Effect of posture on intraperitoneal pressure and peritoneal permeability in children.

The posture of the patient influences both the intraperitoneal pressure (IPP) and the peritoneal permeability. We have studied the effects of the supine and the upright position in six children. Two peritoneal equilibration tests (PET) of 90-min dwell time each were performed consecutively, firstly in the supine position and then in the upright position. The same amount of dialysate was instilled (1,000 ml/m2; isotonic 1.36% dextrose) for each PET. Using the same filling volume, the IPP was significantly higher in the upright position (18.4 +/- 4.8 cm H2O) than in the supine position (8 +/- 2.4 cm H2O). The mean percentage IPP increase was 130% +/- 35%. The decline in glucose resorption rate from the dialysate during the PET was significantly lower in the upright position. Despite this greater relative loss of osmotic gradient in the upright than the supine position, no significant difference in net ultrafiltration was noted after 90 min of dwell. The peritoneal equilibration ratio during the PET was lower in the upright than the supine position for urea, creatinine, and phosphate. These results favor performing peritoneal dialysis in a supine position, both to increase dialysis efficiency and to reduce patient discomfort.

Wiedemann-Rautenstrauch syndrome. A case report and review of the literature.

In 1977 Rautenstrauch and Snigula reported on two sisters with a previously undescribed, progeria-like syndrome. Two years later Wiedemann described two unrelated males with the same condition. Since than only a few published cases appeared in the literature. We had the opportunity to study a boy affected by this extremely rare condition. This boy was born after intrauterine growth retardation. At birth two natal teeth were present. OFC was normal despite apparent macrocephaly. During infancy a progeroid appearance was noted with sparse hair, prominent scalp veins, greatly widened anterior fontanelles, malar hypoplasia, and generalized lipoatrophy. The face was triangular with a small maxilla and a protuding chin, the eyes were low-set, the eyebrows and eyelashes were scanty. At the age of 3.5 years there was striking general deficiency of subcutaneous fatty tissue apart from accumulation of adipose tissue on the buttocks and flanks, growth was retarded, mental development was at the low borderline of normal. Cholesterolemia was at the upper range of normal, there was an increase of triglycerides: 3.31 mmol/L (Normal < 1 mmol/L). Other progeroid syndromes such as Hutchinson-Guilford, Berardinelli-Seip, De Barsy, leprechaunism, Cockayne and Hallerman-Streiff could be excluded as well as the CDG syndrome. This condition is most probably inherited as an autosomal recessive trait.

Glucose-charged dialysate for children on hemodialysis: acute dialytic changes.

Glucose has been omitted from hemodialysates in the recent past. Currently, there is a tendency to include glucose in dialysates at physiological concentrations between 100 and 200 mg/dl (5.56-11.12 mmol/l). In adult patients, this induces, over the dialysis session, a significant uptake of glucose, with some benefits, i.e., avoidance of caloric loss, but also with some metabolic risks, i.e. decreased dialytic potassium removal secondary to an insulin-dependent intracellular potassium shift. We have performed a crossover study in five stable children (mean age 11.7 years) with normal fasting glucose on chronic bicarbonate hemodialysis. The dialysis prescription of 3-h sessions was changed only in terms of the glucose dialysate concentration, being either glucose free or containing 9.17 mmol/l (165 mg/dl) glucose; dialysates were potassium free. Twenty sessions were analyzed for each group by whole dialysate collection (glucose, potassium, phosphate) and serum concentration analysis during and post dialysis (glucose, potassium, phosphate, insulin). Glucose-free dialysis was associated with a patient net glucose loss of 113 +/- 12 mmol/session (nearly 20 g). Conversely, with the glucose-charged dialysate a small uptake of glucose was noted [13.8 +/- 2.1 mmol/session (nearly 2 g)]. At the end of the session, serum glucose was lower with the glucose-free dialysate (4.64 +/- 0.52 mmol/l) than the glucose-charged dialysate (6.11 +/- 0.92 mmol/l). Conversely, serum insulin was higher with the glucose-charged dialysate (38 +/- 17 mU/l) than the glucose-free dialysate (19 +/- 9 mU/l). There were no significant differences either for dialytic removal of potassium (70 vs. 73 mmol/session) or phosphate (20 vs. 22 mmol/session), with and without glucose dialysates. Our study, contrary to previously published data in adults, demonstrated that in children the use of a physiological concentration of glucose in the dialysate (165 mg/dl) avoids dialytic glucose loss without a significant decrease in dialytic potassium removal.

Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.

Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.

Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs.

Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized. Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs. Itraconazole does not influence ceftriaxone kinetic behavior. The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation [SD], 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively. Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance).

Improved dialysis dose by optimizing intraperitoneal volume prescription thanks to intraperitoneal pressure measurements in children.

An optimal intraperitoneal volume (Vip) may be the most critical and least-used option to enhance higher clearances of small solutes. A higher Vip is more effective in increasing small solute clearances when compated to a lower Vip and more frequent exchanges. Additionally, a higher Vip generates minimal intraperitoneal pressure (Pip) in the supine position. Therefore, the highest tolerated Vip should be used at night while the child is sleeping in the supine position. Therefore, in 5 children, mean age 7 years, 4 months, on continuous cyclic peritoneal dialysis (CCPD) (Baxter HomeChoice), we tested the impact of Vip on tolerance (measured by Pip) measurements, and efficiency [assessed by daily Kt/Vurea and weekly creatinine clearance (Kcreatinine]. Basal Pip was determined for the usually prescribed Vip. Then Vip was increased during a morning outpatient study day, in 30-minute stages, stepping up to an increase of 25% of the basal Pip (upper limit 18 cm of water) level reached at the so-called optimized Vip used for the prescription of an optimal total dialysate volume for a 4-week period. The latest study week was compared to the prestudy week. The optimized Vip of 1230 +/- 70 mL/m2 was significantly higher than the basal Vip, 940 +/- 90 mL/m2. The dialysis dose improved both in terms of Kt/V urea from 0.23 +/- 0.02 to 0.29 +/- 0.03 and Kcreatinine from 60 +/- 5 to 76 +/- 9 L/1.73 m2/week. The supine position allowed the 25% Pip increment from 10.2 +/- 2.5 to 12.5 +/- 3.1 cm water, without any obvious clinical side effects.

Siblings with congenital renal tubular acidosis and nerve deafness.

Two siblings (a boy and a girl) had congenital renal tubular acidosis (RTA) with nephrocalcinosis. Hearing loss due to nerve deafness was diagnosed at 13 1/2 and 9 years of age, respectively. The parents, who are second cousins, are healthy. They have another boy who is unaffected. This is in accordance with an autosomal recessive gene. The association of RTA and deafness was first noted by Royer in 1967, and so far some 50 cases have been described. The literature is reviewed.

Use of intraperitoneal pressure, ultrafiltration and purification dwell times for individual peritoneal dialysis prescription in children.

Tolerance of peritoneal dialysis is, in a part, dependent on intraperitoneal dialysate volume. Measurement of intraperitoneal pressure (IPP) in cm of water is easy to perform especially with the twin bag Y set (Baxter). Today we use IPP for following surgical catheter implantation (delaying, starting and progressing with peritoneal dialysis) and for optimizing ultrafiltration and purification. Efficiency of peritoneal dialysis is dependent on adequate ultrafiltration (UF) and on adequate purification (solute clearances). These two goals seem apparently conflicting in terms of duration of dwells: short dwell time enhances UF capacity and conversely long dwell time enhances solute clearance. Peritoneal equilibration test (PET) allows an approach to the ultrafiltration time: the point at which the overtime dialysate urea saturation and glucose desaturation curves cross, called APEX time. PET allows also an approach of the purification time: the point at which dialysate (D) to plasma (P) concentration ratios over time are high. Because the value of phosphate as uremic factor of morbidity, we have chosen the time for D/P phosphate equal to 0.6 as a purification phosphate dwell time (PPT). A total of 17 patients were studied, over a five-year period allowing 142 determinations. APEX times (range 18 to 71 min) and PPT (range 105 to 238 min) were spread over a wide distribution. PPT and APEX times were significantly shorter in children younger than 3 years of age than in children older than 10 years of age. PPT were nearly four times longer than APEX times. The knowledge of these conflicting ultrafiltration and purification times should help, in our view, in the individual choice of the PD modality: if UF is the major goal, short dwell times should be used (automatic PD); if purification is the major goal, long dwell times should be used (CAPD); if both are the target goal, tidal PD should be discussed.

Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender. Arbeitsgemeinschaft für Pädiatrische, Nephrologie.

The clinical course of 66 boys and 49 girls with autosomal recessive polycystic kidney disease recruited from departments of paediatric nephrology was investigated over a mean observation period of 4.92 years. This is a selected study group of children from departments of paediatric nephrology who in most cases survived the neonatal period, since birth clinics did not participate. The median age at diagnosis was 29 days (prenatal to 14.5 years). We observed decreased glomerular filtration rates (GFRs) in 72% (median age at onset of decrease of GFR < 2 SD, 0.6 years; range, 0-18.7 years), and 11 patients developed end-stage renal disease. Hypertension requiring drug treatment was found in 70% (median age at start of medication, 0.5 years; range, 0-16.7 years). Kidney length was above the 97th centile in 68% of patients, and kidney length did not increase with age or deterioration of renal function. Urinary tract infections occurred in 30%, growth retardation in 25%, and clinical signs of hepatic fibrosis were detected in 46%. Thirteen patients (11%) died during the observation period, 10 of them in the first year of life. There was a statistically significant sex difference in terms of a more pronounced progression in girls. The survival probability at 1 year was 94% for male patients and 82% for female patients (p < 0.05) in this study. Urinary tract infections occurred more frequently in girls (p < 0.025) and were observed earlier. In addition, more girls had impaired renal function, developed end-stage renal disease and showed growth retardation; these differences, however, were not significant. For the children in this study, however, our results indicate that the long-term prognosis in the majority of cases is better throughout childhood and youth than often stated.

Relationship between intraperitoneal hydrostatic pressure and dialysate volume in children on PD.

As a result of the theoretical risk of an excessive increase in intraperitoneal pressure (IPP) in association with peritoneal dialysis, reduction of instilled intraperitoneal dialysate volume (IPV) is often proposed in infants compared to adults; a further reduction is often noted in neonates compared to children. To better evaluate the significance of this risk, we have tested the relationship between the IPP (cm of water) and the IPV (mL/m2) in our population of children on peritoneal dialysis (n = 17) during the last three years. IPP was measured after a nocturnal dialysis session, during a morning study day, after sequential exchanges of ten minutes' dwell time each, with progressively increased instilled dialysate volumes from 600 to 1400 mL/m2. Mean IPP values were 8.2 +/- 3.8 cm for a mean IPV of 990 +/- 160 mL/m2 body surface area. These values are lower than the IPP values established for adults (13.4 +/- 3.1 cm), which were given for higher IPV values of 1585 +/- 235 mL/m2. The relationship between IPP and IPV was age-dependent. In neonates, stable IPP values (3.5 +/- 1.6 cm) were noted for IPV from 600 to 800 mL/m2; thereafter, increasing IPV led to an increase in IPP. In the range of 600 to 1200 mL/m2 IPV, no significant increment of mean IPP was noted in infants (4.8 +/- 2.6 cm) and in children (9.6 +/- 2.1 cm). However, increasing the dialysate volume over 1000 mL/m2 induced an overincrement of the individual IPP value in most cases, and the rise of IPP was substantial when IPV rose from 1200 to 1400 mL/m2.

Determination of individual ultrafiltration time (APEX) and purification phosphate time by peritoneal equilibration test: application to individual peritoneal dialysis modality prescription in children.

Efficiency of peritoneal dialysis (PD) is dependent on adequate ultrafiltration (UF) and purification (solute clearance). These two goals apparently seem to conflict in terms of duration of dwells: short dwell time enhances UF capacity and, conversely, long dwell time enhances solute clearance. Peritoneal equilibration test (PET) allows an approach to the ultrafiltration time: the point at which the over time dialysate urea saturation and glucose desaturation curves cross, call APEX time. PET also allows an approach to the purification time: the point at which dialysate-to-plasma (D/P) concentration ratios over time are high. Because of the value of phosphate as a uremic factor of morbidity, we have chosen the time at which D/P phosphate is equal to 0.6 as a purification phosphate dwell time (PPT). A total of 17 patients were studied, over a five-year period, allowing 142 determinations. APEX times (range 18-71 min) and PPT (range 105-238 min) were spread over a wide distribution. PPT and APEX times were significantly shorter in children younger than three years of age than in children older than ten years of age. PPT were nearly four times longer than APEX times. Knowledge of these conflicting ultrafiltration and purification times should help, in our view, in the individual choice of the PD modality: if UF is the major goal, short dwell times should be used (automated PD); if purification is the major goal, long dwell times should be used, as in continuous ambulatory peritoneal dialysis; if both are the target goal, tidal PD should be discussed.

