Hydronephrosis and crossing vessels in children: Optimization of diagnostic-therapeutic pathway and analysis of color Doppler ultrasound and magnetic resonance urography diagnostic accuracy.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is one of the most frequent urological diseases affecting the pediatric population. It can be due to both intrinsic stenosis of the junction and extrinsic causes such as the presence of crossing vessels (CVs), which can be detected by color Doppler ultrasound (CD-US). Magnetic resonance urography (MRU) is a good alternative, but sedation and infusion of a contrast agent are required. OBJECTIVE: The aim of this study was to analyze the diagnostic accuracy of CD-US and MRU in visualizing CVs in pediatric hydronephrosis, in order to decide the correct diagnostic pathway in the pre-operative phase. MATERIAL AND METHODS: A retrospective review was performed of medical records for all patients who underwent surgical treatment for hydronephrosis from August 2006 to February 2016. Ultrasound and scintigraphy had been performed on all patients. Data about CD-US and MRU were collected. A high-level technology ultrasound scanner and a 1.5 T MR scanner were used. The presence of CVs at surgery was considered the gold standard. Sensitivity, specificity, positive and negative predictive values (NPV) were calculated and reported for both of the imaging techniques. RESULTS: A total of 220 clinical charts were reviewed. Seventy-three CVs were identified at surgery (33.2% of UPJO). The median age was statistically higher in the group with CVs compared to the group without CVs (P < 0.001). The sensitivity and NPV of CD-US in detecting CVs were higher than MRU (sensitivity 93.3% vs. 71.7%, NPV 95.7% vs. 77.6%, respectively). DISCUSSION: According to the data, CD-US had higher sensitivity and NPV than MRU, resulting in superior detection of CVs. It is important for a surgeon to know that a child has a CV, especially in older children in which the incidence of extrinsic UPJO is higher. The main limitation of this study was the presence of incomplete data, due to the retrospectivity. CONCLUSIONS: In the pre-operative phase, the CD-US should be considered as the investigation of choice to detect CVs in children with hydronephrosis (Summary Fig). Moreover, CD-US has lower costs than MRU, and sedation with infusion of contrast agent is unnecessary. For the future, it could be useful to lead a prospective comparison between the two imaging techniques.

Use of new peritoneal dialysis solutions in children.

Standard peritoneal dialysis (PD) solutions with low pH and containing high concentrations of lactate and glucose have been demonstrated to negatively affect the peritoneal membrane, mesothelial cell viability, residential peritoneal cells, and also to inhibit phagocytic functions. An increasing body of experimental evidence supports the idea that the peritoneal hypervascularization and fibrosis observed in long-term PD are causally related to the acute and chronic toxicity of conventional PD solutions. A Physioneal (lactate/bicarbonate mixed buffer pH 7-7.4), Physioneal, Extraneal (7.5% icodextrin), Nutrineal (1.1% amino-acid-containing solution) regimen, for example, offers a significant reduction in carbohydrate load (approximately 40-50%), lower exposure to and absorption of glucose degradation products, reduced oxidative stress, and improved volume control when compared with a first-generation DDDD (4 x Dianeal) regimen. The positive aspects of each solution that we have observed in our patients allow a recommendation on the potential benefit of using these solutions in children treated with PD. In fact, data from the literature as well as the results of the studies reported in this paper show that in children the application of neutral pH bicarbonate/lactate-buffered solution for the standard nighttime APD prescription, icodextrin solution for a long daytime dwell, and AA-based solution in malnourished patients is safe and effective. Extended clinical trials should be encouraged to better define the PD schedules for the combined use of these solutions that may be associated with the best clinical efficacy and the highest level of biocompatibility.

Acute effects of simultaneous intraperitoneal infusion of glucose and amino acids.

