Autosomal dominant polycystic kidney disease in children and adolescents

ADPKD in children

Article information

Child Kidney Dis. 2026;30(1):24-32

Publication date (electronic) : 2026 February 27

doi : https://doi.org/10.3339/ckd.25.041

Eunji Mun ¹

, Hee Sun Baek ²

¹Department of Pediatrics, Soonchunhyang University Gumi Hospital, Gumi, Republic of Korea

²Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

Correspondence to Hee Sun Baek Department of Pediatrics, School of Medicine, Kyungpook National University, 807 Hoguk-ro, Buk-gu, Daegu 41404, Republic of Korea E-mail: baekhs@knu.ac.kr

Received 2025 December 31; Revised 2026 February 10; Accepted 2026 February 20.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder and primarily arises from mutations in either the polycystic kidney disease 1 (PKD1) or 2 (PKD2) gene. Although traditionally categorized as an adult-onset disease, cystogenesis often begins in utero, and structural changes may become evident during childhood. Although most pediatric patients with ADPKD remain asymptomatic, hypertension occurs in 20%–40% of cases, and albuminuria may also be present. Both findings represent early, treatable manifestations that can significantly influence long-term prognosis. Ultrasonography is the preferred diagnostic modality; however, genetic testing is indicated in very-early-onset or atypical cases. The cornerstone of disease management is rigorous blood pressure control using renin–angiotensin system inhibitors, along with lifestyle modifications such as sodium restriction and adequate hydration. Early diagnosis and intervention are essential for optimizing long-term clinical outcomes in pediatric patients with ADPKD. This study aimed to provide a comprehensive review of the genetics, pathophysiology, clinical manifestations, diagnosis, treatment, and future management of pediatric ADPKD.

Keywords: Adolescent; Child; Polycystic kidney, autosomal dominant

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder, with an estimated global prevalence of 1 in 400 to 1 in 2,500 individuals [1-4]. Furthermore, ADPKD accounts for approximately 5% to 10% of all cases of end-stage kidney disease (ESKD) in adults, with approximately 50% of patients progressing to ESKD requiring renal replacement therapy, such as hemodialysis or transplantation, by the age of 60 [1,5-7]. Although no single, definitive prevalence rate has been determined in the pediatric population, the estimated overall prevalence of recognized polycystic kidney diseases (PKDs), encompassing both ADPKD and autosomal recessive PKD (ARPKD) forms, is approximately 1 in 10,000 children [1,8]. ADPKD is primarily characterized as an adult-onset disorder; however, cystogenesis frequently commences in utero, resulting in structural disease becoming clinically apparent during childhood [1,5,9-11]. Therefore, as early detection and intervention can positively affect the long-term prognosis of children and adolescents with ADPKD, the aim of this article was to provide a comprehensive review of the genetics, pathophysiology, clinical manifestations, diagnosis, treatment, and future management of pediatric ADPKD.

Classification of ADPKD in children and adolescents

Genotype: PKD1 versus PKD2

Classification of ADPKD by the underlying mutated gene (PKD1 versus PKD2) is a key determinant of disease severity and prognosis in the pediatric population. PKD1 mutations are associated with a significantly more aggressive clinical course, with larger age-adjusted total kidney volumes (TKVs) and a higher cyst burden observed in affected children compared with those harboring PKD2 mutations. Accordingly, children who present with symptomatic disease or early-onset hypertension are disproportionately more likely to harbor PKD1 mutations [8,12,13].

Timing of onset and severity

ADPKD is categorized into several phenotypical subentities based on both the timing of the clinical presentation of the disease as well as its severity. Very-early-onset ADPKD (VEO-ADPKD) is defined by the presence of severe symptoms or clinical evidence of the disease before the age of 18 months; this subentity includes cases diagnosed in utero that involve the presence of oligohydramnios-associated hyperechogenic enlarged kidneys (>2 standard deviations [SDs] according to gestational age), as well as infants presenting with enlarged cystic kidneys (>2 SD according to age, sex, and height) accompanied by hypertension (≥95th percentile) or a decrease in the estimated glomerular filtration rate (eGFR). VEO-ADPKD is a rare manifestation, with such a severe early onset occurring in approximately 2%–5% of children carrying ADPKD-causing mutations [11].

