were the skin commensals Staphylococcus epidermidis and Propionibacterium acnes, followed by S. warneri and S. lugdunensis. The strains of these micro-organisms, particularly those of S. epidermidis, varied in phenotype with respect to their tolerance of the major classes of antibiotics. CONCLUSIONS: Bacteria were common on catheters from patients without symptoms of infection. Up to 4 different bacterial species were found in close association and may represent a risk factor for the future development of peritonitis in patients hosting such micro-organisms.

The effects of low-sodium peritoneal dialysis fluids on blood pressure, thirst and volume status.

BACKGROUND: Poor ultrafiltration is associated with worse outcomes in peritoneal dialysis (PD) patients. This might in part reflect problems associated with salt and water excess. Increasing the diffusive component of peritoneal sodium removal using low-sodium PD fluids might have beneficial effects on blood pressure (BP), thirst and fluid status that could translate into clinical benefits. METHODS: Using a multicentre, prospective, baseline controlled (1 month), non-randomized intervention (2 months) design, two novel solutions designed from predictions using the three-pore model were investigated. In group A ([Na+] = 115 mmol/l), the glucose (G) was increased to 2.0% to compensate for reduced osmolality whereas in group B ([Na+] = 102 mmol/l), it was unchanged (2.5%). Both solutions were substituted for one 3- to 5-h exchange per day and no change was made to the rest of the dialysis regime. RESULTS: Ten patients in group A and 15 in group B completed the study. Both solutions resulted in significant increases (30-50 mmol/dwell) in diffusive sodium removal during the test exchanges, P < 0.001. Ultrafiltration was maintained in group A but reduced in group B. Ambulatory nocturnal mean BP fell in group A [93.1 +/- 10.6 mmHg (+/-SD) versus 85.1 +/- 10.2 mmHg, P < 0.05], but was stable in group B (95.4 +/- 9.4 versus 95.1.1 +/- 10.7 mmHg, NS). Thirst reduced independent of appetite and mood in both groups by 2 months, more markedly in group A. Indices of fluid status, including TBW by bioimpedance and D dilution also improved in group A, P < 0.05, whereas weight increased in group B. CONCLUSIONS: Increasing the diffusive component of sodium removal whilst maintaining ultrafiltration is associated with improvements in BP, thirst and fluid status. The lack of effect seen with uncompensated low-sodium dialysate suggests that these benefits cannot be achieved by manipulation of dialysate sodium removal alone. These observations provide valuable information of the design of future randomized studies to establish the clinical role for low-sodium dialysis fluids.

Physiological properties of the peritoneum in an adult peritoneal dialysis population over a three-year period.

OBJECTIVES: To describe the physiological properties of the peritoneal membrane in adult patients treated with peritoneal dialysis (PD) and to analyze the effects of patient characteristics and time. DESIGN: Observational study. SETTING: Department of Nephrology at the Sahlgrenska University Hospital. METHOD: Peritoneal function was analyzed by the Personal Dialysis Capacity (PDC) test, based on the three-pore theory of capillary transport. The functional PDC variables are absorption, large-pore flow, and the area parameter (A0/deltax), which determines the diffusion of small solutes. The ultra-filtration (UF) coefficient is determined mainly by A0/deltax. PATIENTS: All patients (n = 280) who had at least one PDC test done between September 1990 and August 1999. RESULTS: In 249 patients examined soon after start of PD, area was 19000 (SD 7100) cm2/cm/1.73 m2, large-pore flow 0.112 (SD 0.052) mL/min/1.73 m2, and the UF coefficient 0.071 (SD 0.032) mL/minute/mmHg/1.73 m2. Absorption was 1.54 (SD +2.64, -0.97) mL/min/1.73 m2. Large-pore flow was greater in patients with severe comorbidity than in patients with fewercomorbid conditions. Elderly patients had a lower UF coefficient than did younger patients (p < 0.05). Repeated PDC tests were performed in 208 patients during a mean observation time of 18.4 months. There was a slight increase in the slope of the area-versus-time curve of 54 cm2/cm/1.73 m2 per month (approximately 10% after 3 years, p < 0.01); all other parameters remained constant. CONCLUSION: Patient characteristics have an impact on peritoneal performance already at the start of dialysis. Peritoneal function can remain essentially stable during medium long-term PD.

Dialysis modalities and dyslipidemia.

Progressive renal failure is accompanied by dyslipidemia, which is reflected in an abnormal apolipoprotein profile. It is characterized by increased concentrations of intact and partially metabolized triglyceride-rich apoB-containing lipoproteins. They occur preferentially in very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) as a result of impaired metabolism and clearance. Hemodialysis can moderately attenuate the renal dyslipidemia. In contrast, peritoneal dialysis is associated with further aggravation, including an increase of cholesterol-rich apoB-containing lipoproteins.

Personal dialysis capacity (PDC(TM)) test: a multicentre clinical study.