BACKGROUND: The feasibility of simultaneously infusing glucose and amino acid (AA)-based peritoneal dialysis solutions was tested to determine whether peritoneal dialysis patients could achieve an adequate nonprotein calorie/nitrogen ratio while preventing a marked increase in blood urea nitrogen (BUN), which is usually seen if the AAs are administered without glucose. METHODS: An automatic peritoneal dialysis cycler was used to infuse glucose and AA solutions (3:1) simultaneously during the night. Eight infusions of 1000 mL m2 of body surface area (BSA), with a 60 minute dwell time, were performed in 10 children on peritoneal dialysis. The dialytic effluent was analyzed at every exchange and totaled at eight hours to evaluate volume, glucose, and AA concentration. Blood samples for plasma, glucose, insulin, and free AA determination were drawn at the beginning of automated peritoneal dialysis (APD) session and at each instillation of peritoneal dialysate. RESULTS: The mean glucose absorption was 33.7 +/- 10.0% and the AA absorption was 55.2 +/- 13.2% of the infused amount, and the ratio of nonprotein calorie (derived from glucose) to nitrogen (derived from AA) was 115.4:1. The insulin levels returned to normal only three hours after the beginning of APD. The free AA plasma levels were already increased two hours after dinner and remained high for the entire APD treatment because of the continuous absorption of AA from the peritoneum. The BUN levels did not increase despite the supply of AA. CONCLUSIONS: This APD procedure may improve utilization of AA for protein synthesis, as suggested by the lack of increase of the BUN levels with this regimen.

Site I on human albumin: differences in the binding of (R)- and (S)-warfarin.

The binding of drugs known to interact with area I on human serum albumin (HSA) was investigated using a chiral stationary phase obtained by anchoring HSA to a silica matrix. In particular, this high-pressure affinity chromatography selector was employed to study the binding properties of the individual enantiomers of warfarin. The pH and composition of the mobile phase modulate the enantioselective binding of warfarin. Displacement chromatography experiments evidenced significant differences in the binding of the warfarin enantiomers to site I. The (S)-enantiomer was shown to be a direct competitor for (R)-warfarin, while (R)-warfarin was an indirect competitor for the (S)-enantiomer. Salicylate directly competed with (R)-warfarin and indirectly with (S)-warfarin. This behavior was confirmed by difference CD experiments, carried out with the same [HSA]/[drug] system in solution.

The use of the PD Adequest mathematical model in pediatric patients on chronic peritoneal dialysis.

OBJECTIVE: To test the accuracy of the PD ADEQUEST kinetic model in calculating peritoneal transport parameters and to quantify the differences between the results of software simulations and direct measurements in order to assess the reliability of this tool in chronic peritoneal dialysis (PD) pediatric patients. PATIENTS: Twenty-nine patients (mean age: 10 +/- 4 years; range: 4-17), 5 on continuous ambulatory PD, 4 on continuous cycling PD, 19 on nocturnal intermittent PD and 1 in nocturnal tidal PD, all free from peritonitis in the previous 2 months. Fourteen patients were anuric and 15 had a mean glomerular filtration rate of 1.79 +/- 1.23 mL/min, range 0.25-4.82. METHODS: In all patients, 24-hour dialysate and urine collections associated to standard peritoneal equilibration test (PET) were performed using their usual dialytic regimen and fill volume (1023 +/- 159 mL/m2 BSA, range 614-1361). PD ADEQUEST kinetic parameters were compared with pediatric and adult data from literature. The measured weekly normalized total creatinine clearance (CRCL), weekly total Kt/V, and daily net ultrafiltration (UF) were compared with corresponding mathematically modeled values. RESULTS: Kinetic parameters calculated by the PD ADEQUEST program were comparable to adult and pediatric values from previous studies after normalization for BSA. Measured and modeled CRCL and Kt/V showed a good agreement [concordance correlation (rc) 0.937 and 0.768, respectively] with limited median percentage absolute errors (11.6% and 10.2%, respectively). Ultrafiltration showed less favorable results (rc = 0.600 and median percentage absolute error 45%) probably owing to the wide variability of this parameter. When the analysis was restricted to the peritoneal component, the rc coefficients results were 0.745 for CRCL and 0.512 for Kt/V (median absolute error: 11.6% and 15.2%, respectively). CONCLUSIONS: The overall findings of our study show that the PD ADEQUEST kinetic model can be used in pediatric patients for the calculation of kinetic indexes and for mathematical simulation of the various regimens. We also feel that the results yielded by the PD ADEQUEST program are reliable enough for this computerized mathematical model to be used in the prescription management of pediatric patients. Only UF prediction needs to be used with a certain caution on account of the marked variability of this parameter.

