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ABSTRACT: 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.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 05/2013;
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ABSTRACT: 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.
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.
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.
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.
Nephrology Dialysis Transplantation 07/2011; 27(3):1183-90. · 3.40 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Clinical Journal of the American Society of Nephrology 10/2010; 6(2):311-8. · 5.23 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Nephrology Dialysis Transplantation 07/2008; 23(7):2402-5. · 3.40 Impact Factor
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ABSTRACT: 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.
Pediatric Nephrology 09/2005; 20(8):1161-7. · 2.52 Impact Factor
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ABSTRACT: 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.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 03/2005; 25 Suppl 3:S127-9. · 2.10 Impact Factor
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ABSTRACT: 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.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 03/2005; 25 Suppl 3:S141-2. · 2.10 Impact Factor
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ABSTRACT: 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.
Pediatric Nephrology 03/2005; 20(2):200-4. · 2.52 Impact Factor
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Cornelis H Schröder
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ABSTRACT: 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.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 03/2005; 25 Suppl 3:S135-6. · 2.10 Impact Factor
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ABSTRACT: 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.
Journal of the American Society of Nephrology 12/2004; 15(11):2940-7. · 9.66 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Nephrology Dialysis Transplantation 10/2004; 19(9):2296-301. · 3.40 Impact Factor
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ABSTRACT: 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.
Pediatric Nephrology 08/2004; 19(7):785-9. · 2.52 Impact Factor
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Cornelis H Schröder
Pediatric Nephrology 12/2003; 18(11):1085-8. · 2.52 Impact Factor
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Cornelis H Schröder
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ABSTRACT: Anemia is common in chronic renal failure. Guidelines for the diagnosis and treatment of anemia in adult patients are available. With respect to the diagnosis and treatment in children on peritoneal dialysis, the European Pediatric Peritoneal Dialysis Working Group (EPPWG) has produced guidelines. After a thorough diagnostic work-up, treatment should aim for a target hemoglobin concentration of at least 11 g/l. This can be accomplished by the administration of erythropoietin and iron preparations. Although there is sufficient evidence to advocate the intraperitoneal administration of erythropoietin, most pediatric nephrologists still apply erythropoietin by the subcutaneous route. Iron should preferably be prescribed as an oral preparation. Sufficient attention has to be paid to the nutritional intake in these children. There is no place for carnitine supplementation in the treatment of anemia in pediatric peritoneal dialysis patients.
Pediatric Nephrology 09/2003; 18(8):805-9. · 2.52 Impact Factor
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ABSTRACT: Atherosclerotic complications are the main cause of death in adult patients with renal failure. Endothelial dysfunction is a hallmark of early atherosclerotic changes. The numerous risk factors for endothelial dysfunction present in adults are present in children with renal failure, as well. In addition to this, increased stiffness of the arterial tree conveys an increased risk for cardiovascular mortality. The aim of this study is to investigate whether pediatric kidney recipients already show endothelial dysfunction and have increased arterial stiffness.
We investigated 20 pediatric kidney recipients with stable graft function and 20 healthy children. Endothelial function was studied noninvasively with ultrasound and digital signal analysis equipment as the percentage of post-ischemic flow-mediated dilatation (FMD) of the brachial artery. Parameters of arterial distensibility were calculated from distension of the brachial artery during the cardiac cycle, pulse pressure, and baseline diameter.
FMD was significantly less in patients (7.7% +/- 5.4%) than controls (15.0% +/- 7.1%; P < 0.001), indicating endothelial dysfunction in pediatric kidney recipients. Impairment of FMD was found predominantly in patients being treated for hypertension. Arterial distensibility was diminished in patients (3.4 +/- 2.8 versus 5.7 +/- 3.3 10(-3)/mm Hg; P < 0.02), indicating increased stiffness of the arterial tree. Patients had a greater baseline diameter of the brachial artery adjusted for height than healthy controls at equal blood pressure.
These findings suggest arterial wall changes in pediatric renal transplant recipients. They are already at risk for premature development of atherosclerotic complications and cardiovascular mortality.
American Journal of Kidney Diseases 03/2003; 41(3):684-91. · 5.43 Impact Factor
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ABSTRACT: Clinical manifestations of type IV collagen mutations can vary from the severe, clinically and genetically heterogeneous renal disorder, Alport syndrome, to autosomal dominant familial benign hematuria. The predominant form of Alport syndrome is X-linked; more than 160 different mutations have yet been identified in the type IV collagen α5 chain (COL4A5) gene, located at Xq22-24 head to head to the COL4A6 gene. The autosomal recessive form of Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes, located at 2q35–37. Recently, the first mutation in the COL4A4 gene was identified in familial benign hematuria. This paper presents an overview of type IV collagen mutations, including eight novel COL4A5 mutations from our own group in patients with Alport syndrome. The spectrum of mutations is broad and provides insight into the clinical heterogeneity of Alport syndrome with respect to age at renal failure and accompanying features such as deafness, leiomyomatosis, and anti-GBM nephritis. Hum Mutat 9:477–499, 1997. © 1997 Wiley-Liss, Inc.
Human Mutation 12/1996; 9(6):477 - 499. · 5.69 Impact Factor
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European Journal of Pediatrics 07/1995; 154(8):689-689. · 1.88 Impact Factor
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Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 26(6):712-4.
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ABSTRACT: 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.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 26(5):587-92. · 2.10 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
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.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 25(4):352-6. · 2.10 Impact Factor
