Pre-treatment of dairy and breast milk with sevelamer hydrochloride and sevelamer carbonate to reduce phosphate.

INTRODUCTION: Young children and infants with chronic kidney disease are at increased risk of hyperphosphatemia because of high intake of dairy products. Hyperphosphatemia leads to metastatic calcifications and an increased risk of cardiovascular complications. Sevelamer is an effective phosphate binder, but for children it has important practical disadvantages: it clogs enteral feeding tubes and can cause gastrointestinal complaints. Pre-treatment of dairy products to reduce their phosphate content might solve those problems. METHODS: Sevelamer hydrochloride and sevelamer carbonate were suspended in various dairy products (cow's milk, breast milk, baby formula, and tube-feeding formula). Each product was tested with varying concentrations of sevelamer. After suspension, each sample was stored for 10 minutes, allowing the sevelamer to precipitate. The supernatant was decanted and analyzed for pH and for phosphate, calcium, magnesium, potassium, sodium, and chloride content. RESULTS: We observed a significant decrease in the phosphate content of all tested products. With sevelamer hydrochloride, the phosphate reduction was 48% - 91% in the various products, and with sevelamer carbonate, it was 22% - 87%. The highest effectiveness was found in breast milk. A pH increase was found in all products. With sevelamer hydrochloride, a significant increase in chloride occurred. Notably, a significant decrease in calcium content (-75%) was observed in treated breast milk. CONCLUSIONS: Pretreatment of a variety of dairy products with either sevelamer hydrochloride or sevelamer carbonate effectively reduced their phosphate content and might avoid troublesome ingestion of sevelamer in children. The change in pH with sevelamer hydrochloride was remarkable, reflecting buffering mechanisms. The reduction in the calcium content of breast milk is a potential concern and should be carefully considered and monitored during clinical use of sevelamer.

Free water transport in children on peritoneal dialysis is higher with more biocompatible dialysis solutions, higher with older age and declines with time.

BACKGROUND: Water transport in peritoneal dialysis occurs through small pores and aquaporins. Free water transport (FWT) occurs through aquaporins only and gives a reflection of peritoneal aquaporin function. In this study, FWT in children was calculated for the first time in different settings. METHODS: A prospective cohort study was performed; 87 peritoneal equilibrium tests (PETs) were analysed in 65 patients. Three subgroups were analysed: patients with their first PET; patients in their second year on dialysis; patients in their third year on dialysis or thereafter. Patients using 3.86% glucose solution with low pH/high glucose degradation products (GDP) were compared to patients using 3.86% glucose solution with neutral pH/low GDP. Sixteen patients using neutral pH/low GDP solution were followed longitudinally. FWT was calculated using the dialysate/plasma ratio of sodium. RESULTS: The proportional contribution of FWT was significantly higher in patients using dialysis solution with neutral pH/low GDP solution compared to patients using solutions with low pH/high GDP (50 versus 40%). Transcapillary ultrafiltration (TCUF) showed the same trend but was not statistically significant. Total FWT was higher as well. Higher FWT was observed with older age. In the longitudinal group, TCUF and water transport through small pores declined, while FWT remained stable in the first 1.5 years. The contribution of FWT increased in this period (48-61%), then slowly declined again to baseline level during the third year. CONCLUSIONS: Total FWT and relative contribution of FWT were significantly higher with neutral pH/low GDP solution. This can reflect a better preservation of aquaporins. The decline in the contribution of FWT in long-term dialysis could hypothetically implicate aquaporin dysfunction or different trafficking of aquaporins.

Continuous flow peritoneal dialysis: first experience in children with acute renal failure.

BACKGROUND AND OBJECTIVES: Acute renal failure can be treated with different dialysis modalities, depending on patient characteristics and hospital resources. Peritoneal dialysis (PD) can be first choice in situations like hypotension, disturbed coagulation, or difficult venous access. The main disadvantage of PD is the relatively limited efficacy. The aim of this study was to investigate whether continuous flow peritoneal dialysis (CFPD) is a more effective treatment than conventional PD in acute renal failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A pilot study was performed at The Red Cross University Hospital in Cape Town in six patients. Patients were treated with both CFPD and conventional PD for 8 to 16 hours. CFPD was performed with two bedside-placed catheters. After initial filling, dialysate flow rate (100 ml/1.73 m2 per minute) was maintained with an adapted continuous venovenous hemofiltration machine. Ultrafiltration flow rate was set at 2.5 ml/1.73 m2 per minute. RESULTS: Mean ultrafiltration was 0.20 ml/1.73 m2 per minute with conventional PD versus 1.8 ml/1.73 m2 per minute with CFPD. Mean clearances of urea and creatinine were 5.0 and 7.6 ml/1.73 m2 per minute with conventional PD versus 15.0 and 28.8 ml/1.73 m2 per minute with CFPD, respectively. No complications occurred. CONCLUSIONS: In this first report of CFPD in six pediatric patients with acute renal failure, CFPD was on average three to five times more effective for urea and creatinine clearance and ultrafiltration than conventional PD, without any complications observed. CFPD has the ability to improve therapy for acute renal failure.

