INTRODUCTION — Kidney cysts occur in a variety of diseases in children (table 1) [1,2]. Cysts may be due to nonhereditary fetal malformations or genetic disorders, or, rarely, they may be acquired. Cysts may occur as an isolated finding or may be associated with a wide range of extrarenal symptoms.
An overview of the different forms of pediatric kidney cystic disease will be reviewed here.
NONHEREDITARY: CYSTIC DYSPLASIA — Cystic dysplasia of the kidney, defined by microscopic features, is due to parenchymal malformation of the fetal kidney. As a result, the kidney contains primitive ducts and cysts as well as non-kidney 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 of the kidney is also often associated with antenatal obstruction of the urinary tract, eg, posterior urethral valves or ureteropelvic junction 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 dysplasia of the kidney 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). 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 [3]. The cause of MCDK is unclear. There may be an underlying genetic predisposition [4,5]. 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 CHD1L, ROBO2, HNF1B, and SALL1 genes [4].
●Epidemiology – The incidence of MCDK varies according to the country and the study, ranging from 1 per 3600 to 1 per 4300 live births [6,7]. It is the most frequent kidney cystic disease diagnosed antenatally [8]. MCDK may involve both kidneys, but most cases are unilateral, with the left kidney being more often affected [9]. MCDK occurs more frequently in boys than in girls [10]. In the majority of cases, involution of the MCDK occurs, as demonstrated by repeat ultrasound examination [11,12]. 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 [13-15].
●Presentation and clinical manifestations
•Antenatal – MCDK is commonly detected by antenatal ultrasonography (image 2 and image 3). In case of bilateral MCKD, ultrasonography shows a severe oligohydramnios.
•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 [11,16,17].
•Low risk of malignancy – The rate of malignant transformation of MCDK is small, if at all increased, or comparable with nonaffected kidneys in the general population [16-18].
•Low risk of hypertension – The rate of hypertension is comparable with that of the general population [11,16,19]. In a systematic review of 29 studies, six cases of hypertension in the entire pool of 1115 patients were noted, an lower incidence than that found in the general pediatric population [19].
•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 [15]. 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 obstruction, or genital abnormalities [3,17,20-22]. VUR is the most common kidney abnormality, occurring in up to 21 percent of contralateral kidneys of affected patients [3,16,17,21,23].
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 [17,24].
●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, 6 months, 2 years, 5 years, 10 years, and 15 years of age [25]. Serial ultrasounds also may detect any significant damage to the contralateral kidney due to recurrent urinary tract infection.
•Routine follow-up that includes blood pressure measurement [26], urinalysis to detect proteinuria, and kidney function studies (eg, serum creatinine), in children with contralateral abnormalities who are at risk for developing chronic kidney disease [17].
●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 [3,27], it is usually low grade and generally resolves in early life [24,27]. Patients with MCDK and VUR are more likely to have ultrasonographic abnormalities of the contralateral kidney [3,28,29]. If there is significant contralateral hydronephrosis or a history of urinary tract infection, 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 [28].
•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 [30]. Although other centers have used renal scintigraphy as a diagnostic tool [31], 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 [32].
•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 [33]. In addition, a review article reported that data from the National Wilms' Tumor Study Pathology Center demonstrated only 1 case of MCDK among more than 6000 cases of nephroblastoma [34].
For patients with an equivocal diagnosis, follow-up kidney ultrasound is important to confirm the diagnosis of MCDK and to exclude other diseases, such as cystic Wilms tumor [35].
Segmental multicystic dysplasia — There are case reports of segmental multicystic dysplasia that typically involves of the upper pole of a duplex collecting system [36-38]. 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 — Genetic disorders associated with cystic kidney disease are summarized in the table (table 2).
●Autosomal recessive polycystic kidney disease (see "Autosomal recessive polycystic kidney disease in children")
●Autosomal dominant polycystic kidney disease (ADPKD) (see "Autosomal dominant polycystic kidney disease (ADPKD) in children")
●HNF1b-nephropathy (kidney cysts and diabetes syndrome) – The kidney cysts and diabetes syndrome (MIM #137920) is a form of monogenic diabetes. It is an autosomal dominant disorder compromised of kidney 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 kidney cysts, variants of HNF1b have been identified in approximately 15 to 30 percent of individuals as the underlying etiology of kidney cystic disease [39,40]. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Hepatocyte nuclear factor-1-beta'.)
