Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.

The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.

New insights into spontaneous intestinal perforation using a national data set: (2) two populations of patients with perforations.

BACKGROUND: Spontaneous intestinal perforation (SIP) is increasingly common in the premature infant and has been demonstrated to be associated with early postnatal administration of glucocorticoids and indomethacin. Before survival of the extremely low birth weight (ELBW) infant, SIP was thought to be a rare, congenitally acquired disease sporadically affecting the muscularis of the distal intestine. These disparate views of etiology have not been previously reconciled in the literature. OBJECTIVES: (1) To establish a cohort of SIP patients in a national data set. (2) To use timing of diagnosis as a unique data element and thereby differentiate between SIP cases which are susceptible to postnatal risk factors versus those occurring at or immediately after birth (and therefore not exposed to postnatal risk factors). METHODS: A large identified national data set was used to retrospectively look at timing of diagnosis and then the cohort was divided into postnatal treatment groups for further subanalyses. This analysis resulted in the division of the cohort into early and late diagnosis SIP subcohorts. These were then queried retrospectively by univariate analysis to look for differences in demographics between the two (using a P-value < 0.05). RESULTS: There were 633 patients with SIP evaluated in this data set. The early SIP cohort (0-3 days) was made up of 116 infants with a median BW of 1.401 kg, whereas the late cohort (4-14 days) held 386 infants with a median BW of 775 g. Infants with early SIP were significantly more likely to: be male, have higher Apgar scores, have not received antenatal steroids, surfactant or required mechanical ventilation. CONCLUSIONS: Two populations of infants acquire SIP: ELBW infants acquire SIP on average between 7 and 10 days of life after exposure to indomethacin and glucocorticoids (either endogenous or exogenous), and infants with early SIP (0-3 days) who are significantly less likely to have been exposed to postnatal risk factors and are less premature.

New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure.

BACKGROUND: Spontaneous intestinal perforation (SIP) is increasingly common in the premature infant and is associated with significant morbidity. Indomethacin use has been implicated as a co-risk factor for SIP when combined with glucocorticoids, but previous evidence argued against indomethacin being an independent risk factor when used prophylactically. OBJECTIVES: (1) To establish a homogeneous cohort of SIP patients in a national data set and to contrast them to patients with surgical necrotizing enterocolitis (NEC). (2) To test the hypothesis that early post-natal indomethacin is independently associated with SIP. METHODS: A large de-identified data set was retrospectively queried by diagnosis, and then multiple antenatal and post-natal variables were tested by both univariate and multivariate analysis to identify associations with SIP. Sub-analyses were also performed to look at the timing of drug administration. RESULTS: There were 2105 patients evaluated in the data set. Patients were divided into matched controls (n = 581), those with SIP without report of NEC (n = 633) and those with NEC requiring surgery (n = 891). Infants with SIP were more likely to have a patent ductus arteriosus and more likely to be treated with vasopressors than either control or NEC patients. Compared to infants with NEC, patients with SIP were smaller, less mature and required more support. SIP was also diagnosed earlier than NEC (median of 7 vs 15 days). Patients with SIP were more likely to be treated with indomethacin, hydrocortisone or both on days of life 0-3 than controls. CONCLUSIONS: (1) Surgical NEC and SIP have significant differences in presentation, demographics and morbidity. (2) A detailed look at drug timing revealed that early post-natal indomethacin is independently associated with SIP.

The epidemiology, prevalence and hospital outcomes of infants with gastroschisis.

OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter.

Galanin receptor subtypes.

The neuropeptide galanin, which is widely expressed in brain and peripheral tissues, exerts a broad range of physiological effects. Pharmacological studies using peptide analogues have led to speculation about multiple galanin receptor subtypes. Since 1994, a total of three G-protein-coupled receptor (GPCR) subtypes for galanin have been cloned (GAL1, gal2 and gal3). Potent, selective antagonists are yet to be found for any of the cloned receptors. Major challenges in this field include linking the receptor clones with each of the known physiological actions of galanin and evaluating the evidence for additional galanin receptor subtypes.