Early-onset ADPKD (EO-ADPKD) is defined as clinical evidence of severe disease between the ages of 18 months and 15 years. EO-ADPKD is characterized by the presence of enlarged cystic kidneys (>2 SD with respect to age, sex, and height) with concomitant hypertension (≥95th percentile) or a decrease in the eGFR. A “child with ADPKD” refers to an individual who meets the general diagnostic criteria for ADPKD but does not fulfill the specific criteria for VEO-ADPKD or EO-ADPKD. Finally, a “child at risk of ADPKD” is defined as an individual with the potential for disease heritability given the existence of a relative known to be affected by ADPKD (Fig. 1) [11].

Fig. 1.

Classification of ADPKD in children and adolescents. VEO, very-early-onset; ADPKD, autosomal dominant polycystic kidney disease; SD, standard deviation; HTN, hypertension; eGFR, estimated glomerular filtration rate; EO, early-onset.

Imaging-based classification

The Mayo Imaging Classification (MIC) is a prognostic classification system widely used in clinical practice for predicting the rate of disease progression based on patient age and TKV, as measured by magnetic resonance imaging (MRI) or computed tomography (CT). The system categorizes patients into Class 1 (typical ADPKD), which is characterized by bilateral, diffuse cyst distribution and is further stratified into five subclasses (1A–1E) reflecting increasing risk of progression. In contrast, Class 2 (atypical ADPKD) accounts for approximately 5%–10% of cases and includes patients with unbalanced cyst distributions, such as unilateral, segmental, or lopsided involvement, and is generally associated with a significantly slower decline in kidney function compared with Class 1 disease [2,14].

Comparison with adult-onset ADPKD

ADPKD is predominantly considered an adult-onset disorder, with approximately 50% of affected individuals progressing to ESKD and requiring kidney replacement therapy, most commonly hemodialysis or kidney transplantation, by 60 years of age [1,8,15]. In contrast, pediatric patients remain largely asymptomatic; however, when clinical signs do occur, they most frequently manifest as hypertension (in 20%–40% of cases) or gross hematuria [8]. Extrarenal manifestations that are prevalent in adults, such as hepatic cysts and intracranial aneurysms (ICAs), which occur in >80% and 8–12% of cases, respectively, are exceedingly rare during childhood, resulting in very few reports of clinically significant complications in the pediatric population [5,6,8,16].

Genetics and pathogenesis

ADPKD most commonly results from pathogenic variants in either the PKD1 gene on chromosome 16, which accounts for approximately 85% of cases, or the PKD2 gene on chromosome 4, responsible for the remaining 15%. Genotype is a major determinant of prognosis: PKD1 mutations are associated with a more aggressive clinical course, including earlier symptom onset and progression to ESKD typically by the mid-50s. In contrast, PKD2 mutations generally confer a milder phenotype with slower disease progression, often delaying the onset of ESKD until age 70 [1,5,8,11]. Two protein products, polycystin-1 (PC1) and polycystin-2 (PC2), form a heterodimeric complex that localizes in the primary cilia of renal tubular epithelial cells; thus, ADPKD is classified as a prominent form of systemic ciliopathy [1,17-19].

The loss of PC1/PC2 function disrupts intracellular calcium (Ca²⁺) homeostasis and leads to a pathological elevation of cyclic adenosine monophosphate levels, which induces the activation of downstream signaling cascades that drive epithelial cell proliferation, fluid secretion, fibrosis, and inflammation, including the mammalian target of rapamycin (mTOR), mitogen-activated protein kinase/extracellular signal-regulated kinase, and Wnt pathways (Fig. 2) [2,5,17]. Cystogenesis is believed to follow a "two-hit" model. In ADPKD, an initial germline mutation (the “first hit”) typically occurs in one PKD1 or PKD2 allele, with the initiation of cyst formation requiring a secondary somatic event (the “second hit”), such as the inactivation of the remaining wild-type allele. Genetic modifiers and environmental factors, including acute kidney injury, can further modulate disease progression. Fundamentally, cystogenesis is triggered when functional PC1 or PC2 levels fall below a critical threshold [1,19,20].

