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Contains fulltext : 51617raaijmakers.pdf (Publisher’s version ) (Closed access) To determine the efficacy and safety of intraperitoneal administration of darbepoetin in children with renal anemia on peritoneal dialysis, we conducted a single-arm, retrospective, two-centre study in which children were treated with intraperitoneal darbepoetin at the end of nightly intermittent peritoneal dialysis. Controls were those children treated with intraperitoneal erythropoietin six months before conversion to darbepoetin. Children were converted with the conversion factor 200 units erythropoietin=1 microg darbepoetin. Children who started with darbepoetin, started with 0.45 microg/kg/week. Nineteen children entered the study. The mean age was 6.8 years. Eight children were converted from 201 U/kg/week intraperitoneal erythropoietin to 1.0 microg/kg/week intraperitoneal darbepoetin. They were treated for a median period of 31.5 months. Median darbepoetin dose for an adequate erythropoesis over this period was 0.79 microg/kg/week. All 19 children were treated with darbepoetin for a median period of 13.4 months. The median dose for an adequate erythropoesis over this period was 0.63 microg/kg/week. The peritonitis incidence during this study was once every 25.1 months. Three children developed hypertension; one child developed headache. These complications developed after a rapid increase of hemoglobin concentration. Intraperitoneal administration of darbepoetin is effective and safe for children on peritoneal dialysis.

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 Dt/D0 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 Dt/D0 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.

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.

ObjectivesTo 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.DesignIPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2with 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/m2and 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.PatientsIPP 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).ResultsMean 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.ConclusionsIPP 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.

Item does not contain fulltext 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.

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.

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

Objective To provide guidelines on choosing dialysis solutions for children on chronic peritoneal dialysis (PD). Setting European Paediatric Peritoneal Dialysis Working Group. Data Source Literature on the application of PD solutions in children ( Evidence), and discussions within the group ( Opinion). Conclusions Glucose is the standard osmotic agent for PD in children ( Evidence). The lowest glucose concentration needed should be used ( Opinion). Low calcium solution (1.25 mmol/L) should be applied, wherever possible, with careful monitoring of parathyroid hormone levels ( Opinion). The use of amino acid-containing dialysis fluids can be considered in malnourished children, although aggressive enteral nutrition is preferred ( Opinion). There is insufficient evidence documenting the efficacy of intraperitoneally administered amino acids ( Evidence). When ultrafiltration and/or solute removal are insufficient, poly-glucose solutions are a welcome addition to the treatment of children on nocturnal intermittent PD ( Evidence). However, in the absence of any reported long-term experience with children, their use must be closely monitored ( Opinion). Bicarbonate would appear to be the preferred buffer for PD in children, but more in vivo studies are required before it replaces the present lactate-containing solutions ( Evidence/Opinion).

ObjectiveTo evaluate the use of the combination of cefazolin and ceftazidime for initial treatment of peritoneal dialysis (PD)-related peritonitis in pediatric patients.DesignRetrospective nonrandomized study.SettingPediatric dialysis units of the University Medical Center of Utrecht and Nijmegen, The Netherlands.Patients40 children (median age 5.4 years) who were treated with PD during the study period of 4.5 years.InterventionsAll 50 episodes of peritonitis that occurred during the study period were evaluated by review of medical records. Patients were given intraperitoneal ceftazidime 500 mg/L dialysis fluid, and cefazolin 500 mg/L as a loading dose, followed by a maintenance dose of ceftazidime 125 mg/L and cefazolin 100 mg/L, intraperitoneally, 4 times daily. Antibiotics were continued for 14 days.ResultsAfter identification of the causative microorganism, one of the antibiotics was discontinued in 34 cases, and the antibiotic schedule was adapted in 2 cases. All cases were initially cured within 3 days. In 5 cases (10%), there was a peritonitis with the same organism recurring within 2 weeks after completion of treatment. There were 4 cases of PD-related peritonitis caused by pseudomonas, all of which were cured.ConclusionsThe antibiotic combination of cefazolin and ceftazidime is effective for the initial therapy of PD-related peritonitis in children. The toxic complications of aminoglycosides are avoided with this combination.

