Moderate and severe fetal pyelectasis: Correlation between prenatal aspects and postnatal outcome.

BACKGROUND: Renal pelvic dilatation (RPD) is a frequent finding in fetal ultrasound. The aim of the study is to correlate the prenatally detected moderate and severe pyelectasis with the postnatal outcome. METHODS: A retrospective analysis involving 90 cases of prenatally detected moderate and severe RPD referred to our prenatal diagnosis centre with 18 months of urological follow-up. Prenatal ultrasound was correlated with postnatal renal function, assessed by plasmatic creatinine and/or renal scintigraphy performed before surgery. RESULTS: Cases were divided between two groups according to postnatal management: group A including 35 newborns (38.9%) that needed surgical treatment and group B with 55 patients (61.1%) who were managed conservatively. The group A presented higher median RPD (18 mm, IQR 12-25 mm) compared to the group B (11 mm, IQR 10-14 mm). The most common anomaly detected within group A was pelvi-ureteric junction (PUI) obstruction (43%). Within group B 32 cases (58%) showed spontaneous resolution of hydronephrosis during postnatal follow up. In case of moderate pyelectasis the risk of postnatal surgery was 25% and raised to 60% for severe RPD. In our study, 29 newborns showed pathologic scintigraphies: 25 required surgery while 4 did not find indication for surgery due to ipsilateral renal function irreversible damage. 6 patients had high creatinine level (>0.6 mg/dl). 35 cases out of 90 (39%) developed monolateral irreversible renal function impairment. CONCLUSION: Moderate and severe RPD are often correlated with postnatal renal damage, therefore a close multidisciplinary follow-up is required. Prenatal scanning is highly predictive of postnatal outcome and can address properly the prenatal counseling.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), ß-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

Extracorporeal membrane oxygenation support in a newborn with lower urinary tract obstruction and pulmonary hypoplasia: a case report.

BACKGROUND: Survival of neonates with intrauterine renal insufficiency and oligo- or anhydramnios correlates with the severity of secondary pulmonary hypoplasia. Early prenatal diagnosis together with repetitive amnioinfusions and modern intensive care treatment have improved the prognosis of these neonates. Extracorporeal membrane oxygenation is an established treatment option, mainly applied to neonates with pulmonary hypoplasia caused by congenital diaphragmatic hernia. However, a few case reports of extracorporeal membrane oxygenation in neonates with lower urinary tract obstruction have been published. CASE PRESENTATION: We describe a case of a Caucasian male infant with prenatally diagnosed lower urinary tract obstruction and secondary pulmonary hypoplasia who was delivered spontaneously at 36 + 2 weeks of gestation. Venovenous extracorporeal membrane oxygenation was initiated on the first day of life for severe respiratory failure and consecutive hypoxemia despite treatment with inhaled nitric oxide and high-frequency oscillation. The patient was supported by extracorporeal membrane oxygenation for 10 days and extubated 6 weeks later. Hemofiltration was required on the second day of life because of renal insufficiency and was later replaced by peritoneal dialysis. The child was discharged after 4 months with nasal high-flow mild oxygen therapy and peritoneal dialysis. CONCLUSION: Neonatal extracorporeal membrane oxygenation support is a possible treatment option for neonates with lower urinary tract obstruction and pulmonary hypoplasia.

Renal failure from birth-AKI or CKD? Questions.

A case is presented of a neonate born at 32 weeks of gestation with intra-uterine growth retardation. The renal scan performed at 31 weeks showed oligohydramnios but normal kidneys. The neonate was oliguric from birth and required early peritoneal dialysis. Her urine showed heavy proteinuria, and the plasma albumin was very low. Post-natal ultrasonography showed large bright kidneys with reduced corticomedullary differentiation but no dysplastia; arterial and venous flow was normal on Doppler ultrasound. The quiz discusses the differential diagnosis with particular reference to whether this picture represents acute kidney injury with expected improvement or chronic kidney disease. Further questions discuss mechanisms of renal failure in this situation. Finally, with reference to previous case reports and series, a correlation between a specific mutation and this severe phenotype is proposed.

Label-free quantitative urinary proteomics identifies the arginase pathway as a new player in congenital obstructive nephropathy.

