INTRODUCTION — Renal cysts occur in a variety of diseases in children (table 1). Cysts may be due to nonhereditary fetal malformations or genetic disorders, or, rarely, they may be acquired. Cysts may also occur as an isolated finding or as part of a syndrome.
An overview of the different forms of pediatric renal cystic disease will be reviewed here.
NONHEREDITARY: CYSTIC RENAL DYSPLASIA — Cystic renal dysplasia, defined by microscopic features, is due to renal parenchymal malformation of the fetal kidney. As a result, the kidney contains primitive ducts and cysts, and nonrenal tissues such as cartilage, fat, and hematopoietic tissue. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Kidney parenchymal malformations'.)
Cystic dysplasia is also often associated with antenatal obstruction of the urinary tract, eg, posterior urethral valves (PUV) or ureteropelvic junction (UPJ) obstruction. Cystic dysplasia is frequently observed in the atrophic pole of a kidney with duplicated ureters or an ectopic ureterocele.
Multicystic dysplastic kidney — The most severe form of cystic renal dysplasia is the multicystic dysplastic kidney (MCDK).
Pathology, epidemiology, clinical manifestations, and course
●Pathology – The MCDK consists of numerous noncommunicating cysts separated by dysplastic tissue (picture 1 and picture 2 and image 1 and image 2). There is typically no identifiable kidney tissue, although in some cases some minimal functional kidney tissue may exist in the dysplastic area. The ureter is absent or atretic [1]. The cause of MCDK is unclear. There may be an underlying genetic predisposition [2,3]. This was illustrated by a study that analyzed coding exons of genes associated with congenital anomalies of the kidney and urinary tract (CAKUT) in a large cohort of children with CAKUT that reported MCDK was associated with mutations in the CHD 1L, ROBO2, HNF 1B, and SALL1 genes [2].
●Epidemiology – The incidence of MCDK varies according to the country and the study, ranging from 1 per 3600 to 1 per 4300 live births [4,5]. MCDK may involve both kidneys, but most cases are unilateral, with the left kidney being more often affected [6]. MCDK occurs more frequently in boys than in girls [7]. In the majority of cases, involution of the MCDK occurs as demonstrated by repeat ultrasound exam [8,9]. The rate of involution is generally greatest during the first two to three years of life and completed at a median age of 5.5 years [10-12].
●Presentation and clinical manifestations
•Antenatal – MCDK is commonly detected by antenatal ultrasonography (image 3 and image 4).
•Postnatal – Since symptoms and complications are very uncommon, MCDK is typically identified postnatally only if there is a palpable mass or incidental identification by imaging performed for another condition. Extrarenal malformations also may be seen (eg, heart defects, esophageal or intestinal atresia, or myelomeningocele) and workup for these anomalies may identify MCDK as an concomitant condition.
●Course
•Involution without intervention – In most cases of MCDK, the natural history without intervention is involution of the affected kidney. Case series report that 60 percent of MCDK completely involute within the first five years of life [8,13,14].
•Low risk of malignancy – The rate of malignant transformation of MCDK is small, if at all increased, or comparable to nonaffected kidneys in the general population [13-15].
•Low risk of hypertension – The rate of hypertension is comparable to that of the general population [8,13,16]. In a systematic review of 29 studies, six cases of hypertension in the entire pool of 1115 patients were noted, an incidence that is lower than that found in the general pediatric population [16].
•Contralateral kidney – The contralateral kidney undergoes compensatory hypertrophy, which begins in utero and is typically observed by three years of age, resulting in a kidney size that is greater than two standard deviations beyond the mean length [12]. The absence of compensatory hypertrophy suggests abnormalities of the contralateral kidney including rotational or positional anomalies, hypoplasia, areas of dysplasia, vesicoureteral reflux (VUR), ureterocele, ureteropelvic junction (UPJ) obstruction, or genital abnormalities [1,14,17-19]. VUR is the most common kidney abnormality, occurring in up to 21 percent of contralateral kidneys of affected patients [1,13,14,18,20].
Management — Because most cases of MCDK naturally involute without any long-term complications, affected individuals are typically managed conservatively (ie, observation). However, long-term follow-up is required because individual patients with contralateral abnormalities may develop kidney impairment as noted above [14,21].
