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Autosomal dominant polycystic kidney disease (ADPKD) in children

Autosomal dominant polycystic kidney disease (ADPKD) in children
Literature review current through: Sep 2023.
This topic last updated: Apr 30, 2023.

INTRODUCTION — Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder, occurring between 1 in 400 and 1 in 1000 live births [1]. Affected individuals typically do not develop symptomatic disease until adulthood. Not uncommonly, asymptomatic children may be identified while undergoing abdominal imaging for screening due to a family history of ADPKD or incidentally for an unrelated issue. However, a small percentage of individuals with ADPKD will present in infancy and childhood with early-onset and rapidly progressive disease.  

The clinical features, diagnosis, screening, and management of ADPKD in children will be reviewed here. Discussions of other cystic diseases, including autosomal recessive polycystic kidney disease (ARPKD) are found separately in the program, as is discussion of ADPKD in adults. (See "Autosomal recessive polycystic kidney disease in children" and "Renal cystic diseases in children" and "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis" and "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations" and "Autosomal dominant polycystic kidney disease (ADPKD): Treatment".)

GENETICS AND PATHOGENESIS — ADPKD (previously called adult polycystic kidney disease) is a dominant inherited disorder characterized by cystic dilatations in all parts of the nephron. Variants in one of two genes, PKD1 or PKD2, account for most cases of ADPKD. These genes encode proteins localized to the primary cilia of renal epithelial cell, which are involved with intracellular calcium signaling and activation of cyclic AMP. How variants of these genes result in cyst formation, however, remains unclear.

PKD1 variants – A variant in the PKD1 gene (MIM #173900), which is located on chromosome 16 and encodes polycystin 1, is present in 78 percent of patients with ADPKD [2].

PKD2 variants – Most of the remaining patients (approximately 15 percent) have a variant in the PKD2 gene (MIM *173910), which encodes polycystin 2 and is located on chromosome 4.

Although a third ADPKD gene locus has been postulated for a few affected kindreds, it has not been well substantiated [3]. Variants in GANAB and DNJB11 genes have been associated with atypical forms of ADPKD [4,5].

De novo (new) variants arise in 7 to 10 percent of affected individuals. These individuals will not have a family history of ADPKD.

The genetics and pathogenesis of ADPKD are discussed in detail separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Genetics of the disease and mechanisms of cyst growth".)

PATHOLOGY — In affected individuals with ADPKD, renal involvement is characterized by cystic dilatations in all parts of the nephron, including Bowman's space and all tubular segments (picture 1). In the early stages, there may be only a few macrocysts (>10 mm) irregularly distributed. Approximately 17 percent of children with ADPKD will demonstrate unilateral renal findings at initial screening [6]. It is possible that high-resolution ultrasound will reveal cysts as small as 2 to 3 mm, but there have been no studies documenting the number of cysts using high-resolution ultrasound in children [7]. Later, both kidneys become enlarged due to the formation of macrocysts in the cortex and in the medulla (picture 2).

Cysts in the liver and pancreas are common in adults with ADPKD, but are infrequently observed in pediatric patients. Congenital hepatic fibrosis occurs in patients with autosomal recessive polycystic kidney disease and is extremely rare in patients with ADPKD; thus it may be used to differentiate between the two genetic polycystic diseases [8,9]. Cerebral vessel malformations have also been rarely described in children with ADPKD [10]. An increased risk of mitral valve prolapse has also been reported in affected patients. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations" and 'Differential diagnosis' below and "Autosomal recessive polycystic kidney disease in children".)

CLINICAL PRESENTATION AND MANIFESTATIONS

Overview — Although most individuals with ADPKD remain asymptomatic until the fourth decade of life, increasingly, (asymptomatic) children with ADPKD are being identified after undergoing abdominal imaging for screening based on a family history or as an incidental finding of cysts for an unrelated condition. ADPKD in asymptomatic children may be detected due to hypertension and/or mild proteinuria [11,12]. In addition, approximately 2 to 5 percent will present with early-onset and rapidly progressive kidney disease during childhood [7]. It remains unclear why some children present with early onset of disease and others remain asymptomatic. Although siblings of affected children have a significant risk of early disease [13,14], this relationship within families is not absolute, as some infants with severe disease can have a parent with milder form of ADPKD and stable renal function [15]. (See "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Epidemiology'.)

