The complexity of sleep disorders in dialysis patients.

BACKGROUND: Dialysis patients experience a high burden of physical and emotional symptoms directly affecting their sleep and quality of life. In this study, objective and subjective measurements to quantify sleep were performed, compared with those of healthy controls, and associated with burden of comorbidity and uraemic toxicity. METHODS: A total of 64 dialysis patients were included-10 peritoneal dialysis, 42 in-centre daytime haemodialysis (HD) and 12 in-centre nocturnal HD patients-as well as one-to-one age- and gender-matched healthy controls. Assumed and actual sleep time, sleep efficiency and fragmentation index were measured by actigraphy for at least two consecutive nights. Patients and controls also completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The patients' blood was sampled to determine concentrations of a representative series of uraemic toxins and the Davies-Stoke comorbidity index was derived from medical records. RESULTS: Apart from the assumed sleep time, all objectively and subjectively measured sleep parameters were worse in the dialysis group compared with the healthy controls. No differences were seen in any of the measured sleep parameters among the different dialysis groups. None of the objectively measured sleep parameters were associated with ISI or PSQI scores in dialysis patients, while sleep times were related to the subjective scores in the healthy cohort. Objectively assessed sleep parameters were associated to neither the uraemic toxicity load nor the Davies-Stoke score. CONCLUSIONS: Independent of the modality, dialysis patients have sleep quality much worse than age- and gender-matched healthy controls. The objectively measured sleep parameters could not be associated to the subjective score, uraemic toxicity or comorbidity score, highlighting the need for objective measurements of sleep and clinical guidelines to aid patient management.

Transport of neutral IgG2 versus anionic IgG4 in PD: implications on the electrokinetic model.

BACKGROUND: It is debated whether transperitoneal membrane transport of larger (charged) molecules in peritoneal dialysis can be partially governed by the electrokinetic model. In this model, it is postulated that streaming potentials are generated across the capillary wall by forced filtration of an ionic solution, for example transcapillary ultrafiltration induced by osmotic forces as in peritoneal dialysis. We investigated the presence of streaming potentials in the process of transperitoneal transport in Peritoneal Dialysis (PD) patients by measuring ratios of dialysate concentrations of IgG2 (neutral) and IgG4 (negative), both 150kD, under different conditions of transcapillary ultrafiltration. METHODS: Adult PD patients randomly got two consecutive dwells of 120 min each, with either 2 L Physioneal 1.36% or 3.86% glucose dialysis fluid (Baxter, USA) as their first dwell. A blood sample was taken at the test start, and dialysate samples were taken at 5, 15, 30, 60 and 120 min. IgG2 and IgG4 concentrations were measured (ELISA) and ratios calculated. RESULTS: In 10 patients (65 ± 17 years, 20 ± 17 months on dialysis), drained volume after 120 min was different between the 1.36% (1950 [1910; 2020] mL) and 3.86% (2540 [2380; 2800] mL) glucose dwells (P = 0.007). At none of the time points and irrespective of glucose concentration, a significant difference was found between the IgG2/IgG4 ratios at any time point. CONCLUSION: Our data failed to demonstrate a difference in the transport ratios of two macromolecules with same molecular weight but different charge, as would be expected by the electrokinetic model, and this despite sufficient differences in transcapillary ultrafiltration. CLINICAL TRIAL REGISTRY: Belgian Registration Number B670201523397 (20/1/2015); prospective randomized trial.

The choice between deceased- vs living-donor renal transplantation in children: Analysis of data from a Belgian tertiary center.

Pediatric renal transplantation with a living donor (LD) has superior outcome, but there is a paucity of studies analyzing the reasons for not undertaking living donation in West-European countries. The aim of this study was to retrospectively review the choice of donor source in our center. We also aimed to identify factors which prevented transplantation with a LD. This retrospective study was performed including children aged 2-19 years who underwent kidney transplantation (KT) at the Ghent University Hospital between 1996 and 2016. Relevant data were collected from medical files to identify the main medical, psychological, and socio-economic factors influencing the choice of the donor source. There were 48 patients (boys n = 33) who underwent KT. Thirty-nine patients received a deceased donor (DD) kidney and nine patients received a LD kidney. Sixteen of 48 transplantations were preemptive. The reasons for DD KT included socio-economic factors such as single caregiver families, one or both parents with a criminal record or convictions and religious or cultural constraints (n = 15), medical considerations (n = 13), refusal of the close relatives/parents to donate (n = 7), and acceptance of an organ from a DD while prospective donor was undergoing medical screening (n = 4). The low incidence of living kidney donation can be explained by socio-economic and medical factors. Refusal to donate is a potentially modifiable factor and strategies aimed at education and guidance of the families might contribute to a higher incidence of living donation in our setting.

Removal of Different Classes of Uremic Toxins in APD vs CAPD: A Randomized Cross-Over Study.

