Difference in urinary protein-to-creatinine ratio using the benzethonium chloride and pyrogallol red methods in children.

BACKGROUND: The appropriate reference value of the urinary protein-to-creatinine ratio (PCR) for proteinuria may change when the urinary pyrogallol red (PR) protein assay method is changed to the benzethonium chloride method (BC). This study aimed to evaluate the difference between BC-based PCR (BC-PCR) and PR-based PCR (PR-PCR) values in children. METHODS: We compared the BC-PCR and PR-PCR values in the same first-morning urine samples without significant proteinuria in school urine screening settings. The upper limit of the reference values was set at the 97.5th percentile. RESULTS: Notably, 133 samples from 124 individuals (female: 62%, age: median 12.3 years, range 6.3-16.9 years) were collected between August 2020 and October 2022. The diagnoses included 34 normal individuals and 99 with asymptomatic hematuria. The urinary protein (UP) concentrations measured using the BC (BC-UP) and PR (PR-UP) methods were in a linear relationship; however, the BC-UP concentrations were higher than the PR-UP concentrations (mean of differences: 11.2, 95% confidence interval (CI): 11.0-13.4 mg/dL). Also, the BC-PCR values were higher than the PR-PCR values (mean of differences: 0.090, 95% CI: 0.082-0.098 g/gCr). The BC-PCR showed a body-size-related decrease, reflecting a body-size-related urinary creatinine increase. The suggested BC-PCR reference values for proteinuria were 0.25 and 0.17 g/gCr for elementary (6-12.4 years) and junior high school students (12.5-16 years), respectively. These values were higher than those of the PR-PCR and need further studies. CONCLUSIONS: When evaluating PCR results, the urinary protein assay should be stated.

Evaluation of the diagnostic accuracy of lower urinary tract symptoms (LUTS) in uncomplicated UTI in Pakistani women.

OBJECTIVE: To evaluate the diagnostic accuracy of lower urinary tract symptoms in uncomplicated urinary tract infection in women. Methods: The cross-sectional study was conducted from September 2020 to December 2021 after approval from the ethics review board of Jinnah Postgraduate Medical Centre, Karachi, and comprised data of women aged at least 16 years from 8 institutions across Pakistan. Data included menstruation status, symptoms, urinalysis and organisms found in urine samples. The association of urinalysis variables with symptoms among culture-positive patients was measured to assess the certainty of positive diagnosis. Data was analysed using SPSS 23. RESULTS: Of the 457 women with mean age 37.87±13.9 years, 182(39.8%) had a positive urine culture. Dysuria was the most significant symptom 120(65.9%), followed by daytime frequency 114(62.6%) amongst culture-positive patients. On urinalysis, 139(76.3%) had white blood cells, and 66(36.2%) had haematuria. Dysuria along with the presence of leucocyte esterase had the highest diagnostic utility (p=0.002). Urgency along with haematuria was strongly predictive of urinary tract infection (p=0.058). Conclusion: The diagnosis of uncomplicated urinary tract infection in women could be reliably made based on a combination of symptoms along with urine analysis without urine culture.

[Non glomerular microscopic hematuria : when to search for neoplasia, how and for whom?] / Hématurie microscopique non glomérulaire : recherche de néoplasie quand, comment et pour qui ?

Microscopic hematuria (MH) is a frequent biological finding. In most cases, the etiology is benign, symptomatic and reversible. The diagnostic approach allows classifying hematuria as glomerular or non-glomerular. For non-glomerular hematuria, the risk of urinary tract neoplasia is 5% and should always be evaluated1. To use resources efficiently, patients requiring additional and invasive exam must be identified and distinguished from those who will only require a follow up. This article reviews the diagnostics approach of MH by integrating the new recommendations of the American urology association published in 2020.

L'hématurie microscopique (HM) est une trouvaille biologique fréquente. Dans la plupart des cas, l'étiologie est bégnine, symptomatique et réversible. L'approche diagnostique permet de classer les hématuries en glomérulaire ou non glomérulaire. Lors d'hématurie non glomérulaire, le risque de néoplasie des voies urinaires s'élève à 5 % et devrait toujours être évalué. Pour utiliser de manière efficace les ressources, il convient de détecter les patient-es pour lesquel-les des examens complémentaires, parfois invasifs, doivent être entrepris d'emblée et de pouvoir les différencier de celles et ceux pour lesquel-les un suivi peut être suffisant. Cet article reprend l'approche diagnostique de l'HM en y intégrant les nouvelles recommandations de l'Association américaine d'urologie parues en 2020.

