[Urinary tract infections in children]. / Infections urinaires en pédiatrie.

Urinary tract infection (UTI) is relatively frequent in children. The younger the child is, the more symptoms are atypical. UTI is often associated with functional or malformative uropathy, such as vesico-ureteral reflux or obstruction. Appropriate imaging studies should be carried out in every infected child. The prognosis of uncomplicated UTI is very good, but is less favorable when the UTI is associated with urological abnormalities. Development of pyelonephritic scars can lead to kidney scarring, for which the occurrence of intrarenal reflux is probably responsible . Short-term treatment is recommended for uncomplicated UTI. Uncomplicated UTI with frequent relapses requires prophylactic chemotherapy; this treatment should also be considered when UTI is associated with vesico-ureteral reflux. Surgery is indicated in the presence of major urological malformations. Whether medical or surgical, the treatment of UTI should be followed by urine cultures whenever the child presents with fever. The antibiotic treatment of acute pyelonephritis must be started immediately, preferentially by intravenous route. A switch to oral treatment can be made after obtaining the results of the antibiogram. UTI represents a major risk in neonates; it should preferably be managed in specialized centers.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

[Aggression to the immature kidney]. / Agression du rein immature.

The main causes for acute renal failure (ARF) in the newborn include endogenous factors (such as hypotension, hypovolemia, hypoxemia, perinatal asphyxia, and neonatal septicemia) and exogenous factors such as mechanical ventilation, nephrotoxic agents (antibiotics, indomethacin, ibuprofen, angiotensin converting enzyme inhibitors, and tolazoline). These conditions determinate vasoactive disturbances interfering with the delicate balance of intrarenal vasoconstrictor and vasodilator forces, which regulates the glomerular filtration rate (GFR) in the healthy term, and particularly in the premature infant. Factors influencing renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. Plasma creatinine concentrations should be used with some caution for ARF diagnosis in the first days of life. General measures of kidney protection include correcting abnormalities in fluid homeostasis, adequate ventilation and rational choice of drugs. Moreover, in order to protect the kidney, different compounds have been proposed such as diuretics (furosemide and torasemide), and dopaminergic agents (dopamine, dopexamine). With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and antibodies against endothelin may in the near future be used to prevent or ameliorate the prognosis of the neonatal stressed kidney. The main renal replacement therapies are possible in the newborn. However preventive measures are easily available in the neonatal period and they often represent the most efficacious procedures.

The renal hemodynamic effects of Aspirin in newborn and young adult rabbits.

A group of neonatal (n=10) and 12-week-old (n=12) anesthetized, ventilated New Zealand white rabbits received an acute i.v. dose (40 mg/kg body weight) of acetylsalicylic acid (ASA, Aspirin). In the neonatal animals, i.v. ASA caused within 20 min a significant (P<0.01) fall in renal blood flow and glomerular filtration rate (GFR), with an equally significant (P<0.01) increase in filtration fraction and renal vascular resistance. The latter indicates greatly augmented renal vasconstriction or more precisely reduction in intrarenal vasodilatation by inhibition of vasodilatory prostaglandin (PG) synthesis. Urine volume decreased. The 12-week-old young adult animals responded in a similar, but significantly attenuated fashion. These experiments demonstrate that inhibition of PG synthesis in neonatal animals causes very rapid, reversible vasoconstriction, with a reduction in GFR. In addition, this study confirms previous observations that the renal hemodynamic response to the inhibition of PG synthesis is far more pronounced in neonatal animals than in (young) adult rabbits.

Dipstick measurements of urine specific gravity are unreliable.

AIM: To evaluate the reliability of dipstick measurements of urine specific gravity (U-SG). METHODS: Fresh urine specimens were tested for urine pH and osmolality (U-pH, U-Osm) by a pH meter and an osmometer, and for U-SG by three different methods (refractometry, automatic readout of a dipstick (Clinitek-50), and (visual) change of colour of the dipstick). RESULTS: The correlations between the visual U-SG dipstick measurements and U-SG determined by a refractometer and the comparison of Clinitek((R))-50 dipstick U-SG measurements with U-Osm were less than optimal, showing very wide scatter of values. Only the U-SG refractometer values and U-Osm had a good linear correlation. The tested dipstick was unreliable for the bedside determination of U-SG, even after correction for U-pH, as recommended by the manufacturer. CONCLUSIONS: Among the bedside determinations, only refractometry gives reliable U-SG results. Dipstick U-SG measurements should be abandoned.

