Autosomal dominant polycystic kidney disease (ADPKD) is a systemic ciliopathy caused by pathogenic variants in the PKD1 or PKD2 genes and predominantly affects the kidneys [1–3]. With an estimated incidence of 3.96 per 10,000 individuals, ADPKD has traditionally been considered as an adult-onset disease. However, growing evidence, reinforced by the 2025 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, indicates that clinically relevant manifestations may already occur during childhood [1–3]. Pediatric studies have shown that children with ADPKD may present early complications, particularly proteinuria and hypertension, reported in up to 30% of cases [4, 5]. Additionally, early cardiovascular and metabolic alterations have been described, such as increased arterial stiffness, endothelial dysfunction, low-grade systemic inflammation, and subtle cardiac structural changes, suggesting early cardiometabolic involvement, namely alterations in lipid parameters and biomarkers of oxidative stress [6].

Because simple kidney cysts are uncommon in children, ADPKD is usually suspected based on imaging findings in the presence of a positive family history. According to KDIGO 2025, a presumptive diagnosis can be established in an at-risk child with at least one renal cyst [1]. Prenatal suspicion may arise from fetal ultrasound findings in fetuses with an affected parent, while genetic testing provides definitive diagnosis and is recommended for atypical cases, in the absence of family history, or when imaging findings are inconclusive. In pediatric patients, the decision to pursue genetic testing requires careful consideration of both diagnostic benefit and ethical implications [1].

Several clinical complications, such as hypertension, proteinuria, and macroscopic hematuria have been associated with a faster renal function decline in ADPKD [7, 8]. In children, correlations between kidney size, cyst burden, and elevated ambulatory blood pressure have been reported [9]. Nevertheless, unlike in adults, where prognostic tools such as the PROPKD score are available [10], no validated prognostic model exists for pediatric ADPKD.

The aim of this study was to characterize the clinical manifestations of ADPKD in a pediatric population and to explore potential early predictors of complications in this age group.

We conducted a retrospective descriptive study based on the analysis of clinical data from all individuals under 18 years of age diagnosed with ADPKD, who were followed at a tertiary referral hospital in central Portugal, between January 1999 and December 2024. Data collected included demographic characteristics, height and weight percentiles, family history, and renal function by estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. Ultrasonographic parameters were also recorded, including kidney length converted to age-adjusted Z-scores using published pediatric reference data (14), total number of cysts, largest cyst diameter, and cyst complexity, classified according to the Bosniak system.

Disease-related clinical manifestations considered in this study were predefined as urinary tract infections, non-nephrotic proteinuria, hypertension (clinic measurements ≥ 95th percentile for age, sex, and height), enuresis or nocturia, nephrolithiasis, and macroscopic hematuria.

Statistical analysis was performed using IBM SPSS Statistics 24^®, and statistical significance was defined as P < 0.05.

According to national legislation and institutional policy, this retrospective study using fully anonymized clinical data was exempt from institutional review board approval.

This retrospective study was conducted using fully anonymized clinical data collected as part of routine clinical care and was performed in accordance with the ethical principles of the Declaration of Helsinki. According to national legislation and institutional policy, ethics committee approval was not required.

Sixty-seven pediatric patients with either a presumed diagnosis of ADPKD (defined by the presence of an affected parent and at least one renal cyst) or a genetically confirmed diagnosis were included (52.2% male). A family history of ADPKD was present in 97.0% of cases, with maternal transmission in 61.2%. The mean age at first evaluation was 7.4 ± 5.5 years. At the time of data collection, the mean age was 9.5 ± 5.9 years for males and 14.4 ± 4.5 years for females. Twelve children (17.9%) were diagnosed within the first 2 years of life. Prenatal renal cystic abnormalities compatible with a subsequent diagnosis of ADPKD were documented in six patients (9.0%).

Renal ultrasound revealed a mean kidney length Z-score of 1.94 ± 2.43. Ten or more renal cysts were observed in 59.7% of patients. Cyst complexity was classified as Bosniak category II or higher in 41.8% of the cohort, including 3.0% with category IIF lesions. Renal function data were available for 54 patients (78%), with a mean eGFR of 97.9 ± 15.1 mL/min/1.73 m². Among these patients, 12 (22.2%) met criteria for chronic kidney disease stage II.