Fig. 2.

Intracellular signaling pathways involved in cyst formation and growth in ADPKD. PC1, polycystin-1; PC2, polycystin-2; PDE, phosphodiesterase; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; CFTR, cystic fibrosis transmembrane conductance regulator; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; mTOR, mammalian target of rapamycin.

Clinical presentation

Most children and adolescents with ADPKD are asymptomatic [20], and experience clinical manifestations that are typically mild compared with the severe complications observed in adulthood; nevertheless, early signs necessitating intervention may arise.

Structural and functional changes in the kidneys

The development of renal cysts commences in utero or during early childhood, and ADPKD is identified in the majority of pediatric patients based on the incidental detection of these cysts [6,21]. As these cysts undergo progressive enlargement, the kidneys may exhibit clinical signs of nephromegaly, and a steady increase in the TKV is frequently observed [22,23]. Although most children with ADPKD maintain a normal or preserved GFR throughout childhood, often masked by compensatory glomerular hyperfiltration, existing risk factors, such as hypertension and a rapid increase in cyst burden, can promote future functional decline [10,16].

Cardiovascular and hemodynamic complications

Hypertension represents the most common and earliest clinical manifestation of pediatric ADPKD, typically developing while renal function remains within the normal range and affecting approximately 20%–40% of children and adolescents with the disease [24-26]. In these pediatric patients, the presence of left ventricular hypertrophy or an increase in the left ventricular mass index can be an early indicator of cardiovascular complications, even in those whose blood pressure is within the high–normal range [13,27].

Urologic complications

Cyst hemorrhage-induced gross hematuria has been reported in approximately 10%–14% of pediatric patients with ADPKD, and hematuria may occasionally be precipitated by seemingly minor trauma [3,10]. Mild proteinuria or albuminuria is also a common finding in approximately 20%–40% of children with ADPKD. Furthermore, a reduction in urinary concentrating capacity, which can lead to symptoms such as enuresis, polyuria, and increased urination frequency, has been reported in approximately 58% of pediatric patients [5,26]. Urinary tract infections and urolithiasis may arise as complications; however, abdominal or flank pain caused by cyst expansion, although common in adults, is not a typical presenting symptom in children and adolescents [3,6].

Other extrarenal manifestations

In children and adolescents with ADPKD, extrarenal manifestations are less common than in adults. Hepatic cysts are rare in childhood, with a prevalence of <5% detected by ultrasonography; however, MRI has identified hepatic cysts in up to 55%–58% of adolescents and young adults aged 15–24 years. Cardiac valvular abnormalities, most notably mitral valve prolapse, have been reported in approximately 12% of pediatric patients, although more recent studies have suggested a lower prevalence comparable to that of the general pediatric population. ICAs are exceedingly uncommon in children, with occurrence typically not reported before 20 years of age [3,6,11,13]. In contrast, VEO-ADPKD may present with features that overlap with ARPKD, including fetal pulmonary hypoplasia and hepatobiliary abnormalities resembling congenital hepatic fibrosis. Accordingly, pediatric gastroenterologists, in collaboration with pediatric nephrologists, should consider ADPKD in the differential diagnosis of infants presenting with biliary tract malformations [26,28,29].

Diagnosis

In clinical practice, the diagnosis of ADPKD in children and adolescents is most often prompted by screening individuals with a positive family history or by incidental findings during routine health evaluations, as the majority of pediatric patients remain asymptomatic. Accordingly, diagnosis typically relies on a thorough family history in combination with radiologic imaging. Although imaging remains the standard first-line diagnostic approach, molecular genetic testing to identify PKD1 or PKD2 variants is recommended in selected situations, such as when imaging findings are inconclusive, when no known family history suggests a de novo mutation, or when excluding disease in young potential kidney donors. While availability may be limited by cost and access, genetic testing offers definitive diagnostic and prognostic value [8,10,11].

