Renal failure in neonates

Case study 1

A baby boy is born to a 29-year-old gravida 3, para 2 mother at 35 ² ⁄ ₇ weeks’ gestation. The pregnancy was complicated by oligohydramnios and a concern for right renal agenesis, left renal dysplasia, and preterm labor. Maternal testing: rapid plasma reagin (RPR) negative, hepatitis B surface antigen negative, group B Streptococcus (GBS) colonization negative, and human immunodeficiency virus (HIV) negative. Amniocentesis demonstrated a normal male karyotype. He was born via vaginal delivery (VD). His Apgar scores were 6/7/8, and his birth weight was 2510 g.

Case study 1 (continued)

The patient was admitted to the NICU. A renal ultrasound showed a small, mildly echogenic right kidney (2.12 cm) without hydronephrosis and a slightly larger mildly echogenic left kidney (2.62 cm) with dilatation of the left renal pelvis without caliectasis. The bladder appeared normal. A VCUG revealed bilateral grade 3 vesicoureteral reflux and he was started on amoxicillin prophylaxis ( Fig. 18.1 ). The BUN is 13 mg/dL and the creatinine is 2.2 mg/dL.

Neonatal hyperkalemia and management

Hyperkalemia (K >6.0 mEq/L) can be a life-threatening complication of neonatal AKI. Premature neonates have lower GFR and relative resistance to aldosterone, limiting their ability to excrete potassium. Therefore reducing potassium intake by lowering potassium from total parenteral nutrition (TPN) or intravenous fluid (IVF) and/or use of low potassium formula (Similac PM 60/40 or breast milk) is an important precaution in the management of neonatal AKI. Administration of sodium polystyrene resins can be used to achieve the exchange of potassium for sodium, but direct oral or rectal administration might carry risks in neonates as it has been reported to cause intestinal ischemia, obstruction, and perforation. Potassium intake can be further decreased by premixing sodium polystyrene with Similac PM 60/40 or breast milk allowing the potassium to precipitate out. After allowing the precipitate to settle, the supernatant is decanted for oral/gastric administration (so that there is no direct administration of the resin).

For acute management of hyperkalemia, an electrocardiogram (ECG) should be performed to evaluate the effects of hyperkalemia on the heart’s electrical activity. Calcium gluconate should be administered in the presence of ECG changes. As concomitant acidosis will drive potassium out of cells and elevate the serum potassium, sodium bicarbonate should be administered to treat acidosis but is not used when metabolic acidosis is not present. Administration of IV glucose and insulin can be used in the acute setting to stimulate potassium entry into cells and temporarily lower serum potassium. However, insulin and glucose will not enhance excretion of potassium. In the nonanuric patient, IV furosemide can be administered to increase potassium excretion but is not an evidence-based intervention. More recently, inhaled albuterol (salbutamol) has been used to treat infants with elevated serum potassium values. Small randomized clinical trials indicate the drug is effective, but it has not been evaluated in a large randomized trial. If medical management fails, dialysis is indicated for potassium removal.

Case study 1 (continued)

On further questioning, it is discovered that the patient has an older sibling with a renal transplant for congenital kidney disease.

Embryonic kidney development

The kidneys are derived from the intermediate mesoderm. There are three sets of embryonic kidneys during embryogenesis: the pronephros (at 3 weeks’ gestation), mesonephros (at 4 weeks’ gestation), and metanephros (at 5 weeks’ gestation) ( Fig. 18.2 ). The pronephros and most of the mesonephros degenerate. The mesonephric duct (Wolffian duct) gives rise to epididymis, vas deferens, seminal vesicles, and ejaculatory ducts in males. The mature human kidneys develop from the metanephros. The ureteric bud, which is an outgrowth of the mesonephric duct in both males and females, invades the metanephric mesenchyme and undergoes sequential branching morphogenesis to form the collecting ducts. The tips of the ureteric bud induce nephron formation in the mesenchyme. Thus the number of ureteric bud branches will influence nephron number. Defects in the budding, migration, and branching of ureteric bud can lead to congenital abnormalities of the kidneys (e.g., renal aplasia, hypoplasia, dysplasia) and urinary tract deformities such as ureteral pelvic junction (UPJ) or ureteral vesical junction (UVJ) obstruction and vesicoureteral reflux.

The inductive signals originating from the ureteric bud stimulate mesenchymal to epithelial transition, and spheres of epithelial cells known as renal vesicles are the earliest form of the developing nephron. The developing nephrons go through a series of morphologic changes, forming a comma- and then S -shaped bodies. Segments of the S -shaped body will differentiate into the distal tubule, proximal tubule, and glomerular podocytes. Endothelial cells migrate into the cleft of the S -shaped body to form the glomerular endothelial cells of the capillaries. The molecular signals that drive nephrogenesis require reciprocal interactions between the ureteric bud and surrounding metanephric mesenchyme. Genetic defects in the signaling pathways can result in congenital anomalies of the kidney and urinary tract (CAKUT).

The first glomeruli form by 9 weeks, and nephrogenesis continues until 34 to 35 weeks’ gestation. The ureters and bladder form around the same time as the metanephric kidney. Glomerular filtration begins at the gestational age of 9 to 10 weeks. Fetal urine is the major source of amniotic fluid from approximately 16 weeks’ gestation onward. Thus obstruction of urinary outflow (as may occur in posterior urethral valves) or renal aplasia/severe dysplasia leads to low urine production and will present with oligohydramnios during the pregnancy. Oligohydramnios is associated with poor fetal lung development as the lack of sufficient amniotic fluid diminishes fetal breathing and thoracic movements that are required for proper lung maturation.

CAKUT are the leading causes of end-stage renal disease (ESRD) in children in North America. Obstructive uropathy from posterior urethral valves, followed by renal hypoplasia/aplasia/dysplasia, are the most common causes of children requiring dialysis in infancy.

Posterior urethral valves are membranes at the junction of the prostatic and bulbar urethra. Although the pathophysiology of this condition is not fully understood, these membranes are thought to form during normal development. However, failure to recanalize during urethral development leads to bladder outlet obstruction. In the face of high-pressure obstruction, bladder differentiation is impaired and a thick-walled bladder develops. The dilation of the prostatic urethra can lead to the classic keyhole sign on a fetal ultrasound. The exposure of the developing kidneys to obstruction results in varying degrees of renal dysplasia.

CAKUT may be associated with both syndromes (e.g., Trisomy 21) and monogenic defects ( ). Monogenic causes of CAKUT often have extrarenal manifestations. For example, PAX2 mutations are associated with renal colobomas. The renal coloboma syndrome is an autosomal dominant disorder associated with optic nerve colobomas or dysplasia and renal defects (including hypodysplasia with or without VUR). As discussed earlier, advanced genetic technologies can help discover genetic mutations that underlie these malformations. Identifying the underlying defect allows for appropriate studies and consultations to identify and manage extrarenal disease.

Case study 1 (continued)

The clinical course over the next week was remarkable for fever with hemodynamic instability and a low urine output of 0.25 mL/kg/hour. He required multiple fluid boluses and was started on broad spectrum antibiotics. Table 18.2 lists other pertinent laboratory data and clinical information.