AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

Acute Kidney Injury↗

PubMed2002

Role of renal PGE2 in the adaptation from foetal to extrauterine life in term and preterm infants.

Urinary PGE(2) concentrations were assayed using a new EIA method, in 16 preterm and 18 term neonates at birth and 3 days later, since there is evidence that PGE(2) in urine are likely to reflect their renal generation and then could be correlated with kidney maturation or renal problems. PGE(2) concentrations were not different at birth (1.50+/-1.12 vs 1.56+/-1.94 ng/day), while resulted significantly higher in preterms, compared to terms, three days after birth (2.22+/-1.23 vs 1.39+/-0.79 ng/day). This increase in daily PGE(2) excretion observed only in preterm neonates could be due to an increased renal biosynthesis as a mechanism of compensatory response to prevent further decrements in renal plasma flow, since prostanoids play an important role in protecting the immature kidney from high levels of angiotensin II. Otherwise, the passive reabsorption of PGE(2) along the distal nephron could be altered because of kidney immaturity. The measurement of PGE(2) in urine of neonates, particularly prematures, could be useful to provide a better understanding of the homeostatic function of the kidney in the phase of adaptation to extra-uterine life.

Adaptation, Physiological↗

PubMed2002

Netilmicin effect on urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) in preterm newborns with and without anoxia.

The study aim was to evaluate urinary excretion of Retinol Binding Protein (RBP), compared with urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), in preterm infants with anoxia and netilmicin treatment. Urinary RBP and NAG were evaluated in 83 preterm newborns divided in 4 groups: 37 healthy preterm newborns (controls); 14 with neonatal anoxia; 16 treated with ampicillin + netilmicin; 16 with neonatal anoxia and treated with ampicillin + netilmicin. RBP was determined by an automated nephelometric technique and NAG by a colorimetric method on 5-h urine samples in the first week of life. Results showed that urinary excretion of RBP (average from first week values) was 1.06+/-0.67 g/mol creatinine (mean +/- SD) in controls, 1.99+/-1.41 in antibiotic-treated newborns, 3.99+/-4.57 in anoxic newborns and 3.75+/-3.48 in anoxic newborns under antibiotic treatment. When gestational age was not considered, a marked effect of anoxia (P<0.001) and a borderline effect of netilmicin (P<0.059) on RBP excretion were detected by ANOVA. However when gestational age was also considered by analysis of covariance, it appeared as the strongest predictor of RBP excretion (P<0.001), while the effect of netilmicin was no longer significant (P=0.181). The effect of anoxia persisted, although less remarkable (P=0.010). Conversely anoxia did not affect urinary NAG excretion, which was rather correlated with gestational age and netilmicin administration. The authors conclude that RBP and NAG urinary excretion may be used to discriminate between neonatal anoxia and netilmicin treatment, respectively as etiologic factors of renal tubular damage in the newborn.

Acetylglucosaminidase↗

PubMed2002

Unresolved questions regarding the mediaeval child.

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Child↗

PubMed2001

Impaired L-arginine uptake in platelets from type-2 diabetic patients.

The L-arginine uptake of resting platelets from type-2 diabetic patients and control subjects was measured and the kinetic parameters defined. The effect of platelet stimulation with agonists was also investigated. Kinetic studies showed that the K(m) value for L-arginine transport was not different in patients compared with control subjects, while V(max) was significantly decreased in patients compared with controls. Moreover, agonists able to mobilize Ca(2+) produced a further decrease in the L-arginine uptake in controls and in patients, suggesting that Ca(2+) intracellular levels down-regulate L-arginine transport in platelets from both control subjects and patients. Data suggest that drugs designed to control intracellular Ca(2+) might restore platelet function in diabetic patients.

Aged↗

PubMed2001

Cefixime in urinary tract infections with special reference to pediatrics: overview.

Cefixime is a third-generation oral cephalosporin that is highly active against a broad range of gram-negative and some gram-positive aerobic bacteria. In non-complicated urinary tract infections it is at least as effective as other usual treatments, and has a low rate of side effects. Several clinical studies have been performed on cefixime in urinary tract infections both in adults and children. On the basis of the literature data, cefixime could be indicated in the treatment of non-complicated urinary tract infections in children either as monotherapy or as switch therapy.

Bacterial Infections↗

PubMed2001

Renal transport of antibiotics and nephrotoxicity: a review.