A proposed mechanism for early-onset disease is the inverse relationship with the level of polycystin function. Support for this theory is provided by the presentation of early and rapidly progressive disease in infants with a "contiguous gene" syndrome in whom there is a large deletion in both PKD1 and the immediately adjacent gene for tuberous sclerosis [16]. Early-onset disease has also been associated with hypomorphic PKD or PKHD1 variants (resulting in reduced PKD1 activity) from the unaffected parent in addition to the expected familial germ-line defect in the affected parent (resulting in no PKD1 activity) [17,18]. (See "Renal manifestations of tuberous sclerosis complex" and "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis" and "Autosomal dominant polycystic kidney disease (ADPKD): Genetics of the disease and mechanisms of cyst growth", section on 'PKD1 and PKD2 genes'.)

Neonates — Several case reports and series have reported severe ADPKD presenting in neonates with similar findings (oligohydramnios, massively enlarged kidneys, respiratory distress, and impaired kidney function) to those seen in neonates with autosomal recessive polycystic kidney disease (ARPKD) [19-24]. These patients typically have rapidly progressive disease resulting in end-stage kidney disease (ESKD) in childhood. Although early-onset ADPKD was once thought to have a uniformly poor prognosis, newer data suggest that a relatively low percentage of patients diagnosed in the fetal or neonatal stage will progress to ESKD during childhood [25]. (See "Autosomal recessive polycystic kidney disease in children", section on 'Neonatal'.)

Older infants and children — Most children with ADPKD are asymptomatic and are identified by ultrasound screening because of a positive family history or incidentally when ultrasound is performed for an unrelated clinical condition as noted above. However, approximately 2 to 5 percent of affected children will present with early onset of disease with similar renal findings as those of affected adults [7,15,26]. In contrast, the extrarenal manifestations of ADPKD commonly seen in adults (eg, cysts in the liver and pancreas) are infrequently or rarely observed in pediatric patients. (See "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations" and "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".)

Kidney manifestations — In children, the presentation of ADPKD varies, with a clinical spectrum ranging from rapidly progressive disease with large hyperechoic kidneys to asymptomatic children with renal cysts found either by chance during evaluation for nonrenal abdominal symptoms or by ultrasound screening of children with positive family history. In most pediatric case series, the diagnosis is made by the detection of cysts by renal ultrasonography in the setting of a positive family history [15,27].

Although most affected children do not become symptomatic until adulthood [28], pediatric patients may have any of the following renal findings associated with ADPKD [25,27,29-32]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations".)

Hypertension – Hypertension is observed in approximately 20 to 35 percent of children with ADPKD [33,34]. In addition, 50 percent of them lack a physiologic nocturnal BP dipping and 18 percent have isolated nocturnal hypertension [34]. Renal function is usually normal when hypertension is first noted. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring", section on 'Dipping'.)

Renal concentrating defect with polyuria and polydipsia [35].

Proteinuria [36].

Urolithiasis is a rare complication in children with ADPKD. If kidney stones are found by ultrasonography, additional investigations should be performed to detect other risk factors [7].

Rarely, impaired kidney function (decreased glomerular filtration rate [GFR]) is observed.

In addition, children may present with the following symptoms similar to those seen in affected adults [30]:

Gross hematuria

Flank and abdominal pain, which may be caused by infection, urolithiasis, or cyst hemorrhage

Enuresis

Progression of kidney disease — In the vast majority of children with ADPKD, kidney function (ie, GFR) is within the normal range with signs of decreasing GFR that typically do not start until adulthood. However, a subset of children with rapidly progressive disease who present before 18 months of age are at risk for developing ESKD during childhood [25,31,37].

The frequency of symptoms increases with the severity of kidney involvement and disease progression independent of kidney function. A single center that prospectively followed children (>90 percent with normal GFR) identified by radiologic screening in offspring of parents with ADPKD reported that the risk of flank or back pain and hypertension increased for children with severe disease, defined as those >10 cysts compared with those with moderate disease [29]. In addition, increased renal volumes was associated with increased risk of hypertension, hematuria, or proteinuria [37-40]. The total kidney volume based on imaging has been used to identify high-risk patients for progression of chronic kidney disease and is discussed separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Identification of high-risk patients'.)