Children on continuous ambulatorial peritoneal dialysis: muscle and plasma proteins, amino acids and nutritional status.

The aim of the study was to investigate plasma and muscle amino acid (AA) levels in children on continuous ambulatory peritoneal dialysis (CAPD) and their relationship to various indices of nutritional status. Ten children with a mean age of 6.4 +/- 5.6 yrs were evaluated. Muscle biopsies and venous blood samples were taken after an overnight fast. Muscle samples were obtained from rectus abdominis. Data were compared with those of a control group of 22 children who were undergoing elective surgery. Informed consent was obtained from the parents. The plasma concentration of most of the essential AA (valine, leucine, isoleucine, lysine, methionine and tyrosine) were significantly reduced and the levels of some non essential AA (aspartic acid, glycine, citrulline, 1-3 methihystidine, taurine + alanine) were significantly higher than in the controls. Muscle intracellular free essential AA concentrations, except the low levels of valine and leucine did not differ significantly from values in the controls. Among non essential AA, aspartic acid, glutamic acid and ornitine showed significantly increased intracellular concentrations. No significant correlations were found between plasma and muscle AA concentration and ASP (alkali-soluble protein)/DNA ratio, serum albumin, transferrin, bicarbonate levels and duration of CAPD. Instead, a significant correlation was noted between the muscle ASP/DNA ratio, an indicator of the amount of cell proteins per cell unit, and age (r = 0.714, p < 0.05). Muscle Branched chain AA levels were significantly correlated to body mass index (BMI) (r = 0.648, p < 0.05).

Is the response to rhGH in peritoneal dialysis patients less effective than in patients with chronic renal insufficiency.

Data on the effects of rhGH treatment in children on peritoneal dialysis are limited. In general rhGH therapy seems to be less effective compared with results on patients with chronic renal failure on conservative treatment. Our experience suggests that rhGH can stimulate growth in children on CPD, and that the efficacy of such therapy is reduced after the first year of treatment, although the rhGH is still active.

Protein and calorie intake, nitrogen losses, and nitrogen balance in children undergoing chronic peritoneal dialysis.

We performed 22 nitrogen balance (NB) studies of three days' duration in 19 children (8.7 +/- 3.8 years) on chronic peritoneal dialysis (CPD) for 19.4 +/- 16.4 months. The dietary intakes were assessed by the double weighing method. Total nitrogen, protein, urea, and creatinine were analyzed in the dialysate and urine collected daily. Total nitrogen was also determined in the feces collected over the whole NB study period, using vegetable charcoal as a marker. The protein intake was 1.64 +/- 0.50 g/kg/day, corresponding to 126 +/- 40% of the recommended daily allowance (RDA) for normal children of the same age, and the calorie intake (diet+glucose from dialysate) reached 75 +/- 26% of RDA. Nitrogen losses were: 0.177 +/- 0.052 g/kg/day with peritoneal fluid and urine, and 0.028 +/- 0.018 g/kg/day with feces. The NB, positive in 17 out of 22 studies, ranged from -116 to +167 mg/kg/day (mean 44.0 +/- 66.2 mg/kg/day). A direct and significant correlation between NB and nitrogen intake (g/kg/day) (r = 0.562, p < 0.05) and total calorie intake (cal/kg/day) (r = 0.483, p < 0.05) has been observed. These data confirm the need to ensure in children on CPD an adequate nutritional intake, and further support the efforts to improve calorie intake.

Nutritional status in children receiving chronic peritoneal dialysis.