BACKGROUND: The assessment of the peritoneal membrane capacity and physiology of the individual patient is becoming increasingly important. It allows the prescription of an individualized peritoneal dialysis (PD)-regimen, and the monitoring of peritoneal membrane function over time. The PDC(TM) program offers the possibility to evaluate the peritoneal membrane characteristics and to predict solute and water removal by simulation of different treatment regimens. METHODS: This study evaluates the relevance of the PDC(TM) program when routinely used. The PDC(TM) data of 336 patients from nine different centres in Europe were evaluated. RESULTS: The area parameter was 20 985+/-7578 cm/1.73 m(2) (mean+/-SD). The reabsorption of fluid after dissipation of glucose, Jv(AR), was 1.97+/-1.00 ml/min/1.73 m(2). The large pore fluid flux, Jv(L), was 0.11+/-0.07 ml/min/1.73 m(2). A multivariate model for prediction of serum albumin included dialysate protein loss, Jv(L), Jv(AR), nPCR, A(0)/deltaX, BMI and gender (R(2)=0.81, P<0.001). Total clearance fell with increasing PD duration (P<0.001). A negative relation between A(0)/deltaX and ultrafiltration (rho=-0.26, P<0.05), a positive relation between A(0)/deltaX and peritoneal creatinine clearance (rho=0.52, P<0.05) and urea clearance (rho=0.36, P<0.05), and a positive relation between measured peritoneal creatinine and urea clearance (rho=0.64, P<0.01) was observed. CONCLUSIONS: In summary, the present study shows that the PDC(TM) program is a robust, accurate method to describe the peritoneal membrane transport characteristics. Analysis of PDC(TM) data of large groups of patients, especially if followed up over time, can give interesting information on the physiology of the peritoneal membrane and the impact of different parameters on it.

The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being.

BACKGROUND: Malnutrition occurs frequently in patients with end-stage renal disease (ESRD). Gastrointestinal (GI) symptoms may lead to reduced food intake, resulting in malnutrition and impaired well-being in these patients. The prevalence of GI symptoms in various chronic renal failure (CRF) groups is unexplored. We assessed the prevalence of GI complaints in patients on either haemodialysis (HD), peritoneal dialysis (PD), or in the pre-dialysis stage. Patients with and without diabetic nephropathy were also compared. METHODS: A total of 233 patients with CRF (128 HD, 55 PD, and 50 pre-dialytic patients) completed two self-administered questionnaires: the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale (GSRS), which measures GI symptoms. The values were compared with reference values obtained from the general population. The association between GI symptoms and serum (s-)albumin was also studied. RESULTS: The total GSRS score in patients with CRF was significantly higher than the reference values (HD 2.14 (1.97-2.31), PD 2.24 (2.00-2.48), and pre-dialytic patients 2.03 (1.82-2.25) vs controls 1.53 (1.50-1.55; P<0.001). When comparing CRF subgroups there was no overall difference between the groups, but PD patients had more severe reflux and eating dysfunction. In patients with diabetic nephropathy, only eating dysfunction was significantly more common than in the non-diabetic patients. There was a negative correlation between GI symptoms and psychological general well-being in CRF patients (Rho=-0.46, P<0.001) indicating that patients with a high GI symptom profile have impaired psychological general well-being. A negative correlation was found between eating dysfunction and s-albumin (Rho=-0.33, P<0.01). CONCLUSION: The prevalence of GI symptoms is high in patients with CRF and is associated with impairment in psychological general well-being. Presence of dialysis or not, type of dialysis, and presence or absence of diabetes mellitus seem to have limited impact on GI symptoms.

Nutritional status in peritoneal dialysis: studies in body composition, lipoprotein metabolism and peritoneal function.