Obstructive nephropathy is a frequently encountered situation in newborns. In previous studies, the urinary peptidome has been analyzed for the identification of clinically useful biomarkers of obstructive nephropathy. However, the urinary proteome has not been explored yet and should allow additional insight into the pathophysiology of the disease. We have analyzed the urinary proteome of newborns (n = 5/group) with obstructive nephropathy using label free quantitative nanoLC-MS/MS allowing the identification and quantification of 970 urinary proteins. We next focused on proteins exclusively regulated in severe obstructive nephropathy and identified Arginase 1 as a potential candidate molecule involved in the development of obstructive nephropathy, located at the crossroad of pro- and antifibrotic pathways. The reduced urinary abundance of Arginase 1 in obstructive nephropathy was verified in independent clinical samples using both Western blot and MRM analysis. These data were confirmed in situ in kidneys obtained from a mouse obstructive nephropathy model. In addition, we also observed increased expression of Arginase 2 and increased total arginase activity in obstructed mouse kidneys. mRNA expression analysis of the related arginase pathways indicated that the pro-fibrotic arginase-related pathway is activated during obstructive nephropathy. Taken together we have identified a new actor in the development of obstructive nephropathy in newborns using quantitative urinary proteomics and shown its involvement in an in vivo model of disease. The present study demonstrates the relevance of such a quantitative urinary proteomics approach with clinical samples for a better understanding of the pathophysiology and for the discovery of potential therapeutic targets.

Hepatoblastoma and hypoplastic kidneys: a new association.

Both hepatoblastoma and hypoplastic kidneys are rare in children. A review of all patients with hepatoblastoma treated at our institution between 1993 and 2011 revealed three cases of hepatoblastoma occurring in children with hypoplastic kidneys and significantly impaired renal function. Two patients were treated with doxorubicin-based therapy without cisplatin. One was treated with carboplatin. The former two are long-term survivors while the third patient died of sepsis following chemotherapy. This association is unlikely due to chance alone and chemotherapy regimens without cisplatin may be effective in treating these children.

Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance.

BACKGROUND AND OBJECTIVES: During the newborn period and early infancy, renal function matures, resulting in changes in the glomerular filtration rate (GFR). This study was performed to quantify developmental changes in the GFR in (pre)term neonates by use of amikacin clearance as proof of concept. The model was used to derive a rational dosing regimen in comparison with currently used dosing regimens for amikacin. METHODS: Population pharmacokinetic modelling was performed in nonlinear mixed-effect modelling software (NONMEM version 6.2) using data from 874 neonates obtained from two previously published datasets (gestational age 24-43 weeks; postnatal age 1-30 days; birthweight 385-4650 g). The influence of different age-related, weight-related and other covariates was investigated. The model was validated both internally and externally. RESULTS: Postmenstrual age was identified as the most significant covariate on clearance. However, the combination of birthweight and postnatal age proved to be superior to postmenstrual age alone. Birthweight was best described using an allometric function with an exponent of 1.34. Postnatal age was identified using a linear function with a slope of 0.2, while co-administration of ibuprofen proved to be a third covariate. Current bodyweight was the most important covariate for the volume of distribution, using an allometric function. The external evaluation supported the prediction of the final pharmacokinetic model. This analysis illustrated clearly that the currently used dosing regimens for amikacin in reference handbooks may possibly increase the risk of toxicities and should be revised. Consequently, a new model-based dosing regimen based on current bodyweight and postnatal age was derived. CONCLUSIONS: Amikacin clearance, reflecting the GFR in neonates, can be predicted by birthweight representing the antenatal state of maturation of the kidney, postnatal age representing postnatal maturation, and co-administration of ibuprofen. Finally, the model reflects maturation of the GFR, allowing for adjustments of dosing regimens for other renally excreted drugs in preterm and term neonates.

Mechanism of alcohol-induced impairment in renal development: Could it be reduced by retinoic acid?

1. Prenatal alcohol exposure impairs kidney development, resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid (RA) is critically involved in kidney development and it has been proposed that a diminished concentration of RA is a contributing factor to fetal alcohol syndrome. 2. In the present study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by coculture with exogenous RA and that examining the expression profile of key genes involved in the development of the kidney would provide insights into the potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous RA (10-20 nmol/L) without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2%) had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated by coculture with retinoic acid. 4. Gene expression analysis identified changes in the expression of enzymes involved in the metabolism of alcohol in conjunction with changes in key regulators of kidney development, including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through coculture with RA. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.

False-positive newborn screening mimicking glutaric aciduria type I in infants with renal insufficiency.