UNLABELLED: ♦ AIM: In this study, we investigated, and this for the different classes of uremic toxins, whether increasing dialysate volume by shifting from continuous ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal dialysis (APD) increases total solute clearance. ♦ METHODS: Patients on peritoneal dialysis were randomized in a cross-over design to one 24-hour session of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal), and the other week the alternate regime, each patient serving as his/her own control. Dialysate, blood and urine samples were collected and frozen for later batch analysis of concentrations of urea, creatinine, phosphorus, uric acid, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes, total and free fractions were determined. Total, peritoneal and renal clearance (K) and mass removal (MR) of each solute were calculated, using validated models. ♦ RESULTS: In 15 patients (11 male, 3 diabetics, 56 ± 16 years, 8 on CAPD, time on peritoneal dialysis 12 ± 14 months, and residual renal function of 9.9 ± 5.4 mL/min) dialysate over plasma ratio for creatinine (D/Pcrea) was 0.62 ± 0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD (13.3 ± 0.5 L vs 8.5 ± 0.7 L and 1.3 ± 0.5 L vs 0.5 ± 0.7 L), whereas urine output was lower (1.0 ± 0.5 L vs 1.4 ± 0.6 L). Total clearance and MR tended to be higher for CAPD vs APD for all small and water soluble solutes, but mainly because of higher renal contribution, with no difference in the peritoneal contribution. For the protein-bound solutes, no differences in clearance or mass removal were observed. ♦ CONCLUSION: Although the drained dialysate volume nearly doubled, APD did not result in better peritoneal clearance or solute removal vs classic CAPD. APD resulted in better ultrafiltration, but at the expense of residual urinary output and clearance.

Acute central haemodynamic effects induced by intraperitoneal glucose instillation.

BACKGROUND: The supposed lack of a haemodynamic impact of peritoneal dialysis (PD) has been challenged recently by the finding of a mild increase of peripheral blood pressure (BP) during an acute dwell. It is not clear whether, besides the effect of changes in intraperitoneal (IP) volume and/or pressure, IP glucose instillation and absorption plays a role in this. Therefore, we tested the impact of IP instillation of glucose on the evolution of central haemodynamic parameters, using SphygmoCor, during an acute dwell with two different glucose concentrations. METHODS: Stable, non-diabetic PD patients (N = 22) were treated consecutively in a randomized, cross-over design (A then B or B then A) with one 1.36% (A) and one 3.86% (B) physioneal dwell of 100 min. Central BP was measured with SphygmoCor and blood was sampled for serum glucose and insulin levels every 20 min. Insulin resistance was defined as a Homeostatic Model Assessment Index (HOMA-index) >1.4. RESULTS: Serum glucose levels rose during both the 1.36% and the 3.86% dwell, whereas insulin levels rose only during the 3.86% dwell. The increase of both glucose and insulin levels was more pronounced in patients with insulin resistance (11/22 patients). There was, however, no accompanying change versus baseline in haemodynamic parameters (carotid systolic blood pressure, diastolic BP, heart rate or augmentation index). CONCLUSION: Despite substantial increases in blood glucose and insulin levels, there was no accompanying change in central haemodynamic parameters during an acute PD dwell with low or high glucose concentrations.

The personal dialysis capacity test is superior to the peritoneal equilibration test to discriminate inflammation as the cause of fast transport status in peritoneal dialysis patients.

This study evaluated the potential of the Personal Dialysis Capacity (PDC) test to discriminate fast transport status (FTS) as a consequence of inflammation versus FTS because of other causes. This distinction is important because new therapeutic options such as icodextrin and automated peritoneal dialysis can abolish the negative impact on outcome of FTS if fast transport is not caused by inflammation. A PDC test and a Peritoneal Equilibration Test (PET) were performed in 135 incident PD patients. Membrane characteristics were related with baseline biochemical parameters and C-reactive protein. After correction for other covariates, only large pore flux (J(v)L) but not surface area over diffusion distance (A0/dX) or dialysate over plasma concentration was related to C-reactive protein. Using the PDC test for detection of inflammation, positive and negative predictive values were 16/36 and 80/99, respectively, whereas with PET, positive predictive value was 5/20 and negative predictive value 92/115 (chi2 = 0.009). In a Cox regression for patient survival with correction for age, a J(v)L higher than expected by the surface area over diffusion distance, predicted outcome (P = 0.04). Patients with inflammation had a higher J(v)L (0.21 +/- 0.12 versus 0.17 +/- 0.09; P = 0.06) and a lower ultrafiltration (89 +/- 631 versus 386 +/- 601 ml/d; P = 0.06) and urine output (878.45 +/- 533.55 versus 1322 +/- 822 ml/d; P = 0.023) than patients without inflammation. There was no difference for surface area over diffusion distance (A0/dX) or dialysate over plasma concentration. A PDC test yields far more information about the peritoneal membrane characteristics than a PET. A J(v)L higher than expected by the A0/dX is an indicator of inflammation and is related to an increased mortality. The PET is not able to discriminate between FTS because of inflammation versus because of anatomic reasons, whereas the PDC test does.

A randomized clinical trial with a 0.6% amino acid/ 1.4% glycerol peritoneal dialysis solution.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Specific characteristics of peritoneal leucocyte populations during sterile peritonitis associated with icodextrin CAPD fluids.