Neuropeptide Y: a powerful modulator of epithelial ion transport.

Neuropeptide Y (NPY) is a major gut peptide localized in the intestinal mucosa of several mammalian species. Ileal mucosa from rabbit and guinea-pig was mounted in Ussing chambers in order to study the effect of NPY on short circuit current. Neuropeptide Y inhibited the short circuit current when applied to the serosal side of the tissue. The maximum change in short circuit current was -50 +/- 6 microA cm-2 in the rabbit ileum and -49 +/- 14 microA cm-2 in the guinea-pig ileum. The EC50 was 3 X 10(-8) M in both species. Pretreatment of rabbit ileum with the alpha 2-adrenoceptor antagonist, yohimbine (1 X 10(-6) M) for 10 min did not reduce the response of the tissue to neuropeptide Y (1 X 10(-7) M). When applied serosally to rabbit ileal mucosa, the related peptide YY caused a maximum change in short circuit current of -60 +/- 13 microA cm-2; the EC50 was 2 X 10(-9) M. Isotopic flux studies in rabbit ileum showed that 1 X 10(-7) M neuropeptide Y enhanced mucosal-to-serosal Na+ and Cl- fluxes and reduced serosal-to-mucosal Cl- flux. Replacement of chloride with gluconate on both sides of the tissue significantly reduced the change in short circuit current produced by neuropeptide Y (1 X 10(-7) M), as did a similar replacement of bicarbonate. It is concluded that neuropeptide Y and peptide YY are the most potent neurotransmitters or hormones so far described in their ability to attenuate electrogenic transport in the small intestine.

Prevention of retrosternal adhesions after pericardiotomy.

Because repeat sternotomies are becoming much more prevalent with repeat coronary bypass operations, prevention of direct adhesions of the heart and grafts to the back of the sternum by use of synthetic or xenograft material to close the pericardiotomy has become a matter for investigation. In this study bovine and equine glutaraldehyde-processed xenografts were implanted bilaterally in dogs for implant intervals of 6 weeks and 3, 6, 9, and 12 months. The bovine and equine xenografts both performed well in resisting the adhesion of the heart to their inner surfaces and less well in resisting adhesion of the lung and chest wall to their outer surfaces. The bovine xenograft had a higher percentage of adhesion-free surface on all the surfaces evaluated; however, one of our 12-month bovine pericardial xenograft implants exhibited significant multifocal calcific degeneration. Although pericardial xenografts generally have performed well when implanted in the dog, Gallo, Artiñano, and Duran recently expressed concern about their performance in humans. Along with our finding of calcification, their concern suggests a cautious approach to clinical application.

Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system.

Our group has recently reported the expression cloning of the human neuropeptide Y Y2 receptor DNA and subsequently the cloning of the rat homologue. These studies have made it possible to localize the mRNA encoding this NPY receptor subtype in rat tissues. We have, thus, carried out in situ hybridization studies, using radiolabeled oligonucleotide probes to the rat Y2 receptor mRNA, to determine the distribution of Y2 mRNA in rat brain and limited peripheral ganglia. Probe specificity was confirmed by testing antisense and sense probes in transfected cells. In rat brain, hybridization signals obtained with the antisense probes were discrete and were restricted to neuronal profiles in specific subregions of the cortex, hippocampus, amygdala, thalamus, hypothalamus, mesencephalon and pons. Among the regions exhibiting the most intense labeling were the CA3 region of the hippocampus, the arcuate nucleus of the hypothalamus and layer 3 of the piriform cortex. Other regions containing labeled neurons included the medial amygdala, the centromedial thalamic nucleus, the dorsal raphe, the dorsal motor nucleus of the vagus and the trigeminal ganglion. The present results indicate that the mRNA encoding the Y2 receptor is discretely localized in the rat brain and that the distribution is generally consistent with previous radioligand-binding studies. This study should help clarify the relationship between the Y2 receptor distribution and functional studies of NPY receptor subtype classification and provides further evidence for the involvement of the Y2 receptor in multiple physiological processes.