Proteomic profiling and identification in peritoneal fluid of children treated by peritoneal dialysis.

BACKGROUND: Proteomic technologies offer a high-throughput analysis of the expression of proteins in biological samples. The global analysis of the proteins in peritoneal dialysis (PD) fluid will provide a better understanding of the biological processes of the peritoneal membrane. METHODS: The dialysate of nine paediatric PD patients was collected from peritoneal equilibrium tests with 3.86% glucose. Proteins were separated on a 10% SDS-PAGE gel and in-gel digested with trypsin. Peptide mixtures were analysed using nanoLC-MS/MS and results were searched against the NCBI database. RESULTS: A total number of 189 proteins were identified in the PD fluid of nine patients, with 88 proteins shared by all patients. These 88 proteins accounted for 47% of the identified proteins and >90% of the total protein content in the analysed samples. Proteins were subdivided into eight different classes according to function. CONCLUSIONS: This study gives a representative overview of the proteins present in PD fluid. The proteins in PD fluid reflect plasma proteins as well as local peritoneal processes. Potentially interesting proteins are revealed.

No significant differences in peritoneal fluid handling in children using PH-neutral or acidic solutions.

OBJECTIVES: 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. DESIGN: 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). SETTING: Pediatric dialysis unit in a tertiary institute. PATIENTS: Stable pediatric PD patients. MAIN OUTCOME MEASURES: Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. RESULTS: 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. CONCLUSION: 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.

Endothelial function in pediatric patients on peritoneal dialysis: the need for data.

Cardiovascular complications are emerging as the primary cause of death for patients with childhood end-stage renal disease. Children with end-stage renal failure are subjected to many of the risk factors for cardiovascular disease identified in adult patients. Dysfunction of the endothelium is presently regarded as a first but reversible step in the development of atherosclerosis. Noninvasive techniques to assess endothelial function have been recently developed and have been proven to predict future mortality in adult patients. These techniques are readily applicable to pediatric patients. Endothelial dysfunction has been demonstrated in children in all stages of renal failure. Data on pediatric patients treated with peritoneal dialysis are currently lacking, however. Considering the abundance of cardiovascular risk factors specific to treatment with peritoneal dialysis, such studies should be initiated.

How to increase adequacy of peritoneal dialysis in children?

Since children on dialysis are treated most often with nightlyintermittent peritoneal dialysis, adequacy of dialysis is determined by the number and duration of cycles, the volume of the dialysis fluid applied, and the choice of dialysis solution. The number and duration of cycles are dependent on the maximal acceptable duration of night rest and the permeability properties of the peritoneal membrane. The latter can be established by performance of a peritoneal equilibration test. The volume used should be about 1200 mL/m2 body surface area, and intraperitoneal pressure should be between 5 and 15 cm H2O. The dialysis solution administered should have a glucose concentration as low as possible, and an icodextrin daytime dwell may be considered.

Sodium sieving in children.

Sodium sieving is a consequence of dissociation between the amount of water and sodium transported over the peritoneal membrane. This dissociation occurs in the presence of aquaporin-mediated water transport. Sieving of sodium can be used as a rough measure for aquaporin-mediated water transport. Icodextrin contains glucose polymers, inducing ultrafiltration by colloid osmosis. Therefore, aquaporins play a minor role in ultrafiltration, which is confirmed by the absence of sodium sieving. Icodextrin is very suitable for the daytime dwell in children on a nightly intermittent peritoneal dialysis regimen. Ultrafiltration obtained with icodextrin is similar to ultrafiltration obtained with 3.86% glucose after a 12-hour dwell. When using icodextrin in children, it is also confirmed by the absence of sodium sieving that the aquaporins play a minor role in ultrafiltration.

Evaluation of intraperitoneal pressure and the effect of different osmotic agents on intraperitoneal pressure in children.

