NeoQuest September 2024: Renal Mass in a Term Neonate

A term male neonate is born via spontaneous vaginal delivery with a prenatal course notable for multiple cysts in the left kidney detected on fetal ultrasonogram at 20 weeks of gestation. At birth, a mass is palpated in the left hemiabdomen. The infant’s blood pressure and urine output are within expected ranges. A renal ultrasonography and renogram of the left kidney are obtained (Figure 1). The right-sided kidney appears enlarged without cysts. The remainder of the physical exam is normal.

Figure 1. A. A renal ultrasonography demonstrates a bulky left kidney with multiple cysts (yellow arrow) with retained corticomedullary differentiation. B. A renogram suggests a non-functioning left kidney. Image from: Raghavendra PR, Nair S, Nathan MV, Haribalakrishna A, Thakkar H. A term neonate with a renal mass. Neoreviews. 2024;25(9):e578–e581.¹

Which of the following is associated with this infant’s most likely diagnosis?

1. Abnormalities in PKD1 gene located on chromosome 16
2. Abnormalities in PKHD1 gene located on chromosome 6
3. Involution of cysts over time
4. Occipital encephalocele
5. Retinal degeneration

Answer: C. Involution of cysts over time

Explanation:

The infant described in this vignette was prenatally diagnosed with unilateral cystic kidney disease, which can have a multitude of underlying causes. Some of the different medical conditions associated with cystic kidneys are reviewed below.

Multicystic dysplastic kidney (MCDK) is a severe form of renal dysplasia where both small and large cysts occupy space in immature, primitive, and undifferentiated kidneys (Figure 2).² MCDK can result from pathogenic variants in multiple genes linked to kidney development.^2,3 Prenatal ultrasonography may show hyperechoic kidneys with the early development of renal cysts, which sometimes can be seen as early as 20 weeks of gestation.^2,3,4 If cysts are identified on ultrasonography at or before 20 weeks of gestation, the diagnosis is much more likely to be MCDK than polycystic kidney disease.³ In cases of bilateral MCDK, total kidney function can be severely impaired and is associated with higher mortality.² In unilateral MCDK, the contralateral kidney hypertrophies to compensate for the affected side.² Nephrectomy of the affected kidney is often not required, as cysts can involute over time (Option C).^2,3 Unlike other cystic renal diseases, MCDK is not associated with an underlying ciliopathy.^2,5 Multiple genes associated with ureteric bud development have been implicated in MCDK, but much about the disorder remains unknown.³ In this patient, renal ultrasonography reveals multiple non-uniform cysts with retained corticomedullary differentiation (Figure 1A), and a technetium-99m ethylendicysteine scan (also referred to as a renogram) demonstrates non-visualization of the tracer on the left side (Figure 1B), suggestive of a non-functioning left kidney. These features, including compensatory increased size of the right kidney, are consistent with a diagnosis of unilateral MCDK.

Figure 2. Postnatal ultrasonography reveals a multicystic dysplastic kidney with non-uniform, large cysts. Image from: Setty S, Parikh P. A neonate with facial asymmetry. Neoreviews. 2019;20(10):e608–e611.⁴

Polycystic kidney disease (PKD) exists in two separate, distinct forms: autosomal dominant (ADPKD) and autosomal recessive (ARPKD). ADPKD is most commonly caused by abnormalities in PKD1, a gene on chromosome 16 that encodes the polycystin 1 protein (Option A), while fewer cases are caused by abnormalities in PKD2, a gene on chromosome 4 that encodes the polycystin 2 protein.³ ARPKD is due to alterations in the PKHD1 gene on chromosome 6 (Option B). Bilateral renal cysts seen in ADPKD are progressive and are rarely present in the neonatal period, however, the neonatal presentation of ADPKD is similar to that of ARPKD.³ Many patients with ADPKD will not demonstrate symptoms in childhood, but approximately half will progress to stage end-stage renal disease over the course of several decades.³ Renal disease in patients with ARPKD can vary in severity and typically presents as large kidneys that are echogenic on prenatal ultrasonography with multiple small cysts that may not appear until later in gestation (Figure 3).³ The amniotic fluid volume may initially be normal but declines as gestation advances.³ Those who are severely affected can develop the Potter syndrome phenotype with a flattened nose, pulmonary hypoplasia, and deformities of the spine and extremities.³ Patients with ARPKD are at risk for common complications of chronic kidney disease, such as anemia, hypertension, osteodystrophy, and cognitive deficits. The patient described here has large, non-uniform renal cysts with cystic involvement of only one kidney, making a diagnosis of ADPKD or ARPKD less likely.