Molecular biology and pharmacology of galanin receptors.

Galanin was first isolated 15 years ago. Diversity of galanin receptors has been suspected from the study of native tissues and functional responses to galanin and galanin-like peptides in vitro and in vivo. The recent application of molecular biologic techniques to clone galanin receptors has extended this diversity. So far, three galanin receptor subtypes, GALR1, GALR2, and GALR3, have been cloned from both human and rat. Their molecular structure, pharmacologic profiles, tissue distribution, and signal transduction properties have been partially elucidated.

Current arterial prostheses. Experimental evaluation by implantation in the carotid and circumflex coronary arteries of the dog.

Five types of 4-mm diameter arterial prostheses (three Dacron, one expanded Teflon, one preserved umbilical vein) were studied in the dog to assess graft thrombogenicity. Separate experiments involving six hours of controlled blood flow, one-week carotid implantation, and aortocoronary implantation were performed. In general, graft thrombogenicity derived from controlled flow study was more predictive of a graft's long-term implantation success than were one-week implantation results. In order of increasing thrombogenicity, we ranked grafts studied as follows: noncrimped Dacron, expanded Teflon, crimped Dacron, umbilical vein. Results of 19 experimental left coronary artery implantations using Dacron or Teflon prostheses are reported that indicate grafts with low measured thrombogenicity are most likely to succeed in this site. Data presented in this report suggest there is reason to evaluate noncrimped, kink-resistant, porous Dacron grafts for use both in the left coronary artery and below the knee when there is compelling clinical indication and no autogenous vessels are available.

A structure-activity analysis of the cloned rat and human Y4 receptors for pancreatic polypeptide.

We cloned and expressed the rat Y4 receptor for pancreatic polypeptide (PP). Structure-activity profiles derived from 125I-PP binding assays and [cAMP] radioimmunoassays reveal a selective receptor interaction with rat PP vs. neuropeptide Y (NPY) or peptide YY (PYY). Rat and human Y4 receptor clones share 75% amino acid identity. Based on [cAMP] radioimmunoassay, the human Y4 receptor exhibits a less selective interaction with rat PP vs. NPY or PYY and a greater dependence on N-terminal PP residues, relative to rat Y4. Differences in sequence and structure-activity profiles suggest the rat be used with caution to model human Y4 receptor function.

Cloning and characterization of the human galanin GALR2 receptor.

We present the molecular cloning and characterization of the human galanin receptor, hGALR2. hGALR2 shares 85%, 39%, and 57% amino acid identities to rGALR2, hGALR1, and hGALR3, respectively. hGALR2, along with rGALR2, can be distinguished from the other cloned galanin receptors by a tolerance for both N-terminal extension and C-terminal deletion of galanin, as well as by a primary signaling mechanism involving phosphatidyl inositol hydrolysis and calcium mobilization. By RT-PCR, GALR2 mRNA was abundant in human hippocampus, hypothalamus, heart, kidney, liver, and small intestine. A weak GALR2 mRNA signal was detected in human retina, and no signal was detected in cerebral cortex, lung, spleen, stomach, or pituitary.

A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells.