Chronic peritoneal dialysis (CPD), widely used in uremic children, may have contrasting effects on the nutritional status of patients. Metabolic and nutritional abnormalities due to the combined effects of uremia per se, glucose absorption from the dialysate and catabolic factors, such as protein and amino acid losses into dialysate, poor appetite, and recurrent episodes of peritonitis are the most important. Although CPD allows for fewer dietary restrictions and supplies an extra amount of calories by glucose absorbed with the peritoneal fluid, when protein and energy intakes are assessed the protein intake was almost sufficient or more than that prescribed, whereas the energy intake was low. In CPD children the standard deviation score for weight, height, triceps skinfold thickness, and midarm circumference has been reported as more severely impaired in children less than ten years old. Anthropometric parameters did not worsen during CPD treatment. Plasma proteins and albumin are reported as being low in CPD children. The dietary intake and protein losses have been considered to be the most important determinants of the albumin level in CPD patients. The reported average dialysate losses of free amino acids (AA) during CPD in children vary from 0.02 to 0.03 g/kg/day in different studies. The patterns of plasma AA in CPD is represented by reduced levels of branched chain AA and of other essential amino acids and increased concentrations of some nonessential AA. Several factors may influence plasma AA profile: uremia per se, hormonal alterations, protein and AA losses, and dietary intake. A more specific uremic AA pattern is found in muscle, the largest pool of free AA in the body. Studies on muscle AA in adults on CPD are conflicting: some authors have reported several muscle AA alterations, but others have shown an almost normal pattern. Low valine and leucine muscle levels have been reported in children on CPD.

Muscle and plasma amino acids and nutritional status in kidney-transplanted children.

Nutritional status, assessed by anthropometric and biochemical methods, protein and amino-acid (AA) composition and muscle water were evaluated in 11 kidney transplanted children and in a control group of 10 children with normal renal function who were undergoing elective surgery. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when the peritoneal catheter was removed in the transplanted children. The mean time from the transplantation to the study time was 97 +/- 14 days (range 72-114 days). Height was reduced in the transplanted children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were normal. The body mass index was over the 50 degree percentile in nine of the eleven children. The muscle contents of total, extracellular, and intracellular water, alkali-soluble protein (ASP), DNA and the ASP/DNA ratio were not significantly different in transplanted children from those in the controls. Plasma leucine and taurine levels were significantly decreased, whereas plasma citrulline and alanine levels and the glycine/serine ratio were increased. Muscle threonine, alanine+taurine, glycine and aspartic acid levels as well as the glycine/serine ratio were increased in the transplanted children. Transplanted children show an almost normal muscle AA profile and a plasma AA pattern that seems to be related to the prednisone therapy.

Proteolytic activity and free amino acid concentrations in polymorphonuclear leucocytes.

Polymorphonuclear granulocytes (PMN) are valuable tools for evaluating amino acid (AA) metabolism in nucleated cells, although variations of free amino acid concentrations due to the methods used for the separation of the cells and the procedures used for lysis have been reported. Furthermore, analytical variations in PMN AA concentration may be induced by protease activation during preparation, so that free AA detected in cells could originate from proteolysis other than from the physiological metabolic pathways and transport systems. To study this possibility we measured granulocyte protease activity and AA concentrations in cell suspensions processed with and without the addition of antiproteolytic agents. Granulocyte AA concentrations and protease activity in samples treated with antiproteolytics were 8-15 times lower than in samples processed without antiproteolytics. The use of protease inhibitors throughout the sample preparation is necessary for reliable estimation of free AA in granulocytes.

Nutritional status and muscle amino acids in children with end-stage renal failure.

Nutritional status, assessed by anthropometric and biochemical methods, and muscle water, protein and amino acid composition, were evaluated in a control group of 10 children with normal renal function who were undergoing elective surgery, and in 15 children with end-stage chronic renal failure. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when a peritoneal catheter was implanted in the uremic children. Height and body weight were reduced in the uremic children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were essentially normal. The muscle contents of total, extracellular and intracellular water, and of alkali-soluble protein (ASP), DNA and the ASP-DNA ratio were not significantly different in uremic children from those in the controls. Plasma leucine, isoleucine, tyrosine, valine, and serine levels were significantly decreased, whereas plasma citrulline, 1-methylhistidine and 3-methylhistidine levels were increased. Muscle isoleucine and valine levels and the valine/glycine ratio were low in the uremic children. Our results demonstrate that children with chronic renal failure and growth retardation may maintain a satisfactory nutritional status but exhibit amino acid abnormalities typical of uremia.

