Serum soluble interleukin 2 receptor (sIL-2R) as a marker of acute rejection in renal transplant children.

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.

CYP3A5 Genotype and Time to Reach Tacrolimus Therapeutic Levels in Renal Transplant Children.

BACKGROUND: CYP3A5 gene polymorphism rs776746 has been associated with lower tacrolimus dose requirements and bioavailability in both adults and children. This variant causes a loss of CYP3A5 activity owing to a splice site variant leading to a truncated inactive enzyme. The aim of this study was to determine if the rs776746 gene polymorphism is related to the time to reach tacrolimus therapeutic levels in renal transplant children. METHODS: A prospective study was performed in renal transplant children receiving tacrolimus as part of their immunosuppressive regime. CYP3A5 genotype was determined by direct sequencing. Tacrolimus trough levels and serum creatinine at 1 week and 1 month after renal transplantation was obtained from clinical chart. RESULTS: A total of 42 patients were included; 19 (45.2%) were female, 23 (54.8%) received living-donor transplants, and 21 patients expressed CYP3A5*1/*1 or CYP3A5*1/*3. Tacrolimus dose was higher in expressers at week 1 (0.13 vs 0.10 mg/kg/d; P = .011), and week 4 after transplantation (0.17 vs 0.09 mg/kg/d; P < .0001). At 4 weeks after renal transplantation, only 9 patients from the expressers group (42.8%) had levels ≥7 ng/mL, in contrast to 18 in the nonexpressers group (85.7%; Fisher exact P = .008). CONCLUSIONS: Tacrolimus dose was significant higher in functional CYP3A5 expressers. Only 42.8% of such expressers had tacrolimus trough levels ≥7 ng/mL at 1 month after transplantation despite dose adjustments. Long-term follow up is needed to address the consequences of early post-transplantation bioavailability differences due to CYP3A5 genotype.

Bacterial-induced diarrhoea.

In diverse parts of the world, many bacterial strains have been recognised as the causative agents of diarrhoea. Great achievements have been made in perceiving the varied mechanisms which explain their intestinal pathogenicity. These achievements include the elucidation of the 5 mechanisms of disease production by Escherichia coli, the mechanisms of action of Shigella, Salmonella, Campylobacter and Yersinia, new information about antimicrobial-associated colitis caused by Clostridium difficile and the recognition of microbes such as Aeromonas hydrophila and Pleisomonas shigelloides. Information is available on the use and indications of antimicrobial treatment in children with diarrhoea of bacterial aetiology which is proven or suspected by clinical symptomatology or simple laboratory procedures. Finally, the usefulness of oral rehydrating solutions has been appreciated in the prevention as well as in the correction of diarrhoeal dehydration.

Clinical experience in Mexico with a new oral rehydration solution with lower osmolality.

A clinical trial was conducted to compare the safety and efficacy of a new oral rehydration solution (ORS) with that of the ORS recommended by the World Health Organization (WHO). One hundred thirty infants with dehydration due to acute diarrhea were randomized into two groups: 68 infants received the WHO ORS containing sodium and glucose in a concentration of 90 and 111 mmol/L, respectively, and an osmolality of 311 mosm/kg (ORS-90); 62 infants received an ORS containing sodium and glucose in a concentration of 60 and 90 mmol/L, respectively, with an osmolality of 240 mosm/kg (ORS-60). Treatment failure was noted in seven infants (10.3%) in the ORS-90 group; the causes of failure were high stool output (three cases), persistent vomiting (three cases), and ileus (one case). Only one patient in the ORS-60 group (1.6%) was considered a failure because of high stool output. No significant differences were noted in the serum sodium levels in either group of patients, both in relation to the natremia seen on admittance or that seen after rehydration. A trend was observed toward correction of hypernatremia or hyponatremia with both types of ORS. A similar situation was observed with respect to the variations seen in serum potassium levels. The results from this study suggest that there may be clinical advantages of using an ORS with concentrations of sodium and glucose and a total osmolality lower than that of ORS-90, because of the lower incidence of treatment failures.

Usefulness of fractional excretion of sodium in critically ill pre-term newborns.

The purpose of this prospective study was to measure the fractional excretion of sodium (FENa) in critically ill pre-term newborns (PTNB) in order to determine its cut point in the diagnosis of acute renal failure (ARF). This study included 52 newborns and was conducted from May, 1994 to May, 1995. Patients were divided in two groups: patients without ARF in group A (n = 47) and patients with ARF in group B (n = 5). No statistically significant differences were found in birth weight, extrauterine life span, serum sodium levels, urine creatinine and urinary volumes between the two groups, but there was a difference in gestational age, urinary sodium concentration and serum creatinine levels. Sensitivity and specificity were determined, and the critical level of FENa was 4% or greater for ARF diagnosis. The average FENa value for Group A was 1.4 +/- 1.4% with a median of 0.92%. In Group B, average FENa was 6.9 +/- 2.9% with a median of 8.5% (P < 0.001). We conclude that FENa is a valuable tool for the assessment of renal function in critically-ill PTNB, in spite of all other factors present in this population that could modify its values.