BACKGROUND: Icodextrin dialysate used for peritoneal dialysis contains an iso-molar glucose polymer solution, which provides sustained ultrafiltration over long dwell times and is considered a valuable approach to reduce intraperitoneal glucose exposure. However, several side effects have been described, including abdominal pain and allergic and hypersensitivity reactions. Also, reactions compatible with chemical peritonitis have been reported. Over the period of a few months (January 2002-May 2002), a remarkable increase in the number of continuous ambulatory peritoneal dialysis (CAPD) patients using icodextrin dialysate diagnosed with sterile peritonitis was observed in our unit. METHODS: Five of the CAPD patients using icodextrin dialysate in our unit and diagnosed with sterile peritonitis were screened for leucocyte count and leucocyte differentiation during a follow-up period of 77 +/- 23 days. In addition, expression of CD14, a receptor for lipopolysaccharide (LPS), on the peripheral and peritoneal monocyte population was analysed. These results were compared to CAPD patients suffering from bacterial peritonitis. RESULTS: The peritoneal leucocyte count of CAPD patients using icodextrin dialysate and diagnosed with sterile peritonitis did not decrease significantly before treatment with icodextrin dialysate was interrupted, whereas it currently disappeared within 2-4 days in proven bacterial peritonitis. The sterile, cloudy icodextrin effluent contained an excess of macrophages on the day of diagnosis, whereas in bacterial peritonitis essentially an increase in the granulocyte population was observed. No elevation in the eosinophil population was observed. In contrast to bacterial peritonitis, we observed no increase in CD14 expression on the peripheral and peritoneal macrophages on the day of presentation and during the follow-up period. CONCLUSIONS: Specific batches of the icodextrin CAPD fluids contain a macrophage chemotactic agent, which causes a sustained inflammatory state in the peritoneal cavity. Because no increase in the expression of the LPS receptor CD14 could be observed, the increased peritoneal leucocyte count is probably not caused by LPS or LPS-like (possibly peptidoglycan-like) contamination.

The impact of healthy start peritoneal dialysis on the evolution of residual renal function and nutrition parameters.

The optimal time to start renal replacement therapy remains controversial. Residual renal function (RRF) and nutrition status being important prognostic factors, the present study evaluates the impact of timely start of peritoneal dialysis (PD) on their evolution. Our study used a prospective database on pre-end-stage renal disease patients at a tertiary care center. We included 18 patients who were planned to start PD at a GFR > 8 mL/min between 1 January and 31 December 1999. At the start of PD (month 0), creatinine clearance (CCr) was 11.3 +/- 3.9 mL/min, actual glomerular filtration rate (GFR) was 8.6 +/- 3.3 mL/min, and Kt/V was 1.56 +/- 0.65. The monthly declines of GFR and CCr before and after the start of PD were -0.47 +/- 0.64 mL/min (GFR) and -0.59 +/- 0.46 mL/min (CCr), and -0.06 +/- 0.30 mL/min (GFR) and -0.05 +/- 0.39 mL/min (CCr) respectively (p = 0.034 and 0.001, respectively). Before the start of PD, CCr was 21.9 +/- 4.6 mL/min (month -12) and 18.1 +/- 4.8 mL/min (month -6, p < 0.001). After the start of PD, CCr was 12.0 +/- 4.3 mL/min (month 3), 11.5 +/- 4.9 mL/min (month 6), and 13.1 +/- 5.4 mL/min (month 12, p = 0.9). Serum albumin dropped until just before the start of PD: 3.89 +/- 0.59 g/dL (month -6) and 3.78 +/- 0.51 g/dL (month -3) versus 2.56 +/- 1.60 g/dL (month 0, p = 0.04). Serum albumin then increased to 3.42 +/- 0.95 mg/dL (month 3 after the start of PD) and 3.35 +/- 0.86 mg/dL (month 6 after the start of PD, p = 0.04). In the months preceding the start of PD, the normalized protein catabolic rate (nPCR) dropped from 1.41 +/- 0.36 g/kg daily (month -6) and 1.34 +/- 0.46 g/kg daily (month -3) to 1.12 +/- 0.25 g/kg daily (month 0). It then stabilized at 1.17 +/- 0.25 g/kg daily (month 3) and 1.18 +/- 0.17 g/kg daily (months 6). One patient died owing to a cerebrovascular accident after 18 months of PD, and one was transferred to hemodialysis because of ultrafiltration failure after 19 months of PD. During 264 patient-months, 14 peritonitis episodes occurred. Of the 14 episodes, 12 resolved without complication, and the catheter was replaced in 2 episodes. After timely start of PD, the rate of RRF decline decreases. Already, at a GFR > 8 mL/min, uremia has a negative impact on nutrition parameters. Timely initiation of PD could reverse the negative evolution of albumin and stop the decline of nPCR. No severe complications related to PD were seen. In view of the important impact of RRF and nutrition on patient outcome, our data may favor an early start of PD.