ObjectiveTo explore further the mechanisms leading to immune deficiency in chronic renal failure and the role of dialysis treatment in these mechanisms.DesignCross-sectional and longitudinal analysis.PatientsWe studied 39 children treated with peritoneal dialysis (PD), 23 children treated with hemodialysis (HD), 33 children not yet dialyzed [chronic renal failure (CRF)], and 27 healthy children. Peritoneal cells were also obtained from PD children for analysis.MethodsWhite blood cells (WBCs) were isolated from blood and peritoneal dialysis effluent by centrifugation. The number of CD2+, CD4+, and CD8+T cells, B cells, and natural killer cells were measured by flow cytometry.ResultsThe total peripheral blood lymphocyte count was lower in PD children (2.6 x 109/L), HD children (2.1 x 109/L), and CRF children (2.0 x 109/L) compared with healthy children (3.1 x 109/L, p < 0.05). The B lymphocyte count was also lower in PD children (0.34x109/L), HD children (0.22 x 109/L), and CRF children (0.33 x 109/L) compared with healthy children (0.52 x 109/L, p < 0.01). Numbers of CD4+T cells were not different, but numbers of CD8+T cells were lower in PD children (0.56 x 109/L), HD children (0.63 x 109/L), and CRF children (0.53 x 109/L) compared with healthy children (0.77 x 109/L, p < 0.05). The count of natural killer cells was lower in PD children (0.21 x 109/L), HD children (0.17 x 109/L), and CRF children (0.18 x 109/L) compared with healthy children (0.50 x 109/L, p < 0.0001). The CD4/CD8 ratio of lymphocytes in peritoneal effluent was 0.8 versus 1.9 in peripheral blood ( p < 0.001). The CD2/CD19 ratio was not different. The cell subsets remained stable during the first year of PD treatment. The CD2/CD19 ratio in peritoneal effluent was higher in children with a peritonitis incidence ≥ 1 per year.ConclusionsThe reduced numbers of B lymphocytes, CD8+T cells, and natural killer cells found in CRF children, dialyzed or not, may favor the frequent occurrence of infections.

The use of recombinant human erythropoietin (rhEPO) has greatly facilitated the treatment of anemia in children with chronic renal failure, but is expensive. Several reports on adult patients have shown that supplementation with L-carnitine can decrease the requirement for rhEPO. The objective of this study was to investigate the effect of oral supplementation with L-carnitine on the rhEPO requirement in children on dialysis. We investigated 16 children on dialysis (11 hemodialysis, 5 peritoneal dialysis) with a median age of 10.2 years. All children were stable on rhEPO treatment at least 3 months before study entrance. After obtaining baseline data, all children were supplemented with L-carnitine 20 mg/kg/day. Data were collected for 26 weeks. Follow-up was completed for 12 patients (8 hemodialysis, 4 peritoneal dialysis). At baseline free carnitine (32+/-18 micromol/l) and total carnitine levels (54+/-37 micromol/l) were normal. At the end of the study free carnitine levels had increased to 97+/-56 micromol/l (P0.05) and total carnitine levels to 163+/-90 micromol/l (P0.05). There was no significant change in rhEPO requirement. Hemoglobin level or hematocrit did not change significantly during the study. In conclusion we could not demonstrate a beneficial effect of supplementation with L-carnitine on rhEPO requirement in children on dialysis.