The renal excretion of a drug can essentially be divided schematically into three functional processes: glomerular filtration, tubular reabsorption and tubular secretion. When assessing nephrotoxicity, the tubular secretion system, which allows transport of the drug from the blood to the urine via the tubular cells, is particularly important. Historically, two distinct tubular secretion mechanisms have been described for drugs: one via organic cations and the other via organic anions. More recently, a third tubular secretion mechanism has been identified, mediated by P-glycoprotein. In the present review, a number of examples will be given relating to antibiotic-induced kidney damage determined via the tubular reabsorption mechanism (aminoglycosides, amphotericin B) and via the tubular secretion mechanism (cephalosporins, vancomycin), respectively. Drug transport within the tubular cells is the first fundamental stage in the onset of the nephrotoxic process. Knowledge of these concepts is important for the prevention of iatrogenic kidney damage, particularly in patients with underlying disease receiving concomitant treatment with several potentially nephrotoxic molecules.

Absorption↗

PubMed2001

[Itinerant teachers of child care in Lazio, 1927-1928].

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Child↗

PubMed2000

Pyelectasis and hydronephrosis in the newborn and infant.

UNLABELLED: The aim of this review is to describe the present status of prenatally diagnosed pyelectasis and hydronephrosis. Ultrasonographic definitions are presented, along with guidelines for the management of urinary tract dilatations. Isolated pyelectasis without caliceal involvement rarely constitutes a pathological situation and does not require any particular diagnostic or therapeutic measures. Obstructive dilatation is characterized by an obstacle to normal urinary flow situated at any level in the urinary tract, with consequent stagnation of urine and dilatation upstream of the obstruction. If the obstruction is not correctly treated it can cause a progressive deterioration of renal function. The presence of ureterectasia plays a crucial role in the diagnostic algorithm and a micturitional cystourethrography is necessary to look for a vesicoureteric reflux (VUR). The significance of urinary tract dilatation is discussed in detail. CONCLUSION: In newborns with pyelectasis or hydronephrosis the paediatrician's goal should be to strike the right balance between excessive medical intervention and sufficient intervention for the diagnosis of potentially dangerous conditions.

Dilatation, Pathologic↗

PubMed2000

Amphotericin B-induced nephrotoxicity: a review.

Amphotericin B is the gold standard for antifungal treatment for the most severe mycoses. However, adverse effects are common, with nephrotoxicity being the most serious, occurring early in the course of treatment, and usually being reversible in most patients. Tubular damage is a well known problem associated with amphotericin B therapy but acute renal failure is the most serious complication. Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B. A new approach has been to complex the drug with lipids or entrap it in liposomes. This review will concern amphotericin B-induced nephrotoxicity, whose mechanisms are not completely clear. Nephrotoxicity seems related to direct amphotericin B action on the renal tubules as well as to drug-induced renal vasoconstriction. The main mechanisms of nephrotoxicity suggested in the literature are presented. The clinical picture at different ages (adults, children, newborns), interactions of clinical significance, strategies for prevention of amphotericin B-induced nephrotoxicity are summarized. To provide optimal patient care, it is imperative that the clinician understand the etiology of and the signs and symptoms associated with nephrotoxicity, as well as interventions to prevent nephrotoxicity in patients receiving amphotericin B.

Age Factors↗

PubMed2000

[Leonardo da Vinci and his studies on the human fetus and the placenta].

OBJECTIVE: To review the accuracy of Leonardo's anatomical studies of the female external genitalia and the foetus, particularly those concerning the umbilical cord with its blood vessels. BACKGROUND: The anatomical drawings of Leonardo da Vinci which are now stored in the Windors Castle near London were reviewed and the accuracy of the details of the genital apparatus and foetus was evaluated. A written comment characterizes many of his drawings. RESULTS: He described accurately the position of the uterine blood vessels and the relationship between the pelvic organs. However his drawing and description of the female external genitalia and human placenta was incorrect because his understanding of it was inadequate. He believed that the human placenta had cotyledons like that of the ungulate uterus (drown side A of sheet 19). At the top of that sheet some Leonardo's details of the anatomic relationship are shown. CONCLUSIONS: In our opinion, Leonardo's misunderstanding is probably because he was only able to perform one anatomical dissection of a pregnant women and foetus and therefore his knowledge was limited. The resulting documentation of the pregnant women and foetus was therefore heavily supplemented with his enormous experience in animal anatomy.

Famous Persons↗

PubMed2000

[Neonatal resuscitation: a fascinating story!].

