Abstract
Background
This study assessed the clinical features, prevalence of kidney and urinary manifestations, and progression of chronic kidney disease (CKD) in patients with Kabuki syndrome (KS).
Methods
This retrospective cohort study enrolled patients with KS who visited a single tertiary center from 2003 to 2023.
Results
Sixty-five patients (28 boys) were diagnosed with KS at a median age of 2.7 years (interquartile range [IQR] = 1.0–9.3) and followed until a median age of 9.4 years (IQR = 5.5–14.3). Genetic analysis identified KMT2D and KDM6A mutations in 59 and 3 patients, respectively. Congenital anomalies of the kidneys and urinary tract (CAKUT) were found in 21 of 62 patients (33.9%), whereas 7 of 62 patients (11.3%) patients had nephrolithiasis and/or nephrocalcinosis. Meanwhile, 19 of 56 patients (33.9%) progressed to CKD. CKD-free survival analysis illustrated that 25% and 50% of these patients progressed to CKD stage G2 at median ages of 5.8 and 24.6 years, respectively. Younger age at diagnosis and the presence of bilateral kidney anomalies were identified as significant predictors of CKD progression. CAKUT and cardiorenal syndrome were the leading causes of CKD.
Conclusions
One-third of patients with KS exhibited various kidney or urinary abnormalities, and 34% progressed to CKD. Screening for kidney or urinary issues and regular follow-up of kidney function are essential for KS management.
Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information
Supplementary Information
The online version contains supplementary material available at 10.1007/s00467-025-06815-0.
Keywords: Kabuki syndrome, Chronic kidney disease, Congenital anomalies of kidney and urinary tract, Nephrolithiasis
Introduction
Kabuki syndrome (KS; OMIM 147920) is a rare genetic syndrome caused by pathogenic variants in KMT2D (formerly MLL2; MIM #602,113) or KDM6A (MIM #30,012). Initially described independently in 1981 by Niikawa et al. and Kuroki et al., KS is characterized by five cardinal features: distinctive facial features, skeletal anomalies, dermatoglyphic abnormalities, intellectual disability, and short stature [1, 2]. The most prominent characteristic, the typical facial phenotype, includes long palpebral fissures with eversion of the lateral third of the lower eyelids and arched, broad eyebrows, giving the characteristic resemblance to the stage makeup used in Kabuki, a traditional Japanese theater form [3].
KS is associated with varied phenotypic features that affect multiple organ systems, including congenital heart defects and congenital anomalies of the kidneys and urinary tract (CAKUT). The incidence of CAKUT in patients with KS ranges 30–43%, being more common in individuals with KMT2D mutations [4–6]. CAKUT encompasses a broad spectrum of malformations, ranging from mild to severe, and it can lead to chronic kidney disease (CKD). There are reports of kidney failure requiring kidney transplantation caused by CAKUT and/or congenital heart defects in patients with KS [7–10]. However, few studies have specifically evaluated kidney function in patients with KS. This study assessed the clinical features, prevalence of kidney and urinary manifestations, and progression of CKD in patients with KS.
Materials and methods
Study design
This retrospective, single-center cohort study included all patients with KS who visited Seoul National University Children’s Hospital between August 2003 and August 2023. The diagnosis of KS was established according to the international consensus diagnostic criteria issued in 2019 [3]. Clinical, laboratory, and radiographic data were retrospectively collected from patients’ medical records and reviewed. The study was approved by the Seoul National University Hospital Institutional Review Board (IRB no. H-2309-043-1464).