Renal and Urinary Conditions: Glomerulonephritis.

Glomerulonephritis (GN) encompasses a heterogeneous group of disease processes. It accounts for approximately 20% of chronic kidney disease and is the second most common cause of kidney failure worldwide. A study of a cohort of Medicare patients found that approximately 1.2% were affected. GN should be suspected in patients with unexplained hematuria, particularly with persistent hematuria with red blood cell casts and/or acanthocytes, and proteinuria. Other presenting features include purpura (in children) and hypertension. When GN is suspected based on test results, patients should be referred to a nephrologist for further evaluation and consideration of kidney biopsy, which is the gold standard diagnostic test. GN is categorized as acute (sudden onset of hematuria and proteinuria) or chronic (with irreversible scarring on biopsy). Acute GN is more likely to be reversible. Initial management consists of supportive and protective measures, including blood pressure control, drugs to block the renin-angiotensin system, and lifestyle modifications to minimize cardiovascular risk. The underlying cause should be treated when possible. Subsequent management depends on the specific type of GN and might include antimicrobial therapy and/or immunosuppressive therapy when appropriate.

Assessment of urine metabolite biomarkers for the detection of S. haematobium infection in pre-school aged children in a rural community in Zimbabwe.

BACKGROUND: Early diagnosis of urogenital schistosomiasis is key to its control and elimination. The current gold standard microscopic examination techniques lack sensitivity in detecting light Schistosomiasis infections in pre-school aged children thus it is urgent to develop diagnostic tools that may be integrated into control programs. In this study, we evaluated the diagnostic performance of urine metabolite biomarkers using a chemical reagent strip in the detection of S. haematobium infection in pre-school aged children. METHODS: A case-control study was conducted involving 82 pre-school aged children that were age and sex matched. Urine samples were collected for 3 consecutive days and were evaluated using urine filtration gold techniques as the gold standard method. The samples were simultaneously measured for metabolite biomarkers specifically haematuria, proteins, ketones, nitrites, glucose, bilirubin and urobilinogen using chemical reagent strips. Pearson correlation test was used to measure the relationship between S. haematobium infection and the urine metabolite biomarkers. RESULTS: The diagnostic performance of urine biomarkers were correlated with the microscopic examination urine filtration technique. Haematuria (r = 0.592, p = 0.0001) and proteinuria (r = 0.448, p = 0.0001) were correlated to S. haematobium infection. Negative correlations with p > 0.05 were recorded for ketones and urobilinogen. Highest sensitivity was 65.9 % (CI, 49.4 - 79.9) for haematuria whilst protein (albumin) biomarker had a lower specificity value of 43.9 % (28.5 - 60.3). Inversely, highest sensitivity was 87.8 % (73.8 - 95.9) for proteinuria whilst haematuria had a lower sensitivity value of 82.9 % (67.9 - 92.8). The positive predictive values ranged from 57.7 % (41.6 - 72.2) to 79.4 % (65.5 - 88.7) whereas negative predictive values ranged from 70.8 % (60.8 - 79.2) to 52.0 % (48.7 - 55.3). With respect to diagnostic efficiency, haematuria had a fair diagnostic performance with an area under the curve of 0.76 followed by proteinuria with proteinuria whilst the remaining metabolites fail discriminating ability with an area under the curve of <0.5. CONCLUSION: Although haematuria and protein biomarkers in urine are moderately sensitive and specific, they are important morbidity indicators of urogenital schistosomiasis in pre-school aged that may be utilised during screening in schistosomiasis control programs. We recommend comprehensive analysis of biomarkers using metabolomics techniques to identify novel urine biomarkers.

Clinical utility of dipstick urinalysis in assessing fitness to dive in military divers, submariners, and hyperbaric personnel.