●Routine monitoring – Our current management approach for patients with unilateral MCDK includes:
•Serial ultrasonographic evaluation to monitor contralateral kidney growth and MCDK involution at birth, and at 6 months, 2 years, 5 years, 10 years, and 15 years of age [22]. Serial ultrasounds also may detect any significant kidney scarring to the contralateral kidney due to recurrent urinary tract infection.
•Routine follow-up that includes blood pressure measurement [23], urinalysis to detect proteinuria, and kidney function studies (eg, serum creatinine), especially in children with contralateral abnormalities who are at risk for developing chronic kidney disease [14].
●Other typically unnecessary tests and interventions – We do not routinely perform any of the following in the management of MCDK.
•Voiding cystourethrogram (VCUG) – Performing a VCUG is unnecessary in patients with two successive normal ultrasound scans of the contralateral kidney because it is highly unlikely that clinically significant VUR is present. Although VUR has been reported to occur in 4 to 21 percent of contralateral kidneys [1,24], it is usually low grade and generally resolves in early life [21,24]. Patients with MCDK and VUR are more likely to have ultrasonographic abnormalities of the contralateral kidney [1,25,26]. If there is significant contralateral hydronephrosis or a history of urinary tract infection, then a VCUG should be performed. A meta-analysis of 37 studies that enrolled 2057 patients reported that 17 percent of patients with unilateral MCKD have VUR in the contralateral kidney, 41 percent of which is dilatating VUR [25].
•Renal scintigraphy – We do not routinely perform renal scintigraphy as it does not change our management approach, and in some cases, there is detectable function of MCDK on renal scintigraphy making this an unreliable diagnostic study [27]. Although other centers have used renal scintigraphy as a diagnostic tool [28], we and others find a high predictive value of kidney ultrasound for the diagnosis of MCDK without the need of renal scintigraphy to confirm the diagnosis [29].
•Surgical resection – We do not recommend resection of the affected kidney. Although it has been suggested that resection eliminates the risk of malignancy; there is no evidence of increased risk of malignancy in MCDK kidneys, particularly Wilms tumor. This was illustrated in a systematic literature review of 26 studies, in which there were no cases of Wilms tumor in the 1041 children with a unilateral MCDK [30]. In addition, a review article reported that data from the National Wilms Tumor Study Pathology Center demonstrated only one case of MCDK among more than 6000 cases of nephroblastoma [31].
However, an unequivocal diagnosis of MCDK is important because patients in whom the diagnosis is equivocal may actually have another potentially life-threatening disease, such as cystic Wilms tumor [32].
Segmental multicystic dysplasia — There are case reports of segmental multicystic dysplasia that typically involves of the upper pole of a duplex collecting system [33-35]. These patients are managed conservatively similar to those with more extensive involvement. This entails ongoing follow-up care including monitoring of blood pressure and kidney function and serial ultrasonography to demonstrate involution and spontaneous resolution.
GENETIC DISORDERS — (table 2)
Polycystic kidney disease — Polycystic kidney disease in children is due to two hereditary conditions, which are discussed separately:
•Autosomal recessive polycystic kidney disease (see "Autosomal recessive polycystic kidney disease in children")
•Autosomal dominant polycystic kidney disease (see "Autosomal dominant polycystic kidney disease (ADPKD) in children")
Glomerular renal cysts — Glomerular cysts are present in many genetic disorders [36,37].
●HNF1b-nephropathy (Renal cysts and diabetes [RCAD] syndrome) — The renal cysts and diabetes (RCAD) syndrome (OMIM#137920) is a form of maturity-onset diabetes of the young (MODY). It is an autosomal-dominant disorder compromised of renal cysts, diabetes mellitus, increased risk of autism, elevated liver enzymes, hyperuricemia, and pancreatic and genital malformations. It is due to pathologic variants of the HNF1b gene, which encodes hepatocyte nuclear factor-1-beta. In case series of children with unexplained renal cysts, variants of HNF-1-beta have been identified in approximately 15 to 30 percent of individuals as the underlying etiology of renal cystic disease [38,39].
HNF-1-beta is a regulator of gene expression in several organs, including the liver, the kidney, the intestine, and the pancreas, and variants of HNF1b are associated with a wide spectrum of kidney abnormalities, of which renal cortical cysts is the most common manifestation [40]. There is no correlation between the genotype and the phenotype, with a high intrafamilial variability of the phenotype [40]. De novo mutations occur in 50 percent of cases.