OBJECTIVES: To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell. DESIGN: IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2 with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m2 and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated. PATIENTS: IPP was established in 30 patients with median age of 4.5 years (range 1.0 - 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 - 10.9 years) and median treatment period of 12 months (range 5.6 - 122.3 months). RESULTS: Mean IPP was 12.0 +/- 6.5 cm H2O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin. CONCLUSIONS: IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.

Etiology and epidemiology of end-stage renal disease in Dutch children 1987-2001.

In this retrospective study 351 children (<16.0 years) with end-stage renal disease (ESRD) accepted for renal replacement therapy (RRT) in the four Dutch pediatric centers were analyzed for the period 1987-2001. The data were compared with a previous study performed in 1979-1986. Eighty patients were of non-Dutch origin. An annual ESRD incidence of 5.8 patients per million of the child population (p.m.c.p.) was calculated, without significant changes with time. The final prevalence in Dutch children under 15 years of ESRD was 38.7 p.m.c.p. The most frequent primary renal disease leading to ESRD was urethral valves, with a significant increase vs. the previous observation period (14% vs. 6%). The distribution of primary renal diseases was similar in patients of non-Dutch origin and in Dutch patients. Peritoneal dialysis was the most frequent dialysis procedure initially applied (62% vs. 26% in the earlier observation period). Thirteen percent of all first transplantations (n=278) were pre-emptive and 19% from living donors. Five-year graft survival after a living-donor and a cadaver graft was 80% and 73%, respectively. Overall patient survival after 10 years on RRT was 94%.

IgG and complement receptor expression in children treated by peritoneal dialysis.

Children treated by peritoneal dialysis (PD) are at increased risk of infections. IgG receptors (FcgammaRs) and complement receptors (CRs) on white blood cells (WBCs) are important for the phagocytic process. We have investigated FcgammaR and CR expression on monocytes, macrophages and neutrophils in blood and in peritoneal dialysis effluent (PDE) of 39 PD children. WBCs were isolated from blood and PDE, labelled with FITC-conjugated CD16 (FcgammaRIII), CD32 (FcgammaRII), CD64 (FcgammaRI), CD11b (CR3) and CD35 (CR1) monoclonal antibodies, and analysed by flow cytometry. Peritoneal cells had lower percentages of FcgammaR-positive or CR-positive cells than blood. On the other hand, the receptor number per cell [mean fluorescence intensity (MFI)] was higher on peritoneal macrophages and neutrophils than blood, except for CD16. The FcgammaR and CR expression in blood and dialysate did not change significantly during the first year of PD treatment. During a peritonitis episode the MFI of all receptors in blood increased only on monocytes, with the exception of CD32. The percentages of FcgammaR-positive and CR-positive macrophages and neutrophils in the PDE increased, whereas the MFI did not increase consistently. Peritoneal cells of PD children showed a lower percentage of FcgammaR-positive and CR-positive neutrophils and macrophages, combined with an increased MFI, indicating a state of activation. Blood and peritoneal cells are capable of up-regulating the receptor expression during peritonitis but probably not to a maximum level.

Hemodialysis acutely impairs endothelial function in children.

Cardiovascular disease is the main cause of death for patients with end-stage renal disease (ESRD), including young adults. The appearance of endothelial dysfunction is an early stage in the development of atherosclerosis. There are conflicting data on the effect of hemodialysis on endothelial function in adults, but there are no studies in children. This study compares endothelial function of children on hemodialysis with healthy controls and describes the effect of a regular dialysis session on endothelial function. We studied 10 healthy children and 10 children on dialysis, before and after a regular midweek hemodialysis session. Endothelial function was studied non-invasively with ultrasound equipment as the percentage of post-ischemic flow-mediated dilation (FMD) of the brachial artery. In children on dialysis, FMD was 6.0+/-4.1%, while it was 14.2+/-5.8% in healthy controls (P=0.002). Hemodialysis induced a further decrease of FMD to 1.8+/-2.7% (P=0.003). Baseline diameter or distensibility of the brachial artery did not change. Systolic blood pressure, mean arterial pressure, and pulse pressure decreased, while diastolic blood pressure and heart rate did not change. This study demonstrates that children on hemodialysis have endothelial dysfunction. A hemodialysis procedure induces further endothelial dysfunction in children with ESRD. This repeated insult on the endothelium with maintenance hemodialysis may contribute to the cardiovascular risk of these children.

Peritoneal transport characteristics with glucose polymer-based dialysis fluid in children.

