Serum and urine acute kidney injury biomarkers in asphyxiated neonates

Background

We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates.

Methods

AKI biomarkers were measured in 13 asphyxiated neonates born at ≥36?weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥1.5?mg/dl for >24?h or rising values >0.3?mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10.

Results

Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia–no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1.

Conclusions

sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.     

Longitudinal patterns of urine biomarkers in infants across gestational ages

Background

Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age.

Methods

Fifty-two infants ranging from 24 to 41 weeks’ GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD).

Results

Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m² with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p?=?0.002. When factored by urine creatinine CysC/cr?+?ALB/cr were the most significant functional markers with AUC?=?0.79; p?=?0.004; sensitivity 96 %; specificity 58 %.

Conclusions

Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.

     

Impact of varicocelectomy on urine dopamine value in patients with premature ejaculation and varicocele

Dopamine is an important regulator of male sexual function and behaviour. Decreased levels of this substance have been observed in blood and seminal plasma of infertile men. Hence, this study was carried out to determine the impact of varicocelectomy on 24‐hr urine dopamine values in patients with both premature ejaculation (PE) and varicocele. In this prospective study, 55 consecutive patients with premature ejaculation and grade 2 or 3 varicocele were enrolled. The urine dopamine level was measured in a 24‐hr sample by HPLC method in a single laboratory centre. Two samples were gathered from each patient, one before and the other 1 month after varicocelectomy. The mean initial and final 24‐hr urine dopamine levels were 259.6 ± 86.3 and 602.9 ± 88.4 micrograms, respectively, showing statistically significant increase (p = .0001), while there was no statistically significant difference between urine volume and creatinine. However, the change in intravaginal ejaculation latency time value was not statistically significant at this short time visit. According to our findings, varicocelectomy results in a significant increase in 24‐hr urine dopamine levels in patients with premature ejaculation and varicocele. However, the effect of this change on premature ejaculation in the long term has yet to be determined.     

Serum cystatin C during 30 postnatal days is dependent on the postconceptional age in neonates

Background

Cystatin C (CysC) is a promising endogenous marker for renal function. However, the reference serum CysC level is not sufficiently studied in neonates. This study was conducted to investigate the reference level of serum CysC for neonates, including very low birth weight infants according to the postconceptional age (PCA).

Methods

Serum CysC levels were measured in 883 blood samples (246 neonates including 127 premature infants). Infants with symptoms or signs of acute kidney injury, systemic illness, congenital anomaly, or renal pathology were excluded. CysC levels were analyzed for association between subgroups dichotomized by postnatal age and PCA.

Results

Reference ranges of serum CysC were determined and a decreasing trend of CysC levels was observed as PCA increased, except for the first 3 postnatal days. CysC levels were negatively correlated with gestational age at birth, and PCA (P?<?0.001), while positively correlated with postnatal age and serum creatinine (P?<?0.001).

Conclusion

The reference level of serum CysC was determined according to postnatal age and PCA. As the reference CysC level was dependent on gestational age and PCA, consideration of these parameters is warranted when assessing CysC levels in neonates.     

Magnesium homeostasis in premature and full-term neonates

Renal handling of magnesium (Mg) has not been comprehensively studied in the newborn period due to the difficulty, until recently, of measuring the diffusible fraction of plasma Mg (UfMg). In the present study this methodology was used to assess Mg homeostasis in 84 newborn infants of different postconceptional age (26–42 weeks), weight (720–4,830 g) and postnatal age (1–72 days). Very premature infants (postconceptional age less than 35 weeks) had significantly higher values of plasma Mg than mature newborn infants. Plasma Mg related inversely to postconceptional age, weight, plasma total protein and plasma calcium, and directly to plasma potassium. Stepwise multiple regression analysis revealed that postconceptional age was the unique factor contributing to variations in plasma Mg. Plasma values of UfMg were the same in preterm as in term infants but, when expressed as a fraction of total plasma Mg (UfMg/Mg), they were significantly lower in very preterm infants. Fractional excretion of Mg and the ratio of urine Mg to urine creatinine did not vary as a function of postconceptional age. These results indicate that plasma UfMg is kept constant at different gestational ages despite variations in total plasma Mg; furthermore, no functional immaturity is present for renal tubular reabsorption of Mg, even in very low birth weight infants.     

