Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection.

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.

[Clinical and genetic analysis of a newborn with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION: The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.

Clinical and genetic analysis of a newborn with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome.@*METHODS@#The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out.@*RESULTS@#The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved.@*CONCLUSION@#The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.

Maternal risk associated with the VACTERL association: A case-control study.

BACKGROUND: The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors. METHODS: A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). RESULTS: Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL. CONCLUSION: We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL.

Impact of prenatal ultrasound diagnosis for fetal renal abnormalities: Study Protocol.

BACKGROUND: This study will evaluate diagnostic accuracy and management outcome studies involving patients assessed with prenatal ultrasound diagnosis (PUD) for fetal renal abnormalities (FRA). METHODS: We will search the following electronic databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, Springer, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure for diagnostic accuracy studies from inceptions to the present without language restrictions. Two authors will independently screen studies, collect data, and assess methodological quality.We will use RevMan V.5.3 and Stata V.12.0 software for data pooling and statistical analysis. RESULTS: In this study, we will assess sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio to determine the diagnostic accuracy of PUD for the treatment of patients with FRA. CONCLUSION: This study will provide latest evidence for the diagnostic accuracy of PUD for FRA. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019151306.

Perioperative hyperkalemia in hemodialysis patients undergoing parathyroidectomy for renal hyperparathyroidism.

The present study investigates the incidence of perioperative hyperkalemia and the influence factors of serum potassium levels during and after parathyroidectomy (PTX) in hemodialysis patients with renal hyperparathyroidism (rHPT). A total of 204 hemodialysis patients with refractory rHPT undergoing successful total parathyroidectomy with autotransplantation (tPTX + AT) were analyzed retrospectively. Hyperkalemia was defined as serum potassium levels ≥ 5.5 mmol/L. The preoperative baseline level of serum potassium (K base+ ) was defined as a mean of the three preoperative prehemodialysis serum potassium levels. The higher levels of serum potassium during and immediately after surgery were recorded as K d0+ and the peak prehemodialysis serum potassium levels 3 days after surgery as K d3+ . 136/204 (66.7%) patients suffered from hyperkalemia during or immediately after surgery and 65/204 (31.9%) patients were affected with prehemodialysis hyperkalemia 3 days after surgery. K base+ was the only influencing factor for K d0+ . Serum K base+ , preoperative serum alkaline phosphatase, and total calcium supplement dosage during intravenous calcium supplement were the influencing factors for K d3+ . In the case of PTX, the serum potassium levels of patients with higher serum K base+ and severe postoperative hypocalcemia need to be monitored with extended attention perioperatively.

Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats.

Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose. At non-lethal doses, AYA enhanced embryolethality and the incidence of foetal soft-tissue and skeleton anomalies. This study suggested that AYA is developmentally toxic and that its daily use by pregnant women may pose risks for the conceptus.

NAD Deficiency, Congenital Malformations, and Niacin Supplementation.

BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. We tested the function of the variant by using assays of in vitro enzyme activity and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system. RESULTS: Variants were identified in two genes that encode enzymes of the kynurenine pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNU proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway. The patients had reduced levels of circulating NAD. Defects similar to those in the patients developed in the embryos of Haao-null or Kynu-null mice owing to NAD deficiency. In null mice, the prevention of NAD deficiency during gestation averted defects. CONCLUSIONS: Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice. (Funded by the National Health and Medical Research Council of Australia and others.).

Morphometric abnormalities in spleen and kidney of the progeny of mice fed American cranberry extract (Vaccinium macrocarpon) during pregnancy and lactation.

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

Association of Unilateral Renal Agenesis With Adverse Outcomes in Pregnancy: A Matched Cohort Study.