[Exposure in utero to immunosuppressives]. / Exposition aux immunosuppresseurs in utero.

The number of pregnant women receiving immunosuppressive therapy is increasing. Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Despite the maternal and fetal risks of these pregnancies, the proportion of surviving infants is improving and the possibility that a pregnancy could occur in these women during their childbearing years should be considered. All immunosuppressant drugs and their metabolites cross the placenta, raising questions about the long-term outcome of the children exposed to these agents in utera. There is no increased risk of congenital anomalies. However, there is an elevated incidence of prematurity, intrauterine growth retardation (IUGR) and therefore low birthweight, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporin, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes. The follow-up of these infants should be carefully organized and multidisciplinary, taking the perinatal context into account.

[Polyuria, pollakiuria, and nocturia in children: diagnostic and therapeutic approach]. / Polyurie, pollakiurie et nycturie chez l'enfant: approche diagnostique et thérapeutique.

Polyuria is defined as the passage of large volumes of diluted urine secondary to an abnormality of urine concentration. This disorder can result either from deficient secretion of vasopressin (cranial diabetes insipidus), or from renal resistance to vasopressin (nephrogenic diabetes insipidus), primary polydipsia, osmotic diuresis, electrolytic disorders or drugs. Suspicion of impaired renal concentration ability can be confirmed by a fluid deprivation test. The administration of exogenous vasopressin allows to clarify the pathogenetic mechanism. Once the mechanism responsible for polyuria has been clarified it is mandatory to search for underlying causes. Treatment of polyuria should be causal, if its origin is known, and/or symptomatic in order to prevent severe dehydration. Symptomatic treatment of cranial diabetes insipidus consists of administering exogenous vasopressin. Salt restriction associated to a combined administration of hydrochlorothiazide/amiloride or hydrochlorothiazide/indomethacin can reduce urine output by 20 to 50% in case of nephrogenic diabetes insipidus. Pollakiuria is defined as a daytime urinary frequency. It can be isolated or may be a manifestation of lower urinary tract infections, bladder instability, nephrolithiasis or concentrated acidic urines. Detailed history and physical examination represent major clues to diagnostic. Therapy of pollakiuria can be causal or symptomatic using anticholinergic drugs or reeducation in case of bladder instability. Nocturia is characterized by voluntary nocturnal micturitions secondary to conditions inducing impaired renal concentration ability, or to heart failure.

[Hyperaminoaciduria in children]. / Les hyperaminoaciduries chez l'enfant.

Hyperaminoaciduria is a major disorder to be considered in the event of growth and mental retardation, convulsion and other unexplained clinical symptoms. This review should enable the general practitioner to determine the conditions necessitating urinary and blood amino acid analyses in order to improve the treatment of children presenting rare pathologies, the prognosis of whom depends on the rapidity of the intervention. The diagnosis and treatment of hereditary and renal hyperaminoaciduria are discussed and a physiological and physiopathological synthesis of the tubular reabsorption of amino acids is presented. The different clinical entities associated with hyperaminoaciduria are then briefly described according to their origin (renal or prerenal).

[Kinetics of potassium transfer during hemodialysis]. / Cinétique des transferts de potassium en cours d'hémodialyse.

INTRODUCTION: In order to study whether the removal of potassium in haemodialysis patients could be increased, we analyzed the kinetics of potassium transfer in the dialyzer. METHOD: 40 patients were included in the study. We studied: a) in vitro potassium exchanges between erythrocytes and plasma; b) plasma and erythrocyte potassium concentrations at dialyzer input and output; c) potassium transfers into the dialysate, using plasma clearance and direct measurement in the collected dialysate and d) erythrocyte potassium concentrations at the beginning and the end of dialysis. RESULTS: In vitro, there is virtually no potassium transfer between erythrocytes and plasma. In vivo, erythrocyte potassium concentration is not affected by the dialyzer (98.7 +/- 6.4 mmol/l to 97.7 +/- 7.5 mmol/l, p = NS). Potassium transfer levels determined by calculated plasma clearance were similar to values obtained by measuring potassium in dialysate (0.71 +/- 0.10 mmol/min vs 0.68 +/- 0.10 mmol/min, p = NS). These results suggest that erythrocytes do not participate in potassium exchange in the dialyzer. This was confirmed by measured erythrocyte potassium concentrations, which were the same at the beginning and the end of dialysis (104.0 +/- 5.6 mmol/l vs 104.2 +/- 5.0 mmol/l, p = NS).