Overall, 19 of the 67 patients (28.4%) developed at least one ADPKD-related clinical manifestation during follow-up (mean duration 4.0 ± 4.3 years). Among the 54 patients with available eGFR data, 17 (31.5%) experienced complications.

The most frequent complications were urinary tract infections (11.9%), non-nephrotic proteinuria (8.9%), hypertension (8.9%), enuresis or nocturia (7.5%), nephrolithiasis (4.5%), and macroscopic hematuria (1.5%). Children who developed complications were significantly older than those without complications (14.2 ± 5.2 vs. 10.9 ± 5.0 years; P = 0.015). Overall, complications occurred more frequently in females than in males (43.8% vs. 14.3%; P = 0.008). In contrast, male patients had significantly lower eGFR values compared with females (93.0 ± 16.1 vs. 103.1 ± 15.6 mL/min/1.73 m²; P = 0.015). No association was observed between the presence of complications and eGFR decline. Sex- and age-related differences and their association with renal function are summarized in Table 1.

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Table 1. Demographic, Clinical, and Imaging Characteristics of Pediatric Patients With ADPKD

No significant associations were identified between the occurrence of complications and weight percentile, kidney dimensions, cyst number, cyst complexity, or largest cyst diameter. The distribution of kidney length Z-scores in patients with and without complications is shown in Figure 1. Ultrasonographic parameters were not associated with differences in eGFR. The relationship between kidney length Z-score and eGFR is illustrated in Figure 2. Linear regression analysis evaluating the association between age and eGFR is presented in Figure 3, showing no significant correlation. Similarly, the distribution of largest cyst diameter according to the presence of complications is illustrated in Figure 4. Finally, eGFR values according to cyst complexity (Bosniak categories II and IIF) are presented in Figure 5.

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Figure 1. Relationship between kidney length Z-score and the presence of ADPKD-related complications in children with ADPKD. Box-and-whisker plot showing the distribution of kidney length Z-scores in patients with and without complications. ADPKD: autosomal dominant polycystic kidney disease.

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Figure 2. Relationship between kidney length Z-score and estimated glomerular filtration rate (eGFR) in children with ADPKD. Scatter plot illustrating eGFR values across kidney length Z-scores in the study cohort. ADPKD: autosomal dominant polycystic kidney disease.

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Figure 3. Relationship between age and estimated glomerular filtration rate (eGFR) in children with ADPKD. Scatter plot with linear regression showing the association between age and eGFR. ADPKD: autosomal dominant polycystic kidney disease.

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Figure 4. Relationship between largest cyst dimension and the presence of ADPKD-related complications in children with ADPKD. Box-and-whisker plot showing the distribution of largest cyst dimensions in patients with and without complications. ADPKD: autosomal dominant polycystic kidney disease.

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Figure 5. Relationship between cyst complexity and estimated glomerular filtration rate (eGFR) in children with ADPKD. Box-and-whisker plot showing eGFR values according to Bosniak cyst complexity categories (II and IIF). ADPKD: autosomal dominant polycystic kidney disease.

Consistent with KDIGO 2025 recommendations and previous pediatric studies, our cohort demonstrates that ADPKD may manifest clinically early in life, with a substantial proportion of affected children developing complications during follow-up. Hypertension and proteinuria, well-established contributors to cardiovascular and renal impairment [4, 9], were among the main complications observed. Early identification and treatment of these modifiable factors remain essential to improve long-term outcomes in pediatric ADPKD [1, 9, 11].

In our cohort, maternal transmission was observed in 61.2% of cases. As ADPKD follows an autosomal dominant inheritance pattern, an approximately equal distribution between maternal and paternal transmission would generally be expected. The slightly higher maternal transmission observed in our cohort likely reflects random variation or cohort-specific referral patterns rather than a true parent-of-origin effect.