BACKGROUND: Data regarding the effect of a solitary kidney during pregnancy have come from studies of living kidney donors. We evaluated the risk for adverse pregnancy outcomes in women with a single kidney from renal agenesis. STUDY DESIGN: Matched cohort study. SETTING & PARTICIPANTS: Using data from 7,079 childbirths from an integrated health care delivery system from 1996 through 2015, we identified births from women with renal agenesis. Only first pregnancies and singleton births were included. After excluding those with diabetes and kidney disease, 200 women with renal agenesis were matched 1:4 by age (within 2 years), race, and history of hypertension to women with 2 kidneys. PREDICTOR: Renal agenesis defined by International Classification of Diseases, Ninth Revision (ICD-9) codes prior to pregnancy. OUTCOMES: The primary outcome was adverse maternal outcomes, including preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, and hospital length of stay. Adverse neonatal end points were considered as a secondary outcome and included low birth weight (<2,500g) and infant death/transfer to acute inpatient facility. RESULTS: Mean gestational age at delivery was 37.9±2.1 weeks for women with renal agenesis compared to 38.6±1.8 weeks for women with 2 kidneys. Compared with women with 2 kidneys, those with renal agenesis had increased risk for preterm delivery (OR, 2.88; 95% CI, 1.86-4.45), delivery by cesarean section (OR, 2.11; 95% CI, 1.49-2.99), preeclampsia/eclampsia (OR, 2.41; 95% CI, 1.23-4.72), and length of stay longer than 3 days (OR, 1.81; 95% CI, 1.18-2.78). Renal agenesis was not significantly associated with increased risk for infant death/transfer to acute facility (OR, 2.60; 95% CI, 0.57-11.89) or low birth weight after accounting for preterm delivery (OR, 2.11; 95% CI, 0.76-5.88). LIMITATIONS: Renal agenesis was identified by ICD-9 code, not by imaging of the abdomen. CONCLUSION: Women with unilateral renal agenesis have a higher risk for adverse outcomes in pregnancy.

Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.

Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2-/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g-1·day-1) for the first 10 days after birth ameliorated impaired kidney development in COX-2-/- pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2-/- pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na+/K+-ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2-/- mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2-/- mice and improves kidney function.

Laparoscopic selective clipping of upper moiety vasculature and ureter without partial nephrectomy: A novel technique for pediatric urinary incontinence due to ectopic ureter associated with poor functioning upper renal moiety.

OBJECTIVE: The aim of this study was to present a novel laparoscopic technique for persistent urinary incontinence in pediatrics due to ectopic ureter associated with poor functioning upper renal moiety. METHODS: This technique consisted of laparoscopic clipping of the upper moiety artery and vein. The ectopic ureter was also clipped afterwards without upper pole partial nephrectomy. RESULTS: The patient was a seven-year-old girl with persistent urinary incontinence and confirmation of duplex kidney with poor functioning upper moiety in pre-operative investigations. The upper moiety ureter was ectopically drained to the vaginal cavity. She was immediately dry after surgery and discharged on the second postoperative day. During the follow-up period of 14 months, she was continent and symptom-free. Hydronephrosis was not visualized in follow-up ultrasonography. CONCLUSIONS: This laparoscopic upper renal moiety vascular and ureteral clipping without partial nephrectomy could serve as a promising, safe and simple alternative in the treatment of patients with ectopic ureter associated with poor functioning renal moiety. Also, ipsilateral normal functioning moiety would not be associated with potential morbidity in this technique.

Cardiovascular Phenotypes in Children with CKD: The 4C Study.

BACKGROUND AND OBJECTIVES: Cardiovascular disease is the most important comorbidity affecting long-term survival in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Comorbidity in Children with CKD Study is a multicenter, prospective, observational study in children ages 6-17 years old with initial GFR of 10-60 ml/min per 1.73 m2. The cardiovascular status is monitored annually, and subclinical cardiovascular disease is assessed by noninvasive measurements of surrogate markers, including the left ventricular mass index, carotid intima-media thickness, and central pulse wave velocity. We here report baseline data at study entry and an explorative analysis of variables associated with surrogate markers. RESULTS: A total of 737 patients were screened from October of 2009 to August of 2011 in 55 centers in 12 European countries, and baseline data were analyzed in 688 patients. Sixty-four percent had congenital anomalies of the kidney and urinary tract; 26.1% of children had uncontrolled hypertension (24-hour ambulatory BP monitoring; n=545), and the prevalence increased from 24.4% in CKD stage 3 to 47.4% in CKD stage 5. The prevalence of left ventricular hypertrophy was higher with each CKD stage, from 10.6% in CKD stage 3a to 48% in CKD stage 5. Carotid intima-media thickness was elevated in 41.6%, with only 10.8% of patients displaying measurements below the 50th percentile. Pulse wave velocity was increased in 20.1%. The office systolic BP SD score was the single independent factor significantly associated with all surrogate markers of cardiovascular disease. The intermediate end point score (derived from the number of surrogate marker measurements >95th percentile) was independently associated with a diagnosis of congenital anomalies of the kidney and urinary tract, time since diagnosis of CKD, body mass index, office systolic BP, serum phosphorus, and the hemoglobin level. CONCLUSIONS: The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.