Nonrenal manifestations — Clinical manifestations that involve nonrenal organs include:

Cardiac abnormalities – A study from the previously mentioned prospective cohort reported increased left ventricular mass index in children with blood pressure above the 75th percentile for age, sex, and height prior to any observed increase in kidney volume [39]. Studies have also reported a variable incidence of mitral valve prolapse in 1 to 12 percent of cases [41,42].

Cysts in other organs – Liver cysts were thought to be uncommon in children but magnetic resonance (MR) studies have shown the presence of hepatic cysts in 58 percent of patients before the age of 25 years [43]. However, pancreatic, ovarian, intestinal, and splenic cysts are rarely observed in children.

Intracranial aneurysms – Aneurysmal rupture in childhood resulting in a subarachnoid or intracerebral hemorrhage is extremely rare. Screening is not recommended since there are no clear treatment or intervention guidelines for unruptured cerebral aneurysms in children [44-46]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Cerebral aneurysm'.)

DIAGNOSIS

Positive family history — In children, the diagnosis of ADPKD is typically established by a positive family history and confirmed by ultrasonography by the detection of one or more cysts [6,7]. Approximately 95 percent of affected individuals show ultrasonographic evidence of ADPKD by the age of 20 years and almost 100 percent by the age of 30 years. However, the reported rate of false negative result is 38 percent for children less than five years and approximately 20 percent in older children with PKD1 variant [47]. As a result, repeat imaging is necessary in younger children with a positive family history and an initial negative study [48]. Ultrasound-based criteria in patients greater than 15 years of age have been established for diagnosis or exclusion of ADPKD in patients with a positive family history (table 1) and are discussed separately. (See "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Patients with a family history of ADPKD'.)

Computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive modalities in detecting renal cysts, but are more expensive tests with known associated risks: radiation with CT and need for sedation with MRI in young children. As a result, ultrasound remains the preferred initial diagnostic modality as it is noninvasive, does not require sedation in young children, and is the most inexpensive imaging modality [7,49]. (See 'Genetic testing' below and 'Screening' below.)

In affected neonates with a positive family history for ADPKD, enlarged and hyperechogenic kidneys detected by ultrasound are suggestive of the diagnosis of ADPKD. However, these findings are similar to those seen in neonates with autosomal recessive polycystic kidney disease (ARPKD), diffuse cystic dysplasia, and other ciliopathies [50]. Positive family history and absence of biliary dysgenesis make ADPKD a more likely diagnosis and differentiates it from ARPKD. (See 'Differential diagnosis' below.)

No positive family history — Less frequently cysts suggestive of ADPKD are detected as an incidental finding on imaging performed for another unrelated condition in children with no apparent family history of ADPKD. In these children, renal ultrasounds should be performed on the parents and a diagnosis of ADPKD is made if renal cysts are detected in either parent. In families where the parents are young (under 30 years of age), ultrasound evaluation of the grandparents may be needed to establish the diagnosis [51].

If the work-up for parents (or grandparents) does not reveal cystic renal disease, ADPKD is still a strong possibility (given the 10 percent rate of de novo mutations). Genetic testing is suggested if a definitive diagnosis is warranted.

Genetic testing — Genetic testing, which is costly and generally not necessary, is reserved for the following clinical settings [7]:

Early-onset and rapidly progressive ADPKD in infancy or early childhood. This is often due to unusual genetic complexity, which may result from biallelic mutations with at least one weak PKD1 or PKD2 hypomorphic allele [18], mutation of a cystic disease gene other than PKD1 or PKD2 mosaicism, or coinheritance of a second mutation in another cystic disease gene, modifier genes. Genetic testing is suggested as it may provide important information for genetic counseling and future family planning.

Incidental finding of renal cysts with progressive disease (increasing number of cysts or kidney volume) and a negative work-up for parents (or grandparents).