With respect to imaging modalities, ultrasonography is the most widely used and safest screening tool in children, as it avoids ionizing radiation and the need for sedation. Age-dependent diagnostic criteria based on cyst number are well established for individuals aged ≥15 years; however, in younger children with a positive family history, the presence of even a single renal cyst is highly suggestive of ADPKD. MRI and CT provide superior sensitivity for detecting small cysts, accurately quantifying cyst burden, and measuring TKV. Although CT carries potential risks related to radiation exposure and contrast use in pediatric patients, it remains a practical alternative in clinical settings when MRI is unavailable or contraindicated [1,3,8,30].

Prognosis and risk stratification models

Although MRI-derived height-adjusted TKV (htTKV) is considered the prognostic gold standard in adults with ADPKD, application of the MIC in patients younger than 15 years often underestimates disease severity [31]. In pediatric patients, structural progression, particularly cyst growth, may occur despite preserved kidney function and normal eGFR, highlighting the need for prognostic criteria that account for growth and developmental changes unique to childhood [8]. To address these limitations, the Leuven Imaging Classification (LIC) was developed specifically for children and adolescents with ADPKD (0–18 years). Although ongoing studies are evaluating the use of MRI-derived measurements within this framework, the LIC primarily relies on three-dimensional ultrasonography as its preferred imaging modality. This approach is particularly advantageous in pediatric populations, as it avoids ionizing radiation exposure associated with CT and reduces the need for sedation or concerns related to claustrophobia frequently encountered with MRI. By plotting htTKV against age-specific reference curves adapted from the MIC, the LIC stratifies patients into five distinct stages (A–E), providing a more accurate assessment of progression risk in children [8,31]. A comparison between the LIC and MIC models is presented in Table 1.

Table 1.

Comparison of MIC and LIC in ADPKD

Accurate prognostic assessment in pediatric ADPKD requires integration of both genotype and imaging biomarkers, such as htTKV within the LIC model, beyond clinical diagnosis alone. Genotype plays a critical role, as PKD1 mutations are associated with a substantially more severe clinical course than PKD2 mutations. Incorporation of the LIC model enables more precise risk stratification for rapid disease progression in children with ADPKD.

The PROPKD score is an established prognostic algorithm in adult ADPKD that integrates genetic data with early clinical features to predict the risk of progression to ESKD. The score assigns points based on four variables: male sex, onset of hypertension before 35 years of age, first urologic event (e.g., gross hematuria or cyst infection) before 35 years of age, and mutation type (PKD1 truncating, PKD1 nontruncating, or PKD2). Total scores range from 0 to 9 and classify patients into three risk categories: low risk (0–3 points), associated with a low likelihood of ESKD before 70 years of age; intermediate risk (4–6 points), with expected progression to ESKD in the late 50s to 60s; and high risk (7–9 points), indicating early progression to ESKD in the 40s or 50s. Notably, several PROPKD components, including hypertension, genotype, and gross hematuria, also serve as significant prognostic indicators in pediatric patients [8,32].

Treatment and management

The early detection and rigorous treatment of hypertension to mitigate the long-term risk of cardiovascular and renal complications is the cornerstone of pediatric ADPKD management. Currently, no disease-modifying pharmacological interventions are routinely administered in children with ADPKD specifically for delaying disease progression [11,16,26].

