The impact of dialysis solution biocompatibility on ultrafiltration and on free water transport in rats.

This study compares different peritoneal dialysis fluids (PDF) in rats over a short contact time. For greater accuracy, net ultrafiltration (UF) and peritoneal transport indices, mass transfer area coefficient (MTAC) were scaled for the in vivo peritoneal surface area recruited (ivPSA) measured by microcomputerized tomography. Wistar rats underwent nephrectomy (5/6ths), were randomized into two groups and given 1.5% glucose PDF, either conventional acidic lactate (n = 14) or pH neutral bicarbonate (BicaVera) (n = 13); MTAC and UF were measured using a 90-min peritoneal equilibrium test (PET), fill volume (IPV) of 10 ml/100 g; small pore fluid transport was determined from sodium balance and used to calculate free water transport (FWT). Each ivPSA value was significantly correlated with the actual IPV, which varied from one rat to another. At 90 min of contact, there was no difference in recruited ivPSA in relation to PDFs. There was a difference (p < 0.01) in net UF/ivPSA 0.45 vs. 1.41 cm(2)/ml for bicarbonate versus lactate, as there was in the proportion of FWT with bicarbonate (42 ± 5% of net UF) compared to lactate (29 ± 4% of net UF). Net UF for individual values of ivPSA differs between conventional PDF and more biocompatible solutions, such as bicarbonate PDF. This observed change in UF cannot be fully explained by differences in glucose transport. The changes in FWT may be explained by the impact of the PDF biocompatibility on aquaporin function.

Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

Frasier syndrome, a potential cause of end-stage renal failure in childhood.

The diagnosis of Frasier syndrome is based on the association of male pseudohermaphroditism (as a result of gonadal dysgenesis), with steroid-resistant nephrotic syndrome due to focal and segmental glomerular sclerosis (FSGS), which progresses to end-stage renal failure (ESRF) during adolescence or adulthood. Frasier syndrome results from mutations in the Wilms' tumour suppressor gene WT1, which is responsible for alterations in male genital development and podocyte dysfunction. We describe the case of a 7-year-old girl who was referred to the paediatric emergency department with ESRF. Haemodialysis was started immediately because of severe hypertension and hyperkalaemia. In view of the fact that our patient had a past medical history of pseudohermaphroditism, we suspected that the acute presentation in ESRF may be related to a new diagnosis of Frasier syndrome. Our hypothesis was confirmed on examination of the medical records. There had been no medical follow-up for several years and, in particular, no renal imaging or functional assessment had ever been performed. This lack of surveillance explains why our patient presented with ESRF much earlier in this disease than expected and subsequently had to undergo kidney transplantation at a very young age.

Endoscopic Mic-Key button placement for continent vesicostomy.

INTRODUCTION: The use of a gastrostomy button for intermittent emptying of the bladder has been already proposed. The aim of this study was to describe a percutaneous button placement under endoscopic control as a safe, minimally invasive technique. MATERIALS AND METHODS: The percutaneous gastrostomy kit, according to the Russell gastrostomy tray (Cook; Cook, Bloomington, IN), was used under cystoscopic control. The U-stitche technique, according to Georgeson, allowed us to secure the bladder to the abdominal anterior wall. A guide was introduced into the bladder through a needle. Three dilatators, respectively 12, 14, and 16 FR, allowed the path for a probe or, immediately, the gastrostomy button (Mic-Key; Ballard Medical Products, Draper, UT). RESULTS: Over 2 years, 10 percutaneous continent vesicostomies were performed for patients with a neurogenic bladder. Patients were from 5 months to 19 years old. The procedure was safe. No major complication was observed except for only minor ones. DISCUSSION: When intermittent urethral catheterization cannot be established, Mitrofanoff continent urinary diversion seems to be a major surgery for patients and their parents. In addition, for some patients, intermittent bladder emptying may be required for a transitory period. For all these reasons, there is a place for a reversible vesicostomy with a minimally invasive procedure. Button vesicostomy seems to be a good alternative. In this article, we propose a percutaneous technique with an endoscopic control. If this kind of treatment is effective, it may avoid further major surgery. CONCLUSIONS: Percutaneous button vesicostomy placement under endoscopic control is safe and feasible and must be evaluated with large series.

Daily on line haemodiafiltration promotes catch-up growth in children on chronic dialysis.