In these settings, we prefer using a next-generation sequencing panel rather than testing for single ADPKD genes, as there is a possible concomitant mutation (either in the PKD1 or PKD2 or another gene associated with renal disease) in children with severe disease or those without a family history for ADPKD [7]. The panel should cover PKD1, PKD2, PKHD1, Daz-interacting zinc-finger protein 1-like (DZIP1L), and HNF1B, plus genes for other ciliopathies such as nephronophthisis and Bardet-Biedl syndrome.

Genetic testing can also be performed in a child with equivocal imaging results and a well-established family history of ADPKD and known genetic mutation, if requested by the family. In this case, genetic testing can be performed using Sanger sequencing of the PKD1 and PKD2 genes.

Genetic testing for ADPKD is discussed in greater detail separately. (See "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Specific role of genetic testing'.)

SCREENING — For children with a positive family history of ADPKD, routine screening for ADPKD in at-risk children less than 18 years of age is controversial. Although some advocate that screening not be performed in children because the adverse consequence of a positive diagnosis prior to symptoms in young individuals (eg, career, educational, emotional, and insurability issues) far outweigh any benefits (as there is a current lack of effective therapy), others suggest that early diagnosis provides an opportunity for maximal anticipatory care (eg, optimal blood pressure control) and the future opportunity to benefit from new therapies as they are developed [7,52].

Our approach to screening at-risk children with a positive history of ADPKD is consistent with published guidelines from a panel of experts in the field [7]:

Parents or legal guardians should be counseled about the inheritance of ADPKD and the potential harms and benefits of diagnostic screening. If appropriate, teenagers and competent younger children should be involved whenever possible in the discussion and decision-making process.

Diagnostic screening should be offered to at-risk children if desired by parents (legal guardians) and competent children after counseling.

For all at-risk asymptomatic children, ongoing monitoring for high blood pressure and proteinuria should be performed irrespective of whether diagnostic screening is performed.

If the decision is made not to perform diagnostic screening, parents need to be made aware that it is their responsibility to inform their children of the risk of ADPKD when their offspring reach the legal age of consent.

Ultrasonography is the preferred modality for screening in children at-risk for ADPKD. It is the least invasive and most cost-effective option. Sonographic detection of one or more kidney cysts is suggestive of a diagnosis of ADPKD in a child with a positive family history. However, as noted above, false negative results are reported in approximately 40 percent of children less than five years and approximately 20 percent of older children with PKD1 mutation [47]. As a result, repeat imaging is necessary in younger children with a positive family history and an initial negative study [48]. (See 'Diagnosis' above.)

Ultrasonography can also be used for antenatal diagnostic screening [26,53,54]. Most antenatal studies have been performed between 31 and 36 weeks gestation, usually at the request of the parents. Enlarged, hyperechogenic kidneys are the primary finding, but cysts may be visible [55,56]. However, the ultrasonographic finding of enlarged, echogenic kidneys is similar to those detected in cases of autosomal recessive polycystic kidney disease. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The diagnosis of ADPKD is relatively straightforward in a child with a positive family history, characteristic renal ultrasound findings, and extrarenal features. When no family history of ADPKD is present, but the sonographic findings are consistent with ADPKD, screening of parents should be performed. In patients without a family history of ADPKD, other cystic kidney diseases must be considered. However, given the relatively high rate of de novo mutations, the presence of multiple cysts in each kidney is very suggestive of ADPKD. Other genetic diseases (eg, tuberous sclerosis, von Hippel Lindau disease, autosomal dominant tubulointerstitial kidney disease, HNF1B associated renal disease) can be associated with kidney cysts.

In neonates with severe disease, the typical findings of enlarged, echogenic kidneys may be similar to those observed in cases with autosomal recessive polycystic kidney disease (ARPKD). Infants with ARPKD also have congenital hepatic fibrosis and may demonstrate characteristic features of hepatomegaly, increased echogenicity of the liver, and dilatation of the peripheral intrahepatic ducts and the main bile ducts. However, these abnormalities are only present clinically in approximately 40 percent of affected neonates. Therefore, the absence of liver abnormalities does not preclude the diagnosis of ARPKD. (See "Autosomal recessive polycystic kidney disease in children", section on 'Hepatobilirary manifestations' and "Autosomal recessive polycystic kidney disease in children", section on 'Imaging'.)