Antenatal ultrasound examination may detect enlarged hyperechogenic kidneys, renal cysts, renal dysplasia, unilateral or bilateral multicystic kidney disease (MCKD), or unilateral renal agenesis.
The severity of kidney disease is variable, ranging from very severe prenatal kidney failure to normal kidney function in adulthood [40]. In a study of 62 children with genetically proven HNF1-beta nephropathy, half of the cohort had documented prenatal renal dysplasia [41]. At the end of follow-up (mean 5.2 years, range 1 month to 19 years), ultrasound evaluation detected bilateral dysplasia in 46 cases (74 percent), unilateral dysplasia with contralateral agenesis in 4 cases, unilateral dysplasia in 3 cases, and no dysplasia in one patient. Kidney function also varied with end-stage kidney disease (ESKD) occurring in 5 patients (median age of 15 months), normal glomerular filtration rate (GFR) in 36 patients, GFR between 60 and 89 mL/min per 1.73 m2 in 15 patients, and the remaining 6 with GFR between 15 and 60 mL/min per 1.73 m2. Genetic analysis confirmed no correlation between genotype and phenotype. Approximately one-third of patients had hyperuricemia at a median age of one year, 20 percent had elevated liver enzymes at a median age of 11 years, and four patients had recurrent episodes of hyperglycemia and/or elevated HbA1c. In this cohort, only one patient had a genital abnormality (hypoplastic testicles).
●Nephronophthisis: NPHP2 variant — Cortical microcysts occur in combination with chronic tubulointerstitial nephritis in patients with variants of NPHP2, which encodes the protein inversin [42]. This autosomal recessive disorder results in ciliary dysfunction and is typically associated with severe hypertension and progression to end-stage kidney disease (ESKD) before two years of age. Nephronophthisis due to variants of NPHP2 (inversin) is discussed separately. (See "Genetics and pathogenesis of nephronophthisis", section on 'NPHP2 gene'.)
●Oral-facial-digital syndromes — Oral-facial-digital (OFD) syndromes are characterized by malformations of the oral cavity, the face, and the digits due to ciliary dysfunction. OFD1 (OFD1 OMIM #311200) is the most frequent of these disorders, caused by variants of the OFD1 (located on the Xp22 region), which encodes a centrosomal protein localized in the basal body of the primary cilia [43]. This disorder is lethal before birth in males. Females present with oral malformations (clefts of the palate and tongue-gingival frenula, abnormal dentition), craniofacial anomalies (facial asymmetry, hypertelorism, micrognathia, pseudocleft upper lip), abnormal hair, and digital malformations (brachydactyly, syndactyly, clinodactyly, and polydactyly). Neurological anomalies are observed in 40 percent (intracerebral cysts, agenesis of the corpus callosum, cerebellar anomalies) of cases and variable degrees of intellectual disability in half of the patients. Kidney disease consists of bilateral renal cysts, the majority being glomerular cysts. Patients with renal cystic disease may progress to kidney failure [44,45].
●Autosomal dominant tubulointerstitial kidney disease: Uromodulin – Variants of UMOD, encoding Tamm-Horsfall protein, have occasionally been observed in families presenting with glomerulocystic kidney disease phenotype [46,47]. Patients present with progressive chronic kidney disease, hyperuricemia, and gout.
●Other genetic syndromes — Glomerular cysts are observed in other genetic syndromes including Jeune syndrome, Zellweger syndrome, brachymesomelia-renal syndrome, and trisomy 13 (table 3) [48,49]
Tubular cysts — Cysts due to tubular dilation and injury are associated with the following genetic disorders (table 3).
●Meckel-Gruber syndrome is a rare and lethal autosomal recessive disorder characterized by bilateral renal cystic dysplasia, posterior encephalocele, hepatic ductal dysplasia, cleft palate, and postaxial polydactyly [50]. Meckel-Gruber syndrome is associated with defects in the MKS1 OMIM #24900 (located at 17q23) and MKS2 OMIM #603194 (located at 11q13) [51,52]. In addition, variants in the NPHP6, RPGRIP1L, and TMEM67 (also known as the MKS3 gene) can cause either Meckel-Gruber or Joubert syndrome. Products of these affected genes are all involved with ciliary function [53]. These syndromes are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of nephronophthisis", section on 'Joubert syndrome' and "Clinical manifestations, diagnosis, and treatment of nephronophthisis", section on 'Meckel syndrome'.)
