A Term Neonate with a Renal Mass

A 27-year-old multigravida woman is referred to our institute for abnormal antenatal ultrasonography findings suggestive of fetal renal anomalies and delivers a neonate via vaginal delivery at 40 weeks of gestation. Ultrasonography at 32 weeks shows a bulky left kidney with multiple cysts (the largest measuring 1.8 × 1.8 cm), with the right kidney showing mild pelvicalyceal dilatation measuring 6.5 mm, and a normal amniotic fluid volume. No other anomalies are noted, and the mother has no medical or obstetric illness. The neonate is born out of a nonconsanguineous marriage and cries immediately after birth, with a birthweight of 2,680 g.Vital parameters, including blood pressure (BP), are within normal limits. On examination, a mass is palpated in the left lumbar region, which is soft and ballottable on bimanual compression, suggestive of an enlarged left kidney. The right kidney is not palpable, and there is no hepatosplenomegaly. The genital examination shows clitoromegaly (1.3 cm) with hyperpigmentation noted around the genitals, umbilicus, and axilla (Fig 1). There is no evidence of abnormal facies or any other dysmorphism, with the rest of the systemic examination being normal. The neonate was admitted to the NICU for further evaluation of renal mass with a disorder of sexual differentiation.Congenital hydronephrosisMulticystic dysplastic kidneyAutosomal recessive polycystic kidney diseaseDenys-Drash syndromeMeckel-Gruber syndromeWilms tumorNeuroblastomaThe neonate passed urine within 24 hours and had normal urine output throughout the NICU stay. Arterial blood gas levels; serum creatinine, sodium, and potassium levels; and urine routine tests, including protein level and microscopy, are normal. The neonate is on exclusive breastfeeding throughout, and BP and growth monitoring continue to be normal. Ultrasonography of the abdomen and kidney shows a bulky left kidney with multiple cysts in the cortex, which measure on average 5.9 × 2.8 cm. These cysts are arranged in a nonuniform manner with a retained corticomedullary differentiation. There are no cysts communicating with the renal pelvis, no significant pelvicalyceal dilatation, and a normal ureter and bladder (Fig 2). The right kidney also appears bulky, with multiple tiny cysts in the cortex with a retained corticomedullary differentiation.A steroid liquid chromatography–mass spectrometry profile was performed after corticotropin stimulation to evaluate the disorder of sexual differentiation. The details are given in the Table.A technetium-99m ethylenedicysteine scan shows nonvisualization of the left kidney suggestive of a nonfunctioning left kidney. The right kidney shows normal cortical function with normal excretion (Fig 3). Ultrasonography of the liver and brain have no evidence of any cysts, and ultrasonography of the abdomen of the parents is also normal. Direct renin activity is greater than 500 μg/L.The whole exome sequence shows a homozygous mutation in CYP11B1, exon 5 c.874G>T, autosomal recessive suggestive of congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase deficiency (11β-OHD) CAH. No other abnormal genes suggestive of cystic kidney disease were detected; hence, the pathology could be attributed to sporadic in origin.The actual diagnosis is left-sided multicystic kidney disease (MCKD) with 11β-OHD CAH.MCKD is the most common cause of palpable renal mass and the most detected cystic renal anomaly in prenatal ultrasonography. (1) Unilateral MCKD occurs in 1 in 4,000 fetuses, and bilateral cases occur in 1 in 10,000. (2) Solid cystic dysplasia and hydronephrosis are the 2 described forms of this condition in which numerous cysts, undifferentiated epithelium, and primitive ducts replace the normal renal tissue, leading to the absence of identifiable renal parenchyma. This occurs due to the failure of integration and branching of the ureteric bud into metanephros during development. (3)Unilateral MCKD is nonhereditary and sporadic and has been reported in various conditions, such as Bardet-Biedl syndrome, Zellweger syndrome, Mayer-Rokitansky disease, etc. There is a paucity of literature reviewing the association of unilateral MCKD with 11β-OHD CAH. (1)The differentiating features of MCKD include the presence of an enlarged kidney with large cortical cysts arranged in a nonuniform manner with retained corticomedullary differentiation and a renogram confirming a nonfunctioning kidney. MCKD is usually unilateral, and there is a compensatory enlargement of the other kidney with associated hydronephrosis due to vesicoureteral reflux, ureteropelvic junction, and ureterovesical obstructions seen in the contralateral kidney in up to 20% to 33% of patients. The presence of significant hydronephrosis or a breakthrough urinary tract infection are indications for micturating cystourethrogram. (4)Complete cyst regression occurs in nearly half of the patients with MCKD by age 7 years. (5) Because neoplasms arise from the stromal rather than the cystic component, even if the cysts regress, the likelihood of developing a neoplasm and hypertension is not altered. However, the presence of both is an indication of nephrectomy and occurs in up to 0.2% to 1.2% and 1 in 1,200, respectively. (4) Thus, the most important aspect of follow-up is being certain that the solitary kidney is functioning normally.On the evaluation of the disorder of sexual differentiation, 11β-OHD CAH was diagnosed in our neonate. Despite having this simple virilizing type of CAH, with no evidence of chronic kidney disease due to MCKD at present, the neonate having high aldosterone activity is a masquerading finding. The absence of hypokalemia and hypertension despite such a high aldosterone level makes this even more unique. We hypothesize that these findings could be due to the overstimulation of the renin-aldosterone axis due to renin produced by MCKD cysts and partial deficiency rather than the complete absence of the 11β-OHD enzyme. This puts the neonate at higher risk for earlier-onset hypertension subsequently, although the mean age of hypertension in children with MCKD has been reported to be 4 years and older. (6)Another interesting finding is the presence of cortical cysts in the contralateral kidneys, which are smaller and with retained renal function. This is probably due to the antenatal exposure to high aldosterone levels, which is reported to occur in older children and adults with hyperaldosteronism (7) and is unlikely to be a bilateral disease because the involvement of both kidneys is universally fatal and presents with chronic kidney disease in the neonatal period among survivors.The neonate is started on hydrocortisone tablets at 5 mg/m2 per day in 3 divided doses, which were given after pulverizing the crushed tablet according to the required dose and after mixing it with the mother’s milk. There are no electrolyte abnormalities or hypertension noted throughout the NICU stay. Exclusive breastfeeding is continued throughout the hospital stay, and discharge is at 21 days old. Currently, she is 3 months old and is on regular follow-up with normal growth and neurodevelopment and plans for 3 monthly BP and serum electrolyte assessments. The parents have been advised regarding optimizing the dose of hydrocortisone during illness and the need for strict growth and BP monitoring.Unilateral multicystic dysplastic kidney disease presenting as an abdominal mass may be asymptomatic in the neonatal period.The presence of large cortical cysts arranged haphazardly with absent renal activity on renal scan is diagnostic of multicystic kidney disease.Preserving the function of the contralateral kidney and monitoring for hypertension and growth is the key aspect of management in these neonates.The association of 11β-hydroxylase deficiency congenital adrenal hyperplasia and multicystic kidney disease can present a diagnostic dilemma due to affection of the renin-aldosterone pathway.American Board of Pediatrics Neonatal-Perinatal Content SpecificationUnderstand the basic enzymatic defects involved in the various types of congenital adrenal hyperplasia.The authors thank Dr Sangeeta Ravat, dean, Seth G.S. Medical College, and King Edward Memorial Hospital, Mumbai, India, for granting permission for publication.