Glutaric aciduria type I (GA I), an autosomal-recessive deficiency of glutaryl-CoA-dehydrogenase, leads to encephalopathic crises resulting in irreversible neurological damage. As early diagnosis and implementation of appropriate treatment has significant benefit for these patients, GA I has been implemented in the extended newborn screening program in several countries. Screening parameter is glutarylcarnitine (C5DC) with its ratios. From 1 January 2005 until 31 December 2008, 173,846 newborns were examined by neonatal screening in our screening center. C5DC and/or at least three C5DC/acylcarnitine ratios were increased in 53 newborns (0.03%) and persisted in 11 infants after recall. GA I was not confirmed in any of these infants, but all 11 infants were suffering from renal insufficiency due to congenital (5/11) or acquired (6/11) renal disease. C5DC was shown to be significantly associated with renal affection and was significantly higher in infants with congenital renal insufficiency than in those with acquired renal insufficiency (p = 0.011). Creatinine correlated significantly with C5DC (p = 0.001) and all C5DC/acylcarnitine ratios, mainly with C5DC/(C8 + C10), C5DC/C0, C5DC/C2, C5DC/C4, and C5DC/C8 (for all: p = 0.001). Glutarylcarnitinemia associated with renal insufficiency has not yet been studied systematically. Renal damage in neonates might lead to disturbances in renal transporter systems of glutaric acid and its metabolites and a decreased excretion of C5DC, thus resulting in an increase of plasma C5DC. Therefore, newborns presenting with a positive screening indicating GA I may be considered not only to suffer from GA I but from renal insufficiency as well.

Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy.

BACKGROUND: Renal insufficiency is associated with the development of cardiovascular disease. OBJECTIVES: This study investigated whether reduced fetal renal mass resulted in renal insufficiency, hypertension, cardiac dysfunction and whether these changes progressed with age. METHODS AND RESULTS: Fetal uninephrectomy was performed at 100-day gestation (term, 150 days) and studies performed in male sheep from 6 weeks to 24 months of age. Renal function declined with age in sham animals as demonstrated by increasing plasma creatinine levels and urinary excretion of albumin. The age-related decline in renal function was exacerbated in animals that had undergone fetal uninephrectomy. Evidence of renal insufficiency was indicated from as early as 6 weeks of age with elevations in plasma creatinine (Ptreatment < 0.001), urea (Ptreatment < 0.001) and sodium (Ptreatment < 0.05) levels in uninephrectomized lambs as compared with sham animals. At 6 months, urinary albumin excretion (P < 0.001) was increased and urinary sodium excretion (P < 0.001) decreased in the uninephrectomized animals. By 24 months, renal function had deteriorated further with significant progression of albuminuria (P(treatment x age) < 0.001). Elevation of mean arterial pressure (approximately 15 mmHg) was associated with significantly increased cardiac output, stroke volume and plasma volume at 6 months; arterial pressure (approximately 27 mmHg) had increased further in uninephrectomized animals at 24 months and was driven by increased total peripheral resistance. Cardiac functional reserve (dobutamine challenge) was reduced in uninephrectomized animals at 6 and 24 months of age (Ptreatment < 0.001), and this was associated with left ventricular enlargement (P < 0.001) and reduced fractional shortening (P < 0.01). CONCLUSION: Fetal uninephrectomy causing a reduction in nephron endowment results in an accelerated age-related decline in renal function. This is associated with an early onset of elevated blood pressure and impairments in cardiac structure and function.

Síndrome de Potter / Potter's syndrome

El síndrome de Potter es un conjunto de trastornos asociados con insuficiencia renal y deficiencia de líquido amniótico en los productos de la concepción antes de nacer. Se describe el caso clínico de una madre de 35 años de edad, a la cual se le diagnosticó mediante ultrasonografía la existencia de un grave oligohidramnios y feto con las características fenotípicas y morfológicas de los afectados por dicha enfermedad(AU)

Renal aplasia is the predominant cause of congenital solitary kidneys.