Objectives To study longitudinal changes in trans-capillary ultrafiltration (TCUF) and marker clearance (MC), as a reflection of lymphatic absorption, in children on peritoneal dialysis (PD). To present data on fluid kinetics in infants younger than 2.5 years, using an intraperitoneal volume of 1200 mL/m2 body surface area (BSA). Design The study involved a 4-hour dwell of 1200 mL/m2 BSA of dialysis fluid containing 3.86% glucose with Dextran 70 as volume marker. Cumulative TCUF and cumulative MC were measured. Setting A tertiary-care university hospital. Patients A follow-up period of 33 months of serial (1 – 4) peritoneal equilibration tests (PETs) was studied in 20 children with a median age of 6.4 years (range 2.1 – 15.4 years). Fluid kinetics in 5 additional infants with a median age of 1.4 years (range 0.5 – 2.5 years) was measured. Results Cumulative TCUF was 1041 mL/1.73 m2 at 1 – 3 months after start of PD, 1026 mL/1.73 m2 at 7 – 9 months, 1021 mL/1.73 m2 at 11 – 13 months, and 756 mL/ 1.73 m2 at 26 – 33 months (NS). Cumulative MC was 235 mL/1.73 m2 at 1 – 3 months after start of PD, 311 mL/ 1.73 m2 at 7 – 9 months, 395 mL/1.73 m2 at 11 – 13 months, and 509 mL/1.73 m2 at 26 – 33 months (NS). In infants, cumulative TCUF was 755 ± 237 mL/1.73 m2; cumulative MC was 400 ± 214 mL/1.73 m2. Conclusions Transcapillary ultrafiltration and marker clearance do not change in children > 2.5 years during the period studied. Fluid kinetics does not differ between infants < 2.5 years and older children when intraperitoneal volumes of 1200 mL/m2 BSA are used.

Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin. Background The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane is affected in the inherited renal disorder Alport's syndrome (AS). Approximately 85% of the AS patients are expected to carry a mutation in the X-chromosomal COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is also present in the epidermal basement membrane (EBM). It is predicted that approximately 70% of the COL4A5 mutations prevent incorporation of this chain in basement membranes. Methods We investigated whether or not COL4A5 defects could be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were obtained from 22 patients out of 17 families and two biopsy specimens from healthy males were used as controls. Results In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female). In three other patients with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively, the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was found in three patients of six families with a diagnosis of AS and in one family of a group of four families with possible AS. Conclusions The (focal) absence of COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and prenatal DNA diagnosis are possible in the family of the patient.

Chronic renal failure (CRF) is associated, especially in young children, with delayed cognitive development of unknown origin. As cerebrospinal fluid (CSF) reflects the composition of the extracellular fluid of the brain, not only plasma but also CSF amino acids concentrations were determined in 8 infants (age 2-8 months) and 3 children (age 26, 32 and 56 months) with CRF (creatinine clearance 13 +/- 9 ml/min/ 1.73 m2). In three of these children investigations were repeated after six weeks of CAPD treatment. In the infants, a significant decrease was found in CSF of alpha-aminobutyric acid, valine, isoleucine, leucine, tyrosine, tryptophane, histidine and n-zeta-methyl-1-lysine, whereas there was a significant increase of 3-methylhistidine. In plasma serine, valine, leucine, tyrosine and histidine were significantly decreased, whereas there was a significant increase of aspartic acid, citrulline, and 3-methylhistidine. These abnormalities remained constant after the start of CAPD except for the normalization in CSF and plasma of 3-methylhistidine. These data indicate a generalized disturbance of amino acids in young children with CRF. An abnormal substrate is offered to the neurons and astroglia in children with CRF.

ObjectiveTo measure the urea and creatinine kinetics in a pediatric populationPatients and MethodsIn 19 children treated with peritoneal dialysis (PD) KT/V, urea and creatinine clearances (Ccr) were measured. Thirteen children were on continuous ambulatory peritoneal dialysis (CAPD) and 6 on nightly intermittent peritoneal dialysis (NIPD).ResultsMean KT/V per week was 2.31 ±0.78 and mean creatinine clearance 74 ±47 L/week/1. 73 m2. There was no difference in dialytic KT/V between patients treated with CAPD and NIPD (1.75 ±0.21 vs 1.76 ±0.50). The correlation between KT/V urea and creatinine clearance was 0.9 (pConclusionsMean KT/V in this patient group was higher than the values reported for most adult patient groups. Residual renal function considerably contributes to this high KT/V. It is not clearly defined which KT/ V should be aimed for, since criteria for adequate dialysis are multifactorially determined and therefore difficult to interpret.

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 alpha 5 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.

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.

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.

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.