Association of HLA class I antigen deficiency related to a TAP2 gene mutation with familial bronchiectasis.

Two siblings with pansinusitis, nasal polyps, and bronchiectasis were found to have histocompatibility lymphocyte antigen (HLA) class I antigen deficiency ("bare lymphocyte syndrome") and dysfunction of natural killer cells. Reduced class I cell surface expression resulted from a single mutation in the TAP2 gene, which is located in the class II region of the major histocompatibility complex and encodes subunit 2 of the class I peptide transporter. The defect was transmitted in an autosomal recessive manner. This deficiency did not lead to severe viral infections but was apparently associated with susceptibility to bacterial infections of the respiratory mucosae. We suggest that class I HLA typing should be systematically performed in children with unexplained bronchiectasis.

Nutritional effects of KT/V in children on peritoneal dialysis: are there benefits from larger dialysis doses?

Dialysis adequacy is monitored by urea kinetic modeling (UKM), in particular by calculation of KT/V (normalized whole body urea clearance) and PCRN (normalized protein catabolic rate). All children on peritoneal dialysis from our unit (7 children; mean age 7 years, 8 months) participated in our study (dialysis research program of the French Registry of Peritoneal Dialysis). Every month analysis of dialysate and urine collections and blood samples were compared to a 3-day diet survey to analyze the relations between doses of dialysis (KT/V) and nutrition [dietary protein intake (DPI) and caloric intake]. Calculated protein intake and DPI were also compared. Spearman correlation coefficients were used to assess the association between variables. KT/V values were spread over a wide range (0.8-2.8, mean 1.9). KT/V was positively (weakly) correlated to PCRN (p = 0.07, y = 0.24x + 1.08, r = 0.2), but not to DPI. No correlation could be found between PCRN and DPI, but doses of dialysis (KT/V) were positively correlated to caloric intake (p = 0.001, y = 28.97x + 13.66, r = 0.424). We assume that the correlation between KT/V and PCRN is not necessarily the reason, but only a calculation effect. On the contrary, the positive correlation between KT/V and caloric intake allows us to speculate that more efficient dialysis enhances appetite.

[Role of peritoneal dialysis for the treatment od terminal renal insufficiency in the child]. / Place de la dialyse péritonéale pour le traitement de l'insuffisance rénale terminale chez l'enfant.

Peritoneal dialysis (PD) is the most common used method of treatment for end stage renal failure, specially adapted for home dialysis, easily applicable even for infants. PD creates a degree of independence but also of responsibility. PD failed out with time (transfered to hemodialysis) secondary to familial and medical (peritonitis) exhaustions. Anyway PD has become in children under 15 years old, the more used dialysis modality in many countries (Canada, USA, Australia, England, Italy, Germany, Holland, ...) but remained rarely performed in France (economical, political, social or medical environment reasons). Reduction of waiting time for transplantation should favor the development of PD. Home treatment by PD is without doubt the best dialysis condition in terms of optimal children development but is really a familial charge.

Management of fluid overload in infants by tidal peritoneal dialysis: is there a benefit compared with continuous cycling peritoneal dialysis?

Dialysed infants are sometimes characterized by a hyperpermeable peritoneal state. In this situation decreasing dwell time and/or increasing dialysate tonicity are usually proposed to achieve adequate ultrafiltration (UF). We have investigated UF capacity under different peritoneal dialysis modalities in three infants. UF was not obtained with isotonic continuous ambulatory peritoneal dialysis (CAPD), and was only achieved with short dwell times and hypertonic CAPD. For the prescription of automated peritoneal dialysis, a shorter dwell time of hourly sequences is needed, which consequently decreases the phosphate diffusion time. Continuous cycling peritoneal dialysis with sequences of 1 h allowed efficient UF [UF/glucose absorption (UF/G) 4.2 +/- 0.9] but the dialysate/plasma (D/P) phosphate ratio was low (0.47 +/- 0.12). In contrast, tidal peritoneal dialysis gave a better UF/G ratio (6.8 +/- 0.7) without a decrease in the D/P phosphate ratio (0.64 +/- 0.18).