Is ciprofloxacin safe in patients with solitary kidney and upper urinary tract infection?

The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7-day treatment with intravenous ciprofloxacin. Urinary N-acetyl-beta-d-glucosaminidase, alpha 1-microglobulin, and estimated glomerular filtration rate (eGFR) of these patients were measured at the initiation and at the end of treatment. In 47.37% patients NAG diminished under ciprofloxacin treatment. This observation has the significance of favourable evolution of the tubulointerstitial lesions caused by UTI and lack of nephrotoxic effects; 52.63% cases presented an increase of urinary NAG, a fact that suggests a nephrotoxic effect of ciprofloxacin. The evolution of urinary alpha 1-microglobulin was similar to that one of urinary NAG. Only one of three cases with chronic kidney disease (CKD) stage 5 presented acute kidney injury, associated with increase in the tubular markers. In spite of the high variability of the urinary biomarkers, UTI evolved favourably in these cases; eGFR increased in 16 out of 19 patients, a fact which is indicative of a good outcome of renal function, even in patients with elevated levels of the tubular damage biomarkers. This observation supports the hypothesis that eGFR may be dissociated from the biomarkers which assess tubular injury. In SK patients the occurrence of AKI is not frequent, although the urinary biomarkers rise in some patients treated with ciprofloxacin. This is related not only to the nephrotoxic effect of the drug, but probably to the association of other factors (allergy, individual susceptibility). In SK patients, renal tubular biomarkers, especially NAG, allow monitoring of tubular injury and impose caution in prescribing ciprofloxacin treatment, mainly to patients at risk. Ciprofloxacin is relatively safe regarding its nephrotoxicity, while caution is required in vulnerable patients.

Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: A case-control study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous group of birth defects with a variety of genetic and nongenetic factors suspected of involvement in the etiology. However, little is known about risk factors in specific CAKUT phenotypes. Therefore, we studied potential maternal risk factors in individual phenotypes within the CAKUT spectrum. METHODS: Questionnaire data were collected from parents of 562 children with CAKUT and 2139 healthy controls within the AGORA data- and biobank. Potential maternal risk factors investigated included folic acid use, overweight and obesity, smoking, alcohol consumption, subfertility, and diabetes mellitus. We performed logistic regression analyses to assess associations between these potential risk factors and CAKUT phenotypes. RESULTS: Increased risks of CAKUT were observed for folic acid use and maternal obesity, while fertility treatment by in vitro fertilization or intrauterine insemination and diabetes diagnosed during pregnancy also seem to be associated with CAKUT. Use of multivitamins reduced the risk (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.2-1.0) as opposed to use of folic acid supplements only (OR, 1.3; 95% CI, 1.0-1.8). Folic acid use was associated with duplex collecting systems (OR, 1.8; 95% CI, 1.0-3.4) and vesicoureteral reflux (OR, 1.8; 95% CI, 1.1-2.9) in particular. A relatively strong association was observed between diabetes during pregnancy and posterior urethral valves (OR, 2.6; 95% CI, 1.1-5.9). CONCLUSION: Use of folic acid only seems to be counterproductive for prevention of CAKUT, in contrast to multivitamin use. Furthermore, we observed differences in risk factor patterns among CAKUT phenotypes, which stress the importance of separate analyses for each phenotype. Birth Defects Research (Part A) 106:596-603, 2016. © 2016 Wiley Periodicals, Inc.

Vitamin D deficiency in a patient with HDR syndrome.

The case of a patient with clinical symptoms, laboratory and imaging findings of hypoparathyroidism, sensorineural deafness, renal dysplasia HDR, or Barakat syndrome (hypoparathyroidism, deafness, renal dysplasia), and vitamin D deficiency, is presented. A Caucasian man aged 51 years with a history of chronic hypocalcaemia since childhood, was admitted with hypertonia of the body and extremities, and loss of consciousness. On admission, he was found to have severe hypocalcaemia, hyperphosphataemia, severe hypoparathyroidism, low serum magnesium and mild renal insufficiency. Calcium gluconate was administered intravenously supplemented with magnesium, and the patient recovered consciousness while clinical and laboratory findings improved. Evaluation revealed left renal aplasia and sensorineural deafness affecting both ears. Vitamin D deficiency was also present. He was given calcium and vitamin D supplements orally, and the hypocalcaemia was corrected. This case is described as it is an extremely rare case of HDR syndrome with concurrent vitamin D deficiency.