Chronic renal failure in young children is associated with impaired cognitive development, but recent studies present a more optimistic perspective. An important question is whether the earlier initiation of renal replacement therapy (RRT) might prevent the reported developmental retardation. The cognitive development of 31 patients (age

Objective During continuous ambulatory peritoneal dialysis (CAPD), activation of complement in the peritoneal cavity may theoretically occur, with inappropriately high or low levels of certain complement factors in dialysate as a consequence. In a group of children on CAPD, it was tested whether levels of a number of complement factors in dialysate were in the range that was predicted on the basis of their molecular weight. Design Serum and dialysate levels of C1 q, C3, C4, C3d, B, D, and P were measured after a night dwell in children on CAPD. Simultaneously, four non-complement proteins (β2-microglobulin, albumin, IgG, and α2macroglobulin) were also measured in dialysate and serum. Assuming a linear relationship between the log base 10 of the dialysate/serum ratio of these non-complement proteins and the log base 10 of their molecular weight, the expected ratios of all complement factors were determined. The differences between actual and predicted ratios were tested using a modified t-test, taking into account the inaccuracy of the estimate. Setting University hospital. Patients A group of 14 children on CAPD, with a median age of 7.8 years (range 2.1–13.2). These children had been on CAPD for a median period of 42.4 months (range 0.4 89.1). Results The ratios of factor D (p < 0.001) and C3d (p = 0.035) were elevated, whereas those of C3 (p < 0.001), C4 (p < 0.001), and factor P (p = 0.012) were decreased. Conclusions Relatively low dialysate/serum ratios of C4, C3, and factor P could be caused by intraperitoneal consumption of complement. High levels of C3d are compatible with this. High dialysate/serum ratios of factor D indicate intraperitoneal production of factor D. These results provide evidence for activation of complement in the peritoneal cavity in children on CAPD. A further reduction of already low levels of complement factors in dialysate as a result of this may impair host defense.

Data concerning 100 consecutive renal transplantations in children were analyzed to determine factors enhancing the risk of renal transplant thrombosis. The incidence of renal transplant thrombosis was high, at 12%. It is concluded that in addition to young age and low body weight of recipient and young age of the donor, also a high preoperative urine production contributes to the occurrence of thrombosis. Children with hypoplastic or dysplastic kidneys are at greater risk for thrombosis. Considering the influence of high urine production of the native kidneys, it may be possible to prevent thrombosis by albumin and ample fluid administration.

A COL4A3 gene mutation and post-transplant anti-α3(IV) collagen alloantibodies in Alport syndrome. The X-linked Alport syndrome is associated with mutations and deletions in COL4A5 gene, one of six genes which constitute the α-chains of type IV collagen in basement membranes. The autosomal recessive form of Alport syndrome is characterized by mutations and deletions in the COL4A3 and COL4A4 genes. A fraction of Alport patients who undergo renal transplantation develop anti-glomerular basement membrane (GBM) nephritis, which results in loss of the renal allograft function. Recently, the target for alloantibodies from an X-linked Alport patient with complete COL4A5 gene deletion was determined to be the α3 chain of type IV collagen. The present study characterized the post-transplant alloantibodies from an autosomal recessive Alport patient with anti-GBM glomerulonephritis and a COL4A3 gene mutation which predicted a loss of 85% of the α3(IV) NC1 domain. The specificity of these new antibodies were studied using glomerular basement membrane constituents and recombinant type IV collagen domains. The results establish the target for the alloantibodies from an autosomal recessive Alport patient with COL4A3 deletion as principally the α3(IV) collagen chain, similar to the post-transplant alloantibodies from X-linked Alport patients with COL4A5 gene deletions. The absence of α3 (IV) chain in the GBM of patients with both these forms of Alport syndrome, due either to a failure of synthesis or a failure of assembly, presumably leads to a loss of immunologic tolerance for the α3(IV) NC1 domain in transplanted allografts.