BACKGROUND: Congenital solitary kidneys, which are susceptible to renal failure, have been considered mostly due to unilateral renal agenesis and partly due to renal aplasia. Risk of familial recurrence and of other associated anomalies is known to be much higher in renal agenesis than in renal aplasia. However, differential diagnosis between the two renal anomalies is difficult, and renal agenesis has been found much less frequently in ultrasound screening studies of fetuses than in autopsy studies. METHODS: In order to investigate the nature and incidence of the congenital solitary kidney, the present study performed ultrasound screening of the kidneys in 4000 newborn babies. A diagnosis of renal agenesis was made when ultrasound identified no renal parenchyma and renoscintigraphy showed no renal function, and renal aplasia when there was a renal parenchyma without any function. RESULTS: Primary screening detected 52 babies suspected of having small kidneys and one baby with a multicystic dysplastic kidney, but no baby with renal agenesis. Forty-seven of the 53 babies underwent a second ultrasound scanning at one month of age. Three small kidneys in three babies further decreased in size, had no function and were diagnosed as renal aplasia (which has an incidence rate of one in 1300). Follow-up ultrasound studies showed further regression in all three, which became very hard to distinguish by one year of age. CONCLUSIONS: The present study showed that ultrasound in the neonatal period could identify the aplastic kidney, which had a reniform shape, not rudimentary, during the newborn period, and regressed rapidly thereafter. These findings indicate that most renal agenesis diagnosed clinically thus far might more correctly be renal aplasia.

Early primary valve ablation for posterior urethral valves.

Early diagnosis and the use of new pediatric endoscopic equipment have significantly improved the survival of infant boys with posterior urethral valves. The sequelae of urethral obstruction in these patients includes abnormalities in the urethra, bladder, ureters, and kidneys. The question remains of how best to treat all valve patients to maximize function of the entire urinary tract. Our experience with early valve ablation (EVA) suggests that the damaged bladder and upper tracts have a potential to heal if the obstruction is removed and the bladder is allowed to fill and empty cyclically in the first few months of life. One year after EVA, even patients with severe obstructive changes show return of normal bladder capacity and compliance, and resolution or improvement in reflux. Unfortunately, the renal insufficiency associated with valves often is secondary to primary renal dysplasia, with many patients progressing to renal failure and transplantation. Upper tract diversion has failed to improve long-term outcome in patients with renal dysplasia; furthermore, it jeopardizes the potential for bladder healing and normal bladder function. Therefore, even for patients with renal insufficiency, early primary ablation should be used as the definitive treatment for posterior urethral valves.

Prenatal maternal indomethacin use resulting in prolonged neonatal renal insufficiency.

The short-term use of indomethacin has been shown to be relatively safe and effective in halting premature labor. Its use has been associated with adverse renal effects in both the fetal and newborn periods that are generally transient and resolve on discontinuation of the drug. However, limited data suggest that prolonged prenatal exposure to indomethacin may be harmful to the fetus. We report a case of prolonged severe renal dysfunction characterized by oligohydramnios and postnatal anuria, azotemia, and ultrasonographic kidney abnormalities associated with the long-term prenatal use of indomethacin. Although partial resolution was observed, a moderate decrease in renal function persists. Prenatal maternal indomethacin use represents a potential cause of renal dysfunction in the newborn infant that may be only partially reversible.

Growth of uremic infants on forced feeding regimens.

Infants born with congenital renal insufficiency generally grow poorly during the first years of life and incur a height deficit that is rarely regained. Actual energy and protein requirements have not been determined for these children. In 12 infants with creatinine clearances less than 70 ml/min per 1.73 m2, growth and nutrient intakes were monitored during the first 2 years of life. Forced feeding regimens after 3 months of age, including gastrostomy in 3 patients, were necessary to maintain energy intakes near 100% of the recommended dietary allowance (RDA). Protein intakes averaged in excess of 140% RDA. Linear growth did not correlate with either energy or protein intakes, suggesting that neither was a limiting factor to growth. Length velocity standard deviation score (LV-SDS) did not correlate with degree of renal insufficiency at any age, but average LV-SDS did relate significantly and inversely to C-terminal parathyroid hormone (PTH) levels. Growth parameters, including LV-SDS and weight velocity SDS (WV-SDS) were lowest at 6 months of age. Weight and length SDS followed with a maximum decline at 12 months of age. While weight for length SDS remained normal and WV-SDS showed recovery during the 2nd year, LV-SDS remained negative. Length SDS stabilized near--2 SDS. In summary, these data suggest that the major height deficit in infants with renal insufficiency is incurred during the first 6 months of life. Ponderal indices suggested that very early nutritional deficits may have been a primary contributor to subsequent height deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal perinatal nephropathy with onset in intrauterine life.

A girl, born at 29 weeks' gestation, died of renal failure aged 16 days. Postmortem histology showed diffuse mesangial sclerosis with failure of development of the cortex. This is an unusual cause of neonatal renal failure, and it demonstrates the effect of disease arising in utero and influencing the development of the kidney.