This thesis is based on clinical studies including virtually all patients treated with peritoneal dialysis in Gothenburg during the 1990s. The patients had a fundamentally altered body composition compared to healthy subjects, characterised by a reduction in body cell mass and body fat already at start of dialysis. During PD treatment. a further decrease in body cell mass was observed. Energy stores tended to normalise during the first years of treatment and remained constant thereafter, or declined subsequently. Extracellular water, calculated from the four-compartment model, was increased when patients started PD treatment and increased further, in parallel to the reduction in body cell mass. These alterations were seen in combination with a normal. or slightly reduced, body weight. Standard methods of assessing nutritional status may therefore not be valid in the dialysis population. Prediction equations to estimate total body water, used in measurements of dialysis adequacy, give erroneous results in PD patients, as shown in a study on our PD population. This may have important clinical consequences, especially in wasted patients. Reduced muscle mass is a marker of protein-energy malnutrition, and therefore simple and reliable methods to measure muscle mass are warranted. When lean body mass was calculated from creatinine generation rate and compared to lean body mass estimated from measurements of total body potassium. the agreement between the two methods was low. Furthermore, when repeated measurements of creatinine generation rate were performed, the variation coefficient was unacceptably high. Thus. creatinine generation rate cannot be recommended as a method to evaluate somatic protein status in PD patients. The lipoprotein metabolic derangements are pronounced in PD patients. in which a further increase in cholesterol and cholesterol-rich apoB-containing lipoproteins are added to the already pre-existing renal dyslipidemia. characterised by increased concentration of triglycerides and triglyceride-rich complex lipoproteins. There are indications that dialytic variables may influence this development. When peritoneal function was assessed by the Peritoneal Dialysis Capacity test at start of dialysis, it was observed that peritoneal function reflected patient characteristics and co-morbidity. Patients with systemic disease had enhanced diffusion capacity compared to patients with primary renal disorders. Furthermore, in patients with more severe co-morbidity. peritoneal protein losses were increased. Finally, elderly patients had ultrafiltration conditions that were different from those of younger patients. Peritoneal function remained essentially stable during medium-long term follow up. Body composition features in dialysis patients are similar to those seen in severe disease in general. Thus, it is difficult to separate the effects of malnutrition from the effects of the underlying disease. Specific standards for nutritional status adapted for patients with renal failure are required.

Alterations in lipoprotein composition in peritoneal dialysis patients.

OBJECTIVE: Dyslipidemia is common among patients with end-stage renal disease, whether treated by hemodialysis (HD) or peritoneal dialysis (PD). To better understand the specific lipoprotein abnormalities in PD patients, we measured the lipid and apolipoprotein (Apo) composition of the four major classes of plasma lipoproteins in PD patients, HD patients, and healthy control subjects: very low density (VLDL), intermediate density (IDL), low density (LDL), and high density lipoproteins (HDL). DESIGN: Fasting plasma samples were obtained from 15 nondiabetic PD patients, 15 nondiabetic HD patients, and 16 healthy control subjects, all from a cross section of patients and subjects in the region of Göteborg, Sweden. Lipoproteins were isolated by preparative ultracentrifugation, and lipid and apolipoprotein concentrations were measured by gas chromatography and electroimmunoassay, respectively. RESULTS: Alterations in lipoprotein composition were apparent in all four lipoprotein density classes from PD and HD patients. VLDL contained a significantly higher concentration of ApoCIII in both HD and PD patients, and an elevation of free cholesterol, triglyceride, ApoB, ApoCII, and ApoE in PD patients. IDL from both PD and HD patients contained an excess of free and esterified cholesterol and triglyceride and significantly elevated levels of ApoB, ApoCII, ApoCIII, and ApoE. LDL had a higher concentration of ApoB in PD patients and elevated triglyceride and ApoCIII in both PD and HD patients. HDL isolated from PD patients had lower free cholesterol and ApoAI levels compared to control subjects, but these were not significantly different from HD patients. CONCLUSIONS: An increase in lipid and apolipoprotein mass in IDL, and an enrichment of ApoCIII in VLDL, IDL, and LDL were observed in both HD and PD patients. The predominant alteration in lipoprotein composition distinguishing PD patients from HD patients was an elevation of ApoB in LDL. Further study of these alterations in lipoprotein composition in PD patients will be helpful in understanding the underlying causes of dyslipidemia and, ultimately, to the selection of hypolipidemic drugs or other treatments to reduce the cardiovascular risks associated with dyslipidemia in these patients.

Limitations in anthropometric calculations of total body water in patients on peritoneal dialysis.

Having an accurate estimation of total body water (TBW) is essential for the evaluation of dialysis efficacy in peritoneal dialysis (PD) patients. In this study, TBW volumes were measured by tritium dilution (TBW(THO)) in 165 PD patients and compared with TBW calculations according to the Watson formulas. An alternative anthropometric formula based on the present PD population was also developed and validated in an independent sample of 29 PD patients. Furthermore, the relation between TBW(THO) and body surface area (BSA) according to the formula of Gehan was analyzed. Body composition was assessed by a four-compartment model, based on measurements of TBW(THO) and total body potassium. Mean values of TBW by the Watson formulas were almost identical to TBW(THO), and the correlation coefficient for the relationship of calculated to measured volumes was 0.89 (P = 0.001). However, both anthropometric formulas-the Watson formulas as well as the new, alternative one-overestimated TBW in obese patients and vice versa in lean patients. Similarly, TBW was underestimated in patients who were overhydrated. The correlation coefficient between TBW(THO) and BSA was 0.708 for males and 0.797 for females (P = 0.0001 for both). In obese patients, the relationship was even closer (r = 0.924 and 0.911, respectively). In conclusion, anthropometric formulas to calculate TBW showed a considerable intraindividual variability compared with measured values. This was related to body composition features, such as degree of obesity and hydration. In contrast, BSA correlated closely to TBW in obese individuals. TBW as estimated by anthropometric formulas must be analyzed with caution, especially in the very obese or very lean patient.