Item does not contain fulltext AIM: The present studywas designed to retrospectively evaluate the use of renal biopsies prior to cyclophosphamide therapy. The aim of the study was to determine in how many cases histological outcome of the biopsies had subsequently changed the decision to treat or refrain from treatment. PATIENTS AND METHODS: Between January 1980 and September 2001, 85 children with steroid-sensitive nephrotic syndrome (SSNS) underwent a renal biopsy in the University Hospitals of Utrecht and Nijmegen before the start of an 8-week cyclophosphamide treatment. MCNS was suspected in all children because of the following criteria: edema, proteinuria, hypoalbuminemia, absence of macroscopic hematuria and in rare cases microscopic hematuria, no permanent hypertension, normal C3 serum level, a normal glomerular filtration rate as determined by creatinine clearance and age > 1 year. Cyclophosphamide therapy was indicated because of a frequently relapsing (FR) course of illness in 8 children, because of steroid dependence (SD) in 22 children and because of combined FR and SD in 55 children. Steroid-resistant children were excluded from this study. RESULTS: Histology confirmed the diagnosis MCNS in 84 out of 85 children. In addition to MCNS, IgA deposits were observed in renal specimens of 2 children. In 1 SD child, the initial diagnosis MCNS was changed 3 years later when a repeated biopsy showed progression into focal segmental glomerulosclerosis (FSGS). CONCLUSION: In summary, no renal biopsy is required prior to cytotoxic therapy in children with uncomplicated steroid-sensitive nephrotic syndrome.

Item does not contain fulltext 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. 01 maart 2012

Objective Previous measurements of peritoneal fluid handling in children treated by continuous ambulatory peritoneal dialysis (CAPD) were performed with human albumin as a fluid marker. A major disadvantage of this substance is that endogenous patient albumin enters the peritoneal cavity during the dwell period. For this reason perito neal fluid kinetics were measured in a group of children on CAPD, using autologous hemoglobin as a volume marker. Design Autologous hemoglobin was added to dialysate containing 1.36% glucose as a volume marker. Marker clearance (MC), which is presently the best available approximation of lymphatic absorption in the clinical setting, and transcapillary ultrafiltration (TCUF) were measured during a 4-hour dwell. Setting University hospital. Patients Children on CAPD (N=9), with a median age of 8.1 years (range 2.1–13.2 years). Results MC was 521±166 mL/4 hour/1.73 m2, which is high compared to the literature data on adult CAPD patients. TCUF was 519±92 mL/4 hour/1.73 m2, which is similar to data concerning adult patients. TCUF reached no maximum during the 4-hour dwell, and the deviation of the TCUF curve from linear was markedly less than usually seen in adult patients. Conclusions MC in children treated with CAPD is higher when compared to the literature data on adults. Difficulties to achieve sufficient ultrafiltration in children could be caused by relatively small differences between MC and TCUF from the beginning to the end of the dwell.

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The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised.

ObjectiveDuring continuous ambulatory peritoneal dialysis (CAPD), the loss of complement factors via the dialysate may cause complement deficiencies. This hypothesis was tested in a group of children treated with CAPD.DesignClassical (CH50) and alternative (AP50) complement activity and serum levels of factors C1 q, C3, C4, C3d, B, D, and P in CAPD patients were compared to normal controls and to children with preterminal renal failure.SettingPatients were seen in a university hospital; normal controls were seen in an outpatient clinic of a general hospital.PatientsA group of 22 children on CAPD was compared to a normal control group of 44 children and to a group of 12 children with preterminal renal failure with a creatinine clearance below 25 mL/min/1.73 m2.ResultsCH50, AP50, C3, and B were not significantly different from the control group in both the CAPD and preterminal groups. Factors C1q (p=0.01) and C4, C3d, D, and P (pConclusionsThere is no deficiency of complement in children treated with CAPD. High levels of C3d and D can be explained by the reduction of their elimination by the kidney. The increased levels of the other factors are presumably due to increased synthesis in renal failure. This does not seem to be caused by CAPD.

Peritoneal handling of glucose and metabolites is reported to be higher in young children treated with CAPD than in older children. Reference curves for the standardized peritoneal equilibration test (PET) are not available for younger ages. The present study describes the results of the PET in 19 children (mean age 5.0 years, ranging from 0.3–15) during the first month of CAPD treatment. No age dependency for the handling of glucose, urea, and creatinine could be established when the group was subdivided into 1. children below the age of 3 years, and 2. children above that age. There was, however, a significant correlation between equilibration of creatinine and age, indicating more rapid equilibration at younger ages.