Scarce data are available on the use of glucose polymer-based dialysate in children. The effects of glucose polymer-based dialysate on peritoneal fluid kinetics and solute transport were studied in pediatric patients who were on chronic peritoneal dialysis, and a comparison was made with previously published results in adult patients. In nine children, two peritoneal equilibration tests were performed using 3.86% glucose and 7.5% icodextrin as a test solution. Dextran 70 was added as a volume marker to calculate fluid kinetics. Serum and dialysate samples were taken for determination of urea, creatinine, and sodium. After calculation of the initial transcapillary ultrafiltration (TCUF) rate, it was possible to calculate the contribution of aquaporin-mediated (AQP-mediated) water transport to ultrafiltration for icodextrin and 3.86% glucose and the part of L(p)S (the product of the peritoneal surface area and the hydraulic permeability) caused by AQP. In children, the transport parameters were similar for the two solutions, except for TCUF, which was lower for icodextrin (0.9 ml/min per 1.73 m(2)) as compared with 3.86% glucose (4 ml/min per 1.73 m(2)). Transport parameters were similar in children and adults for glucose, but with icodextrin, TCUF and marker clearance were significantly lower in children. AQP-mediated water flow was 83 versus 50% with glucose (child versus adult; P < 0.01) and 18 versus 7% with icodextrin (P < 0.01). Data indicate that transport parameters in children using icodextrin are similar to glucose except for TCUF. Differences are explained by the absence of crystalloid osmosis and that TCUF was determined after a 4-h dwell. Comparison of transport parameters and peritoneal membrane characteristics between children and adults reveal that there seem to be differences in the amount and functionality of AQP. However, there are no differences in clinical efficacy of this transport pathway because the absolute flow through the AQP is identical in both groups using 3.86% glucose.

IGG and complement receptor expression on peripheral white blood cells in uraemic children.

BACKGROUND: Phagocytosis of IgG- or complement-opsonized bacteria and antibody production by lymphocytes are regulated by cell surface receptors for IgG (FcgammaRI, FcgammaRII and FcgammaRIII) and complement (CR1 and CR3). We measured the effect of uraemia and dialysis treatment on FcgammaR and CR expression on leukocytes in blood. METHODS: Blood samples were obtained from children: 40 treated with peritoneal dialysis (PD), 23 with haemodialysis (HD), 46 not yet dialysed (CRF) and 33 healthy (HC). White blood cells, isolated from EDTA-blood by centrifugation after cell fixation with paraformaldehyde, were labelled with FITC-conjugated CD16 (FcgammaRIII), CD32 (FcgammaRII), CD64 (FcgammaRI), CD11b (CR3) and CD35 (CR1) monoclonal antibodies and analysed by flow cytometry. RESULTS: In PD, HD, CRF and HC, monocytes and neutrophils were all positive for FcgammaR and CR, except for CD16 on monocytes (20% positive). Lymphocytes expressed CD16 and CD32 but not CD64. PD, HD and CRF children had lower percentages of CD16(+) and CD32(+) lymphocytes compared with HC. The percentage of CD11b(+) lymphocytes was lower only in PD and the percentage of CD35(+) lymphocytes was lower in HD and CRF compared with HC. The median CD32 mean fluorescense intensity (MFI) on lymphocytes, monocytes and neutrophils was lower in PD, HD and CRF compared with HC. On the other hand, CD11b MFI on lymphocytes, monocytes and neutrophils was higher in PD, HD and CRF children compared with HC. CD16 and CD64 MFI were not different among the groups and CD35 MFI was only lower on lymphocytes from PD, HD and CRF compared with HC. CONCLUSIONS: In children with chronic renal failure, whether dialysed or not, FcgammaRII expression on lymphocytes, monocytes and neutrophils was reduced and CR3 expression was increased. Furthermore, CR1 expression on lymphocytes, important for the humoral response, was lower in children with renal failure. Age and uraemia are associated with these abnormalities and might contribute to impaired immune function in children with chronic renal failure.

Growth hormone therapy influences endothelial function in children with renal failure.

Endothelial dysfunction, an early step in atherogenesis, is prevalent in children with renal insufficiency. Endothelial dysfunction in growth hormone deficiency is reversed by growth hormone (rhGH) therapy. Renal failure induces growth hormone resistance at the receptor and post-receptor level, which can be overcome by rhGH therapy. This study investigates the influence of rhGH therapy in children with renal failure on flow-mediated dilation (FMD) of the brachial artery, a marker of endothelial function. We studied 8 patients, who were on rhGH for at least 6 months, and 8 healthy children for comparison. FMD of the brachial artery was measured non-invasively as the percentage increase in diameter during post-ischemic hyperemia. Patients were studied at baseline, after 4 weeks interruption of rhGH therapy, and 4 weeks after resumption of therapy. FMD was significantly lower in patients (4.7%) than healthy controls (13.8%) ( P=0.01). During the administration of rhGH, FMD was significantly higher (3.9%) than during interruption of the treatment (1.4%) ( P=0.04). Our data support the theory that a disturbance in the GH-IGF axis contributes to the endothelial dysfunction of renal failure. Treatment with rhGH not only improves growth but may also favorably influence the risk for atherogenesis.