Definitions
The diagnoses of CAKUT, nephrocalcinosis, and nephrolithiasis were based on findings from kidney imaging studies, including ultrasonography and computed tomography. CAKUT was defined as abnormalities of kidney number, size, morphology, position, and/or abnormalities of outflow tract including the pelvis, ureter, or urinary bladder [11]. Bilateral kidney anomalies were defined as the presence of hypoplasia, dysplasia, or agenesis in both kidneys. Nephrocalcinosis was diagnosed and graded based on kidney ultrasonography as follows: grade 0, no echogenicity; grade 1, mild echogenicity around the medullary pyramid borders; grade 2, moderate echogenicity around and inside the pyramids; grade 3, severe echogenicity of all pyramids [12]. Hypercalciuria was defined as urine calcium/creatinine ratio exceeding 0.2 mg/mg. CKD stages G2 and G3 were defined by estimated glomerular filtration rates (eGFRs) of 60 to < 90 mL/min/1.73 m2 and 30 to < 60 mL/min/1.73 m2, respectively, in accordance with the GFR categories of the Kidney Disease: Improving Global Outcomes 2024 guidelines [13]. eGFR was calculated using the creatinine-based Chronic Kidney Disease in Children under 25 (CKiD U25) formula for children, adolescents, and young adults [14]. The diagnosis of congenital heart defects (CHD) was based on echocardiography. Left-sided obstructive CHD was defined as coarctation of aorta, bicuspid aortic valve, aortic or mitral stenosis, and hypoplastic left heart syndrome [15, 16].
Genotype–phenotype correlation
For the causative gene-based analysis, patients were categorized into the KMT2D and KDM6A groups. To evaluate genotype–phenotype correlations within the KMT2D group, patients were further classified into predicted loss-of-function (pLoF) and non-pLoF variant groups based on variant type. Pathogenic nonsense, frameshift, splicing variants, and deletions were classified as pLoF variants, whereas missense and in-frame variants were classified as non-pLoF variants. For the variant location-based analysis, the pLoF variant group was further subdivided into the C-terminus group, which included variants located in or after exon 39 of KMT2D, and the non-C-terminus group, which included variants located before exon 39 of KMT2D [17]. Since all non-pLoF variants were located in or after exon 39 of KMT2D, location-based analysis was not applicable in the non-pLoF variant group.
Statistical analysis
Statistical analyses were performed using IBM® SPSS® Statistics 29.0 (IBM, Armonk, NY, USA) and R version 4.2.2. Data were reported as medians and interquartile ranges (IQRs). Categorical variables were analyzed using Fisher’s exact test, whereas continuous variables were compared using the Mann–Whitney U test. CKD-free survival was evaluated using Kaplan–Meier survival analysis. Cox proportional hazards regression was employed to identify predictive factors for CKD-free survival. Variables with P < 0.200 in univariate analysis were included in the multivariate Cox proportional hazards model. Significance was indicated by P < 0.05.
Results
Patient characteristics
In total, 65 children with KS of Korean descent, including 28 boys, were enrolled in this study (Table 1). The median age at diagnosis was 2.7 years (IQR = 1.0–9.3), and the median age at the last follow-up was 9.4 years (IQR = 5.5–14.3). All patients underwent genetic testing, including Sanger sequencing, targeted exome sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification, or whole genome sequencing (Supplementary Table 1). Most patients (90.8%) had KMT2D mutations, whereas three patients each harbored KDM6A mutations and unidentified mutations. The KMT2D mutations consisted of various types, including frameshift mutations (n = 23), nonsense mutations (n = 21), missense mutations (n = 8), splicing site mutations (n = 6), and deletion (n = 1).
Table 1.