Figure 3. A. Ultrasonography of a large, echogenic kidney with multiple small cysts. B. Gross appearance of an enlarged kidney with multiple small cysts. Image from: Cohen JN, Ringer SA. Congenital kidney abnormalities: diagnosis, management, and palliative care. Neoreviews. 2010;11(5):e226-e234.³

The presence of bilateral large polycystic kidneys (Figure 4), along with occipital encephalocele, hepatic fibrosis, and occasionally postaxial polydactyly, is suggestive of a diagnosis of Meckel-Gruber syndrome (Option D).² Meckel-Gruber syndrome is a rare, lethal autosomal recessive disorder caused by variants in multiple genes that encode transition zone proteins at the base of cilia.^2,6 Other than renal disease, the patient described in this example does not have features consistent with Meckel-Gruber syndrome.

Figure 4. An infant with Meckel-Gruber Syndrome with an occipital encephalocele and enlarged abdomen secondary to large polycystic kidneys. Image from: Bishara N, Clericuzio CL. Common dysmorphic syndromes in the NICU. Neoreviews. 2008;9(1):e29–e37.⁷

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive condition that involves renal malformations and other anomalies such as hypogonadism, intellectual impairment, obesity, polydactyly or other extremity abnormalities, and retinal degeneration (Option E).² Renal involvement in BBS is variable, as some cases are characterized by normal renal anatomy, while other cases are associated with unilateral or bilateral renal cysts; urinary tract malformations; ectopic, duplex or horseshoe kidneys; or absent kidneys.² Prenatal ultrasonography will most likely demonstrate enlarged, hyperechoic kidneys without the expected cortico-medullary differentiation.² The infant described in this vignette retains cortico-medullary differentiation and is not reported to have the other characteristic anomalies associated with BBS, making this diagnosis less likely.

Did you know?

• Genetic testing is advised in the antenatal evaluation of renal cysts due to significant overlap in the phenotype of fetal cystic kidney disease.² It is recommended to test for multiple genes simultaneously through polycystic kidney disease or ciliopathy gene panels by next-generation sequencing or whole exome sequencing.²

What syndromes or genetic disorders are associated with MCDK?

To find the answer, please read the following article:
Heidenreich LS, Bendel-Stenzel EM, Hanna C. Genetic etiologies, diagnosis, and management of neonatal cystic kidney disease. Neoreviews. 2022;23(3):e175 –e186.²

NeoQuest September 2024 Authors:

Allison N. J. Lyle, MD, MA, University of Louisville School of Medicine
Lila S. Nolan, MD, Washington University School of Medicine in St. Louis

References: 

1. Raghavendra PR, Nair S, Nathan MV, Haribalakrishna A, Thakkar H. A term neonate with a renal mass. Neoreviews. 2024;25(9):e578–e581
2. Heidenreich LS, Bendel-Stenzel EM, Hanna C. Genetic etiologies, diagnosis, and management of neonatal cystic kidney disease. Neoreviews. 2022;23(3):e175–e186
3. Cohen JN, Ringer SA. Congenital kidney abnormalities: diagnosis, management, and palliative care. Neoreviews. 2010;11(5):e226–e234
4. Setty S, Parikh P. A neonate with facial asymmetry. Neoreviews. 2019;20(10):e608–e611
5. Fong J, De Beritto T. Congenital anomalies of the kidneys and urinary tract. Neoreviews. 2024;25(2):e78–e85
6. Feldenberg R, Beck A. Congenital diseases of the kidneys: prognosis and treatments. Neoreviews. 2017;18(6):e345–354
7. Bishara N, Clericuzio CL. Common dysmorphic syndromes in the NICU. Neoreviews. 2008;9(1):e29–e38