HNF1b is a regulator of gene expression in several organs, including the liver, kidney, intestine, and pancreas, and variants of HNF1b are associated with a wide spectrum of kidney abnormalities, of which kidney cortical cysts is the most common manifestation [41]. There is no correlation between the genotype and phenotype, with a high intrafamilial variability of the phenotype [41]. De novo mutations occur in 50 percent of cases.
Antenatal ultrasound examination may detect enlarged hyperechogenic kidneys, kidney cysts, kidney 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 [41]. In a study of 62 children with genetically proven HNF1-beta nephropathy, one-half of the cohort had documented prenatal kidney dysplasia [42]. 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 four cases, unilateral dysplasia in three cases, and no dysplasia in one patient. Kidney function also varied, with kidney failure occurring in five 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 six patients 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 1 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 hemoglobin A1c. In this cohort, only one patient had a genital abnormality (hypoplastic testicles).
●Bardet-Biedl syndrome – Bardet-Biedl syndrome is an autosomal recessive disorder characterized by truncal obesity, hypogenitalism in males or genital abnormalities in females, 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 kidney failure during childhood. Variants in at least 14 genes have been described in patients with this syndrome [43]. The genes most frequently involved are BBS1 on chromosome 11q13, BBS10 on chromosome 12q, BBS2 on chromosome 16q21, and BBS9 on chromosome 7p14 [44]. (See "Obesity: Genetic contribution and pathophysiology", section on 'Bardet-Biedl syndrome'.)
●Nephronophthisis – This 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 resulting in kidney disease and extrarenal manifestations including retinal degeneration, cerebellar ataxia, and liver fibrosis.
Variants of the NPHP1 gene are the most common, being reported in approximately 20 percent of cases. Patients present with juvenile nephronophthisis. Variants in each of the other genes contribute less than 3 percent each. 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'.)
Variants of NPHP2, which encodes the protein inversin, are associated with cortical microcysts and chronic tubulointerstitial nephritis [45]. This autosomal recessive disorder results in ciliary dysfunction and is typically associated with severe hypertension and progression to before two years of age. (See "Genetics and pathogenesis of nephronophthisis", section on 'NPHP2 gene'.)
●Joubert syndrome – Joubert syndrome (MIM #213300 and others) is an autosomal recessive neurologic disorder characterized by cerebellar vermis hypoplasia resulting in ataxia, polydactyly, hypotonia, developmental delay (often with autism spectrum disorder), neonatal respiratory dysregulation, and abnormal eye movements. Nephronophthisis or cystic kidney dysplasia is seen in approximately one-fourth of cases [46]. A pathognomonic finding on axial magnetic resonance imaging of the brain is the presence of prominent superior cerebellar peduncles, referred to as the "molar tooth sign" of the midbrain-hindbrain junction (image 4). (See "Clinical manifestations, diagnosis, and treatment of nephronophthisis", section on 'Joubert syndrome' and "Overview of cerebellar injury and malformations in neonates", section on 'Cerebellar malformations'.)
●Autosomal dominant tubulointerstitial kidney disease – Variants of UMOD, encoding uromodulin (also known as Tamm-Horsfall protein), have occasionally been observed in families presenting with the glomerulocystic kidney disease phenotype [47,48]. Patients present with progressive chronic kidney disease, hyperuricemia, and gout. Other forms of autosomal dominant tubulointerstitial kidney disease are caused by variants in MUC1 or REN. (See "Autosomal dominant tubulointerstitial kidney disease", section on 'ADTKD due to UMOD pathogenic variants'.)
●Meckel-Gruber syndrome – Meckel-Gruber syndrome is a rare and lethal autosomal recessive disorder characterized by bilateral kidney cystic dysplasia, posterior encephalocele, hepatic ductal dysplasia, cleft palate, and postaxial polydactyly [49]. Meckel-Gruber syndrome type 1 (MIM #249000) is associated with defects in MKS1 [50]. In addition, variants in NPHP6, RPGRIP1L, TMEM216, and TMEM67 (also known as MKS3) can cause either Meckel-Gruber or Joubert syndrome. Products of these affected genes are all involved with ciliary function [51].
●Beckwith-Wiedemann syndrome – Beckwith Wiedemann syndrome (MIM #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 [52]. 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".)