Characteristics of patients with Kabuki syndrome
| Characteristics | Total (n = 65) |
|---|---|
| Sex | |
| Male | 28 (43.1%) |
| Female | 37 (56.9%) |
| Causative gene | |
| KMT2D | 59 (90.8%) |
| Frameshift | 23 (35.4%) |
| Nonsense | 21 (32.3%) |
| Missense | 8 (12.3%) |
| Splicing site | 6 (9.2%) |
| Exonic deletion | 1 (1.5%) |
| KDM6A | 3 (4.6%) |
| Not identified | 3 (4.6%) |
| Median age at diagnosis, years | 2.7 (IQR 1.0–9.3) |
| Median age at the last follow up, years | 9.4 (IQR 5.5–14.3) |
| CAKUT | 21/62 (33.9%) |
| Horseshoe kidney | 8 (12.9%) |
| Ectopic kidney | 7 (11.3%) |
| Hypoplastic kidney | 6 (9.7%) |
| Multicystic dysplastic kidney | 4 (6.5%) |
| Duplex kidney | 2 (3.2%) |
| Unilateral renal agenesis | 1 (1.6%) |
| Ureteropelvic junction obstruction | 1 (1.6%) |
| Nephrolithiasis and/or nephrocalcinosis | 7/62 (11.3%) |
| Kidney and/or ureter stone | 5 (8.1%) |
| Nephrocalcinosis | 4 (6.5%) |
IQR interquartile ranges, CAKUT congenital anomalies of kidneys and urinary tract
Kidney manifestations
Kidney and urinary system was radiologically evaluated in 62 patients (95.4%), revealing CAKUT in 21 patients (33.9%). The specific anomalies included horseshoe kidney (n = 8), ectopic kidney (n = 7), hypoplastic kidney (n = 6), multicystic dysplastic kidney (n = 4), duplex kidney (n = 2), unilateral renal agenesis (n = 1), and ureteropelvic junction obstruction (n = 1; Table 1).
Nephrolithiasis and/or nephrocalcinosis were identified in 7 of 62 patients (11.3%) at a median age of 5.5 years (IQR = 3.6–13.5). Two patients were diagnosed with both nephrocalcinosis and kidney stones. Nephrocalcinosis was localized in the medullary region in all four affected patients and was classified as grade 1. Among these patients, hypercalciuria was detected in all six patients who underwent urinary testing related to stone formation. One patient with hypoplastic left heart syndrome had been prescribed loop diuretics, a drug known to cause hypercalciuria. Two patients required surgical intervention for stone removal, and they subsequently received potassium citrate. Stone analysis revealed calcium oxalate monohydrate and calcium phosphate compositions. Another patient was treated with hydrochlorothiazide and potassium citrate. The remaining four patients did not experience progression of nephrolithiasis and/or nephrocalcinosis without pharmacological intervention. No patients with nephrolithiasis experienced chronic obstruction or recurrent urinary tract infections.
Kidney function and CKD progression
Serum creatinine levels were measured in 56 patients (86.2%), who were subsequently followed until a median age of 7.5 years (IQR = 3.7–13.5) with a median of 7 creatinine measurements (IQR = 1–13.5). Among these patients, 33.9% (n = 19) experienced CKD progression, including progression to stage G2 in 16 patients and stage G3 in 3 patients. Kaplan–Meier survival analysis estimated that 25% and 50% of patients developed CKD G2 at median ages of 5.8 (95% confidence interval [CI] = 3.7–not available) and 24.6 years (95% CI = 16.8–not available), respectively (Fig. 1). To identify predictive factors for CKD progression, Cox proportional hazard models were analyzed, incorporating demographic data, genetic variant types, and the presence and subtypes of CAKUT and CHD. Multivariate Cox proportional hazards analysis demonstrated that younger age at diagnosis and the presence of bilateral kidney anomalies were significant predictive factors for progression to CKD G2 (Table 2). Kaplan–Meier analysis demonstrated a significant difference in CKD-free survival based on the presence of bilateral kidney anomalies (Fig. 2).
Fig. 1.
Chronic kidney disease-free survival of patients with Kabuki syndrome. The solid line represents the survival curve estimated using Kaplan–Meier analysis, with shaded areas indicating the 95% confidence intervals
Table 2.
