Background
Multicystic dysplastic kidney (MCDK), a variant of renal dysplasia, is one of the most frequently identified congenital anomalies of the urinary tract. This article reviews the definition, embryology, epidemiology, etiology, pathology, clinical manifestations, associated malformations, natural history, differential diagnosis, complications, evaluation, management, and prognosis of multicystic dysplastic kidney.
Renal dysplasia, defined as abnormal metanephric differentiation, has variable presentations that cover a spectrum of conditions, including hypoplasia, multicystic dysplasia, and aplasia. Overall, renal dysplasia is the leading cause of end-stage renal disease in children.
Multicystic dysplastic kidney is a form of renal dysplasia characterized by the presence of multiple, noncommunicating cysts of varying size separated by dysplastic parenchyma and the absence of a normal pelvocaliceal system. The condition is associated with ureteral or ureteropelvic atresia, and the affected kidney is nonfunctional. Other terms used to describe this condition include multicystic kidney and multicystic renal dysplasia. Multicystic dysplastic kidney is the most common cause of an abdominal mass in the newborn period and is the most common cystic malformation of the kidney in infancy. See the image below.
Kidney, ureter, and bladder (KUB) images of an infant with a right multicystic dysplastic kidney demonstrate displacement of bowel loops away from the right abdomen.
Pathophysiology
A brief overview of nephrogenesis is provided to highlight the developmental defects that lead to multicystic dysplastic kidney.
The urogenital system is predominantly derived from the intermediate mesoderm of the early embryo. [1] The intermediate mesoderm undergoes epithelial transformation to form the nephric (Wolffian) duct, which extends rostrocaudally in the embryo, adjacent to a tract of mesoderm (the nephrogenic cord). The nephric duct induces the adjacent nephrogenic cord mesenchyme to aggregate and transform into epithelial tubules.
During its caudal migration, the nephric duct induces 3 embryonic kidneys in the nephrogenic cord: pronephros, mesonephros, and metanephros (in a spacial and temporal sequence). When the nephric duct reaches the level of the developing hind limb, it gives rise to a caudal diverticulum, the ureteric bud that invades the metanephric mesenchyme in week 4 of human development.
Metanephros, which becomes the ultimate kidney is the product of reciprocal interactions between the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme forms the proximal components of the nephron from the glomerulus to the distal convoluted tubule. The ureteric bud that invades and branches inside the mesenchyme forms the distal components of the nephron, including the collecting ducts, calyces, pelvis, and ureter.
According to the leading hypothesis, the ureteric bud theory proposed by Mackie and Stephens, multicystic dysplastic kidney results from an abnormal induction of the metanephric mesenchyme by the ureteral bud. [2] This abnormal induction might be due to a problem with the formation of the mesonephric duct, the malformation of the ureteric bud, or the degeneration of the ureteric bud at an early stage. The final structure of the dysplastic kidney depends on the timing of the injury to the ureteric bud and on the effect of the injury on the ureteric bud branching.
Multicystic dysplastic kidney usually develops as a sporadic problem; although, familial occurrence has been reported. [3] Mutations in genes important in ureteric bud development have been identified in syndromes with renal dysplasia, including multicystic dysplastic kidney. Specifically, mutations in EYA1 or SIX1 genes that lead to branchio-oto-renal (BOR) syndrome are associated with renal malformations, including multicystic dysplastic kidney. [4, 5] Mutations in the PAX2 gene, the cause of Renal-coloboma syndrome (RCS), are associated with renal dysplasia. Hereditary MCDK was found in 3 generations of a family that also carried a PAX2 gene mutation. [6]
PAX2 mutations have also been identified in patients with isolated renal hypoplasia/dysplasia. Using predictive analysis, a study identified 2 new sequence variations: a deletion causing a frameshift (c.69delC) and a nucleotide substitution determining a splice site mutation (c.410+5 G/A). These findings suggest that all patients with kidney and urinary tract malformations may benefit from PAX2 molecular analysis. [7]
Exposure to viral infections in utero has been associated with multicystic dysplastic kidney. Cytomegalovirus (CMV), enterovirus, and adenovirus have been implicated in the development of renal dysplasia. Teratogens may also play a role in abnormal renal development. Although, their association with multicystic dysplastic kidney has not been clearly established. Urinary tract obstruction during fetal development causes urinary stasis, cyst formation, and disruption of nephrogenesis; however, the degree of obstruction does not correlate with the severity of dysplasia. Thus, obstruction is not proven as a mechanism of multicystic dysplastic kidney.
Multicystic dysplastic kidney may persist without any change, may increase in size, or may undergo spontaneous involution. Calcification may develop in persistent multicystic dysplastic kidney, particularly in adults, and has been reported as early as age 3 months. Most cases of unilateral multicystic dysplastic kidney undergo spontaneous involution. The change may be due to resorption of the fluid within the cysts. Multicystic dysplastic kidney can be diagnosed prenatally. [8, 9, 10] An involution of prenatally diagnosed multicystic dysplastic kidney has been noted before birth. Some cases of prenatally diagnosed multicystic dysplastic kidney monitored prior to birth demonstrate an initial increase in size followed by involution.
The Multicystic Kidney Registry reported 260 patients with multicystic dysplastic kidney whose cases were managed nonoperatively and whose cases were followed for varying periods as long as 5 years. [11] Approximately 18% of these kidneys were undetectable by age 1 year, 31% were undetectable by age 3 years, and 54% were undetectable by age 5 years. The initial ultrasonographic evidence of involution is a change in cyst distension that precedes a decrease in renal size.
Whether involution of the cysts is associated with involution of the intervening renal parenchyma is unclear. The residual parenchyma may be too small to be identified with conventional diagnostic imaging studies. Avni et al reported a child with prenatally diagnosed multicystic dysplastic kidney who had an operation when aged 3 months without repeat ultrasonography. [12] At surgery, neither renal tissue nor renal vasculature was found.
Epidemiology
Frequency
International
Incidence of unilateral multicystic dysplastic kidney is reported to be 1 in 4300 live births, and the combined incidence of unilateral and bilateral multicystic dysplastic kidney is 1 in 3600 live births. Up to 39% of patients present with associated anomalies in the contralateral kidney. [13] Bilateral multicystic dysplastic kidney occurs in about 20% of prenatally diagnosed cases of multicystic dysplastic kidney. The left kidney is involved in 55% of cases, and the right kidney is involved in 45%.
Mortality/Morbidity
Multicystic dysplastic kidney may persist without any change, may increase in size, or may undergo spontaneous involution. Calcification may develop in persistent multicystic dysplastic kidney, particularly in adults, and has been reported as early as age 3 months. Most cases of unilateral multicystic dysplastic kidney undergo spontaneous involution. Morbidity and mortality are uncommon in patients with a unilateral multicystic dysplastic kidney and a normal contralateral kidney. Morbidity and mortality may result from urinary tract infection (UTI), hypertension, or neoplasia.
Sex
A review of 14 studies that reported on 340 patients with unilateral multicystic dysplastic kidney revealed a male-to-female ratio of 1.48:1. [14]
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Kidney, ureter, and bladder (KUB) images of an infant with a right multicystic dysplastic kidney demonstrate displacement of bowel loops away from the right abdomen.