●Bardet-Biedel syndrome is an autosomal recessive disorder characterized by truncal obesity, hypogenitalism in men or genital abnormalities in women, learning disabilities, retinal dystrophy, postaxial polydactyly, and kidney anomalies, including medullary cysts. Polyuria and polydipsia are common and early symptoms due to a urinary concentrating defect. Urinary tract infections and hypertension are common manifestations. Chronic kidney disease is a major complication and 10 percent of patients progress to ESKD during childhood. Variants in at least 14 genes have been described in patients with this syndrome [54]. The genes most frequently involved are BBS1 on chromosome 11q13, BBS10 on chromosome 12q, BBS2 on chromosome 16q21, and BBS9 on chromosome 7p14 [55]. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus", section on 'Bardet-Biedl syndrome'.)
●Beckwith-Wiedemann syndrome (OMIM #130650) is a genetic disorder due to deregulation of imprinting genes within the 11p15.5 region that results in a pediatric overgrowth disorder with a predisposition for tumor development. Clinical features include omphalocele, macroglossia, and macrosomia with height and weight >97th percentile, asymmetric overgrowth of certain regions of the body, visceromegaly, and tumors [56]. Neonatal hypoglycemia may be observed. Patients develop embryonic tumors such as Wilms tumor, hepatoblastoma, neuroblastoma, or rhabdomyosarcoma. Kidney anomalies include medullary dysplasia, duplicated collecting system, nephrocalcinosis, medullary sponge kidney, cystic changes, diverticula, and nephromegaly. (See "Beckwith-Wiedemann syndrome".)
●Nephronophthisis is an autosomal recessive genetically heterogenic disorder with identified variants in a number of genes that encode proteins involved in the function of primary cilia, basal bodies, and centrosomes. These pathologic variants result in severe tubular damage with thickened basement membranes alternating with groups of dilated or collapsed tubules, moderate interstitial fibrosis, and corticomedullary cysts. (See "Genetics and pathogenesis of nephronophthisis", section on 'Pathology'.)
●Joubert syndrome (OMIM #213300) is an autosomal recessive neurologic disorder characterized by cerebellar vermis hypoplasia resulting in ataxia, polydactyly, hypotonia, developmental delay, neonatal respiratory dysregulation, and abnormal eye movements. NPHP or cystic kidney dysplasia is seen in approximately one-fourth of cases [57]. A pathognomonic finding on axial magnetic resonance imaging (MRI) of the brain is the presence of prominent superior cerebellar peduncles, referred to as "molar tooth sign" of the midbrain-hindbrain junction (image 5).
●Von Hippel-Landau (VHL) is an autosomal dominant disorder characterized by benign and malignant tumors. Patients with VHL are at risk for developing multiple renal cysts and renal cell carcinomas, which occur in approximately two-thirds of patients [58]. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease".)
●Tuberous sclerosis is an autosomal dominant disorder caused by variants of the TSC1 gene or the TSC2 gene. Renal manifestations include angiomyolipomas and renal cell carcinoma. Single or multiple renal cysts are common [59]. Deletions of the TSC2 gene and the PKD1 gene, which lie adjacent to each other on chromosome 16, are responsible for the so-called TSC2/PKD1 contiguous gene syndrome. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis" and "Renal manifestations of tuberous sclerosis complex", section on 'Renal cysts'.)
ISOLATED RENAL CYSTS — Isolated renal cysts are commonly observed within the general population, and the prevalence rises with increasing age. For both affected adults and children, the principle clinical concern is accurately distinguishing simple renal cysts from complex renal cysts that are associated with malignancy or as an initial finding of autosomal dominant polycystic kidney disease. The Bosniak renal cyst classification categorizes cysts based on computerized tomographic (CT) findings into four categories, which separates benign cysts from those that are more likely to be associated with malignancy. (See "Simple and complex kidney cysts in adults", section on 'Bosniak classification of kidney cysts'.)
●Simple renal cysts (Bosniak category I) with a thin wall without septa, calcifications, or solid components are most commonly seen in children. Children with isolated simple cysts, normal renal function, and no renal dysplasia have been followed for several years without evidence of deterioration in kidney function or malignancy [60]. Primary conservative management is recommended. Surgery should be restricted to symptomatic large compressive cysts, increase in cyst size on follow-up imaging, and when there is uncertainty about the underlying diagnosis [61]. Laparoscopic marsupialization may be considered for a simple renal cyst in a symptomatic child [62].