Receptors with seven transmembrane domains (7TM) constitute a large family of structurally and functionally related proteins which respond to various types of ligands. We describe here the cloning and expression of a human 7TM receptor, denoted hFB22 (human Fetal Brain 22), which is the homologue (92% amino acid identity) of a bovine receptor (LCR1) reported by others to bind neuropeptide Y (NPY) with a pharmacological profile of the Y3 receptor subtype. However, upon expression in COS1 (confirmed by Northern analysis), COS7 or CHO-K1 cells, the hFB22 receptor did not confer specific 125I-Bolton-Hunter-NPY, 3H-propionyl-NPY or 125I-peptide YY (PYY) binding sites, in either intact cells or in membrane preparations. Similarly, cells transfected with the corresponding bovine clone (LCR1) did not show specific NPY/PYY binding exceeding that resulting from endogenous binding sites; mock-transfected COS7 cells, used frequently for heterologous expression of receptors, were found to have endogenous specific 125I-NPY binding sites (Bmax = 112 fmol/mg protein; Kd = 0.25 nM). Moreover, the hFB22 transfected cells, when compared to control transfected cells, did not display de novo NPY- or PYY-induced second messenger responses, i.e., (1) inhibition of forskolin-stimulated cAMP accumulation or (2) 45Ca2+ influx. The presence of hFB22 mRNA was detected in several human neuroblastoma cell lines, none of which was found to express Y3-like NPY binding sites. hFB22 displays 39% amino acid sequence identity (in the transmembrane regions) to the human interleukin-8 receptor, and 32-36% amino acid identity to the human receptors of angiotensin II, bradykinin, and n-formylpeptide, but only 23% amino acid identity to the previously described human NPY/PYY receptor of the Y1 receptor subtype. Our results show that hFB22 and LCR1 do not encode NPY receptors, and their true ligand(s) remains to be identified.

Molecular biology and pharmacology of multiple NPY Y5 receptor species homologs.

NPY is a 36-amino acid peptide which exerts its physiological effects through the activation of a family of G-protein coupled receptors. In vivo and in vitro characterization of the recently cloned rat Y5 receptor suggests that it is a primary mediator of NPY-induced feeding (Gerald et al., Nature 1996;382:168-171). We now report the molecular cloning and pharmacological characterization of the human, dog and mouse homologs of the Y5 receptor. With the exception of a 21 amino acid repeat in the amino terminus of the mouse Y5 receptor, the sequence of the four species homologs appear to be highly conserved, with 88% to 97% amino acid identities between any two species. Similarly, the pharmacological profiles of the four species homologs as determined in porcine 125I-PYY binding assays show a great deal of conservation, with the following rank order of affinity: human or porcine NPY, PYY, [Leu31,Pro34]NPY, NPY(2-36), human PP > human [D-Trp32]NPY > rat PP, C2-NPY. Northern blot analysis reveals that the Y5 receptor is widely distributed in the human brain, with the strongest signals detected in the cortex, putamen and caudate nucleus. The chromosomal localization of the human Y5 receptor, previously shown to be overlapping and in the opposite orientation to the Y1 receptor, is determined to be 4q31, the same locus as previously demonstrated for the human Y1 receptor (Herzog et al., J Biol Chem 1993;268:6703-6707), suggesting that these receptors may be coregulated. These Y5 species homologs along with corresponding animal models may be useful in the search for novel therapeutics in the treatment of obesity and related feeding disorders.

Intermittent naloxone attenuates the development of physical dependence on methadone in rhesus monkeys.

Rhesus monkeys that received 15 daily injections of methadone (2 mg/kg i.m.) exhibited a characteristic opiate withdrawal syndrome after injection of naloxone (0.5 mg/kg i.m.) on the 16th day. In comparison, injection of naloxone (0.5 mg/kg i.m.) once every 2 days during a similar 15 day methadone treatment period in these same monkeys significantly attenuated the severity of the opiate withdrawal syndrome exhibited after naloxone injection on the 16th day. Each naloxone administration during the 15 day methadone treatment period elicited an opiate withdrawal syndrome that did not significantly differ on each of the 7 days it was given and was less severe than the syndrome precipitated by naloxone following 15 days of methadone without intermittent naloxone. The lack of increments in the withdrawal response to the seven naloxone injections during the 15 days of methadone treatment and the attenuation of the withdrawal response to naloxone on day 16 after intermittent naloxone administration during the 15 day methadone treatment period support the hypothesis that naloxone modifies opiate receptor mechanisms so that they revert to an agonist-naive state following antagonist exposure. These findings suggest that various agonist and antagonist opiate drug combinations or mixed agonist-antagonist drug could be clinically useful in the management of situations where physical dependence on opiates is a problem.

