Hydronephrosis caused by kidney malrotation.

Hydronephrosis associated with kidney malrotation can be a surgical challenge. We present the case of a 3.5 y.o.-boy presenting with left pyelo-ureteric obstruction caused by kidney hyperrotation (270°) resulting in recurring urinary tract infection. After complete radiological work-up, we opted for a primary laparoscopic ureterocalicostomy, which allowed for complete resolution of the pelvic dilatation. Kidney malrotation can present with a wide variation in anatomic features. Radiological work-up is the cornerstone of surgical strategy planning. Laparoscopic ureterocalicostomy is a useful primary option in unusual anatomical situations

Serum NGAL, BNP, PTH, and albumin do not improve glomerular filtration rate estimating formulas in children.

Glomerular filtration rate (GFR) is difficult to measure, and estimating formulas are notorious for lacking precision. This study aims to assess if the inclusion of additional biomarkers improves the performance of eGFR formulas. A hundred and sixteen children with renal diseases were enrolled. Data for age, weight, height, inulin clearance (iGFR), serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) were collected. These variables were added to the revised and combined (serum creatinine and cystatin C) Schwartz formulas, and the quadratic and combined quadratic formulas. We calculated the adjusted r-square (r <sup>2</sup> ) in relation to iGFR and tested the improvement in variance explained by means of the likelihood ratio test. The combined Schwartz and the combined quadratic formulas yielded best results with an r <sup>2</sup> of 0.676 and 0.730, respectively. The addition of BNP and PTH to the combined Schwartz and quadratic formulas improved the variance slightly. NGAL and albumin failed to improve the prediction of GFR further. These study results also confirm that the addition of cystatin C improves the performance of estimating GFR formulas, in particular the Schwartz formula.Conclusion: The addition of serum NGAL, BNP, PTH, and albumin to the combined Schwartz and quadratic formulas for estimating GFR did not improve GFR prediction in our population. What is Known: • Estimating glomerular filtration rate (GFR) formulas include serum creatinine and/or cystatin C but lack precision when compared to measured GFR. • The serum concentrations of some biological parameters such as neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) vary with the level of renal function. What is New: • The addition of BNP and PTH to the combined quadratic formula improved its performance only slightly. NGAL and albumin failed to improve the prediction of GFR further

Assessment of Damage to Nucleic Acids and Repair Machinery in Salmonella typhimurium Exposed to Chlorine

Water disinfection is usually evaluated using mandatory methods based on cell culturability. However, such methods do not consider the potential of cells to recover, which should also be kept as low as possible. In this paper, we hypothesized that a successful disinfection is achieved only when the applied chlorine leads to both intracellular nucleic acid damage and strong alterations of the DNA repair machinery. Monitoring the SOS system responsiveness with a umuC’-‘lacZ reporter fusion, we found that the expression of this important cellular machinery was altered after the beginning of membrane permeabilization but prior to the total decline of both the cell culturability and the nucleic acid integrity as revealed by Sybr-II staining. Rapid measurement of such nucleic acid alterations by fluorochrome-based staining could be used as an alternative method for assessing the effectiveness of disinfection with chlorine

A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome.

BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin β2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype-phenotype correlations have been reported, often with great clinical variability. We hereby report a novel homozygous nonsense mutation in the LAMB2 gene, associated with a severe phenotype presentation. CASE DIAGNOSIS: We describe a term male infant born from consanguineous parents. The mother previously lost three children in the neonatal period, secondary to undefined renal disease, had two spontaneous abortions, and gave birth to one healthy daughter. The index case presented at birth with bilateral microcoria, severe hypotonia, respiratory distress, and congenital nephrotic syndrome associated with anuria and severe renal failure requiring peritoneal dialysis. The patients' clinical follow-up was unfavorable, and the newborn died at 7 days of life, after withdrawal of life support. Genetic analysis revealed a homozygous nonsense mutation at position c.2890C>T causing a premature stop codon (p.R964*) in LAMB2 gene. CONCLUSION: We here describe a novel nonsense homozygous mutation in LAMB2 gene causing a severe neonatal presentation of Pierson syndrome. This new mutation expands the genotype-phenotype spectrum of this rare disease and confirms that truncating mutations might be associated with severe clinical features

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis.

Heart failure is a worldwide leading cause of death. Diet and obesity are particularly of high concern in heart disease etiology. Gravely, altered nutrition during developmental windows of vulnerability can have long-term impact on heart health; however, the underlying mechanisms are poorly understood. In the understanding of the initiation of chronic diseases related to developmental exposure to environmental challenges, deregulations in epigenetic mechanisms including micro-RNAs have been proposed as key events. In this context, we aimed at delineating the role of micro-RNAs in the programming of cardiac alterations induced by early developmental exposure to nutritional imbalance. To reach our aim, we developed a human relevant model of developmental exposure to nutritional imbalance by maternally exposing rat to high-fat diet during gestation and lactation. In this model, offspring exposed to maternal high-fat diet developed cardiac hypertrophy and increased extracellular matrix depot compared to those exposed to chow diet. Microarray approach performed on cardiac tissue allowed the identification of a micro-RNA subset which was down-regulated in high-fat diet-exposed animals and which were predicted to regulate transforming growth factor-beta (TGFβ)-mediated remodeling. As indicated by in vitro approaches and gene expression measurement in the heart of our animals, decrease in DiGeorge critical region 8 (DGCR8) expression, involved in micro-RNA biogenesis, seems to be a critical point in the alterations of the micro-RNA profile and the TGFβ-mediated remodeling induced by maternal exposure to high-fat diet. Finally, increasing DGCR8 activity and/or expression through hemin treatment in vitro revealed its potential in the rescue of the pro-fibrotic phenotype in cardiomyocytes driven by DGCR8 decrease. These findings suggest that cardiac alterations induced by maternal exposure to high-fat diet is related to abnormalities in TGFβ pathway and associated with down-regulated micro-RNA processing. Our study highlighted DGCR8 as a potential therapeutic target for heart diseases related to early exposure to dietary challenge

Preterm Birth: Long Term Cardiovascular and Renal Consequences.