Predictors of postnatal outcome in neonates with gastroschisis

Background/Purpose

The optimal management of neonates with gastroschisis is unclear, and there is a significant morbidity. We performed a review of neonates with gastroschisis treated at our center of pediatric surgery over the last 21 years to determine predictive factors of outcome.

Methods

Single-center retrospective analysis of 79 neonates with gastroschisis (1989-2009) was done. Length of hospital stay (LOS), days of parenteral nutrition (PN), and survival were outcome measures. Univariate and multiple regression analyses were used.

Results

Overall survival was 92%, and primary closure was achieved in 80%. Median LOS was 25 days, and median duration on PN, 17 days. Intestinal atresia, closed gastroschisis, secondary closure, and sepsis were the primary variables associated with poor outcome independent of other variables, but prematurity also affected outcome. Route of delivery and associated malformations were not related to poorer outcome. Necrotizing enterocolitis did not occur in any of our patients.

Conclusion

Outcome in our patients was favorable as measured by survival, LOS, and days on PN. Primary predictors of poor outcome were factors related to short bowel syndrome and secondary closure, indicating a need to further improve treatment of short bowel syndrome.     

Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates

The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates. J Pediatr Surg 38:251-253.     

中老年人群尿白蛋白与肌酐比值的性别差异研究

尿自蛋白排出量是诊断糖尿病肾病最重要的指标，为了采取标本方便，采用次尿（即晨尿或随机一次尿）测定尿白蛋白与肌酐比值（ACR）来判断其排出量。2005年IDF全球指南和亚太地区IDF指南均提出男女之间有差别的ACR标准，分别为男性≥2．5mg／mmol（22mg／g），女性≥3．5mg／mmol（31mg／g）。我国人群ACR的性别特异性切点的研究目前尚无报道。我们比较了非糖尿病人群ACR测定的结果，为修改我国目前采用的2005年微量白蛋白尿（MAU）诊断标准ACR切点提供数据。     

The effect of dopamine on glomerular filtration rate in normotensive,oliguric premature neonates

We examined the effect of dopamine on glomerular filtration rate (GFR) at infusion rates of 0.5, 2.5, and 7.5 micro g/kg per min in 15 premature neonates. Study infants (mean gestational age 34+/-2 weeks, mean birth weight 2.43+/-0.6 kg) had respiratory distress, were normotensive, and had a low urine output (0.9+/-0.1 ml/kg per hour). GFR was determined by the plasma clearance of inulin after a single bolus injection (200 mg/kg). Four hours after inulin administration, dopamine infusion was begun and continued over 6 h. GFR was estimated before and after beginning the dopamine infusions from the slope of the log of plasma inulin concentration versus time. Gestational age, weight, and baseline GFR were similar in all three groups. With a dopamine infusion rate of 0.5 micro g/kg per min there were no changes in GFR, urine output, heart rate, or blood pressure. At an infusion rate of 7.5 micro g/kg per min there was no change in GFR, although urine output, heart rate, and blood pressure all increased. At 2.5 micro g/kg per min there were significant increases in GFR and urine output, with no changes in blood pressure or heart rate. In oliguric, non-hypotensive neonates, GFR increased significantly at 2.5 micro g/kg per min of dopamine. This probably reflects the effects of afferent vasodilatation and may be important clinically when enhancement of GFR is the major treatment objective.     