Predictive factors for chronic kidney disease progression in patients with Kabuki syndrome
| Variables | Univariate | Multivariate | ||
|---|---|---|---|---|
| Hazard ratio (95% CI) | P value | Hazard ratio (95% CI) | P value | |
| Male sex | 1.101 (0.433–2.800) | 0.840 | – | – |
| Age at diagnosis | 0.741 (0.625–0.880) | < 0.001 | 0.746 (0.609–0.914) | 0.005 |
| Causative gene, KMT2D | 2.858 (0.379–21.550) | 0.308 | – | – |
| KMT2D genotype, pLoF variants | 1.792 (0.238–13.520) | 0.572 | – | – |
| Location of pLoF variants in KMT2D, C-terminus | 0.839 (0.303–2.325) | 0.736 | – | – |
| CAKUT | 3.244 (1.251–8.415) | 0.016 | 1.156 (0.315–4.240) | 0.827 |
| Bilateral kidney anomalies | 4.337 (1.675–11.230) | 0.003 | 3.896 (1.118–13.577) | 0.033 |
|
Nephrolithiasis and/or nephrocalcinosis |
0.722 (0.165–3.160) | 0.666 | – | – |
| CHD | 2.138 (0.753–6.072) | 0.154 | 0.814 (0.244–2.716) | 0.738 |
| Operative treatment for CHD | 1.008 (0.378–2.691) | 0.987 | – | – |
| Left-sided obstructive CHD | 1.356 (0.392–4.691) | 0.630 | – | – |
CI confidence intervals, pLoF predicted loss-of-function, CAKUT congenital anomalies of kidney and urinary tract, CHD congenital heart defect
Fig. 2.
Chronic kidney disease-free survival according to the presence of bilateral kidney anomalies. The solid line represents the survival curve estimated using Kaplan–Meier analysis, with shaded areas indicating the 95% confidence intervals
The characteristics and associated pathologies of the 19 patients with CKD are detailed in Table 3. Among the causes of CKD, seven patients had CAKUT, two had cardiorenal syndrome attributable to a significant congenital heart defect, and four had both conditions. CKD was associated with perinatal factors, including prematurity, low birth weight, or hypoxic injury, in three patients. One patient (ID 40 in Table 3) experienced two episodes of urinary tract infection within a cyst due to infundibular stenosis in the upper pole of a right duplicated kidney and subsequently underwent right partial nephrectomy. No other patients had chronic obstruction or recurrent urinary tract infections contributing to CKD development.
Table 3.
Clinical information of patients who developed CKD (n = 19)
| ID | Sex | Gene | Onset age of CKD G2 (years) | Cause of CKD | Kidney manifestations | Congenital heart defects |
|---|---|---|---|---|---|---|
| 1 | M | KMT2D | 8.1 | CAKUT | Rt renal agenesis | – |
| 3 | F | KMT2D | 4.9 | Prematurity | – | ASD |
| 7 | M | KMT2D | 2.1 | CAKUT and nephrocalcinosis with kidney stone | Bilateral dysplastic kidneys | ASD and small PDA |
| 8 | F | KDM6A | 24.6 | Nephrotic syndrome | – | – |
| 9 | F | KMT2D | 2.1 | CAKUT | Bilateral hypodysplastic kidneys | Small VSD |
| 10 | F | KMT2D | 2.1 | Cardiorenal syndrome | – | HLHS |
| 14 | F | KMT2D | 5.5 | CAKUT and cardiorenal syndrome | Horseshoe kidney | CoA and VSD |
| 15 | F | Not identified | 3.5 | AKI from perinatal hypoxic injury | – | PFO |