The effects of a calcium deficient diet on the mechanical properties and morphology of goose bone.

A control group of geese (Anser anser) on a normal calcium diet for egg laying poultry was compared to egg laying geese on a calcium deficient diet. The ultimate compressive strength and modulus of elasticity of femoral cortical bone from each group were determined by compressing right circular cylinders which were 2.4 mm in height and 0.8 mm in diameter. The bending strength and bending modulus of elasticity of tibial cortical bone were determined by three point bend tests on rectangular prisms which were approximately 25 mm by 0.8 mm by 0.8 mm. Bone calcium content and eggshell calcium content were determined by atomic absorption spectrophotometry. Blood samples were analyzed for free calcium ion concentration. Histological observations included studies of cross-sectional microradiographs, examinations of cross sections stained by a modified Masson's technique, and a determination of fractional area of voids by quantitative microscopy. The average compressive modulus for the control birds was 12.0 GPa (S.D.: 6.2 GPa) while the ultimate compressive strength was 165 MPa (S.D.: 27 MPa). Calcium deprived birds showed slight, but not statistically significant, decreases in both the compressive modulus and compressive strength. The tibial three point bending modulus for the control birds was 16.5 GPa (S.D.: 2.6 GPa) while the ultimate bending strength was 256 MPa (S.D.: 58 MPa). Once again, slight though not statistically significant decreases in the bending modulus and strength were seen in the geese on the calcium deficient diet. The average calcium content (wt%) of the femora of the control birds was 20.5% (S.D.: 4.3%) and 20.6% (S.D.: 4.8%) for the tibiae. No significant differences were noted in the calcium deprived birds. The average fractional void area for the control bird femoral bone was 12.0% (S.D.: 2.6%) and 9.8% (S.D.: 1.8%) for the tibial bone. Significantly greater fractional void areas were noted in the calcium deficient birds as were profound changes in the macrocellular structure of these bones.

Clinically significant gastroesophageal reflux in the at-risk premature neonate: relation to cognitive scores, days in the NICU, and total hospital charges.

OBJECTIVE: The principal objective of this retrospective, cohort study was to determine if clinically significant gastroesophageal reflux (GER) would impair the long-term cognitive and motor development of preterm infants. An additional objective was to determine the effects of clinically significant GER on the length of hospital stay and total hospital charges in preterm infants. STUDY DESIGN: The design was a retrospective, cohort study of 66 preterm infants, followed in the Neonatal Developmental Follow-Up Clinic of The Children's Hospital in Greenville, SC. Thirty-three premature infants with clinically significant GER met the following study criteria: birth dates, 1988 through 1994; lack of gastrointestinal anatomic defects; and lack of acute neurologic injury (defined as no intraventricular hemorrhage greater than Papile's grade I, no periventricular leukomalacia, no seizures, and no history of birth asphyxia). Clinically significant GER was defined as GER associated with moderate to severe apnea (n=29) or GER associated with moderate to severe feeding intolerance (n=4). The study patients were matched as closely as possible with 33 control premature infants for sex (except when twins were used), ethnicity, social risk, gestational age, birth weight, and Apgar scores at 1 and 5 minutes. Social risk was categorized using Hack's Social Risk Scale. Important covariates included apnea, home monitoring, and nasal continuous positive airway pressure. RESULTS: Neurodevelopmental test scores from 7 months of age through 2 years of age did not show any significant differences between premature infants with clinically significant GER and premature infants with no evidence of clinically significant GER. Total hospital charges were statistically different for the clinically significant GER infants and the nonclinically significant GER infants (median $112,916 versus median $63,928, p=0.01). Total neonatal intensive care unit length of stay measures were statistically different between the two groups (median 53 days versus median 40.5 days, p=0.01). CONCLUSION: Even though clinically significant GER may pose a substantial medical risk in premature infants, the long-term cognitive consequences appear to be negligible. Nevertheless, those premature infants with clinically significant GER do consume significantly more hospital resources than matched controls. Early diagnosis and intervention may possibly lessen the impact of medical costs and reduce length of hospital stay.