Fibrin glue used successfully in peritoneal dialysis catheter leakage in children.

BACKGROUND: Acute renal failure in infants and small children is generally treated with peritoneal dialysis (PD). Dialysis has to be started immediately after catheter implantation. Early dialysate leakage can complicate the effectiveness of dialysis. Fibrin glue applied to the external part of the tunnel may stop dialysate leakage and eliminate the need for surgical intervention. The use of fibrin glue in the treatment of PD catheter leakage in children was studied. METHODS: Fibrin glue was used in 8 children (age 0.8 - 57 months) on PD in whom dialysate leakage was seen during the first 24 to 48 hours after catheter insertion. The dialysis volume initially administered was 20 mL/kg body weight. Fibrin glue (1 mL) was applied to the external part of the subcutaneous catheter tunnel through the exit site, as close to the cuff as possible. The occurrence of dialysate leakage and complications such as exit-site or tunnel infection and peritonitis were evaluated. RESULTS: Nine single-cuff straight Tenckhoff catheters were implanted in 8 children. In 5 cases, no subcutaneous tunnel was created. One child had catheter replacement due to obstruction of the catheter; on both occasions, catheter leakage was seen and treated with fibrin glue. In all 8 patients, no relapse of dialysate leakage was seen after application of the fibrin glue. During the time of PD, exit-site infections, tunnel infections, and peritonitis did not occur. CONCLUSION: Fibrin glue is a successful, simple, and safe substance for the treatment of peritoneal dialysate leakage in infants and small children with acute renal failure treated with PD.

Nutritional effects of increasing dialysis dose by adding an icodextrin daytime dwell to Nocturnal Intermittent Peritoneal Dialysis (NIPD) in children.

BACKGROUND: To assess the need to adapt dietary prescriptions, we studied potential effects of increasing the dialysis dose by adding a daytime icodextrin dwell, in children on Nocturnal Intermittent Peritoneal Dialysis (NIPD), on peritoneal amino acids (AA) and albumin loss, AA, albumin, cholesterol and fibrinogen plasma levels and nutritional intake. METHODS: A cross-over study in eight children (age 2-12 years) on NIPD at baseline (week 1). INTERVENTION: to increase dialysis dose we added a daytime dwell with 1100 ml/m(2) icodextrin solution for a week (week 2). MAIN OUTCOME MEASURES: peritoneal albumin loss (quantified by nephelometry) and AA loss (quantified by liquid chromatography mass spectrometry) in the last 72 h dialysate collections of weeks 1 and 2. On days 7 and 14, morning blood sample was taken for urea, creatinine, plasma AA levels, serum albumin, cholesterol and fibrinogen determination. Nutritional intake diaries were kept throughout the study period. RESULTS: Weekly dialysis creatinine clearance increased from 35 to 65 l/1.73 m(2) (P<0.0001) and Kt/V from 1.99 to 2.54 (P<0.01). Peritoneal albumin loss did not change significantly (2.4+/-0.4 to 2.4+/-0.3 g/m(2)/24 h) nor did serum albumin (3.25+/-0.52 to 3.21+/-0.25 g/dl), cholesterol (216+/-73 to 240+/-61 mg/dl) and fibrinogen (385+/-40 to 436+/-64 mg/dl). There was a significant increase in loss of essential (EAA) [1122+/-200 to 2104+/-417 mg/m(2)/week (P<0.0001)] and non-essential amino acids (NEAA) [6160+/-1341 to 10406+/-2899 mg/m(2)/week (P<0.001)]. Plasma AA levels did not change significantly except for a drop in histidine and glutamine. Dietary protein intake did not change from 43+/-12 to 41+/-8 g/m(2)/day, caloric intake from 73+/-21 to 70+/-24 kcal/kg/day. CONCLUSIONS: Increasing dialysis dose by introducing a daytime icodextrin dwell during a week does not affect peritoneal albumin loss, serum albumin, cholesterol and fibrinogen levels nor dietary intake on a short term. There is a significant increase in EAA and NEAA loss without change in plasma levels. We suggest monitoring dietary intake when adding a daytime icodextrin dwell in children.