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.

Solutions for peritoneal dialysis in children: recommendations by the European Pediatric Dialysis Working Group.

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.

Peritonitis in children on peritoneal dialysis in Cape Town, South Africa: epidemiology and risks.

Peritonitis is a frequent complication of peritoneal dialysis (PD) in children as well in adults. Data on PD and peritonitis in pediatric patients are very scarce in developing countries. A retrospective cohort study was performed between 2000 and 2008 with the aim to evaluate PD treatment and peritonitis epidemiology in pediatric patients in South Africa and identify risk factors for peritonitis. Baseline characteristics and potential risk factors of peritonitis were recorded, including housing, socio-economic circumstances, distance to PD center, type of PD, mode of catheter placement, race, presence of gastrostomy tube, weight, and height. Outcome indices for peritonitis were peritonitis rate, time to first peritonitis, and number of peritonitis-free patients. The patient cohort comprised 67 patients who were on PD for a total of 544 months. The total number of peritonitis episodes was 129. Median peritonitis rate was one episode every 4.3 patient months (2.8 episodes/patient-year, range 0-21.2). Median time to first infection was 2.03 months (range 0.1-21.5 months), and 28.4% of patients remained free from peritonitis. Patients with good housing and good socio-economic circumstances had a significantly lower peritonitis rate and a longer time to first peritonitis episode. Peritonitis rate was high in this cohort, compared to numbers reported for the developed world; the characteristics of causative organisms are comparable. The most important risk factors for the development of peritonitis were poor housing and poor socio-economic circumstances. More intensive counseling may be beneficial, but improvement of general socio-economic circumstances will have the greatest influence on PD success.

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.

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.

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.

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.

Vascular function in children after renal transplantation.

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

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.

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.

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.

Generalized tetanus in a 4-year old boy presenting with dysphagia and trismus: a case report.

INTRODUCTION: The low incidence of tetanus in developed countries has resulted in a decreased vigilance of this disease. This raises concern, as the prodromal stadium of a generalized tetanus infection may lack the characteristic paroxysmal muscle spasms. Tetanus can rapidly progress into life-threatening muscle spasms accompanied by respiratory insufficiency and/or autonomic dysfunction. This emphasizes the need for early diagnosis and treatment. CASE PRESENTATION: A 4-year-old Caucasian boy presented with a one-week history of general malaise, mild fever, indolence and anorexia. He subsequently developed dysphagia, sialorrhoea, difficulties opening the mouth and eventually dehydration. Due to parental concerns about the boy's refusal of fluids, a pediatrician was consulted. At that time of presentation he showed signs of trismus and muscle rigidity. Together with the lack of immunization and a toe nail infection, this lead to the suspicion of a generalized tetanus infection. After sedation, endotracheal intubation and ventilation, passive immunization and initiation of antimicrobial treatment, he was immediately transferred to a pediatric intensive care unit (PICU) for further treatment. The frequency and severity of paroxysmal muscle spasms increased progressively during his PICU stay, despite high doses of sedatives. Not before two weeks after admittance, extubation and careful weaning off sedatives was achieved. CONCLUSION: Tetanus infection remains a rare but potentially lethal disease in developed countries. As the full scope of classical symptoms may be absent at first presentation, tetanus should always be considered in non-immunized patients with an acute onset of dysphagia and trismus.

Intraperitoneal treatment with darbepoetin for children on peritoneal dialysis.

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.

Fungal peritonitis in children on peritoneal dialysis.

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.

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.

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%.