Uncovering new physiology in bilateral renal agenesis following amnioinfusion

Case 1

A 22-year-old primigravida was found to have a fetus with bilateral renal agenesis and anhydramnios at the time of anatomy scan at 19 weeks’ gestation. She transferred care in order to pursue serial amnioinfusion with the goal of promoting pulmonary development and survival. She received 23 amnioinfusions via amnioport during the pregnancy. Pregnancy was complicated by preterm rupture of membranes at 25 weeks’ gestation, but this resolved within days and a normal amniotic fluid volume was maintained thereafter.

Preterm labor at 33 and 3/7 weeks led to preterm delivery following prolonged rupture of membranes via cesarean section due to breech presentation. A male was delivered with birth weight of 1900 g and Apgar scores of 1, 6 and 7. The infant was intubated in the delivery room, received surfactant, and was placed on volume-targeted mechanical ventilation. He developed a left tension pneumothorax requiring thoracentesis and chest tube placement. Despite the clinical diagnosis of pulmonary hypoplasia and initial pulmonary hypertension requiring treatment with inhaled nitric oxide, the infant’s pulmonary status steadily improved and he was able to extubate at 6 weeks of life.

The patient developed hypotension within hours after delivery and was placed on an epinephrine infusion. During the first 24 h of life, the infant had profound systolic and diastolic hypotension. Epinephrine infusion was progressively increased to high doses, vasopressin was added as a second agent, and stress dose hydrocortisone (1 mg/kg bolus followed by 0.5 mg/kg every 6 h) was started. Despite these interventions, blood pressures did not ultimately reach age based norms until day of life 3. Initial echocardiography showed normal anatomy and function, but with time, over the first 2 months of life revealed hyperdynamic biventricular function and left ventricular hypertrophy.

The patient was taken to the operating room on day of life 3 for placement of a peritoneal dialysis catheter and central venous catheter for hemodialysis. Due to skin breakdown and catheter problems, the patient was not able to tolerate peritoneal dialysis until nearly 3 weeks of life. In the meantime, he received modified continuous veno-venous hemofiltration (CVVH). The provision of adequate dialysis was frequently limited by hypotension with vasopressor support required for the first 44 days of life. Continued support was necessary intermittently throughout the remainder of the hospitalization with regimens including epinephrine, vasopressin, dobutamine and steroids. The patient was managed with a liberal fluid goal of 80 mL/kg/day initially, and increased through peri-operative period. Once dialysis was initiated, weight gain and positive fluid balance were able to be addressed and improved with adequate ultrafiltration.

The patient was evaluated multiple times for infection during his course including bacterial peritonitis; he was treated once with a prolonged course of broad spectrum intraperitoneal and intravenous antibiotics despite negative cultures. The hypotension noted in this report was clinically distinct from episodes concerning for sepsis, in that it was persistent and not episodic, and during which time inflammatory markers and cultures were negative.

An evaluation for the source of the hypotension was undertaken. Adrenal glands were visualized on renal ultrasound and were described as flat, without splaying of the limbs, with an appearance typical of renal agenesis. An adrenocorticotropic hormone (ACTH) stimulation test and aldosterone levels (19.6 ng/dL) were normal. Renin activity (0.3 ng/mL/h) was within the low-normal range. After discussion with Endocrinology, no further adrenal hormone replacement was pursued. Thyroid function was followed closely, but treatment was never required.

The infant was maintained on a combination of peritoneal and intermittent modified hemodialysis until he was transferred to another institution for continued care at 4 months with plans to support until renal transplant was possible. He died of presumed sepsis at 6 months.

Case 2

A 25-year-old gravida 2 mother was found to have a fetus with bilateral renal agenesis and anhydramnios at the time of anatomy scan at 21 weeks’ gestation. She had received 6 amnioinfusions prior to arrival at our center. She opted to transfer care at 26 weeks in order to pursue further serial amnioinfusion with the goal of neonatal pulmonary survival and early dialysis. She received a total 26 percutaneous amnioinfusions during the pregnancy.

A viable male was born at 36 and 0/7 weeks weighing 2200 g. Delivery followed preterm labor and concern for chorioamnionitis with amniotic fluid sample positive for enterococcus prior to induction of labor. The patient was placed on continuous positive airway pressure (CPAP) in the delivery room with Apgar scores of 8 and 9. Soon after admission to the neonatal intensive care unit (NICU), the infant developed increasing oxygen requirement and respiratory distress necessitating intubation. On chest X-ray, the infant was found to have bilateral pneumothoraces requiring chest tube placement. Antibiotics were initiated due to concerns for chorioamnionitis; blood culture returned negative. The patient received adequate fluid intake to address insensible fluid losses, but otherwise maintained with extreme fluid restriction of 40 mL/kg/day. Initial blood pressures were within normal limits for gestational age, but at approximately 4 h of life, the infant developed profound hypotension requiring vasopressor support. Sepsis was ruled out and respiratory status improved on low ventilator support and low oxygen. Stress dosing with hydrocortisone was started (1 mg/kg every 6 h). The hypotension was refractory to norepinephrine and dopamine infusions. A random cortisol level at 8 h of life was 1.6 μg/dL, within the reference range. Based on the clinical picture of moderate pulmonary hypoplasia and refractory hypotension that would not permit the initiation of either peritoneal or modified hemodialysis, the family opted to redirect care towards comfort and ultimately withdrawal of support. The infant expired at approximately 45 h of life. Autopsy revealed small [lung body weight ratio (LBWR) 0.013] but well-developed lungs. Histology showed lung lobules with a normal delicate architecture and alveolar maturation with no evidence of significant inflammatory cell infiltration. They were described as of adequate volume, weight and development to support adequate ventilation and oxygenation. No echocardiography was performed prior to death, however, no cardiac abnormalities were noted on post-mortem exam. Placenta, fetal membranes and umbilical cord all showed no signs of inflammatory changes or infiltrates. Post-mortem blood culture isolated Escherichia coli, but this was not felt to represent a true infection. The pathologic cause of death was determined to be persistent and unresponsive hypotension of unknown etiology, ultimately secondary to bilateral renal agenesis.