Acute kidney injury in preterm infants with necrotizing enterocolitis.

Purpose: Acute kidney injury (AKI) is an independent predictor of morbidity and mortality in critically ill infants and children. AKI develops in an estimated one-third of the neonatal intensive care unit (NICU) population; however, literature on the incidence of AKI in premature infants with a diagnosis of necrotizing enterocolitis (NEC) is limited. The objectives of this study were to describe the incidence of AKI in infants with radiographically confirmed NEC, assess these infants for independent risk factors associated with development of AKI and evaluate if the presence of AKI is associated with increased mortality. Study design: We conducted a retrospective chart review of premature infants, gestational age (GA) 23-34 weeks, who developed modified Bell's level 2 or 3 NEC while admitted to two tertiary NICUs within our health system between 2010 and 2015. AKI was defined and staged according to modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results: 77 infants with Bell's level II (63.6%) and III (36.4%) NEC were studied. AKI occurred in 42.9% of infants (Stage 1: 18.2%; Stage 2: 13%; Stage 3: 11.7%). Bell's Stage III NEC, lower GA, maternal preeclampsia/eclampsia, gentamicin/vancomycin exposure, and empiric antibiotic use were independently associated with AKI. AKI was strongly associated with mortality (HR 20.3 95%CI 2.5-162.8, p = .005) in an adjusted Cox model. Conclusions: AKI is common in premature infants who develop NEC. More severe NEC was found to be an independent risk factor for AKI. Additionally, AKI in infants with NEC increases mortality risk significantly.

Neonatal acute kidney injury: recording rate, course, and outcome: one center experience.

Background: Neonates, and particularly preterm newborns, are at increased risk for acute kidney injury (AKI) due to immature kidney function. While specific criteria have been defined for AKI in this particular population, this diagnosis is frequently overlooked, and consequently, is often not recorded in patients' medical files. AKI-associated short- and long-term morbidity and mortality underline the importance of this diagnosis Objective: To assess the recording rate of AKI in the neonatal intensive care unit (NICU), and to identify clinical features that may promote awareness to this condition. Study design: The database of one medical center was searched for serum creatinine values above 1 mg% among all the newborns (more than 48 hours old) who were hospitalized in the neonatal intensive care unit (NICU) during the years 2010-2015, and who underwent at least two blood tests during their hospitalization. The files of patients who met acute kidney injury (AKI) diagnostic criteria were searched for AKI diagnosis, maternal, fetal, and postnatal course and outcome. Results: Of 59 newborns who met AKI criteria, 51 (86%) were preterm and 8 term newborns. The respective mean gestational weeks at birth were: 28 ± 3 and 38.5 ± 1, and mean birth weights: 1002 ± 57 and 3157 ± 375 grams. Mortality rates were 14/51 (27%) versus 1/8 (12.5%). Of the 44 survivors, AKI was recorded in the medical files of 9/37 (24%) preterm versus 5/7 (71%) term-newborns. AKI associated with twin pregnancy in preterm neonates: 22 (43%) versus 1 (12.5%) in term-newborn. Unexpected high frequencies of maternal obstetrical problems and cesarean section delivery: 62.5 and 78%, respectively, along with persistently depressed 5-min Apgar 6.6 ± 3.5 were found in term newborns with AKI. Congenital anomalies of the urinary tract (CAKUT) were suspected prenatally on fetal ultrasound in 3 (6%) and 1 (12.5%) of the respective groups, a 10-fold higher rate than that observed in the general population. AKI recurred in 18 (35%) of the preterm and none of the term neonates. Mild AKI episodes (Stage 1-2) occurred in 30/37 (81%) by contrast to severe events (Stage 3) in 4/7 (57%) preterm and term survivors, respectively. Ventilation duration associated significantly with AKI recurrence, and sepsis with mortality: OR 1.25 (95%CI = 1.09-1.43) (p < .001) and OR = 4.65 (95%CI = 1.26-17.2) (p = .014), respectively. Conclusions: We demonstrated underreporting of AKI, particularly among preterm newborns, a population at high risk of developing recurrent episodes. Our data suggest different clinical profiles of AKI among preterm and term neonates: with later onset, milder but recurrent episodes in the former. Increased alertness for AKI diagnosis is needed for neonates with prolonged respiratory support, treated with diuretics and after sepsis. Newborns suspected of CAKUT (Congenital Anomalies of Kidneys and Urinary Tract) as per fetal ultrasound might need closer observation for AKI occurrence.

Antenatal nephromegaly and propionic acidemia: a case report.