Enuresis has a reported prevalence of approximately 5–10% in school-aged children, consistent with epidemiological studies reporting a prevalence of around 7% among children and adolescents [12]. Macroscopic hematuria is uncommon in the general pediatric population, while screening studies report asymptomatic hematuria in approximately 0.5–1% of children [13]. Therefore, although these manifestations are not specific to ADPKD, their occurrence in this context may warrant clinical attention. The prevalence of macroscopic hematuria in our cohort (1.5%) was lower than the 10–14% previously reported [11], which may be partially explained by the younger age of several patients. Older children exhibited a significantly higher frequency of complications, suggesting that clinical burden increases progressively with age despite preserved eGFR. Female patients experienced a higher overall frequency of complications, whereas male patients presented with lower eGFR values. These findings may reflect sex-related differences in early disease trajectories, but could also be influenced by sampling variation or referral patterns. Importantly, we did not identify predictive associations between clinical complications and imaging biomarkers such as kidney size, cyst number, or cyst complexity. This contrasts with one previous study that reported correlations between kidney volume metrics and blood pressure [9]. However, pediatric evidence remains limited by modest sample sizes and the lack of comprehensive longitudinal imaging. KDIGO 2025 guidelines emphasize that no validated prognostic imaging biomarker currently exists for children and that risk stratification in this age group relies primarily on clinical monitoring [1].

The higher frequency of complications observed in females was largely driven by urinary tract infections, which are known to be more prevalent in girls in the general pediatric population. Although females were older at the time of evaluation, no significant association between age and eGFR was identified in regression analysis. Therefore, age alone does not appear to explain the observed sex-related differences in renal function, although the limited sample size may reduce statistical power [11].

Previous studies evaluating predictors of disease progression in ADPKD have produced heterogeneous results. Some clinical characteristics, including male sex, early-onset hypertension, recurrent gross hematuria, and overt proteinuria, have been associated with a more rapid decline in eGFR in certain cohorts. However, evidence remains inconsistent across studies, particularly in pediatric populations in which renal function is generally preserved during the early stages of the disease [1].

Among genetic factors, PKD1 mutations are generally associated with a more severe disease course and a faster decline in eGFR compared with PKD2 mutations. In our cohort, genetic testing was performed in seven patients, all of whom carried PKD1 variants, precluding genotype–phenotype comparisons [1].

Imaging biomarkers such as total kidney volume have also been identified as predictors of renal function decline in adult ADPKD cohorts. However, these parameters were not systematically available in our study, where kidney size assessment relied on ultrasonographic measurements [9].

Finally, previous studies have shown that eGFR decline may be associated with hypertension occurring before the age of 35, as well as with early episodes of hematuria, cyst growth, or infection. The relatively young age of our cohort and the limited duration of follow-up may therefore explain why we did not identify significant predictors of eGFR decline.

The absence of approved disease-modifying therapies for pediatric patients currently restricts management to the prevention and treatment of ADPKD-related complications. Although tolvaptan is approved for adults with rapidly progressive disease and is under investigation in children and adolescents, early recognition of disease manifestations and close longitudinal follow-up remain crucial to optimize supportive care and to ensure timely eligibility for potential future disease-modifying therapies [1, 14]. Accordingly, further studies are needed to identify reliable predictors of complications, refine management strategies, and better characterize the multisystem impact of ADPKD in childhood [6, 14].

Our study is limited by its retrospective design and sample size. Nevertheless, it provides 25 years of real-world data from a pediatric ADPKD cohort, contributing valuable insights into the early clinical course of the disease in childhood.

ADPKD may demonstrate measurable clinical impact during childhood, with relevant rates of urinary tract infections, proteinuria, and hypertension. Although no reliable predictors of complications were identified in our cohort, previous studies have suggested associations between kidney size, cyst number, and hypertension. Larger longitudinal pediatric cohorts are therefore needed to further investigate potential early prognostic markers.

In the absence of validated predictors, early detection and management of modifiable complications, particularly hypertension and proteinuria, remain essential. Both conditions are treatable, and timely intervention may help delay the progression of chronic kidney disease. Structured follow-up, lifestyle counseling, and strict control of blood pressure and proteinuria are key strategies to slow disease progression in children with ADPKD.

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