●Complex renal cysts are uncommon in children.
ACQUIRED RENAL CYSTS — Acquired renal cysts are rare in the general pediatric population.
End-stage kidney disease — As seen in adults with end-stage kidney disease (ESKD), acquired renal cysts may be observed in children with ESKD who are undergoing chronic peritoneal or hemodialysis [63,64]. The incidence of acquired cystic disease rises with increased duration of dialysis as illustrated in one study of 54 children receiving continuous ambulatory peritoneal dialysis [63]. The prevalence of acquired cystic disease was 9, 50, and 80 percent among those who had undergone dialysis for zero to 4 years, 5 to 9 years, and longer than 10 years, respectively. (See "Acquired cystic disease of the kidney in adults".)
Liver transplantation — Acquired renal cysts are common in children who have undergone liver transplantation.
●In one case series from a single center, 33 of 108 children (30 percent) developed renal cysts after liver transplantation [65]. Risk factors for cyst formation included moderate kidney dysfunction, biopsy-proven chronic liver graft rejection, and thrombosis of the retrohepatic vena cava.
●In a second case series of 235 children undergoing liver transplantation at a single center, 11 percent of patients developed one or more renal cysts [66]. Multivariate analysis identified treatment with cyclosporine as the only independent risk factor.
SUMMARY AND RECOMMENDATIONS
●Introduction – Renal cysts occur in a variety of diseases in children (table 1). Cysts may be due to nonhereditary fetal malformations (ie, cystic renal dysplasia) or genetic disorders, or, rarely, they may be acquired. Cysts may also occur as an isolated finding or as part of a syndrome.
●Nonhereditary: cystic renal dysplasia – Cystic renal dysplasia, defined by microscopic features, is due to renal parenchymal malformation of the fetal kidney.
•Multicystic dysplastic kidney (MCDK) is the most severe form of cystic renal dysplasia. It consists of numerous noncommunicating cysts separated by dysplastic tissue with no identifiable kidney tissue (picture 1 and picture 2 and image 1 and image 2). The diagnosis is most frequently made by antenatal ultrasound with an overall incidence of 0.3 to 1 per 1000 live births. (See 'Multicystic dysplastic kidney' above.)
Because the natural history of MCDK is involution of the affected kidney and there are usually no associated complications, we recommend conservative management of MCDK rather than surgical resection (Grade 1B). Management consists of routine follow-up that includes serial kidney ultrasounds to monitor contralateral kidney growth and any evidence of kidney scarring, and involution of the affected kidney. Routine follow-up may also include blood pressure measurements to detect hypertension, urinalysis to detect proteinuria, and kidney function studies (ie, serum creatinine). (See 'Pathology, epidemiology, clinical manifestations, and course' above and 'Management' above.)
●Genetic disorders – Genetic disorders that present with renal cystic disease in children include the following:
•Autosomal recessive and dominant polycystic kidney disease. (See "Autosomal recessive polycystic kidney disease in children" and "Autosomal dominant polycystic kidney disease (ADPKD) in children".)
•Glomerular cortical cysts are associated with genetic syndromes including renal cysts and diabetes (RCAD) syndrome, oral-facial-digital (OFD) syndrome, Jeune syndrome, Zellweger syndrome, brachymesomelia-renal syndrome, and trisomy 13 (table 3). (See 'Glomerular renal cysts' above.)
•Genetic syndromes that may present with tubular-derived cysts include Meckel-Gruber syndrome, Bardet-Biedel syndrome, Beckwith-Wiedemann syndrome, tuberous sclerosis, and nephronophthisis. (See 'Tubular cysts' above.)
●Isolated renal cysts – Isolated renal cysts are commonly observed. Children typically have a simple benign cyst, (characterized by a thin wall without septa, calcifications, or solid components), that needs to be differentiated from a complex cyst, which is associated with an increased risk of malignancy. Computerized tomography can separate benign simple cysts from complex cysts. (See 'Isolated renal cysts' above.)
●Acquired renal cysts – Although acquired renal cysts are rare in the general pediatric population, they are more frequently observed in children with end-stage kidney disease who undergo chronic dialysis and in children after liver transplantation. (See 'Acquired renal cysts' above.)