BACKGROUND: Propionic acidemia (PA) is a rare but severe recessive autosomal disease, presenting with non specific signs in the first years of life. Prenatal diagnosis is invasive (amniocentesis) and limited to suspect cases. No screening test has been described, in particular no correlations between prenatal sonography and PA have been documented so far. CASE PRESENTATION: We report the case of a boy with fetal bilateral nephromegaly and hyperechogenic kidneys, along with neonatal acute kidney injury; no etiology could be found in the first months of life. At 3 months of life, he presented with tachypnea and altered mental status, which lead to the diagnosis of PA. The renal ultrasound at 8 months of life, after a symptomatic treatment of PA had been initiated, showed a regression of the renal abnormalities. CONCLUSION: This case describes PA as a novel cause of large and hyperechogenic kidneys in the antenatal period. It suggests that, when confronted to fetal nephromegaly, hyperechogenic kidneys and risk factors of metabolic disease such as consanguineous parents, PA should be considered, and a prenatal test should be proposed.

[Acute Kidney Failure Due to Urachal Cyst?] / Akutes Nierenversagen bei Urachuszyste?

A 34-year-old para V woman was referred to our centre at 35+1 weeks of gestation for an assumed fetal malformation with prenatal renal impairment and anhydramnios. Prenatal ultrasound demonstrated unilateral renal agenesis; the bladder was not detectable. The baby was born by caesarian section at 36+2 weeks of gestation because of placental insufficiency. Postnatal adaptation was uneventful, but the newborn presented external stigmas of trisomy 21 and progressive renal impairment with anuria. Nevertheless, the postnatal ultrasound showed two enlarged kidneys in loco typico with impaired perfusion but without signs of malformations. In the lower abdomen, a rosette-shaped structure of unknown origin was noted. Its origin could not be cleared by imaging including voiding cystourethrography and colon contrast radiography. Explorative laparotomy identified the structure as a persistent urachal cyst with secondary obstruction of the upper urinary tract. After removal of the urachus with reconstruction of the bladder dome, renal function recovered completely while urine was drained continuously via suprapubic catheter. A voiding cystourethrogram 3 weeks later showed a posterior urethral valve as an additional unexpected diagnosis. The valve was slit at the age of 6 months without complications, the renal function remained stable in the further course. In retrospect, the main cause for the renal failure remains unclear. It appears to be the obstruction due to the space-consuming character of the urachal cyst, especially because the megacystis typically associated with urethral valve was not viewable. Alternatively, the additional proximal stenosis may have only masked the typical findings of PUV.

Renal outcome in children born preterm with neonatal acute renal failure: IRENEO-a prospective controlled study.

OBJECTIVES: Acute kidney injury (AKI) is a severe complication of prematurity, with currently unknown consequences for renal function in childhood. The objective of this study was to search for signs of reduced nephron number in children aged 3-10 years who had been born preterm with neonatal AKI and compare this group to control children. METHODS: IRENEO was a prospective, controlled study conducted in 2013 in Nantes University Hospital. Children who were born at less than 33 weeks gestational age (GA) and included in the LIFT cohort were eligible for entry. Twenty-five children with AKI (AKI-C) and 49 no-AKI children were matched on a propensity score of neonatal AKI and age. AKI was defined as a serum creatinine level higher than critical values: 1.6 mg/dl (GA 24-27 weeks), 1.1 mg/dl (28-29) and 1 mg/dl (GA 30-32). Renal function was evaluated during childhood. RESULTS: Mean age of the children at the time of the study was 6.6 years. No difference in microalbuminuria, estimated glomerular filtration rate (GFR) or pulse wave velocity was observed between the two groups. Renal volume was lower in the AKI-C group (57 vs. 68; p = 0.04). In the entire cohort, 10.8 % had a microalbuminuria, and 23 % had a diminished GFR (median 79 ml/min/1.73 m2). The GFR was lower in children with very low birth weight of <1000 g (99 vs. 107 ml/min/1.73 m2; p = 0.04). CONCLUSION: In children born preterm, neonatal AKI does not seem to influence renal function. However, independent ofAKI, a large proportion of very preterm infants, especially those with very low birth weight, presented with signs of nephron reduction, thus requiring follow-up with a nephrologist.

Effects of Maternal Exposure to Cadmium Oxide Nanoparticles During Pregnancy on Maternal and Offspring Kidney Injury Markers Using a Murine Model.

Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 µg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations.

Rapid and sustained recovery of renal function with transient placement of an intrauretral nephrostomy catheter in an infant with ureteropelvic junction obstruction and acute renal failure.