Involvement of nitric oxide in the vasodilatory response to parathyroid hormone-related peptide in the isolated rabbit kidney.

1. The present study was designed to explore the role of NO derived from L-arginine in the vasodilatory response to synthetic human parathyroid hormone-related peptide-(1-34) in the isolated rabbit kidney perfused in the presence of indomethacin (10 mumol/l) and preconstricted with noradrenaline (7.2 nmol/min). 2. Under control conditions, bolus administrations of acetylcholine (10 mumol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased the preconstriction pressure, by 31%, 71% and 43%, respectively. 3. Bolus administration of 100 mumol/l NG-nitro-L-arginine-methyl ester caused a 20% increment in the perfusion pressure of the noradrenaline-preconstricted kidney. NG-nitro-L-arginine methyl ester inhibited the vasodilatory effect of acetylcholine and parathyroid hormone-related peptide, by 68% and 44%, respectively, but did not alter the verapamil-induced vasodilatation. 4. Unlike L-arginine, the bolus administration of 1 mumol/l of a mono-substituted L-arginine derivative, N-alpha-benzoyl-L-arginine ethyl ester, durable decreased the noradrenaline/NG-nitro-L-arginine methyl ester-induced preconstriction by 57%. 5. Both L-arginine and N-alpha-benzoyl-L-arginine ethyl ester effectively reversed the inhibition induced by NG-nitro-L-arginine methyl ester on the vasodilatation elicited by acetylcholine and parathyroid hormone-related peptide. 6. In conclusion, the formation of NO from L-arginine contributes a substantial part to the vasodilatory action of parathyroid hormone-related peptide. Therefore, parathyroid hormone-related peptide appears to have a place among the renal haemodynamically active substances, whose vasodilatory actions are tuned by NO.

Hydrostatic intraperitoneal pressure in children on peritoneal dialysis: practical implications. An 18-month clinical experience.

Intraperitoneal pressure (IPP) is easy to measure routinely in children on peritoneal dialysis (PD) (especially with the twin bag Y-set) as described in adults: value expressed in centimeters of water, average of IPP (mean IPP) at inspiration and at expiration, with point zero located on the mid-axillary line while the patient rests in a perfectly supine position. IPP remained high during the first two to three days postsurgical peritoneal catheter implantation (15 +/- 4 cm) despite low dialysate volume per exchange (10 mL/kg). Afterwards, IPP decreased (10 +/- 2 cm) despite increasing dialysate volume from 10-50 mL/kg. Mean IPP seemed lower in infants (5 +/- 3 cm) in contrast to children (10 +/- 2 cm) on chronic PD with dialysate volume of 1000 mL/m2. There was a strong negative linear correlation between ultrafiltration (UF) volume and mean IPP with isotonic dialysate (1.36% dextrose concentration). By contrast, there was only a weak positive linear correlation between UF volume and mean IPP with hypertonic dialysate (3.86% dextrose concentration).

Optimization of CCPD prescription in children using peritoneal equilibration test.

Continuous cycling peritoneal dialysis (CCPD) is automatically performed by a cycler as a repetition several times per session of the same programmed exchange. We have investigated the efficiency, in terms of ultrafiltration (UF) capacity and solute clearance (phosphate), of an adapted (optimized) CCPD versus a conventional CCPD. Adapted CCPD was performed manually in order to allow a combination of short dwell times (optimal ultrafiltration) and long dwell times (optimal purification). The ratio of ultrafiltration over glucose absorbed (UF/G) was higher with adapted CCPD (5.7 +/- 0.8) compared with conventional CCPD (4.8 +/- 1.3). Phosphate purification was also enhanced with adapted CCPD (0.21 +/- 0.05 versus 0.16 +/- 0.05 mL/min/kg). These results confirm the usefulness of the concept of adapted CCPD with variable dwell times for optimization of peritoneal dialysis performances in children.