The differential diagnosis of ADPKD in older patients with a negative family history is discussed in greater detail separately. (See "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Differential diagnosis'.)

MANAGEMENT — Supportive care is provided to all children with ADPKD or at-risk for ADPKD in whom diagnostic testing has been deferred until legal age of medical consent. This entails management of blood pressure (BP), focus on reducing proteinuria, dietary measures, and anticipatory guidance to avoid and manage other complications of ADPKD. No specific agent for directed therapy that slows progression of renal disease is recommended, because there are no available data regarding benefit and safety of any drug in children with ADPKD.

Supportive care — The following sections discuss supportive care measures that are provided to all children with or at-risk for ADPKD.

Blood pressure management — As hypertension is the main treatable complication of ADPKD, we provide strict blood pressure (BP) control for children with or at-risk for ADPKD, which includes the following:

BP monitoring – For all children with or at-risk for ADPKD, BP monitoring is performed at least once a year at each annual health care visit [7]. The frequency of monitoring increases with elevation of BP or when antihypertensive therapy is initiated.

Initiation of antihypertensive medication – Although data are lacking regarding optimal BP goals for children with or at-risk for ADPKD, we begin antihypertensive medication when office-based systolic and diastolic blood pressures are repeatedly greater than 90th percentile for age, sex, and height (table 2 and table 3) up to an upper target BP of 110/75 (used in adult patients with ADPKD with an estimated glomerular filtration rate >60 mL/min/1.73 m2), consistent with guidelines from the Kidney Disease Outcomes Quality Initiative (KDOQI) for children with chronic kidney disease [57]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Management of blood pressure' and "Chronic kidney disease in children: Complications", section on 'Pharmacologic therapy'.)

If 24-hour ambulatory blood pressure monitoring (ABPM) data, a more accurate BP measurement than office assessment, is available, we begin antihypertensive medication with a targeted goal of a 24-hour mean arterial BP (MAP) below the 50th percentile for sex and height using pediatric ABPM normative data (table 4 and table 5). This target ABPM goal is based on data showing that intensified BP control slows progression of CKD [58]. (See "Ambulatory blood pressure monitoring in children".)

Antihypertensive medication and target BP goals – When antihypertensive medication is administered, we target office-based BP systolic and diastolic BPs to less than the 50th percentile for age, sex, and height (table 2 and table 3) consistent with the American Academy of Pediatrics (AAP) guidelines [59] and the results of the ESCAPE trial [58]. Considering the need for more medications and higher risk for adverse effects in the short term, other experts in the field use a higher targeted goal of systolic and diastolic BPs to less than the 75th percentile for age, sex, and height [7]. ABPM goals are to maintain MAP below the 50th percentile for sex and height.

Choice of antihypertensive agent – Our preferred drug choice is either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) [40]. These agents have the additional benefit of reducing proteinuria and have been shown to be more beneficial in slowing the progression of CKD than other classes of antihypertensive medications. It should be noted that the results of the HALT-PKD study in adults demonstrated that combination ACE inhibitor and ARB therapy did not provide any additional benefit over ACE inhibitor alone in terms of rates of kidney function decline [60]. In addition, the combination of ACE inhibitor and ARB has an increased risk for adverse effects. (See "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of hypertension", section on 'Choice of agent' and "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers" and "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Combination of ACE inhibitors and ARBs' and "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

Proteinuria — Proteinuria is associated with progression of renal disease in children with CKD. Protein excretion should be monitored in children with or at-risk for ADPKD at the annual health care visit [7]. Although monitoring can be done by urinary dipstick, laboratory evaluation of albumin/creatinine ratio (ACR) or urinary total protein/creatinine ratio are the preferred tests as they are more sensitive and specific measurements [7]. Although there are no direct data, administration of either ACE inhibitors or ARBs can be initiated to reduce urinary protein excretion when proteinuria is detected (urinary protein/creatinine ratio >0.5 mg/mg) [61]. There are no specific recommendations with respect to treatment of microalbuminuria. Subsequent monitoring of BP, especially in normotensive children, is required, as these drugs reduce BP. Dietary protein restriction is not recommended, as there is no evidence of benefit in slowing progression of renal disease.