●Oral-facial-digital (OFD) syndromes – OFD syndromes are characterized by malformations of the oral cavity, face, and digits due to ciliary dysfunction. OFD1 (MIM #311200) is the most frequent of these disorders, caused by variants of the OFD1 gene (located on the Xp22 region), which encodes a centrosomal protein localized in the basal body of the primary cilia [53]. 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). Neurologic anomalies are observed in 40 percent (intracerebral cysts, agenesis of the corpus callosum, cerebellar anomalies) of cases and variable degrees of intellectual disability in one-half of the patients. Kidney disease consists of bilateral kidney cysts, the majority being glomerular cysts. Patients with kidney cystic disease may progress to kidney failure [54,55].
●Von Hippel-Landau disease – Von Hippel Lindau disease is an autosomal dominant disorder characterized by benign and malignant tumors. Patients with von Hippel-Landau disease are at risk for developing multiple kidney cysts and renal cell carcinomas, which occur in approximately two-thirds of patients [56]. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease".)
●Tuberous sclerosis – Tuberous sclerosis is an autosomal dominant disorder caused by variants of the TSC1 or TSC2 genes and characterized by the development of hamartoma in multiple tissues such as the kidneys, brain, and heart [57]. Kidney manifestations include angiomyolipomas, which may be complicated by severe bleeding, and renal cell carcinoma [58]. Single or multiple kidney cysts are common [59]. Deletions of TSC2 and PKD1, which lie adjacent to each other on chromosome 16, are responsible for the so-called TSC2/PKD1 contiguous gene syndrome. (See "Tuberous sclerosis complex: Clinical features" and "Renal manifestations of tuberous sclerosis complex", section on 'Renal cysts'.)
●Other genetic syndromes – Kidney cysts are observed in other genetic syndromes including Jeune syndrome, Zellweger syndrome, brachymesomelia-renal syndrome, and trisomy 13 (table 3) [60,61].
ISOLATED KIDNEY CYSTS — Isolated kidney 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 kidney cysts from complex kidney cysts that are associated with malignancy or as an initial finding of autosomal dominant polycystic kidney disease (ADPKD). In two retrospective studies of patients presenting with what appeared to be simple kidney cysts, ADPKD was subsequently diagnosed in 12.6 and 16.7 percent; no malignancies were reported in patients with ADPKD [62,63]. The Bosniak kidney cyst classification categorizes cysts based on computed tomographic (CT) findings into four categories, which separate 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 kidney cysts (Bosniak category I) with a thin wall without septa, calcifications, or solid components are the most common type of cyst in children. Children with isolated simple cysts, normal kidney function, and no kidney dysplasia have been followed for several years without evidence of deterioration in kidney function or malignancy [64]. Monitoring is recommended.
●Complex kidney cysts are uncommon in children.
ACQUIRED KIDNEY CYSTS — Acquired kidney cysts are rare in the general pediatric population.
Kidney failure — As seen in adults with kidney failure, acquired kidney cysts may be observed in children with kidney failure who are undergoing chronic peritoneal or hemodialysis [65,66]. 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 [65]. The prevalence of acquired cystic disease was 9, 50, and 80 percent among those who had undergone dialysis for 0 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 kidney cysts may be observed in children who have undergone liver transplantation.
●In one case series from a single center, 33 of 108 children (30 percent) developed kidney cysts after liver transplantation [67]. 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 kidney cysts [68]. Multivariate analysis identified treatment with cyclosporine as the only independent risk factor.
SUMMARY AND RECOMMENDATIONS
●Introduction – Kidney cysts occur in a variety of diseases in children (table 1). Cysts may be due to nonhereditary fetal malformations (ie, cystic dysplasia of the kidney) 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 dysplasia – Cystic dysplasia of the kidney, defined by microscopic features, is due to parenchymal malformation of the fetal kidney.
•Multicystic dysplastic kidney (MCDK) is the most severe form of cystic dysplasia of the kidney. It consists of numerous noncommunicating cysts separated by dysplastic tissue with no identifiable kidney tissue (picture 1 and picture 2 and image 1). The diagnosis is most frequently made by antenatal ultrasound (image 2), 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, as well as 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 kidney 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 kidney cysts and diabetes syndrome, oral-facial-digital (OFD) syndrome, Jeune syndrome, Zellweger syndrome, brachymesomelia-renal syndrome, and trisomy 13 (table 3). (See 'Genetic disorders' 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 'Genetic disorders' above.)
●Isolated kidney cysts – Isolated kidney 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. CT can separate benign simple cysts from complex cysts. (See 'Isolated kidney cysts' above.)
●Acquired kidney cysts – Although acquired kidney cysts are rare in the general pediatric population, they are more frequently observed in children with kidney failure who undergo chronic dialysis and in children after liver transplantation. (See 'Acquired kidney cysts' above.)
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