High Activation of the AKT Pathway in Human Multicystic Renal Dysplasia

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

DOZ047.33: Neonatal airway emergency: report of two cases

Objective This paper discusses two cases of congenital airway malformations that presented in NICU in a four-month period. The aim is to present extremely rare evidences that inevitably lead to the death of the patient if not correctly identified during pregnancy. Case 1: male twin born at 34 weeks by emergency caesarean section to a 37-year-old mother. Antenatal history was notable for in vitro fertilization and renal dysplasia. Immediately after delivery, there was respiratory distress, cyanosis, with a 1- and 5-min Apgar score of 0 and 1, respectively. He required ventilation and was supposed intubated orally with significant difficulty with a 2.0 mm ETT. For persistent ventilation problems and severe combined acidosis, the neonatologists tried without success to reintubate the patient. Some hours later, the otolaryngologist was called and was again unable to intubate with flexible laryngoscopy due to an obstruction that prevented advancement of the endotracheal tube past the vocal folds, but since the baby general conditions had been already deteriorated a decision to withdraw the treatment was made. He died after few hours. Postmortem revealed a polymalformative syndrome with subglottic complete diaphragm, a tracheoesophageal fistula 1 cm caudally to the diaphragm and unilateral multicystic renal dysplasia. Case 2: male vaginally delivery at 35 weeks to a 43-year-old mother with gestational diabetes. Antenatally, ‘VACTERL’ association was suspected on the basis of the US and a MRI was planned but not performed because of the early delivery. Following the delivery, there was severe respiratory distress, no audible cry, and ventilation was not effective in relieving the respiratory distress. Subsequent intubation was unsuccessful. An emergency tracheostomy was attempted: the larynx was identified, but only a tracheal stump was present on neck exploration. Postmortem confirmed type II (according to Floyd) tracheal agenesis with the esophagus connect to the main bronchus, renal dysplasia, anal atresia, and single umbilical artery. Conclusion Clinicians need to be aware of congenital airway malformation and subsequent difficulties upon endotracheal intubation and they have to be prepared to plan a multidisciplinary management at the delivery including emergency intubation through esophageal fistula.