Ureteropelvic junction obstruction (UPJO) is a common, congenital urinary malformation in the pediatric age group. In most cases the diagnosis is made antenataly and resolves spontaneously. Postnatal diagnosis is made when symptoms of urinary tract infection or abdominal pain occur. We report a six-month-old girl with single kidney and known vesicoureteral reflux grade IV presenting with severe acute renal failure (ARF), requiring acute peritoneal dialysis (PD).After diagnosis of decompensated UPJO, a nephrostomy was performed, and renal function restored within seven days. UPJO was subsequently treated by open pyeloplasty. To our knowledge, this is the first case of UPJO requiring PD due to severe renal failure in a child. Children with UPJO and major morbidity of the contralateral kidney are at risk of renal failure and should therefore be followed carefully to prevent serious complications.

Nephrotoxic medication exposure in very low birth weight infants.

OBJECTIVE: To quantify exposure to potentially nephrotoxic medications among very low birth weight (VLBW) infants and determine the relationship of nephrotoxic medication exposure to acute kidney injury (AKI) in this vulnerable population. METHODS: We reviewed 107 VLBW infants who survived to discharge from April 2011 to March 2012 and measured exposure to the following nephrotoxic medications: acyclovir, amikacin, amphotericin B, gentamicin, ibuprofen, indomethacin, iohexol, tobramycin and vancomycin. Acute kidney injury was determined by the KDIGO guidelines. RESULTS: Exposure to ≥ 1 nephrotoxic medication occurred in 87% of infants. The most common exposures were gentamicin (86%), indomethacin (43%) and vancomycin (25%). There was an inverse linear relationship between birth weight and nephrotoxic medications received per day (R(2) = 0.169, p < 0.001). Infants with AKI received more nephrotoxic medications per day than those who did not (0.24 versus 0.15; p = 0.003). CONCLUSIONS: VLBW infants are frequently exposed to nephrotoxic medications, receiving approximately two weeks of nephrotoxic medications before discharge or 1 for every 6 d of hospitalization. The greatest exposure occurred among the smallest, most immature infants and those who experienced AKI.

Can peritoneal dialysis be used in preterm infants with congenital diaphragmatic hernia?

Peritoneal dialysis (PD) is considered as the most common form of renal replacement therapy for newborns including preterms with acute kidney injury (AKI). Although there are several reports describing successful PD performed for AKI in preterm infants, there is no data describing the use of PD to treat AKI in preterm newborns with congenital diaphragmatic hernia (CDH), which is one of the contraindications for PD. We present a preterm newborn with CDH, truncus arteriosus and AKI treated with PD and emphasize that PD may be successfully performed with caution even in cases of contraindications when other renal replacement therapies cannot be used.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) and netrin-1: are they effectively improving the clinical management of sepsis-induced acute kidney injury (AKI)?

Neutrophil gelatinase-associated lipocalin (NGAL) and Netrin-1 have been proposed over the past years as emergent biomarkers for the early and accurate diagnosis and monitoring of acute kidney injury (AKI). During the early phases of AKI, a rapid and massive up-regulation of NGAL mRNA takes place in the thick ascending limb of Henle's loop and in the collecting ducts, and therefore, changes in urinary NGAL (uNGAL) excretion seem to be more specific than plasma NGAL in assessing early kidney injury. The availability of a new automated immunoassay for measuring uNGAL facilitates its introduction in the clinical routine, especially in an emergency setting. However, in critically ill newborns AKI often develops during sepsis, which in turn induces an up-regulation of NGAL mRNA in neutrophils. To improve the effectiveness of therapeutic treatment in septic newborns with AKI, there is the need to accurately distinguish NGAL molecular forms originating within the distal nephron from those originating from neutrophils. This concise review summarizes properties and perspectives of uNGAL and Netrin-1 for their appropriate clinical utilization.

Acute kidney injury in critically ill infants: the role of urine Neutrophil Gelatinase-Associated Lipocalin (NGAL).

Acute kidney injury (AKI) has emerged as an important health problem in the intensive care units, especially among infants delivered prematurely. Recent efforts to define and characterize AKI have led to studies of early AKI detection and will ultimately contribute to improvements in AKI outcomes. The discovery of biomarkers for AKI that might enable early recognition and clinical intervention to limit renal injury is therefore of intense contemporary interest. Neutrophil gelatinase-associated lipocalin (NGAL) is the most promising among all emerging markers for AKI; specifically, urine NGAL (uNGAL) predicts renal failure much earlier than serum creatinine. The recent availability of an automated immunoassay for measuring uNGAL in the clinical practice permits to introduce the test in emergency, having a turn around time (TAT) closely comparable with that of serum creatinine. On the basis of data reported in the literature, it is reasonable to forecast an increasing clinical use of uNGAL capable to change our approach to the diagnosis and leading to better preventative and therapeutic interventions which will improve outcomes of critically ill infants with acute kidney disease.

Renal agenesis in an alpaca cria.