Contains fulltext : 71301.pdf (Publisher’s version ) (Closed access) 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.

Background. The passage of proteins across the glomerular filtration barrier is mainly determined by the size of the protein. In nephrotic syndrome (NS) the glomerular permselectivity is affected, causing proteinuria. Some authors suggest the existence of a generalized basement membrane defect. The permeability characteristics of the peritoneal basement membrane in children with NS are not known. Methods. The transperitoneal transport of proteins with a different molecular weight (β 2 -microglobulin MW 11 800 D, albumin MW 69000 D, IgG MW 160000 D, and α 2 -macroglobulin MW 820000 D) was studied in a study group (group A) consisting of six stable nephrotic children (three with glomerulosclerosis and three with congenital nephrotic syndrome, one of them with mesangial sclerosis) and compared to a control group (group B) consisting of eight stable children on peritoneal dialysis. After a dwell of 6h with Dianeal 1.36% dialysate and serum samples were collected. For each patient the dialysate to plasma (D/P) ratios of the four proteins were calculated. The D/P ratios of the nephrotic patients in group A were compared to the D/P ratios of the patients in the control group B. Data were expressed as mean +SD. Results. The values for the D/P ratios (in percentage) of β 2 -microglobulin, albumin, IgG and 12-macroglobulin in group A were 19.6±9.9, 2.7+1.7, 1.6±0.9, and 0.5+0.4, compared to 24.9+10.2, 4.0±2.3, 2.2+1.2, and 0.7+0.3 in the control group B. The ratios were plotted against MW on a double logarithmic scale. In all patients a linear relationship between molecular weight and D/P ratio of the proteins was obtained. The D/P ratios of the study group did not differ significantly from the control group. Conclusion. We conclude that the size selectivity of the capillary permeability is not affected in the peritoneal membrane in children with NS due to glomerulosclerosis and congenital nephrotic syndrome.

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.

Item does not contain fulltext Fungal peritonitis is a rare but serious complication in children on peritoneal dialysis (PD). In this study, risk factors were evaluated, and therapeutic measures were reviewed. A retrospective, multi-centre study was performed in 159 Dutch paediatric PD patients, between 1980 and 2005 (3,573 months). All peritonitis episodes were reviewed. Fungal peritonitis episodes were evaluated based on possible risk factors and treatment strategy. A total of 321 episodes of peritonitis occurred, with 9 cases of fungal peritonitis (2.9%). Candida peritonitis occurred most frequently (78%). Seven patients (78%) had used antibiotics in the prior month. Fungal peritonitis patients had a higher previous bacterial peritonitis rate compared to the total study population (0.13 versus 0.09 episodes/patient*month), with twice as many gram negative organisms. In all fungal peritonitis patients, the PD catheter was removed. In four patients restart on PD was possible. Fungal peritonitis is a rare complication of PD in children, but is associated with high technique failure. The most important risk factors are a high bacterial peritonitis rate, prior use of antibiotics, and previous bacterial peritonitis with gram negative organisms. The PD catheter should be removed early, but in children, peritoneal lavage with fluconazole before removal may be useful to prevent technique failure.

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.

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.

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.

Item does not contain fulltext 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.

In this retrospective study 351 children (

In recent years several new peritoneal dialysis solutions have come onto the market. These solutions differ from the conventional ones with respect to osmotic agent, buffer, and/or calcium concentration. Icodextrin-containing solutions are characterized by slow, but sustained ultrafiltration. Experience in both adults and children has been favorable for the long dwell period, giving rise to both increased ultrafiltration and clearances. The use of icodextrin during the daytime seems ideal in patients on nightly intermittent peritoneal dialysis with a low peritoneal ultrafiltration rate. However, long-term experience still has to be obtained, particularly in children. The application of pH-neutral solutions, containing bicarbonate, lactate, or a bicarbonate/lactate mixture as a buffer, has shown better preservation of peritoneal cells and better tolerance. The standard calcium concentration of 1.75 mmol/l of the dialysis solution is too high in many situations. Individual strategies for an adequate calcium balance are required depending on age, clinical situation, and oral intake of calcium and vitamin D metabolites.

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.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.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.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.