Introduction: Routine dipstick urinalysis is part of many dive medical assessment protocols. However, this has a significant chance of producing false-positive or false-negative results in asymptomatic and healthy individuals. Studies evaluating the value of urinalysis in dive medical assessments are limited. Methods: All results from urinalysis as part of dive medical assessments of divers, submarines, and hyperbaric personnel of the Royal Netherlands Navy from 2013 to 2023 were included in this study. Additionally, any information regarding additional testing, referral, or test results concerning the aforementioned was collected. Results: There were 5,899 assessments, resulting in 46 (0.8%) positive dipstick urinalysis results, predominantly microscopic haematuria. Females were significantly overrepresented, and revisions resulted in significantly more positive test results than initial assessments. Lastly, almost half of the cases were deemed fit to dive, while the other half were regarded as temporarily unfit. These cases required additional testing, and a urologist was consulted three times. Conclusions: To our knowledge, this is the most extensive study evaluating urinalysis in dive medical assessments. In our military population, the incidence of positive test results is very low, and there have not been clinically relevant results over a period of 10 years. Therefore, routinely assessing urine in asymptomatic healthy military candidates is not cost-effective or efficacious. The authors advise taking a thorough history for fitness to dive assessments and only analysing urine when a clinical indication is present.

Clinical Practice Guideline: Microhematuria in Children and Young Adults.

BACKGROUND: Occult blood in the urine, or microhematuria, is a common finding (about 10%) in children and young adults. It is often of brief duration and therefore harmless. In persistent microhematuria, acanthocytes in the urine are a frequently unrecognized early marker of glomerular kidney disease. The purpose of this guideline is to promote the early detection of kidney disease in children and young adults with practical, evidence-based recommendations. METHODS: A systematic search for pertinent publications up to January 2023 was conducted in Pubmed, the Cochrane Database, and Livivo. 474 publications were retrieved, summarized in terms of method and content, and classified by Oxford (2011) evidence level. RESULTS: Approximately 1% of children and young adults have undiagnosed chronic kidney disease. Microhematuria is an early warning sign. A timely nephrological evaluation is indicated if microhematuria persists for 3 to 6 months, if ≥ 5% acanthocytes are detectable in the urine, and if there is also proteinuria, hypertension, or impaired renal function. Ultrasonography of the kidneys and urinary tract is the imaging method of choice; cystoscopy should be avoided. For patients with glomerular microhematuria, molecular genetic testing is recommended. Renal biopsy is recommended in case of florid glomerular diseases, after the determination of various laboratory param eters and clinical findings, including molecular genet ic testing especially in children. CONCLUSION: In the absence of a guideline until now, findings have often been incorrectly assessed, leading either to an inadequate work-up or to excessive diagnostics. As a result, in approximately 30% of young patients, valuable opportunities for early treatment to protect the kidneys have been missed.

A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

PURPOSE: AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. MATERIALS AND METHODS: All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. RESULTS: Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. CONCLUSIONS: In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

Utilization and Timing of Cystoscopy for Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To characterize differences between urologists and advanced practice providers (APPs) in the utilization of cystoscopy for hematuria. METHODS: We identified patients initially evaluated for hematuria by a urologist or urology APP between 2015 and 2020 in the MarketScan Research Databases. We determined whether they received a cystoscopy within 6 months of their urology visit and the number of days until cystoscopy. We used multivariable regression to analyze the association between these outcomes and whether the urology clinician was an advanced practice registered nurse (APRN), physician assistant (PA), or urologist. RESULTS: We identified 34,470 patients with microscopic hematuria and 17,328 patients with gross hematuria. Patients evaluated by urologists more often received a same-day cystoscopy than those evaluated by APPs (13% vs 5.8%). The odds that patients evaluated for microscopic and gross hematuria received a cystoscopy were 46.2% and 26.2% lower, respectively, if they were evaluated by an APRN vs a urologist. Patients seeing an APRN for microscopic and gross hematuria also waited approximately 7 and 14 days longer for their cystoscopy, respectively. No differences were observed for patients evaluated by PAs vs urologists. CONCLUSION: Patients evaluated for hematuria by an APRN were less likely to receive a cystoscopy and had a longer wait until the procedure compared to those evaluated by a urologist; however, no differences were observed between PAs and urologists. Better understanding APP integration into urology clinics is warranted.