BACKGROUND: In children, growth can be used as a measurable parameter of adequate nutrition and dialysis dose. Despite daily administration of recombinant human growth hormone (rhGH), growth retardation remains a frequent problem in children on chronic dialysis. Therefore, we performed an observational prospective non-randomized study of children on in-centre daily on line haemodiafiltration (D-OL-HDF) dialysis with the aim of promoting growth. PATIENTS AND METHODS: Mean age at the start of the study was 8 years and 3 months, and all children had been receiving rhGH treatment for >12 months before enrolment. Mean follow-up time on D-OL-HDF was 20.5 +/- 8 months (range, 11-39 months). Renal residual function was either <3 mL/min/1.73 m(2) or anuric. Vascular access was a fistula (13/15) or a central venous catheter (2/15). Dialysis was delivered daily, six days a week in 3 hourly sessions (18 h/week), in a predilution OL-HDF mode, allowing a high convective volume (18 to 27 L/m(2) body surface area per session), Kt/V(urea) on line measured at least 1.4 per session. RESULTS: Mean growth velocity increased from 3.8 +/- 1.1 cm/year at inclusion to 14.3 +/- 3.8 cm/year during the first year of D-OL-HDF, resulting in a change in height standard deviation score (SDS) over the follow-up period from -1.5 +/- 0.3 SDS to +0.2 +/- 1.1 SDS. Increase in body mass was also noted without impaired control of blood pressure. Time-average deviation for urea (TAD(urea)) was low at 2.5 +/- 0.4 as was TAD(bicarbonate) due to the normal pre and post dialysis bicarbonate levels, respectively, 23.6 +/- 0.5 mmol/L and 26.6 +/- 0.5 mmol/L. The absence of any dietary restrictions permitted a mean protein diet intake (PDI) of 2.5 +/- 0.2 g/kg/day (PDI measured from a 3-day diet survey), contrasting with a mean normalized protein nitrogen appearance (nPNA) of 1.53 +/- 0.12 g/kg/day (nPNA calculated from urea dialytic kinetic). A low C-reactive protein was noted in 13/15 children, and mean beta(2) microglobulin was low, 15.3 +/- 0.3.3 mg/L. CONCLUSIONS: Daily OL-HDF promotes catch-up growth in children despite on chronic dialysis. This catch-up growth if continued, should allow the children to reach their mid-parental target height in the future. It could be speculated that the improved response to rhGH is the result of several combined factors conducting to less malnutrition and to less cachexia.

Importance of the curve shape for interpretation of blood volume monitor changes during haemodiafiltration.

In children, the prescribed ultrafiltration needed to achieve the fixed end session dry weight can induce hypotensive episodes. A variety of on-line devices based on the direct measurement of the hematocrit are available, but these devices nearly always only measure the quantitative variation in the blood volume as the means of identifying a hypotensive occurrence risk. In February 2002, our unit began using an on-line hematocrit measurement available even with infants' blood lines. Since January 2004, this blood volume monitor (BVM) has been used routinely in all dialysis sessions, and 2240 BVM data sets have been recorded and analysed during the last 4 years. Based on our analysis of these data sets, we have determined that, in addition to the described threshold points, which provide a quantitative analysis of the BVM, the qualitative analysis of the BVM, the so-called curve shape, is also of clinical importance. In 91% of the sessions analysed, a very similar "symptom-free" curve shape was noted that consisted of an initial decrease, followed by the BV reaching a "stable" plateau. Additional curve shapes were identified: one with no BV decrease, presumably indicating an overload risk state, and one with a continuous BV decrease, presumably indicating an hypovolemic risk state. In our experience, only 2% of the patients had relevant clinical symptoms that were not visible by BVM.

Hemodialysis and nutritional status in children: malnutrition and cachexia.

Malnutrition is a common state in chronic hemodialyzed children. More than malnutrition, which infers that dietary supplementation would be curative, cachexia, which implies loss of protein stores, are combined factors of impaired linear growth and reduced muscle mass in uremic patients. Adequate diet to prevent malnutrition is of major importance. But to avoid cachexia in children on chronic hemodialysis, the management of acidosis, inflammation, abnormal metabolic rate, and endocrine disturbances should not, be forgotten. Daily hemodialysis regimen using convective flow therapy and ultrapure dialysate, i.e., on line hemodiafiltration together with growth hormone therapy, appears as a hopeful strategy for the chronic dialyzed child to achieve catch-up growth, a parameter of optimal nutrition.

Adequacy of peritoneal dialysis in children: consider the membrane for optimal prescription.