| 16 | M | KMT2D | 9.2 | CAKUT and cardiorenal syndrome | Lt hypoplastic kidney with rt ectopic kidney | VSD, ASD, and PDA |
| 17 | F | KMT2D | 5.8 | CAKUT | Bilateral ectopic kidneys with rt hypoplastic kidney | ASD |
| 20 | M | KMT2D | 7.3 | CAKUT | Bilateral hypoplastic kidneys | – |
| 25 | F | KMT2D | 7.5 | CAKUT and cardiorenal syndrome | Horseshoe kidney | large ASD |
| 35 | M | KMT2D | 4.2 | Unknown | – | – |
| 36 | M | KMT2D | 2.1 | Cardiorenal syndrome | – | VSD and ASD |
| 40 | F | KMT2D | 16.8 | CAKUT | Lt ectopic kidney and rt duplicated kidney (s/p rt partial nephrectomy) |
DOMV and mild MS |
| 46 | F | KMT2D | 3.7 | SGA | – | – |
| 52 | F | KMT2D | 3.6 | CAKUT | Horseshoe kidney | – |
| 62 | M | KMT2D | 4.9 | Unknown | – | – |
| 64 | M | KMT2D | 2.2 | CAKUT and cardiorenal syndrome | Crossed fused ectopic kidney with dysplasia | CoA and VSD |
G, glomerular filtration rate category; M, male; F, female; Rt, right; Lt, left; CKD, chronic kidney disease; AKI, acute kidney injury; CAKUT, congenital anomalies of kidney and urinary tract; ASD, atrial septal defect; VSD, ventricular septal defect; PDA, patent ductus arteriosus; CoA, coarctation of aorta; HLHS, hypoplastic left heart syndrome; PFO, patent foramen ovale; DOMV, double orifice mitral valve; MS, mitral stenosis; SGA, small for gestational age; s/p, status post
The three patients who progressed to CKD stage G3 included one boy (ID 7 in Table 3) with bilateral dysplastic kidneys and nephrocalcinosis who was treated with thiazide and potassium citrate for hypercalciuria. He progressed to stage G3 at 6.1 years old. A girl (ID 10 in Table 3) with hypoplastic left heart syndrome developed stage G3 CKD at 4.4 years old. The third patient was a girl (ID 15 in Table 3) who experienced meconium aspiration syndrome and hypoxic insult at birth, which was complicated by acute kidney injury. This acute kidney injury contributed to the progression of CKD at 3.5 years old.
Genotype–phenotype correlation analysis
Patients with KMT2D mutations were diagnosed with KS at an earlier age than those with KDM6A mutations; however, no significant differences in kidney manifestations were observed between the two groups (Table 4). Among patients with KMT2D mutations, no statistically significant differences were found between the non-pLoF and pLoF variant groups in terms of sex ratio, age at diagnosis, or the prevalence of CAKUT, nephrolithiasis/nephrocalcinosis, and CKD. In the location-based analysis of patients with pLoF variants in KMT2D, the C-terminus group exhibited a significantly higher prevalence of nephrolithiasis and/or nephrocalcinosis compared to the non-C-terminus group. Kaplan–Meier survival analysis showed no significant differences in CKD-free survival based on the causative gene of KS, KMT2D genotype, or the location of pLoF variants in KMT2D (Supplementary Fig. 1).
Table 4.