[Effect of a new amino acid solution in the oral hydration of nursing infants with acute diarrhea. A prospective study]. / Efecto de una nueva solución con aminoácidos en la hidratación oral de lactantes con diarrea aguda. Un estudio prospectivo.

Thirty-two one- to 12-month-old male infants with diarrheal dehydration treated with either the oral rehydration solution recommended by the World Health Organization (WHO), or the same solution modified by the addition of glycerine (60 mmol/L) and glycil-glycine (30 mmol/L), with a total osmolality of 379 mOsm/kg. The patients belonging to the latter group exhibited greater stool losses (10.3 +/- 8.3 vs 8.0 +/- 6.4 mL/kg/hour) and a greater urine volume (10.4 +/- 14.2 vs 4.6 +/- 4.0 mL/kg/6 hours), during the first four to six hours of the rehydration period. The results of this study show, that in contrast with those of other series, the addition of glycine and glycil-glycine to the WHO solution, at the concentrations used in the study, produces greater fecal water losses in children with dehydration due to acute diarrhea.

[Fever of unknown origin. Presentation of 180 pediatric cases]. / Fiebre de origen obscuro. Presentación de 180 casos pediátricos.

Fever of unknown origin (FUO) is a frequent disorder in pediatric age. FUO is defined as the presence of fever over 38.4 centigrades in a patient for more than three weeks in which the etiology remains undetermined. From 30.736 consecutive admittances into our hospital, 180 patients with FUO were detected, and studied in a systematized way and according to a predetermined protocol. FUO was commonly found in children under six years of age. Our patients presented fever from three weeks to six and a half years of evolution; however, in the vast majority of the cases (n = 115) fever had a three weeks course. Several symptoms and physical manifestations other than fever were observed in our patients but they were widely variable and nonspecific. Infectious diseases were the commonest etiological factor encountered; among them, thyroid fever, and urinary tract infections were the most frequent infectious disorder found; in four children fever was associated to ampicillin administration; in 19 patients, fever was no demonstrated. A large number of laboratory investigations were done in the diagnosis of neoplastic diseases. We think that the study of a patient with FUO requires of a systematized approach.

[Water-electrolyte and acid-base disorders. VIII. Respiratory acidosis]. / Alteraciones hidroelectrolíticas y ácido-base. VIII. Acidosis respiratoria.

Acute respiratory acidosis will result from many processes that acutely interfere with the excretion of CO2 by the lungs. CO2 excretion by the lungs can be interfered with by processes that inappropriately decrease minute ventilation, processes that impair the transport of CO2 from the site of production to the lungs for export, and by processes that impair the transfer of CO2 from the blood through the alveolar space to the atmosphere. The underlying clinical syndrome generating the primary hypercapnia will determine the duration of the acidosis as well as the anticipated clinical manifestations attributable to the acidosis.

[Water-electrolyte and acid-base disorders. VII. Metabolic alkalosis]. / Alteraciones hidroelectrolíticas y ácido-base. VII. Alcalosis metabólica.

Metabolic alkalosis is defined as a primary increase in plasma bicarbonate concentration. As a consequence of this increase, systemic alkalemia and secondary hypercapnia develop. In most instances metabolic alkalosis arises from loss of acid through the kidney or gastrointestinal tract. The causes of metabolic alkalosis can be separated into two groups. Those forms of alkalosis responsive to chloride salt administration (e.g., vomiting), are associated with extracellular fluid volume and chloride depletion. In contrast, alkalosis resistant to administration of chloride salt (e.g., primary aldosteronism), is usually associated with extracellular fluid volume expansion and a urine chloride above 20 mEq/L (mmol/L). Metabolic alkalosis; causes; diagnosis; clinical manifestations.

[Water-electrolyte and acid-base imbalance. VI. Metabolic acidosis]. / Alteraciones hidroelectrolíticas y ácido-base. VI. Acidosis metabólica.

Metabolic acidosis results from a disequilibrium between production and excretion of acid. Loss of base from the body through the gastrointestinal tract or in the urine or an increase in metabolic acid production are the three major mechanisms from which metabolic acidosis is generated. Uncomplicated metabolic acidosis is manifested by an increase in blood acidity, hypobicarbonatemia, and hypocapnea. The magnitude of these changes defines the severity wf the acidosis. It is convenient to divide metabolic acidosis into two general categories (hyperchloremic and normochloremic), based on the observed anion gap, as this serves to narrow the differential diagnosis. The normal anion gap is that amount of plasma anion not measure by routine laboratory screening that accounts for the difference between the measured sodium cation (Na+) and anions (Cl +/- HCO3-). Metabolic acidosis; causes; diagnosis; clinical manifestations.

[Water-electrolyte and acid-base disorders. V. Acid-base balance]. / Alteraciones hidroelectrolíticas y ácido-base. V. Equilibrio ácido-base.