EarlyTect BCD, a Streamlined PENK Methylation Test in Urine DNA, Effectively Detects Bladder Cancer in Patients with Hematuria.

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.

Cost of upper tract imaging obtained during hematuria evaluation: Analysis of a national claims database.

INTRODUCTION: To investigate the actual cost of hematuria evaluation using nationally representative claims data, given that the workup for hematuria burdens the healthcare system with significant associated costs. We hypothesized that evaluation with contrast-enhanced computed tomography (CT) confers more cost to hematuria evaluation than renal ultrasound (US). METHODS: Using a national, privately insured database (MarketScan), we identified all individuals with an incident diagnosis of hematuria. We included patients who underwent cystoscopy and upper tract imaging within 3 months of diagnosis. We tabulated the costs of the imaging study as well as the total healthcare cost per patient. A multivariable model was developed to evaluate patient factors associated with total healthcare costs. RESULTS: We identified 318,680 patients with hematuria who underwent evaluation. Median costs associated with upper tract imaging were $362 overall, $504 for CT with contrast, $163 for US, $680 for magnetic resonance imaging (MRI), $283 for CT without contrast, and $294 for retrograde pyelogram. Median cystoscopy cost was $283. Total healthcare costs per patient were highest when utilizing MRI and CT imaging. When adjusted for comorbidities, the use of any imaging other than ultrasound was associated with higher costs. CONCLUSIONS: In this nationally representative analysis, hematuria evaluation confers a significant cost burden, while the primary factor associated with higher costs of screening was imaging type. Based upon reduced cost of US-based strategies, further investigation should delineate its cost-effectiveness in the diagnosis of urological disease.

[Urinary bladder tamponade-an urological emergency]. / Harnblasentamponade ­ ein urologischer Notfall.

BACKGROUND: Urinary bladder tamponade is a urological emergency that is part of the clinical routine of every urologist and requires immediate and adequate diagnosis and therapy. OBJECTIVES: Presentation of the clinical picture of urinary bladder tamponade including etiology, diagnostics, and therapy as well as formulation of recommendations for action for clinical routine. MATERIALS AND METHODS: Structured presentation of the diagnosis and therapy of urinary bladder tamponade with practical recommendations for action based on a current literature search and a clinical case study. RESULTS: Urinary bladder tamponade is a usually painful filling of the urinary bladder with blood clots as part of gross hematuria. The central pillars of diagnostics are anamnesis, targeted physical examination, and sonography. Therapy involves the rapid insertion of a flushing catheter with manual evacuation of the tamponade. A flushing catheter with at least 20 French should be used here. CONCLUSION: Timely diagnosis and prompt treatment are crucial. This usually includes transurethral catheter insertion with manual evacuation. If the tamponade is unsuccessfully removed, further measures such as endoscopic evacuation or, as a last resort, sectio alta or radical cystectomy are available.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

A case of non-lupus full-house nephropathy diagnosed by kidney biopsy but observed IgA nephropathy on second biopsy.

We describe a case of full-house nephropathy without any underlying disease, including systemic lupus erythematosus. A 40-year-old woman was referred to our hospital with mild proteinuria and microscopic hematuria. The patient was diagnosed with immune complex-mediated glomerulonephritis with a predominant mesangioproliferative pattern based on renal histopathological results using full-house immunofluorescence staining. She showed no clinical criteria for the diagnosis of systemic lupus erythematosus, except for kidney disorders, and tested negative for antinuclear antibodies throughout her clinical course. However, in the second kidney biopsy, no C1q or C4 were detected in the immunofluorescence study, suggesting an immunoglobulin A nephropathy-like pattern. The patient responded favorably to corticosteroid treatment. We found a heterozygous CFHR3-CFHR1 deletion. The association between full-house nephropathy and CFHR3-CFHR1 deletion is unknown, but its influence on the histological pattern in our case is suspected. This indicates the diversity in the pathogenesis of non-lupus full-house nephropathy and warrants further investigation.

Prevalence and associated factors for asymptomatic microscopic hematuria in adults in the PERSIAN Guilan cohort study (PGCS).