Dietary and fluid management — Dietary and fluid management entail:

Dietary sodium (salt) restriction – A study in adults showed that 24-hour urinary sodium excretion is associated with the rate of eGFR decline in ADPKD, suggesting that salt restriction should be important in the treatment of ADPKD [62]. The goal for salt intake in children with or at-risk for ADPKD is to achieve the normal recommended low dietary salt intake (<2300 mg per day) [7]. Data from the Centers for Disease Control on salt consumption showed that children in the United States between 6 and 18 years of age far exceeded the recommended goal, with an average intake of approximately 3300 mg.

Increased fluid intake – Increased fluid intake suppresses endogenous vasopressin production, which has been postulated as a mechanism to inhibit cyst growth in patients with ADPKD. However, data are inconclusive on the benefit of high fluid intake, and the amount of fluid intake needed to suppress vasopressin is difficult to achieve. In our practice, we encourage children to drink fluids as much as possible and avoid episodes of hypovolemia [7]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Increased fluid intake'.)

No protein restriction – There is no evidence that protein restriction is beneficial in decreasing renal disease progression [7]. As a result, protein restriction is not necessary in affected children.

Nutrition – In the Halt Progression of Polycystic Kidney Disease (HALT) Study A, overweight, and particularly obesity, were strongly associated with the rate of progression in early-stage ADPKD, as measured by kidney growth and decline in renal function [63]. Childhood lifestyle modifications and dietary intervention strategies addressing overweight might therefore be beneficial to prevent disease progression [64].

Management of complications

Pain management – Abdominal and back pain are reported in 10 to 20 percent of children with ADPKD [7]. In these children, a work-up similar to that performed in any child with abdominal/back pain should be performed to determine the cause of pain (see "Chronic abdominal pain in children and adolescents: Approach to the evaluation" and "Causes of acute abdominal pain in children and adolescents"). Acetaminophen is the preferred drug for pain management, and nonsteroidal anti-inflammatory drugs should be avoided due to potential for increased risk of cyst hemorrhage and renal adverse effects [7].

Urinary tract and cyst infection – Children with ADPKD have a higher risk of lower and upper urinary tract infection (UTI), including cyst infection, compared with those without ADPKD [7]. Cyst infection is a rare occurrence in children with ADPKD. It typically presents with symptoms compatible with upper tract infection (pyelonephritis), including fever. Cyst infection is usually caused by gram-negative bacteria. Antibiotics such as penicillins, cephalosporins, and aminoglycosides are ineffective in penetrating cyst walls and should be avoided. Therefore, and ciprofloxacin and sulfonamides, which have good cyst penetration, should be administered as empiric therapy and continued even if cultures demonstrate bacterial sensitivities to penicillins or cephalosporins [65,66]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of complicated urinary tract infections".)

The diagnosis and treatment of lower UTI are the same as in otherwise healthy children. However, even with lower UTI, empiric treatment with antibiotics that penetrate cysts should be considered, especially in children with large cyst burdens and/or large or complex cysts. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Laboratory evaluation and diagnosis' and "Urinary tract infections in infants older than one month and children less than two years: Acute management, imaging, and prognosis" and "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of complicated urinary tract infections" and "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Diagnostic criteria' and "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of complicated urinary tract infections", section on 'Management'.)

Trauma – Minor trauma increases the risk of cyst rupture. As a result, contact sports should be avoided in children with significant nephromegaly due to numerous and large cysts. The risks of contact sports in children with numerous and large cysts should be explained to the patients and they should be counseled to report any episode of cyst pain or gross hematuria.

Directed therapy — In adults, trials have shown that the vasopressin antagonist, tolvaptan, slows progression of renal disease in patients with a high likelihood of developing end-stage kidney disease (ESKD). However, tolvaptan has significant adverse effects (eg, polyuria and potential for hepatic injury) and may be costly. Post-hoc analyses of the large, randomized trial in adults (TEMPO 3:4) in the subgroup of patients aged 18 to 24 years and with CKD stage 1 showed that tolvaptan significantly slows the increase in total kidney volume with no risk of potential liver injury [67]. There are no available data on its use in younger patients, including safety information. As a result, we do not routinely offer tolvaptan to pediatric patients with ADPKD [7]. Ongoing trials may provide information concerning patient selection, quality of life assessment, cost-effectiveness, safety and tolerability [68,69] . (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Tolvaptan'.)