Modulation of proteinuria and renal xanthine oxidase activity by dietary proteins in acute adriamycin nephrosis in rats: lack of correlation with intra- and extracellular amino acids.

Protein restriction ameliorates proteinuria in acute adriamycin (ADR) nephrosis and decreases the renal levels of xanthine oxidase (XO), a putative mediator of ADR nephrotoxicity. Hypothetically, the effect of protein restriction on renal XO levels may be due to variations in plasma and tissue proteic amino acids (AA). To elucidate this point, the levels of AA in plasma and in renal homogenates were determined in rats with ADR nephrosis and fed diets with different protein contents: (a) high (35%) casein; (b) standard (21%) casein; (c) low (9%) casein; (d) low casein plus a synthetic mixture of Val, Leu and Ile. The protein content of the diet determined certain marked variations in plasma AA: high levels of Val, Leu and Ile were found in rats fed on a high protein diet, while the same AA were low, in rats on low protein regimen. Supplementation of the low protein diet with a synthetic mixture of branched-chain AA (Val, Leu and Ile) normalized the plasma levels of these AA. In spite of these changes, tissue AA were similar in all groups, regardless of the protein contents of the diets. Furthermore, the levels of renal XO and proteinuria were unrelated to variations in plasma AA, since both parameters were low in protein-restricted and protein-restricted AA-supplemented rats while high in rats fed a high or normoproteic diet. These data demonstrate that low protein diets induce marked alterations in plasma AA composition which are similar in may respects to those found in protein malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effect of amino-acid dialysis solution in children on continuous ambulatory peritoneal dialysis.

The study involved eight metabolically stable children, with chronic renal failure on continuous ambulatory peritoneal dialysis (CAPD) whom we followed for 12-18 months. For the first 6 months CAPD was performed with dextrose; for the subsequent 6-12 months the morning exchange was substituted with a 1% amino-acid (AA) solution. The following parameters did not change during the study: serum creatinine, uric acid, inorganic phosphate, serum bicarbonate, potassium, cholesterol, triglycerides, total protein, albumin and transferrin. The only parameter that changed was blood urea nitrogen, which increased moderately. The anthropometric parameters did not show significant variation before and after AA dialysis. The plasma AA profile, which under basal conditions showed lower levels of several essential AAs, improved during the treatment period, with a partial correction of the imbalance. It is possible that this correction of plasma AAs may positively influence the metabolism of some organs such as the brain, muscle and those of the hepatosplanchnic region. The intracellular pool of free AAs, measured in polymorphonuclear leucocytes, was severely altered before the treatment and after 6 and 12 months showed only minor variations. It is possible that some modifications in the proportion of the different AAs in the dialysis solution or an improvement in the concentration or in the number of exchanges per day are necessary in order to change the nutritional status and to modify the intracellular AA pool.

Continuous ambulatory peritoneal dialysis (CAPD) of children with amino acid solutions: technical and metabolic aspects.

The changes in plasma and dialysate amino acids (AA) in 7 continuous ambulatory peritoneal dialysis (CAPD) children after dialysis with a 1% AA solution were compared with a glucose-containing solution. During the AA-exchange, the plasma levels of individual AA reached their peaks after 1 h, with their percentage increments significantly correlated (p less than 0.001) with the ratio of the amount of AA in the bag to the basal plasma concentration. The plasma concentration of methionine, valine, phenylalanine, and isoleucine remained higher than the basal value at 4 h. The amount of AA absorbed was 66% after 1 h, and 86% after 4 h and 6 h, corresponding to 2574 +/- 253 mumol/kg body wt. During glucose-dialysis (1.36%), levels of histidine, methionine, valine, phenylalanine, and isoleucine were significantly decreased in plasma after 1 h, and stayed low throughout the dialysis period. The loss of AA with the peritoneal effluent was 116 +/- 69 mumol/kg/body wt. From this study, it seems that using an AA dialysis solution, with 1 exchange per day, might limit the daily glucose load and compensate for AA losses by supplying an extra amount of AA and by reducing the loss of other AA not contained in dialysis solutions. The AA pattern in plasma following AA-dialysis resembles that observed after a protein meal, with no signs of persistently high, nonphysiological levels.