Although hematuria is not life-threatening, some could be the result of a more severe condition. Our objectives are to report on the prevalence and risk factors of asymptomatic microscopic hematuria (AMH) in the prospective epidemiological research studies of the Iranian adults (PERSIAN) Guilan cohort study (PGCS) population. This cross-sectional study was conducted from 2014 to 2017 and consisted of 10,520 individuals aged 35-70. Data collection was conducted using a questionnaire during a face-to-face interview. The urine analyses (UA) were done up to 2 h after sample collection. Based on a urine microscopy evaluation, AMH is defined as 3 or more red blood cells per high power field (HPF). Simple and multiple logistic regression analysis was conducted to explore factors associated with AMH. The prevalence of AMH in this study was 34.1% and was more prevalent in participants of older ages and female gender as well as those with low educational level, underweight-body mass index (BMI), high physical activity, smoking, alcohol consumption, and kidney stone disease. On the other hand, obesity, opium, and diabetes decreased the likelihood of AMH. The results of the present study shed light on the prevalence and risk factors of AMH and suggested that a significant portion of the study population is affected by AMH. Considering the lack of consensus on a definite clinical guideline for AMH in our country, the results of the present study could be used to design a unit algorithm for screening and therapy of AMH.

The role of URO17® in diagnosis and follow up of bladder cancer patients.

OBJECTIVE: to evaluate the role of urinary URO17® biomarker in the detection of urothelial tumors in haematuria patients and the detection of recurrence in non-muscle invasive bladder urothelial tumors. MATERIALS AND METHODS: Our study was formed of two cohorts of patients, group I represents patients presenting with haematuria (n = 98), while group II represents patients with known non-muscle invasive bladder cancers on their scheduled follow up cystoscopic investigation (n = 51). For both groups, patients were asked to provide urine samples before cystoscopy, either primary as part of the haematuria investigation or as a scheduled follow-up. Urine samples were sent anonymously for standard urine cytology and URO17® biomarker immunostaining. Results were compared to cystoscopic findings using Chi-square analysis and Fisher's exact test (P < 0.05). RESULTS: Group I was formed of 98 patients, with an average age of 60 years. URO17® showed 100% sensitivity and 96.15% specificity with a negative predictive value (NPV) of 100 and a positive predictive value (PPV) of 95.83. The results showed statistical significance with P value < 0.001. Group II was formed of 51 patients, with an average age of 75 years. URO17® was shown to have a sensitivity of 85.71% and NPV of 95.45. Eleven patients of group II were on scheduled BacillusCalmette-Guerin (BCG) and another 5 received Mitomycin C (MMC). The overall results of both groups combined (n = 149) showed statistical significance between flexible cystoscopy results and the results of urinary URO17® and urine cytology. CONCLUSION: URO17® has a potential to be a reliable test for diagnosis and follow up of urothelial cancer patients and a screening tool adjunct to flexible cystoscopy. TRIAL REGISTRATION: Not applicable as the current study is not a clinical trial, as per according to the National Institutes of Health, "studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition."

Whole exome sequencing approach for identification of the molecular etiology in pediatric patients with hematuria.

BACKGROUND: Hematuria is a common condition in clinical practice of pediatric patients. It is related to a wide spectrum of disorders and has high heterogeneity both clinically and genetically, which contributes to challenges of diagnosis and lead many pediatric patients with hematuria not to receive accurate diagnosis and early management. METHODS: In this single center study, 42 children with hematuria were included in Tianjin Children's Hospital between 2019 and 2020. We analyzed the clinical information and performed WES (Whole exome sequencing) for all cases. Then the classification of identified variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpreting sequence variants. For the fragment deletion, qPCR was performed to validate and confirm the inherited pattern. RESULTS: For the 42 patients, 16 cases had gross hematuria and 26 had microscopic hematuria. Molecular genetic causes were uncovered in 9 (21.4%) children, including 7 with Alport syndrome (AS), one with polycystic nephropathy and one with lipoprotein glomerulopathy. The genetic causes for other patients were not related with hematuria. CONCLUSIONS: WES is a rapid and effective way to evaluate patients with hematuria. The analysis of genotype-phenotype correlations of patients with AS indicated that severe variants were associated with early kidney failure. Secondary findings were not rare in Chinese children, thus the clinician should pay more attention to the clinical interpretation of sequencing results and properly interaction with patients and their family.