Safety and Efficacy of Thermal Ablation for Small Renal Masses in Solitary Kidney: Evidence from Meta-Analysis of Comparative Studies.

OBJECTIVE: To evaluate comparative renal functional preservation, perioperative and oncologic outcomes, and complications of thermal ablation (TA) versus partial nephrectomy (PN) in management of Small renal masses (SRMs) in solitary kidney. METHODS AND FINDINGS: Medline, Embase, Web of Science and the Cochrane Library were systematically searched. A meta-analysis for comparative studies comparing TA with PN was performed. According to predefined inclusion criteria, seven datasets were identified from 8 observational studies including a total of 628 patients. Cumulated data showed the changes of creatinine (p=0.02) and estimated glomerular filtration rate (eGFR) (p<0.0001) in TA arm were significantly less than these in PN arm. Significantly less new-set chronic kidney disease (CKD) was observed in TA group (p=0.04). In terms of postoperative dialysis rate, the difference favoring TA was also noted, though there is no statistical significance (p=0.09). With regard to perioperative outcomes, our data demonstrated that patients who underwent TA had significantly shorter operation time (p=0.002), less blood loss (p<0.0001), shorter length of stay (p<0.00001), and less transfusion rate (p=0.01) than those underwent PN. In addition, patients underwent TA suffered less intra- and postoperative complications (p=0.007, p<0.00001; respectively). With regard to oncologic outcomes, disease-free survival (DFS) (p<0.00001) and cancer-specific survival (CSS) (p=0.01) in the PN arm were significantly better than these of the TA arm. But, TA yielded a comparable overall survival to PN (p=0.40). Sensitivity analyses led to very similar results with overall results, and confirmed its stability. CONCLUSIONS: Our analysis indicates that PN have advantage in controlling cancer recurrence. However, TA is associated with significantly better renal functional preservation and perioperative outcomes, and less complications without increasing overall death. Our data suggest that indication for TA may be extended to select younger, healthier patients who desire a much less invasive therapeutic option.

Disorders of mineral metabolism in the newborn.

Disorders of calcium and phosphorus homeostasis present both acute and chronic clinical consequences for newborns. The etiologies responsible range from iatrogenic, idiopathic, and inherited metabolic abnormalities. Maintenance of physiologically normal serum calcium and phosphorus requires complex interactions between the kidneys, gastrointestinal tract, and bone. Calciotropic hormones such as vitamin D and parathyroid hormone, as well as hormones controlling phosphorus homeostasis, such as fibroblast growth factor-23 (FGF-23), are essential in controlling these interactions. In newborns, calcium and phosphorus balance must necessarily be positive in order to provide the requisite building blocks for growth and maturation. Renal tubular handling of these minerals is a key control point in regulating the overall body balance in calcium and phosphorus. Adaptive changes in renal calcium and phosphorus reabsorption in newborns explain how a net positive total body balance of these minerals is achieved. Monogenetic disorders leading to abnormal renal handling of calcium and/or phosphorus have immediate clinical consequences in terms of complications associated with high or low levels of these minerals. Perhaps more importantly, chronic abnormalities of calcium and/or phosphorus, without treatment, may have serious consequences for growth and development of the growing skeleton. This article serves to review calcium and phosphorus regulation in the human body, describe differences in handling of these minerals by the newborn, and review the conditions, both acquired and congenital, that may present with abnormalities in calcium and/or phosphorus in the newborn period.

ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies.

We describe a previously unreported syndrome characterized by secondary (post-natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract in a highly consanguineous family with six affected children. Homozygosity mapping and exome sequencing revealed a novel homozygous frameshift mutation in the basic helix-loop-helix transcription factor gene ARNT2 (c.1373_1374dupTC) in affected individuals. This mutation results in absence of detectable levels of ARNT2 transcript and protein from patient fibroblasts compared with controls, consistent with nonsense-mediated decay of the mutant transcript and loss of ARNT2 function. We also show expression of ARNT2 within the central nervous system, including the hypothalamus, as well as the renal tract during human embryonic development. The progressive neurological abnormalities, congenital hypopituitarism and post-retinal visual pathway dysfunction in affected individuals demonstrates for the first time the essential role of ARNT2 in the development of the hypothalamo-pituitary axis, post-natal brain growth, and visual and renal function in humans.