Management of hypertension and kidney complications

Children at risk of or diagnosed with ADPKD should undergo annual blood pressure assessments beginning at birth. Annual ambulatory blood pressure monitoring (ABPM) is recommended for pediatric patients with ADPKD (aged ≥5 years and height ≥120 cm) who have office blood pressure readings at or above the 75th percentile, as ABPM is highly effective for detecting isolated nocturnal hypertension (INH) and assessing circadian blood pressure patterns. In children with ADPKD presenting with borderline blood pressure (75th–95th percentile), the identification of INH or non-dipping patterns provides a rationale for the early initiation of antihypertensive therapy to potentially attenuate disease progression. Notably, INH is reported in approximately 16%–18% of children with ADPKD who exhibit normal daytime blood pressure [3,11,27]. Upon confirmation of hypertension, renin–angiotensin system (RAS) inhibitors (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) are recommended as first-line pharmacotherapy; such treatment is also indicated in the presence of albuminuria. The recommended target blood pressure is below the 50th percentile with respect to age, sex, and height, or <110/70 mmHg for adolescents aged ≥16 years [3,11]. Furthermore, RAS inhibitors are recommended for those with overt proteinuria or severe albuminuria (albumin-creatinine ratio [ACR] >300 mg/g), and they should be considered for those with moderate albuminuria (ACR 30–300 mg/g) (Fig. 3) [8]. RAS inhibitors, including ACE inhibitors and ARBs, are the preferred first-line antihypertensive agents in children with ADPKD. However, their use is associated with potential adverse effects, including hyperkalemia, acute kidney injury, and symptomatic hypotension; ACE inhibitors may additionally cause a persistent dry cough [11].

Fig. 3.

Management of hypertension and kidney complications. BP, blood pressure; ACR, albumin-creatinine ratio; US, ultrasonography; ICAs, intracranial aneurysms; ABPM, ambulatory blood pressure monitoring; Tx, treatment; RAS, renin–angiotensin system; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; NSAIDs, nonsteroidal anti-inflammatory drugs.

Therapies for delaying disease progression

With respect to modifiable risk factors, children with ADPKD should be encouraged to limit dietary sodium intake to <2 g/day (salt <5 g/day), in accordance with recommendations for the general pediatric population [33]. Avoidance of dehydration through adequate fluid intake and moderation of excessive protein consumption may further help attenuate disease progression. In addition, maintaining a healthy body weight and engaging in regular physical activity should be strongly promoted [3,16]. While tolvaptan, a highly selective vasopressin receptor 2 antagonist, is an approved disease-modifying agent for adults at risk of rapid progression, it should not be routinely administered to children and adolescents; however, off-label use of the drug may be considered at the clinician's discretion for select children at high risk of early progression, as characterized by a large TKV, rapid kidney growth or a family history of early ESKD [11,34]. In contrast, mTOR inhibitors and somatostatin analogues are not recommended for the treatment of pediatric patients with ADPKD. Although pravastatin has been shown to be efficacious in slowing the rate of htTKV expansion in pediatric patients, routine use is not supported by current consensus owing to insufficient evidence regarding its capacity to promote the long-term preservation of renal function (Table 2) [3,11,16,34,35]. Monitoring urine specific gravity (uSG) may serve as a practical surrogate for assessing hydration status and vasopressin suppression in ADPKD management. Maintaining isosthenuria (uSG ≤1.010) provides a clear clinical target, indicating that adequate fluid intake can potentially reduce vasopressin-driven cyst growth [11,24,34].

Table 2.

Medical treatments for delaying ADPKD progression in children and adolescents

Management of other complications

Routine screening for liver cysts, cardiac valvular disease, and ICAs are not recommended for pediatric patients with ADPKD, and diagnostic evaluations should be reserved only for cases in which concerning symptoms are present or when a symptomatic extrarenal manifestation is suspected [3,11]. Notably, screening for ICAs is not recommended until the age of 20 years and should be conducted in accordance with established recommendations in adults. Nevertheless, in pediatric patients who present with symptoms such as persistent headaches or who have a family history of ICAs or subarachnoid hemorrhage, screening for ICAs is recommended even before the age of 20 years. Given the high mortality and severe morbidity associated with ICA rupture, early detection in these high-risk individuals is essential to prevent potentially fatal outcomes [1,5,11]. The management of chronic pain, such as abdominal pain, should be initiated early through a multidisciplinary approach, even in children and adolescents. Furthermore, the use of nonsteroidal anti-inflammatory drugs must be minimized owing to the underlying kidney disease [3,11].