Genotype–phenotype correlations in patients with Kabuki syndrome for kidney and urinary manifestations
| Characteristics | KDM6A (n = 3) | KMT2D (n = 59) | P value | KMT2D (n = 59) | |||||
|---|---|---|---|---|---|---|---|---|---|
| Non-pLoF (n = 8) | pLoF (n = 51) | ||||||||
| Total (n = 51) | Non-C-terminus (n = 32) | C-terminus ( n = 19) |
P valuea | P valueb | |||||
| Sex, male:female | 1:2 | 26:33 | 1.000 | 5:3 | 21:30 | 11:21 | 10:9 | 0.484 | 0.247 |
| Age of KS diagnosis, years |
11.6 (10.8–16.7) |
2.2 (0.7–8.0) |
0.025 |
4.8 (1.9–8.4) |
2.1 (0.6–8.0) |
1.8 (0.6–5.2) |
4.2 (0.6–10.7) |
0.303 | 0.328 |
| CAKUT | 0/2 (0.0) | 20/57 (36.8) | 0.534 | 1/7 (14.3) | 20/50 (40.0) | 14/31 (45.2) | 6/19 (31.6) | 0.243 | 0.387 |
|
Nephrolithiasis and/or nephrocalcinosis |
0/2 (0.0) | 6/57 (10.5) | 1.000 | 0/7 (0.0) | 6/50 (12.0) | 1/31 (3.2) | 5/19 (26.3) | 1.000 | 0.024 |
| CKD G2 | 1/3 (33.3) | 17/50 (34.0) | 1.000 | 1/6 (16.7) | 16/44 (36.4) | 10/26 (38.5) | 6/18 (33.3) | 0.650 | 0.761 |
Values are presented as numbers (%) or median (interquartile range)
pLoF predicted loss of function, KS Kabuki syndrome, CAKUT congenital anomalies of kidneys and urinary tract, CKD chronic kidney disease, G glomerular filtration rate category
aNon-pLoF vs. pLoF
bNon-C-terminus of pLoF vs. C-terminus of pLoF
Discussion
Our study demonstrated that patients with KS exhibit various kidney manifestations, including a CKD progression rate of one-third. The frequency of CAKUT observed in this cohort was consistent with that in previous studies [5, 6, 18]. To our knowledge, this is the first report examining the long-term outcomes of kidney function and the prevalence of nephrolithiasis/nephrocalcinosis in patients with KS.
Whereas previous reports on patients with KS and kidney failure provided insights into the etiologies of CKD in this population [5, 7–10, 19, 20], no follow-up analyses assessed the time course of CKD development. Our study addressed this gap by using CKD-free survival analysis to estimate the time until CKD onset in patients with KS. Through a literature review, we identified seven patients with KS who developed kidney failure. Five of these patients underwent kidney transplantation, one progressed to stage 4 CKD, and one died of kidney failure and pulmonary hypertension (Supplementary Table 2) [5, 7–10, 19, 20]. In six of these patients, CAKUT and/or congenital heart defects contributed to CKD progression, consistent with our findings. Additionally, some of our patients had perinatal factors, including prematurity, small for gestational age, and hypoxic injury at birth, as contributing causes of CKD. In this study, younger age at diagnosis and the presence of bilateral kidney anomalies were associated with CKD progression. Bilateral involvement of kidney anomalies has been shown to influence CKD progression in patients with CAKUT [21, 22], while an earlier age at diagnosis may reflect more severe clinical manifestations of KS. The KDIGO guideline recommends screening individuals at risk for CKD, including those with CAKUT, recurrent kidney stones, and known genetic variants associated with CKD, through both urine albumin measurement and GFR assessment [13]. To mitigate kidney function deterioration, early detection and intervention are crucial. Clinicians should focus on managing modifiable risk factors for CKD progression, such as hypertension and proteinuria, while also promoting lifestyle modifications, including regular physical activity, maintaining an optimal weight, and adhering to a kidney-protective diet, particularly in young children and those with bilateral kidney anomalies [13].
A prior single-center cohort study reported that 3 of 32 patients (9.4%) with nephrolithiasis/nephrocalcinosis had KS caused by KMT2D mutations [23]. No previous studies reported the prevalence of nephrolithiasis/nephrocalcinosis specifically in patients with KS and KMT2D mutations. One study indicated that 2 of 61 patients with KDM6A mutations had nephrolithiasis/nephrocalcinosis [18]. Although the precise mechanisms underlying stone formation in patients with KS remain unclear, our cases of nephrolithiasis/nephrocalcinosis were associated with hypercalciuria, which can lead to calcium crystal deposition in the kidneys. Given that symptomatic stone formation can necessitate surgical intervention in children, clinicians should conduct urinalysis and kidney imaging to facilitate the early detection and management of hypercalciuria and nephrolithiasis in patients with KS. For patients with hypercalciuria, management should include dietary modifications (optimized sodium, protein, and potassium intake), adequate hydration, and pharmacologic interventions such as thiazide diuretics and potassium citrate to reduce urinary calcium excretion and prevent stone formation [24].