The peritoneal dialysis (PD) prescription should be adequate before being optimal. The peritoneal membrane is a dynamic dialyzer: the surface area and the vascular area both have recruitment capacity. At bedside, prescription is based mainly on tolerance of the prescribed fill volume, and therefore a too-small fill volume is often prescribed. A too-small fill volume may lead to a hyperpermeable exchange, with potentially enhanced morbidity-or even mortality-risks. Better understanding of the peritoneal membrane as a dynamic dialysis surface area allows for an individually adapted prescription, which is especially suitable for children on automated PD. Fill volume should be scaled for body surface area (mL/m2) and, to avoid a hyperpermeable exchange, for a not-too-small amount. Fill volume enhancement should be conducted under clinical control and is best determined by intraperitoneal pressure measurement in centimeters of H2O. In children 2 years of age and older, a peak fill volume of 1400-1500 mL/m2 can be prescribed in terms of tolerance, efficiency, and peritoneal membrane recruitment. Dwell times should be determined individually with respect to two opposing parameters: Short dwell times provide adequate small-solute clearance and maintain the crystalloid osmotic gradient (and, thereby, the ultrafiltration capacity). Long dwell times enhance phosphate clearance, but can lead to dialysate reabsorption. The new PD fluids (that is, those free of glucose degradation products, with a neutral pH, and not exclusively lactate-buffered) appear to be the best choice both in terms of membrane recruitment and of preservation of peritoneal vascular hyperperfusion.

Intensified and daily hemodialysis in children might improve statural growth.

In children conventional hemodialysis does not often improve growth. We determined linear growth in five children on in-center intensified and daily hemodialysis (IDd) regimen, with a mean age of 8 years 7 months at enrollment. Four of five were on growth hormone started for a median of 28.5 months before IDd. IDd was delivered 5 to 6 times weekly, for three hours each session. Mean follow up of IDd was 18.6 months. Dropout from IDd was kidney transplantation (n=4) or transfer to another center (n=1). IDd and free diet improved appetite, thereby protein intake, was above 2 g/kg/BW. Median weekly Kt/V(urea) was 9.1 (8.7 to 10.4). Predialysis phosphorus blood levels were higher at the start (2.04+/-0.34 mmol/L) than at end of IDd (1.39+/-0.41 mmol/L) without need for carbonate of calcium in four of five cases. During conventional dialysis ht SDS decreased from -0.8 to -1.44, which occurred predominantly before rhGH start. Conversion to IDd significantly increased growth velocity to a mean of 13 cm/year (10.3-18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of IDd regimen in promising growth velocity, either directly from a higher dialysis dose or indirectly through an improved nutritional status.

The influence of peritoneal surface area on dialysis adequacy.

In children, the prescription of peritoneal dialysis is based mainly on the choice of the peritoneal dialysis fluid, the intraperitoneal fill volume (mL/m2 body surface area (BSA)], and the contact time. The working mode of the peritoneal membrane as a dialysis membrane is more related to a dynamic complex structure than to a static hemodialyzer. Thus, the peritoneal surface area impacts on dialysis adequacy. In fact, the peritoneal surface area may be viewed as composed of three exchange entities: the anatomic area, the contact area, and the vascular area. First, in infants, the anatomic area appears to be two-fold larger than in adults when expressed per kilogram body weight. On the other hand, the anatomic area becomes independent of age when expressed per square meter BSA. Therefore, scaling of the intraperitoneal fill volume by BSA (m2) is necessary to prevent a too low ratio of fill volume to exchange area, which would result in a functional "hyperpermeable" peritoneal exchange. Second, the contact area, also called the wetted membrane, is only a portion of the anatomic area, representing 30% to 60% of this area in humans, as measured by computed tomography. Both posture and fill volume may affect the extent of recruitment of contact area. Finally, the vascular area is influenced by the availability of both the anatomic area and the recruited contact area. This surface is governed essentially by both peritonealvascular perfusion, represented by the mesenteric vascular flow and, hence, by the number of perfused capillaries available for exchange. This vascular area is dynamically affected by different factors, such as composition of the peritoneal fluid, the fill volume, and the production of inflammatory agents. Peritoneal dialysis fluids that will be developed in the future for children should allow an optimization of the fill volume owing to a better tolerance in terms of lower achieved intraperitoneal pressure for a given fill volume. Moreover, future peritoneal dialysis fluids should protect the peritoneal membrane from hyperperfusion (lower glucose degradation products).

Measurement by magnetic resonance imaging of the peritoneal membrane in contact with dialysate in rats.

To be optimal, a peritoneal dialysis prescription should consider the peritoneal surface area recruitment. In fact, as shown by computed tomography imaging, only a fraction of the available anatomic peritoneum is in contact with the dialysate (PDF). Various factors may dynamically affect the recruitment of the wetted membrane: posture, fill volume, PDF composition (biocompatibility), and pharmacologic agents (phospholipids). To precisely determine the peritoneal membrane recruitment capacity, we developed an animal model. In 5/6 bi-nephrectomized rats on peritoneal dialysis, between week 6 and week 8 post surgery, we used MRI to assess the contact area, with the dialysate acting as the contrast medium (fill volume: 10 mL per 100-g rat body weight). The MRI protocol consisted of axially oriented, turbo spin-echo, 3-mm slice, T2 weighted sequences. The contact area was measured using an adapted three-dimensional MRI reconstruction software based on DICOM (digital imaging and communications in medicine) images. The MRI studies (n=10) were successful. They showed that only a fraction of the presumed anatomic area (30% - 40%) was in contact with the PDF Peritoneal MRI in rats is a method that shows potential for assessing peritoneal contact area and its variation under experimental conditions.