Other therapeutic interventions that have been considered but are not recommended, as they lack evidence of benefit, include somatostatin and somatostatin analogues and mammalian target of rapamycin (mTOR) signaling pathway inhibitors. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Approaches we do not use'.)

End-stage kidney disease — As noted above, a few children will progress to ESKD and require renal replacement therapy, including dialysis and kidney transplantation [25,31,37]. Living-related kidney transplantation is the preferred intervention, but potential family donors must be screened for ADPKD [70]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Specific management of End-Stage Kidney Disease' and "Overview of kidney replacement therapy (KRT) for children with chronic kidney disease", section on 'Preemptive transplantation as preferred kidney replacement therapy modality'.)

OUTCOME — As noted previously, children who are diagnosed with ADPKD are likely to have preserved renal function until the fourth decade of life. However, a small subset of symptomatic children will have progressive disease that results in end-stage kidney disease (ESKD) that requires renal replacement therapy [25,31,37]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Specific management of End-Stage Kidney Disease' and "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Identification of high-risk patients'.)

SUMMARY AND RECOMMENDATIONS

Autosomal dominant polycystic kidney disease (ADPKD) is a dominant inherited disorder caused by mutations of either the PKD1 or PKD2 genes. (See 'Genetics and pathogenesis' above and "Autosomal dominant polycystic kidney disease (ADPKD): Genetics of the disease and mechanisms of cyst growth".)

Kidney involvement is characterized by cystic dilatations in all parts of the nephron, including Bowman's space. Cysts in the liver and pancreas are common in adults with ADPKD, but are less frequently observed in pediatric patients. (See 'Pathology' above.)

Most patients with ADPKD present in adulthood; however, a small percentage of patients present with early-onset and rapidly progressive kidney disease during childhood. Although it remains unclear why some individuals have early onset of disease and others remain asymptomatic, it has been proposed that early onset of disease is inversely related to the level of polycystin function. (See 'Overview' above.)

Severe ADPKD can present in the neonatal period with similar findings (oligohydramnios, massively enlarged kidneys, respiratory distress, and impaired kidney function) to those seen in patients with autosomal recessive polycystic kidney disease (ARPKD). Neonates with recessive polycystic disease have congenital hepatic fibrosis and may demonstrate characteristic ultrasound features of hepatomegaly, increased echogenicity of the liver, and dilatation of the peripheral intrahepatic ducts and the main bile ducts, which may distinguish them from those with ADPKD. However, only 40 percent of ARPKD patients have clinical evidence of liver involvement as neonates, so the absence of liver findings does not exclude the diagnosis of ARPKD. (See 'Neonates' above and 'Differential diagnosis' above.)

Most pediatric patients with ADPKD are asymptomatic and are identified by detection of renal cysts by ultrasound screening because of a positive family history or incidentally when ultrasound is performed for an unrelated clinical condition. Although most pediatric patients with ADPKD are asymptomatic, those who present in childhood have similar renal manifestations to those seen in adult patients. These include hypertension, gross or microscopic hematuria, proteinuria, urinary tract or cyst infection, abdominal or back pain, urolithiasis, and, rarely, reduced glomerular filtration rate (GFR) during childhood. (See 'Older infants and children' above and "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Clinical presentation'.)

The diagnosis of ADPKD disease is typically established by a positive family history and kidney ultrasonography, which reveals cysts. However, ultrasonography is not as sensitive a diagnostic test for ADPKD in children compared with adults. The risk of reported false negative results is approximately 40 percent in children less than five years and approximately 20 percent in older children. As a result, repeat imaging may be necessary to make a diagnosis in younger children with a positive family history and an initial negative study [48]. (See 'Diagnosis' above.)