Over the past thousands of years many examples can be found of the treatment given for asphyxia in the apparently dead subject. The resuscitation procedures were applied alike both in adults and in newborn babies. The first reference made to the mouth-to-mouth method was in the Kings'. In the second half of the 1800 many Authors proposed a method to resuscitate the asphyxiated newborn infant, which were still practiced up until the 1930 s. Many other different methods of air and 02 administration to the airway and stomach of an apparently dead newborn were well known and used in the 1800 s and still used in the 1950 s. Other methods used involved the dilatation of the rectum; the immersion in alternating warm and cold water and the use of a larynx tube developed by Chaussier which was then modified by other Authors. The use of tight fitting tracheal tubes and direct tracheal 02 administration after the clearing of the oropharynx using fingers and finally the mouth to mask and mouth to endotracheal tube breathing. All these examples are indicative of the approach taken in the resuscitation of the apparently dead infant. The science of resuscitation and its history continue to evolve....

History, 18th Century↗

PubMed1999

Cystatin C in healthy women at term pregnancy and in their infant newborns: relationship between maternal and neonatal serum levels and reference values.

Human cystatin C, a basic low molecular mass protein with 120 amino acid residues, is freely filtered by the glomerulus and almost completely reabsorbed and catabolized by the proximal tubular cells. Cystatin C has been recently proposed as a new sensitive endogenous serum marker for the early assessment of changes in the glomerular filtration rate. To define a reference basis for future clinical investigations in the perinatal period, we investigated the relationship between maternal and neonatal serum cystatin C in comparison with that of creatinine. We also defined reference values in healthy women at full-term pregnancy and in full-term newborns over the first 5 days of life. Seventy-eight women with uncomplicated pregnancy, aged between 19 and 40 years, and their infant newborns (43 males, 35 females) were enrolled in the study. The gestational age ranged from 37 to 43 weeks, and the birth weight from 2.50 to 4.15 kg. Blood samples were taken from all the women immediately before delivery and from their newborns at birth, 72 and 96 h after birth. Maternal and neonatal renal function was evaluated by standards parameters and by calculating creatinine clearance. In all serum samples, we measured cystatin C, creatinine, and urea. At term gestation, serum cystatin C ranged from 0.64 to 2.30 mg/L. At birth, serum cystatin C values ranged from 1.17 to 3.06 mg/L, significantly decreasing after 3 and 5 days of life. No correlation was found between maternal and neonatal serum cystatin C values (r = 0.09). As cystatin C serum levels in newborns are not significantly correlated with the respective maternal levels, neonatal serum cystatin C may originate almost exclusively in the neonate.

Adult↗

PubMed1999

Antibacterial-induced nephrotoxicity in the newborn.

Antibacterials are the primary cause of drug-induced kidney disease in all age groups and these agents bring about renal damage by 2 main mechanisms, namely, direct and immunologically mediated. For some antibacterials (aminoglycosides and vancomycin) nephrotoxicity is very frequent but generally reversible upon discontinuation of the drug. However, the development of acute renal failure with these agents is possible and its incidence in the newborn seems to be increasing. Antibacterials are very often used in the neonatal period especially in very low birthweight neonates. The role of neonatal age in developing nephrotoxicity has still to be defined. Since the traditional laboratory parameters of nephrotoxicity are abnormal only in the presence of substantial renal damage, the identification of early non-invasive markers of the renal damage (urinary microglobulins, enzymes and growth factors) is of importance. Aminoglycosides and glycopeptides are still frequently used, either alone or in combination, despite their low therapeutic index. Numerous factors intervene in bringing about the kidney damage induced by these 2 classes of antibacterials, such as factors related to the antibacterial itself and others related to the associated pathology as well as pharmacological factors. Nephrotoxicity can be caused by the beta-lactams and related compounds. Their potential to cause nephrotoxicity decreases in the order: carbapenems > cephalosporins > penicillins > monobactams. Third generation cephalosporins are frequently used in neonates. However, they are well tolerated compounds at the renal level. The nephrotoxicity of other classes of antibacterials is not discussed either because they are only used in neonates in exceptional circumstances, for example, chloramphenicol and cotrimoxazole (trimethoprim-sulfamethoxazole) or are not associated with significant nephrotoxicity, for example macrolides, clindamicin, quinolones, rifampicin (rifampin) and metronidazole. Antibacterial-induced nephrotoxicity is an important parameter to be considered when treating the newborn and this is particularly true when use of a combination of different antibacterials and/or drugs with a nephrotoxic potential is being considered. However, other parameters, such as antibacterial spectrum, pharmacokinetics, post-antibacterial effect, clinical efficacy, general adverse effect profile and cost, must also be considered in the choice of antibacterial therapy in the neonate. Knowledge of the renal safety of antibacterials and the correct approach to therapeutic drug monitoring may be useful elements for preventing iatrogenic renal disorders.

Aminoglycosides↗