Previous research suggested that patients with KS caused by KMT2D mutations are more likely to have kidney and urinary abnormalities than those without these mutations [5, 6]. Regarding KDM6A, one study reported a lower prevalence of kidney and urinary tract malformations in patients with KS caused by KDM6A mutations than that in the overall KS population [18]. In our cohort, no significant differences in kidney and urinary manifestations were observed between the KMT2D and KDM6A groups. However, given the limited number of patients with KDM6A mutations, these findings may not be conclusive. We found no correlation between kidney phenotypes and genotypes in patients with KMT2D mutations, consistent with previous studies [5, 6]. A prior study reported all cases with visceral anomalies, including genitourinary abnormalities, were observed in the protein-truncating variant group; however, the sample size of the non-truncating group was small (n = 4) [25]. In our location-based analysis of pLoF variants in KMT2D, nephrocalcinosis and/or nephrolithiasis were more prevalent in patients with variants located towards the C-terminus. The KMT2D gene’s C-terminal region plays a critical role in its function as a histone H3 K4 methyltransferase, influencing gene expression by modulating chromatin structure [17]. Although our findings are limited by the inability to conduct location-based analysis for non-pLoF mutations and the lack of differences in other kidney manifestations, this suggests that pLoF mutations near the C-terminus may be associated with nephrocalcinosis/nephrolithiasis. Similarly, a multicenter cohort study observed greater rates of severe eye involvement in nonsense variants near the C-termini of KMT2D and KDM6A, whereas frameshift variants were not associated with structural ocular abnormalities [17]. However, in our study, when the analysis was restricted to nonsense variants, no significant differences in kidney and urinary manifestations were observed based on variant location (Supplementary Table 3). While a previous study suggested no association between the location of genetic mutations and kidney or urinary manifestations [5], our study is the first to specifically evaluate nephrocalcinosis and nephrolithiasis in this context. Given the limited evidence and lack of clear mechanistic explanation for this association, further studies are needed to validate these findings.
This study had several limitations. First, data collection and analysis were conducted retrospectively. Kidney function assessments and imaging studies were not performed according to standardized protocols, potentially leading to an underestimation of kidney manifestations. Second, the follow-up period was limited, with most patients in our cohort still in their teens, providing limited information on kidney function in adults with KS. Long-term monitoring of kidney function in patients with KS extending into adulthood is essential for both future research and patient care, particularly for the early detection and management of CKD.
In conclusion, more than 30% of patients with KS exhibited kidney or urinary involvement, and 34% progressed to CKD. Therefore, screening for kidney or urinary issues and regular follow-up of kidney function are essential for managing patients with KS. A review article has recommended initial evaluation and organ-specific health surveillance in patients with KS, including baseline kidney ultrasound to assess CAKUT [26]. We recommend blood and urine tests every 2–3 years for kidney function surveillance, along with endocrinologic and immunologic assessments [26]. Additionally, if CKD or nephrolithiasis/nephrocalcinosis is detected, a tailored follow-up schedule should be implemented.
Supplementary information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors thank all the contributors to this work.
Author contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Seongjae Han, Hyeonju Lee, Yo Han Ahn, and Jung Min Ko. The first draft of the manuscript was written by Seongjae Han, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
Open Access funding enabled and organized by Seoul National University.
Data availability
The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.
Declarations
Ethics approval
The study was approved by the Seoul National University Hospital Institutional Review Board (IRB no. H-2309-043-1464).
Conflict of interest
The authors declare no conflict of interest.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Seongjae Han and Hyeonju Lee contributed equally to this article as co-first authors. Yo Han Ahn and Jung Min Ko contributed equally as co-corresponding authors.
Contributor Information
Yo Han Ahn, Email: yhahn@snu.ac.kr.
Jung Min Ko, Email: jmko@snu.ac.kr.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.