Experience with the bipolar prosthesis in hip arthroplasty. A clinical study.

Hip arthroplasty using a bipolar prosthesis was performed in 73 patients (75 hips) with femoral neck fracture, osteoarthritis, rheumatoid arthritis, or degenerative arthritis. Bipolar hip arthroplasty is more conservative than conventional total hip arthroplasty, because methyl methacrylate usually is not needed to fix the bipolar prosthesis to bone. Overall results were 67.1% good to excellent, 20.5% fair, and 12.3% poor; among the arthritic patients, the results were 72.9% good to excellent, 19.1% fair, and 8.5% poor. Complications included one deep wound infection and one arterial embolus; no dislocations occurred.

Impact of duration of rupture of membranes on outcomes of premature infants.

OBJECTIVE: The primary aim of the study was to determine how the risk of adverse outcomes was related to the duration of the latency period and gestational age at birth following preterm premature rupture of the fetal membranes (PPROM). STUDY DESIGN: Retrospective review of infants discharged from 330 neonatal intensive care units. We defined four subgroups based on gestational age: 23 to 25, 26 to 28, 29 to 31 and 32 to 34 weeks. Each gestational age group was evaluated by duration of ROM: <24 h, 1 to 7 days, 8 to 14 days, 15 to 21 days, 21 to 28 days and >28 days and compared with a referent group (PPROM of >24 h but <7 days). RESULT: In all, 239 808 non-anomalous infants 23 to 34 weeks' gestational age were identified; 37 233 (15.5%) had rupture of membranes (ROM) >24 h. Compared with a reference group (PPROM of >24 h but <7 days), the risk of mortality for PPROM of 8 to 14, 15 to 21 and 21 to 28 days varied depending on gestational age at birth. Only PPROM >28 days was consistently associated with increased mortality and decreased likelihood of survival without morbidity in all gestational age subgroups. CONCLUSION: PPROM for >28 days is associated with an increased risk of death and morbidity.

Elevation in plasma creatinine and renal failure in premature neonates without major anomalies: terminology, occurrence and factors associated with increased risk.

OBJECTIVE: The goal of this study was to describe the changes in plasma creatinine levels that occur in prematurely born neonates, to better understand the use of the terms 'renal dysfunction' and 'renal failure' among premature neonates, as well as to evaluate the demographic and outcome characteristics associated with renal problems in preterm neonates who have no major congenital anomalies. STUDY DESIGN: Retrospective review of the Pediatrix neonatal intensive care patient clinical data warehouse. RESULT: The study cohort consisted of neonates born with an estimated gestational age of ≤ 30 completed weeks in whom there was no report of any major anomalies (n=66,526). In this group of 66,526 neonates, there were 64,030 (96.2%) with no report of renal dysfunction or failure, 1239 (1.9%) in whom there was a diagnosis of renal dysfunction and 1257 infants (1.9%) with a diagnosis of renal failure. The clinical circumstances most strongly associated with a diagnosis of renal dysfunction and/or renal failures were low gestational age and birth weight. In addition, multivariate analysis showed that the factors associated with an increased risk of renal problems were vasopressor use during the first 7 days after birth, grade 3 or 4 intraventricular hemorrhage, a patent ductus arteriosus, necrotizing enterocolitis, male gender, the use of indomethacin, a positive blood culture during the first 7 days after birth, the use of high-frequency ventilation in the first 2 days after birth, non-White race and prolonged exposure to antibiotics. Mortality was higher in patients with renal problems than in neonates without renal problems (39.1 vs 10.2%, P<0.01) and higher in neonates with renal failure than in neonates with renal dysfunction (57.6 vs 20.1%, P<0.01). CONCLUSION: Renal dysfunction and/or failure are common diagnoses, especially in extremely premature neonates and there are potentially modifiable factors that increase the risk of renal problems.