结石类型与年龄、性别的相关性研究

目的:对结石成分进行定量分析,探讨结石类型与患者人口学特征、基础疾病等因素的关系。方法:回顾性分析336例泌尿系结石患者,根据结石类型分为单纯草酸钙结石组、草酸钙混合结石组、磷酸钙混合结石组、尿酸结石组、磷酸铵镁结石组、其他成分组。比较不同组间患者年龄、性别、BMI、基础疾病的差异。对单因素分析中P<0.20的影响因素进行多分类Logistic回归分析。结果:所有结石患者中,上尿路结石322例,依次为单纯草酸钙结石(53.1%)、草酸钙混合结石(26.7%)、磷酸钙混合结石(10.9%)、尿酸结石(6.5%)、磷酸铵镁结石(2.2%)、其他结石(0.6%)。单因素分析结果显示,不同组间患者的性别、年龄差异有统计学意义(P<0.05),不同组间患者的BMI、基础疾病差异无统计学意义(P>0.05)。多因素分析结果显示,与老年患者相比,青年患者草酸钙混合结石、磷酸钙混合结石和尿酸结石的优势比(OR)分别为2.47、20.74和0.20(P<0.05);中年患者草酸钙混合结石和磷酸钙混合结石的OR值分别为2.31和7.70(P<0.05)。与男性患者相比,女性患者磷酸钙混合结石和磷酸铵镁结石的OR值分别为5.20和6.74(P<0.05)。结论:不同结石类型的患者具有不同的人口学特征,在年龄和性别上均有明显差异。     

Clinical features and treatment outcome of intussusception in premature neonates

Background/Purpose: Less than 1.3% of all cases of intussusception occur in term neonates. Intussusception in premature neonates (IPN) is exceedingly rare. Its rarity and difficulty to differentiate IPN from common neonatal diseases like necrotizing enterocolitis (NEC) often delays its diagnosis. The authors set out to characterize diagnosis, treatment, and outcome of this rare condition.Methods: The authors analyzed 2 new cases of IPN and 33 previously reported cases from the literature.Results: The 35 patients with IPN had an average gestational age, postconceptual age at diagnosis, and birth weight of 28.4 ± 0.6 weeks (all data, mean ± SEM), 31.1 ± 0.5 weeks, and 1,165 ± 21 g, respectively. Gastrointestinal symptoms first presented at age 8 ± 1 days. A preoperative diagnosis of NEC was assumed in 24 patients, delaying diagnosis by 10 ± 2 days. Intussusception was diagnosed radiographically in 2 patients (1 contrast enema and 1 ultrasound scan) and during surgery or autopsy in the remainder. Resection was reported in 28 patients for bowel that was irreducible, necrotic, or perforated. The overall mortality rate was 20%, mainly owing to sepsis.Conclusions: Intussusception in the premature neonate often is misdiagnosed as NEC, delaying operative intervention. Contrast enema has limited diagnostic capability. Early diagnosis may be achieved with use of ultrasound scan. Intussusception can be treated successfully with resection and primary anastomosis, achieving good results.     

Impact of erectile function and age in men with lower urinary tract symptoms on ejaculatory dysfunction and premature ejaculation

Lower urinary tract symptoms (LUTSs) and ED are clearly correlated, but to date no correlation with ejaculatory dysfunction (EjD) has been identified. Therefore, this study evaluated the impact of erectile function in men with LUTS on EjD and premature ejaculation (PE). Erectile function, PE and EjD of 239 men (mean age, 53.0 ± 10.65 years), International Prostate Symptom Score (IPSS), International Index of Erection Function (IIEF), intravaginal ejaculatory latency time (IELT) and the seven-item Male Sexual Health questionnaire (MSHQ)-EjD were used to compare with the degree of LUTS. Ages were divided into five groups (<40, 40-49, 50-59, 60-69 and >70 years). The IPSS categorized patients into three symptom groups: mild, 1-7; moderate, 8-19; and severe, >19. ED was classified into five categories based on IIEF-EF scores: severe (0-6), moderate (7-12), mild-to-moderate (13-18), mild (19-24) and normal (25-30). The correlations among age, IIEF-EF, IELT and the MSHQ-EjD domain were studied through regression and cross-tabulation analyses. The results revealed that aging significantly affected each item of the MSHQ-EjD (P<0.05). The IIEF-EF domain was also correlated with each question on the MSHQ-EjD (P<0.05). PE (IELT <1 min) increased in incidence as patients got older but was not linked to IIEF-EF (P>0.05). These results indicate that EjD is closely related to age and erectile function, and that PE is closely related to age, although PE is not related to erectile function.     