Less commonly, cysts suggestive of ADPKD are detected as an incidental finding on imaging performed for another unrelated condition. In these children, kidney ultrasounds should be performed on the parents (in some cases, grandparents), and a diagnosis of ADPKD is made if kidney cysts are detected in either a parent or grandparent. Notably, approximately 10 percent of patients will not have a positive family history and have "de novo" mutations but demonstrate typical clinical features of ADPKD.

Genetic testing, which is costly and is usually not necessary, is generally reserved for atypical cases or to rule out ADPKD in children without an affected parent. (See 'Genetic testing' above and "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Diagnosis'.)

In children (less than 18 years of age), screening for ADPKD is controversial. Although some believe the adverse consequences associated with a positive diagnosis prior to symptoms in young individuals (such as career, educational, emotional, and insurability issues) outweigh any benefits, others suggest that early diagnosis provides an opportunity for maximal anticipatory care (eg, optimal blood pressure [BP] control) and the future opportunity to benefit from new therapies. (See 'Screening' above and "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'When to suspect ADPKD'.)

We offer screening to children if desired by the parents (legal guardians) after counseling family members about the inheritance of ADPKD and the potential harms and benefits of diagnostic screening. If appropriate, teenagers and competent younger children should be involved whenever possible in the discussion and decision-making process. Ultrasonography is the preferred modality for screening in children at risk for ADPKD. Sonographic detection of one or more kidney cysts is suggestive of a diagnosis of ADPKD in a child with a positive family history.

The diagnosis of ADPKD is straightforward in children with a positive family history and characteristic renal ultrasound findings. In patients without a family history of ADPKD, other cystic kidney disease must be considered, such as ARPKD. (See 'Differential diagnosis' above and "Autosomal recessive polycystic kidney disease in children" and "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis", section on 'Differential diagnosis'.)

Data on benefit and safety of disease-specific therapy (such as tolvaptan, which has been approved for use in adults) in children with ADPKD are lacking and no specific agent is recommended to slow the progression of renal disease in affected children. Supportive management is provided for all children with or at risk for ADPKD, in whom diagnostic testing has been deferred until legal age of medical consent. This entails rigorous BP control, reduction in proteinuria, dietary measures (no excess salt intake, increased fluid intake, and no protein restriction), and anticipatory guidance to avoid and manage other complications of ADPKD (eg, abdominal pain, urinary tract infection, and avoidance of trauma). (See 'Management' above.)

Strict BP control consists of the following (see 'Blood pressure management' above and "Nonemergent treatment of hypertension in children and adolescents", section on 'Chronic kidney disease' and "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of hypertension" and "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Management of blood pressure'):

-BP is monitored at least once a year.

-We suggest antihypertensive treatment to maintain 24-hour ambulatory BP monitoring (ABPM) target BP goals of mean arterial BP <50th percentile rather than higher target BP goals (Grade 2B). If ABPM levels are not available, we suggest initiating antihypertensive treatment when office-based systolic and diastolic BP repeatedly exceed 90th percentile for age, sex, and height (table 2 and table 3) up to an upper target BP of 110/75 (Grade 2C).

-If antihypertensive medication is required, we suggest targeting office-based systolic and diastolic BP to ≤50th percentile for age, sex, and height (table 2 and table 3) (Grade 2C). Other experts in the field use a higher BP target of ≤75th percentile for age, sex, and height.

-We suggest using an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker as the initial antihypertensive agent rather than another class of antihypertensive agents (Grade 2B).

In adults, trials have shown that the vasopressin antagonist, tolvaptan, slows progression of renal disease in patients with a high likelihood of developing end-stage kidney disease. However, tolvaptan has significant adverse effects (eg, potential hepatic injury and polyuria) and is costly. There are no available data on its use in pediatric patients, including safety information. As a result, we do not suggest using tolvaptan in pediatric patients with ADPKD until there are further data demonstrating it is a safe drug with significant benefit in children with ADPKD (Grade 2C).

Children who are diagnosed with ADPKD are likely to have preserved renal function until the fourth decade of life. However, a few symptomatic children are at risk for progressive disease that results in end-kidney renal disease that requires renal replacement therapy. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Identification of high-risk patients' and "Autosomal dominant polycystic kidney disease (ADPKD): Treatment", section on 'Specific management of End-Stage Kidney Disease'.)

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Topic 15319 Version 29.0

References

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