Conclusions

While the primary disease burden of ADPKD typically manifests in adulthood, a significant proportion of children and adolescents with the disease exhibit early, treatable signs, such as hypertension. The cornerstone of management for these young patients is the early identification and rigorous control of disease manifestations, with the goal of positively impacting long-term prognosis in adulthood. Current guidelines recommend providing balanced counseling to at-risk families, performing regular blood pressure monitoring to detect hypertension and urine testing to identify albuminuria, and avoiding frequent imaging solely to monitor cyst growth. The use of ACE inhibitors or ARBs is particularly emphasized for hypertension management. Although there are currently no approved disease-modifying therapies for pediatric ADPKD, a clinical trial of tolvaptan has demonstrated the agent’s safety and confirmed its pharmacodynamic activity in this patient population. Notably, evidence indicates that genotype and htTKV are the most important prognostic factors determining disease progression and long-term outcomes in both adult and pediatric ADPKD populations. Accurately defining high-risk patient groups who require early intervention from medical, psychological, and economic perspectives, developing pediatric-specific prognostic indicators such as htTKV, and supporting a seamless transition to adult care are particular challenges that must be overcome to improve the clinical outcomes associated with pediatric ADPKD.

Notes

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: EM, HSB

Writing–original draft: EM

Writing–review & editing: EM, HSB

All authors read and approved the final manuscript.

Data availability statement

Data sharing is not applicable as no new data were created or analyzed in this study.

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	MIC	LIC
Target population	Adults (typically aged 15–80 yr)	Infants, children, and adolescents <19 yr
Measurement parameter	htTKV by MRI or CT	htTKV by 3D ultrasound
Formula for cutoff lines	htTKV (mL/m)=A×(1+B/100)^age;	Optimized for children htTKV(mL/m) = C×D^{(age^1.6)};
	A=starting volume (150 mL/m at birth),
	B=annual htTKV growth rates (%) (1.5, 3.0, 4.5, 6.0)^a)	C=starting volume (80, 90, 100, or 110 mL/m at birth),
		D=growth coefficient (1.010, 1.012, 1.015, or 1.018)^a)
Risk stratification	Typical: Class 1A through Class 1E; based on estimated annual htTKV growth rates	Class A through Class E; based on where the htTKV falls relative to the cutoff lines
Risk stratification	Atypical: Class 2
Prediction	Identifies rapid progressors (Classes 1C-1E); identifies candidate for tolvaptan therapy and clinical trials	Identifies rapid progressors and early-onset kidney failure (VEO-ADPKD)
Validation	Highly validated in large adult cohorts; strongly underestimates severity in children (especially <15 yr)	Specifically validated for pediatric cohorts to overcome adult model limitations; superior to MIC for children <10 yr

Drug category	Agent name(s)	Mechanism of action	Side effects	Status for pediatric use
V2 receptor antagonist [3,11,16,34]	Tolvaptan	Blocks V2 receptors; inhibits cAMP, cyst fluid secretion, and cell proliferation	Aquaretic events (polyuria, nocturia), transaminase elevation	Insufficient evidence for routine use
V2 receptor antagonist [3,11,16,34]	Tolvaptan			Off-label use may be considered for cases with high risk of early progression
HMG-CoA reductase inhibitor [3,11,16,35]	Pravastatin	Inhibits HMG-CoA reductase; regulates proliferation, inflammation, and oxidative stress; improves renal blood flow	Generally well-tolerated. No major side effects or growth concerns	Low/insufficient evidence for routine use, despite slowing structural progression
mTOR inhibitors [3,16]	Everolimus, Sirolimus (Rapamycin)	Inhibits mTOR pathway; suppresses proliferation of cystic epithelial cells and cyst growth	Worsening proteinuria, hyperlipidemia, cytopenia, stomatitis, and diarrhea	Not recommended for slowing disease progression owing to lack of efficacy and high toxicity
Somatostatin analogues [3,16]	Octreotide, Lanreotide, Pasireotide	Binds SSTRs; inhibits adenylyl cyclase (AC6) and reduces intracellular cAMP levels, decreasing fluid secretion and growth	GI symptoms (diarrhea, pain), gallstones, hyperglycemia, bradycardia	Not recommended for routine use