Long daytime exchange in children on continuous cycling peritoneal dialysis: preservation of drained volume because of icodextrin use.

Daytime exchanges with glucose osmotic agents often lead to dialysate reabsorption, poor ultrafiltration (UF), positive sodium balance, and restricted purification of uremic toxins. We studied 5 anuric children on continuous cycling peritoneal dialysis (mean age: 10 years, 10 months), comparing icodextrin to a conventional glucose-based dialysate. The same fill volume (980 +/- 290 mL/m2) and the same dwell duration (720 minutes) were used with both solutions for the daytime exchange. In a crossover design, we compared 7.5% icodextrin with 1.36% glucose, and then 1.36% glucose with 7.5% icodextrin. Tolerance, net UF, sodium balance, and solute extraction were analyzed. The Student t-test for paired data was used for statistical analysis. The drained volume was 44% +/- 18% higher during icodextrin exchanges, allowing a mean enhanced sodium extraction of 44 +/- 15 mmol per daytime exchange. The uremic toxin extraction capacity was enhanced under icodextrin: weekly Kt/V urea increased by 0.41 +/- 0.1, weekly creatinine clearance increased by 8.4 +/- 3.6 L/1.73 m2, and phosphate removal increased by 23%. Similarly, beta2-microglobulin extraction increased with icodextrin use. Dialysate protein loss under icodextrin increased from 1.3 +/- 0.6 g to 1.9 +/- 0.96 g per daytime exchange. Icodextrin improved ultrafiltration and purification capacities (urea, creatinine, phosphate, beta2-microglobulin), but the large drained volume directly affected dialysate protein loss.

Daily on-line haemodiafiltration: a pilot trial in children.

BACKGROUND: Despite major improvements in paediatric dialysis over the last two decades, cardiovascular outcome is often poor. As France gives priority to kidney transplantation over dialysis, children in chronic haemodialysis are generally pre-adolescents or adolescents with long medical histories and low compliance. In them, the usual weekly schedule of dialysis is often unsuitable. We conducted a study of conversion to daily dialysis, which allowed an enhanced dialysis dose, a gentle ultrafiltration rate and achievement of dry body weight. METHODS: In this single-centre, observational, prospective, non-randomized study, five oligoanuric dialysis patients (mean age: 13.8 +/- 3.2 years) were converted from standard on-line haemodiafiltration (S-OL-HDF) (4 h, three times/week) to daily on-line haemodiafiltration (D-OL-HDF) (3 h, six times/week). Patient selection was based on both the presence of uraemic cardiomyopathy (left ventricular hypertrophy and reduced fractional shortening) and their reduced therapeutic compliance. The D-OL-HDF parameters were the same as for the S-OL-HDF. RESULTS: Increasing the number of sessions from three to six weekly positively impacted the weekly dialysis dose. On D-OL-HDF, mean arterial blood pressure decreased significantly (from 95 +/- 15 to 82 +/- 13 and 87 +/- 9 mmHg at 6 and 12 months, respectively). Left ventricular hypertrophy decreased and its fractional shortening improved markedly (from 26.6 +/- 17% to 31 +/- 14% and 46.6 +/- 15% at 6 and 12 months, respectively). Pre-dialytic plasma phosphorus also decreased markedly (from 1.87 +/- 0.23 to 1.43 +/- 0.22 and 1.28 +/- 0.29 mmol/l at 6 and 12 months, respectively), as did the calcium-phosphorus product. The post-dialytic recovery time disappeared and so did perception of fatigue. Fasting the day before dialysis to avoid excess weight gain (necessitating longer dialysis) disappeared. Combined with an improved appetite, these changes resulted in higher caloric and protein intake (nPCR), from 1.28 +/- 0.23 to 1.43 +/- 0.24 g/kg at 6 months, and school attendance became regular. The only pre-pubertal child included showed catch-up growth. CONCLUSIONS: Increasing dialysis frequency to daily sessions without shortening the durations of sessions excessively allowed us to overcome the "free diet" imposed on these paediatric, very uncompliant patients. This strategy led to a reduction in blood pressure and an improvement of left ventricular size and function, normalization of pre-dialytic plasma phosphorus and improvements in general well-being and dialysis acceptance. Long-term, however, this protocol is only acceptable for the children if associated with the potential of clinical recovery allowing inscription on the kidney transplantation waiting list.