Heart rate variability in premature neonates pre- and postmethylxanthine administration

Methylxanthines are used to treat or prevent respiratory failure (apnoea) in premature infants both perinatally and perioperatively. Heart rate variability (HRV) is being increasingly used to measure autonomic function. In this study various indices of HRV were compared pre- and postmethylxanthine dosing in 22 infants (aged 24–36 weeks). HRV significantly increased postdosing, particularly in the high frequency (HF) band ( P =0.001 by ANOVA). This increase was more pronounced in the sickest infants. This pattern of increased HRV and %HF is the same that occurs with normal maturation. This suggests that methylxanthine may stimulate and normalize autonomic function.     

The interplay between drugs and the kidney in premature neonates

The kidney plays a central role in the clearance of drugs. However, renal drug handling entails more than glomerular filtration and includes tubular excretion and reabsorption, and intracellular metabolization by cellular enzyme systems, such as the Cytochrome P450 isoenzymes. All these processes show maturation from birth onwards, which is one of the reasons why drug dosing in children is not simply similar to dosing in small adults. As kidney development normally finishes around the 36th week of gestation, being born prematurely will result in even more immature renal drug handling. Environmental effects, such as extra-uterine growth restriction, sepsis, asphyxia, or drug treatments like caffeine, aminoglycosides, or non-steroidal anti-inflammatory drugs, may further hamper drug handling in the kidney. Dosing in preterm neonates is therefore dependent on many factors that need to be taken into account. Drug treatment may significantly hamper postnatal kidney development in preterm neonates, just like renal immaturity has an impact on drug handling. The restricted kidney development results in a lower number of nephrons that may have several long-term sequelae, such as hypertension, albuminuria, and renal failure. This review focuses on the interplay between drugs and the kidney in premature neonates.     

Early awakening and extubation with remifentanil in ventilated premature neonates

BACKGROUND: Morphine is one of the most commonly used drugs for sedation and analgesia during mechanical ventilation, but its pharmacological profile has limitations, such as prolonged duration of action, especially in premature neonates. Because of its very short context-sensitive half-time, remifentanil has rapid onset and quickly decreases in plasma concentration after interrupting administration. The aim of the present study was to compare a continuous infusion of remifentanil and morphine during mechanical ventilation of premature neonates with respiratory distress syndrome (RDS). METHODS: Twenty premature neonates (28-34 weeks) with RDS were randomized in a prospective double-blinded study to receive either a continuous infusion of morphine (n = 10) or remifentanil (n = 10) for mechanical ventilation. The length of time to awaken and extubate the neonate after interrupting opioid administration was recorded. We also recorded stress (COMFORT scale), pain response [Neonatal Infant Pain Scale (NIPS)], hemodynamic and ventilatory variables as well as adverse effects secondary to infusion of the specific opioid. RESULTS: After terminating infusion, the length of time required to awaken and extubate the neonates was 18.9- and 12.1-fold longer, respectively, in the morphine group than in the remifentanil group. Both groups produced good quality sedation and analgesia as evaluated by the NIPS and COMFORT scores. No major side effects were observed. CONCLUSIONS: Our results show an interesting potential for the use of remifentanil in premature neonates. Remifentanil allowed an adequate level of sedation and analgesia as well as rapid recovery after discontinuation. However, further properly designed clinical trials are needed before it can be generally recommended.