Cardiovascular and chronic kidney diseases are a part of noncommunicable chronic diseases, the leading causes of premature death worldwide. They are recognized as having early origins through altered developmental programming, due to adverse environmental conditions during development. Preterm birth is such an adverse factor. Rates of preterm birth increased in the last decades, however, with the improvement in perinatal and neonatal care, a growing number of preterm born subjects has now entered adulthood. Clinical and experimental evidence suggests that preterm birth is associated with impaired or arrested structural or functional development of key organs/systems making preterm infants vulnerable to cardiovascular and chronic renal diseases at adulthood. This review analyzes the evidence of such cardiovascular and renal changes, the role of perinatal and neonatal factors such as antenatal steroids and potential pathogenic mechanisms, including developmental programming and epigenetic alterations. Preterm born subjects are exposed to a significantly increased risk for altered cardiovascular and renal functions at young adulthood. Adequate, specific follow-up measures remain to be determined. While antenatal steroids have considerably improved preterm birth outcomes, repeated therapy should be considered with caution, as antenatal steroids induce long-term cardiovascular and metabolic alterations in animals' models and their involvement in the accelerated cellular senescence observed in human studies cannot be excluded

Transient Arterial Hypertension Induced by Gonadotropin-Releasing Hormone Agonist Treatment for Central Precocious Puberty.

Background: Gonadotropin-releasing hormone agonists (GnRHa) are a safe and effective treatment for precocious puberty. Triptorelin is one of the long lasting GnRHa, which reversibly suppresses the pituitary-gonadal axis. Triptorelin-induced hypertension (HTN) has rarely been reported in the literature. Clinical Case/Methods: We report a 10-year-old girl with central precocious puberty who, during treatment with triptorelin, developed an asymptomatic stage II HTN. Initial workup showed no renal, thyroid, or electrolytes abnormalities. The renal ultrasound showed no parenchymal disease and no increased renal resistance index suggestive of a renal artery stenosis. Echocardiography and ocular fundoscopy were normal. HTN (stage II) was confirmed with ambulatory blood pressure monitoring (ABPM). After extensive literature review, we found 3 other cases of HTN secondary to GnRHa, improving with endocrine treatment cessation. Therefore, antihypertensive treatment was not started immediately in our patient. Indeed, after completion of her treatment with triptorelin, we observed a complete normalization of her blood pressure (confirmed with ABPM) without any medication. Conclusion: Concomitantly to GnRHa treatment, our patient developed HTN, which completely subsided after stopping triptorelin. The complete normalization of her blood pressure, together with a negative workup for HTN strongly speaks for a causal effect of her endocrine treatment. In this setting, estrogen depletion might play a role, although this remains debated

Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine. RESULTS: We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years. CONCLUSIONS: Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD

Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction.

Metabolic syndrome (MetS) refers to cardiometabolic risk factors, such as visceral obesity, dyslipidemia, hyperglycemia/insulin resistance, arterial hypertension and non-alcoholic fatty liver disease (NAFLD). Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing metabolic/hepatic disorders later in life. Oxidative stress and cellular senescence have been associated with MetS and are observed in infants born following IUGR. However, whether these mechanisms could be particularly associated with the development of NAFLD in these individuals is still unknown. IUGR was induced in rats by a maternal low-protein diet during gestation versus. a control (CTRL) diet. In six-month-old offspring, we observed an increased visceral fat mass, glucose intolerance, and hepatic alterations (increased transaminase levels, triglyceride and neutral lipid deposit) in male rats with induced IUGR compared with the CTRL males; no differences were found in females. In IUGR male livers, we identified some markers of stress-induced premature senescence (SIPS) (lipofuscin deposit, increased protein expression of p21 <sup>WAF</sup> , p16 <sup>INK4a</sup> and Acp53, but decreased pRb/Rb ratio, foxo-1 and sirtuin-1 protein and mRNA expression) associated with oxidative stress (higher superoxide anion levels, DNA damages, decreased Cu/Zn SOD, increased catalase protein expression, increased nfe2 and decreased keap1 mRNA expression). Impaired lipogenesis pathways (decreased pAMPK/AMPK ratio, increased pAKT/AKT ratio, SREBP1 and PPARγ protein expression) were also observed in IUGR male livers. At birth, no differences were observed in liver histology, markers of SIPS and oxidative stress between CTRL and IUGR males. These data demonstrate that the livers of IUGR males at adulthood display SIPS and impaired liver structure and function related to oxidative stress and allow the identification of specific therapeutic strategies to limit or prevent adverse consequences of IUGR, particularly metabolic and hepatic disorders