A 4-day-old alpaca cria presented for inappetence that responded to symptomatic treatment. The cria re-presented with acute signs of inappetence and azotaemia. The azotaemia persisted despite intravenous fluid therapy. There was no right kidney on ultrasound and there appeared to be perirenal oedema around the left kidney. A diagnosis of right renal agenesis and acute renal failure of the left kidney was made. The cria failed to improve and was euthanased. Necropsy examination confirmed right renal agenesis and agenesis of the right ureter and right renal artery. A section of left kidney submitted for histological examination revealed diffuse, acute, marked tubular degeneration and nephrosis. The cause of the renal failure in the left kidney was not determined.

Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist.

Fetal and neonatal toxic effects of angiotensin II receptor antagonists have been described in animals and humans. Five cases of fetal or neonatal deaths have been reported following maternal use of sartans for hypertension. We report a case of neonatal transient renal failure following telmisartan therapy during pregnancy. This class of antihypertensive drugs should be avoided during pregnancy and breastfeeding.

Renal aspects of the term and preterm infant: a selective update.

This review discusses new aspects of normal and abnormal renal development that expand insight into the adaptation of the neonatal kidneys to the stress of extrauterine life. Highlighted are some pitfalls in measuring glomerular filtration rate in the neonate mainly caused by postnatal fluctuations in serum creatinine levels. Serum creatinine levels are correlated with the authors' recent finding of tubular reabsorption of creatinine in the immature neonatal kidney. Renal maldevelopment in premature and small-for-date babies has been shown related to serious medical problems in adult life, including hypertension. This finding presents the pediatrician with a new role in the time-honored vocation of preventing disease. Mutations in several genes may be responsible for most cases of congenital or hereditary renal aberrations. Two renal disorders, congenital nephrotic syndrome and neonatal acute renal failure, and one form of treatment modality of newborn infants, renal replacement therapy, are discussed in detail. These conditions are rare in general pediatric practice, but they illustrate some of the new developments in the renal care of the newborn. A word of caution is offered about the use of nonsteroidal anti-inflammatory drugs during pregnancy and the newborn period. All nonsteroidal anti-inflammatory drugs administered indirectly to the unborn fetus and directly to the young newborn impair renal structure (fetus) and function (both fetus and newborn). The new data have been obtained with genetic and molecular biology techniques and with established methods of developmental renal physiology. A better understanding of the pathogenesis of neonatal renal disorders will result in new diagnostic procedures and improved preventive and therapeutic possibilities relevant to the neonate with a renal disorder.

Acute renal failure in a neonate caused by the transplacental transfer of a nephrotoxic paraprotein: successful resolution by exchange transfusion.

Acute renal failure was diagnosed within 6 days of birth in a full-term neonate. The mother was known to have a monoclonal gammopathy, immunoglobulin G (IgG) lambda, discovered a year before pregnancy on being investigated for hematuria and proteinuria. Her renal function was intact. Maternal renal biopsy performed at the time showed a focal proliferative glomerulonephritis with nonfibrillary homogeneous mesangial and intramembranous electron-dense deposits. Immunoperoxidase staining was positive for IgG and lambda and kappa light chains along the glomerular and tubular basement membranes. Pregnancy was uneventful. Protein electrophoresis and immunofixation of the infant girl's serum and urine samples showed the presence of a paraprotein electrophoretically identical to that found in the mother. Exchange transfusion resulted in a rapid improvement of renal function in parallel to the disappearance of the monoclonal component.

Perinatal vasoconstrictive renal insufficiency associated with maternal nimesulide use.

A full-term newborn developed oliguric renal failure at 24 hr of life, which persisted for several days. Her mother ingested therapeutic doses of nimesulide, a non-steroidal anti-inflammatory (cyclo-oxygenase-2 inhibitor) drug, during the last 2 weeks of pregnancy. She was found at delivery to have developed oligohydramnion, esophagitis, and a bleeding peptic ulcer. The infant's fractional excretion of sodium was very low (0.5%) pointing for a severe vasoconstrictive mechanism involved. Renal sonogram showed hyperechogenic medullary papillae, which resolved during convalescence. This case emphasizes the importance of renal prostagandins in the control of vascular tone and sodium homeostasis. This is the first report of an adverse effect of fetal renal circulation by maternal ingestion of nimesulide.

Haemodialysis and ultrafiltration in babies weighing under 1000 g.

Until now it has not be feasible to haemodialyse babies with renal failure who weigh less than 1000 g. Three babies weighing 630, 808, and 1140 g are described. They had multiorgan failure and could not be peritoneally dialysed. They were treated with veno-venous ultrafiltration and haemodialysis using a manual syringe driven technique that required only simple equipment. This method is highly labour intensive, but can provide control of fluid volume and plasma biochemistry in these very sick infants. Their prognosis, however, is determined by the underlying cause of their renal failure, and remains poor.