Disturbances of acid-base homeostasis are frequently associated with many commonly observed disease states. Recognition of abnormal plasma acid-base composition may often direct the clinician to the diagnosis of a specific disease. Simply stated, external hydrogen ion balance exits when the net hydrogen ion production from cellular metabolism equals the net hydrogen ion excretion from the body. Net cellular production of hydrogen ions consist of two components: carbonic acid, which is excreted by the lungs as CO2, and fixed acids, which require renal excretion. The net amount of fixed acid production is determined by cellular metabolism, dietary intake and gut absorption of available base equivalents. The immediate defense of pH is provided by the buffering systems, which also act as transporters of the acid from sites of production to sites of elimination. CO2 exchange by the lungs is responsible for the bulk of acid excretion: more than 99.5 percent of the normal daily acid load and 100 percent of CO2 produced by metabolism are eliminated by this route. On the other hand, the kidney is the only organ capable of excreting an appreciable quantity of fixed acid as titratable acids an ammonium, with the regeneration of bicarbonate buffer. Acid-base; buffering systems; acid-base regulation.

[Water-electrolyte and acid-base imbalance. IX. Respiratory alkalosis]. / Alteraciones hidroelectrolíticas y ácido-base. IX. Alcalosis respiratoria.

Respiratory alkalosis is the consequence of primary hypocapnia of divergent etiologies. Any pathologic process that increases ventilation to levels beyond that required to excrete the CO2 byproduct of metabolism, will result in an inappropriately low systemic pCO2 and a tendency to an alkaline systemic pH. The increased drive to ventilation may be due predominantly to a primary increase in central nervous system activity, either within the respiratory center itself or from more centrally placed areas with neural projections that extend to and control the respiratory center. Alternatively, an increased drive to ventilation may result from an "appropriate" physiologic response to another more important stimulus that overrides the human's needs to protect pCO2 and pH. Hypoxia (of different causes), is the most important and most commonly encountered such stimulus.

[Water-electrolyte and acid-base changes. IV. Water metabolism and water balance]. / Alterciones hidroelectrolíticas y ácido-base. IV. Metabolismo del agua y balance hídrico.

Two interrelated physiologic feedback systems, thirst and antidiuretic hormone, serve to regulate water balance, and thereby body fluid osmolality. These two systems share at least one common receptor component: a device for sensing body fluid tonicity, the hypothalamic osmoreceptor. The output of the osmoregulatory system is subserved by two distinct effector components: oral water ingestion and renal water excretion. Acting in concert, these two processes serve to maintain body fluid osmolality. Under normal circumstances body fluid osmolality is carefully maintained within precisely defined limits. For body fluid osmolality to remain constant, the amount of water lost each day (by insensible, gastrointestinal, and renal routes), must be replenished by the ingestion of water and, to a lesser extent, by the production of "metabolic" water from the catabolism of foodstuffs.

[Polyuria]. / Poliuria.

Polyuria is an important clinical sign that may pass unnoticed to the relatives and to the physician. In this paper, the definition of polyuria and the pathophysiological bases that condition its presence are reviewed. Likewise, the causes of polyuria in pediatric ages are discussed; this allows the clinician to approach the diagnosis in a systematized and organized manner. Finally, the outstanding clinical and laboratory findings of the entities that usually go with polyuria are reviewed; some of them are: neurogenic diabetes insipidus, primary polydipsia, osmotic diuresis, and nephrogenic diabetes insipidus.

[Acute renal insufficiency]. / Insuficiencia renal aguda.

The incidence of acute renal failure in children is higher due to the prevalence of diarrheal dehydration, use of nephrotoxic substances and sepsis. The occurrence in the newborn has increased, probably due to the large number of seriously sick infants maintained in neonatal intensive care units. Various laboratory examinations have been proposed as diagnostic indices of acute renal failure in children. Among these are the urine-to-plasma concentrations of urea and creatinine and the urine-to-plasma osmolality ratio. The fractional excretion of sodium and the so-called renal failure index are the most reliable of the diagnostic tests. The functional abnormalities and complications of acute renal failure include reduced glomerular filtration rate, retention of nitrogenous wastes, hyponatremia, hyperkalemia, metabolic acidosis, hypocalcemia, hyperphosphatemia and hypermagnesemia. The principles of management and treatment of complications are discussed.

[Proteinuria]. / Proteinuria.

The finding of proteinuria in the pediatric age is a frequent phenomenon. Once detected, the immediate goal is to investigate other evidences of renal disease or its participation in systemic diseases. If proteinuria is an isolated finding, its transitoriness, persistence or relation with posture must be determined. Transitory proteinuria is a mild finding with good outlook; however, in patients with orthostatic or persistent asymptomatic proteinuria, the prognosis is uncertain; however, the measures taken must be conservative without restriction of physical activity and only in case of association to other signs, or finding of any change in renal function tests, the possibility of renal biopsy should be evaluated. The presence of proteinuria above 1 g/l. in a patient with acute nephritic syndrome, may be a sign of poor prognosis if it persists over one month and is indicative of renal biopsy. If this same degree of proteinuria is found in a nephrotic syndrome without hematuria or arterial hypertension, the necessity to practice renal biopsy is not indicated, except in the case it does not disappear following adequate treatment with corticosteroids.