The renal hemodynamic effects of ibuprofen in the newborn rabbit.

In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.

Endothelin, angiotensin II and adenosine in acute cyclosporine A nephrotoxicity.

We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. In the present study, we evaluated the role of endothelin (ET), angiotensin II (AII) and adenosine in this experimental model. All animals received CsA (25 mg/kg/day) for 5 days. Renal function parameters were first measured in a 30-min period, showing renal insufficiency in all animals. Then, rabbits were administered bosentan (10 mg/kg; antagonist of ET(AB) receptors), perindopril (20 microg/kg; angiotensin-converting enzyme inhibitor), or theophylline (1 mg/kg; adenosine receptor blocker at micromolar concentrations). After a 40-min equilibration period, renal function was assessed again for 30 min. Bosentan, perindopril and theophylline significantly reduced renal vascular resistance (-28+/-5%, -39+/-7% and -8+/-3%, respectively), and improved renal blood flow (+38+/-15%, +66+/-16% and +20+/-5%), glomerular filtration rate (+33+/-9%, +52+/-13% and +50+/-8%) and diuresis (+48+/-9%, +76+/-19% and +73+/-14%). Filtration fraction was unchanged with bosentan, decreased with perindopril (-10+/-9%) and increased with theophylline (+24+/-5%). The overall results suggest that ET, AII and adenosine are involved in the acute renal failure induced by CsA. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with ET- and adenosine-mediated afferent arteriolar constriction as well as ET- and AII-mediated efferent arteriolar constriction.

Management of acute renal failure in newborns.

Acute renal failure (ARF) is a frequent clinical condition in neonatal intensive care units. Plasma creatinine concentrations should be used with some caution for ARF diagnosis in the first days of life. An intravenous fluid challenge allows differentiation of prerenal failure and intrinsic renal failure. All clinical conditions associated with hypovolemia, hypoxemia, and hypotension in the newborn infant may lead to renal insufficiency, the leading causes being perinatal anoxia-ischemia and sepsis. The initial treatment mainly relies on correction of hypotension, acidosis, and hypoxemia, in order to reduce renal vasoconstriction and improve renal perfusion. If necessary, the main renal replacement therapy is usually peritoneal dialysis even if skilled medical and nursing personnel are available in some neonatal intensive care units to perform hemofiltration and hemodiafiltration safely.

Torasemide is an effective diuretic in the newborn rabbit.

The effect of intravenous (i.v.) torasemide on diuresis and renal function was evaluated in three groups of normoxemic, 5- to 10-day-old, newborn New Zealand White rabbits. The animals of group 1 received 0.2 mg/kg of torasemide i.v., whereas in group 2 an i.v. dose of 1.0 mg/kg was given. The third group of animals received a bolus i.v. dose of 1.0 mg/kg torasemide with continuous i.v. replacement of estimated urinary fluid and electrolyte losses. Torasemide proved to be an effective, potassium-sparing diuretic, without significant effect on glomerular filtration rate (GFR). Renal blood flow (RBF) fell and the renal vascular resistance (RVR) rose in all three groups of animals, although the rise in RVR in group 3 was not significant. These changes in renal hemodynamics were most pronounced in the animals of group 2 and are probably secondary to torasemide-induced hypovolemia (2.8% loss of body weight) and accompanying humoral reactions, such as an increase in angiotensin II (not measured). When the latter is prevented by simultaneous re-infusion of an electrolyte solution (group 3), replacing urinary losses, GFR increases and the changes in RBF and RVR are blunted. We conclude that torasemide is an effective, potassium-sparing diuretic in newborn rabbits. No evidence was found for a vasodilatory action of the drug.