Genetic diagnosis of kidney disease by whole exome sequencing and its clinical application.

The genetic spectrum of genetic kidney diseases (GKD) and the application of genetic diagnoses to patient care were assessed by whole exome sequencing (WES) of the DNA of 172 pediatric or adult patients with various kidney diseases. WES diagnosed genetic diseases in 63 (36.6%) patients. The diagnostic yields in patients with glomerulopathy were 33.8% (25/74 pts) due to variants in 10 genes, 58.8% (20/34) in patients with tubulointerstitial disease due to variants in 18 genes, 33.3% (15/45) in patients with cystic disease/ciliopathy due to variants in 10 genes, 18.2% (2/11) in patients with congenital anomalies of the kidneys and urinary tract (CAKUT) due to variants in two genes, and 12.5% (1/8) in patients with end stage kidney disease (ESKD). The diagnosis rate was high in patients aged <1-6 years (46-50.0%), and low in patients aged ≥40 years (9.1%). Renal phenotype was reclassified in 10 (15.9%) of 63 patients and clinical management altered in 10 (15.9%) of 63 patients after genetic diagnosis. In conclusion, these findings demonstrated the diagnostic utility of WES and its effective clinical application in patients, with various kinds of kidney diseases, across the different age groups.

Changes in Awareness Toward Minor's Organ Donation Through Structured Information; Survey.

This study analyzed survey results regarding awareness of living minors' organ donation. The questionnaires focused on changes in how respondents felt about donations by living minors after eliciting the uncertainty of long-term outcomes for living donors and recipients. The respondents were categorized as minors, adults affiliated with non-medical jobs (Non-Meds), and adults affiliated with medical jobs (Meds). The rates of awareness of living organ donation were significantly different; minors at 86.2%, non-Meds at 82.0%, and Meds at 98.7% (p < 0.001). Only 41.4% of Minors and 32.0% of Non-Meds were aware of organ donation by minors, while 70.3% of Meds were (p < 0.001). The response rate of opposition to organ donation by minors was highest for Meds and remained the same before and after (54.4%-57.7%, p = 0.311). However, the opposition rate in Non-Meds significantly increased (32.4%-46.7%) after learning about the uncertainty of long-term outcomes (p = 0.009). The study found that Non-Meds lacked adequate knowledge regarding organ donation by minors and their potential lethal outcomes. Their attitudes toward organ donation by minors could be changed by giving structured information. It is necessary to provide exact information and raise social awareness regarding organ donation by living minors.

Association between serum total cholesterol and chronic kidney disease progression in children: results from the KNOW-PedCKD.

BACKGROUND: Dyslipidemia can cause cardiovascular disease and increase the fatality rate among children with chronic kidney disease (CKD); this makes early screening and treatment of dyslipidemia crucial. This study aimed to assess the association between the changes in serum total cholesterol levels over time and the degree of CKD progression in children. METHODS: From April 2011 to August 2021, 379 of the 432 participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric CKD (KNOW-PedCKD) were included and divided into 4 categories based on total cholesterol levels (< 170 mg/dL, acceptable; 170-199, borderline; 200-239, high; and ≥ 240, very high). Survival analysis using conventional and time-dependent Cox proportional hazards model were performed for a composite event of CKD progression (≥ 50% decrease in estimated glomerular filtration rate from baseline, a twofold increase in creatinine, or the occurrence of dialysis or kidney transplantation). RESULT: The incidence of composite event of CKD progression was 96.3, 90.4, 87.3, and 270.6 cases per 1000 person-years in the acceptable, borderline, high, and very high categories, respectively. On using the time-dependent Cox proportional hazards model, the hazard ratio of the very high category was significantly higher than that of the acceptable category by 3.13 times as per univariate analysis and 2.37 times as per multivariate analysis. CONCLUSIONS: Very high serum total cholesterol is a significant risk factor for CKD progression in children. Lowering total cholesterol levels below the very high category in children with CKD may delay the progression of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection: A Pediatric Case Report.

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported. This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

Baseline characteristics of participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD).

BACKGROUND: We developed the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD) as a subcohort of KNOW-CKD to investigate the different characteristics of pediatric CKD between countries and races. METHODS: Children aged younger than 18 years with stage 1 ~ 5 CKD were recruited at seven major pediatric nephrology centers in Korea. Blood and urine samples, as well as demographic and clinical data, were collected. From 2011 to 2016, 458 children were enrolled, and the baseline profiles of 437 children were analyzed. RESULTS: The median age of the cohort was 10.9 years old, and 68.0% were males. The median estimated glomerular filtration rate was 53.1 mL/min/1.73 m2. The most common etiology of CKD was congenital anomalies of the kidney and urinary tract (42.6%), followed by glomerulopathies (25.6%). CONCLUSION: We report a cross-sectional analysis of the overall baseline characteristics such as age, CKD stage, and underlying kidney disease of the KNOW-Ped CKD. The cohort will be longitudinally followed for ten years. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Activation of Complement System in Henoch-Schönlein Purpura Nephritis.

Introduction: We studied the association between Henoch-Schönlein purpura nephritis (HSPN) and complement system activation. Methods: We retrospectively reviewed the pathologic findings and medical records of 35 children and 12 adults with HSPN and compared the differences according to C4d positivity in three groups consisting of total 47 patients, 35 pediatric and 12 adult patients, respectively. C4d staining of renal biopsy was additionally performed at the time of diagnosis or retrospectively using archival biopsy material. Results: The overall rate of C4d positivity was 53.2%: 20 (57.1%) of the 35 children and five (41.7%) of the 12 adults. Among the groups there was no significant difference in the severity of proteinuria, renal function, presence of crescents or mesangial proliferation stratified by C4d positivity, unlike IgA nephropathy. Conclusions: We suggest that the activation of complement system is not correlated with the clinical or pathological severity of HSPN.

Incidence of and risk factors for short stature in children with chronic kidney disease: results from the KNOW-Ped CKD.

BACKGROUND: Preserving optimal growth has long been a significant concern for children with chronic kidney disease (CKD). We aimed to examine the incidence of and risk factors for short stature in Asian pediatric patients with CKD. METHODS: We analyzed growth status by height, weight, and body mass index (BMI) standard deviation scores (SDSs) for 432 participants in the KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease. RESULTS: The median height, weight, and BMI SDSs were - 0.94 (interquartile range (IQR) - 1.95 to 0.05), - 0.58 (IQR - 1.46 to 0.48), and - 0.26 (IQR - 1.13 to 0.61), respectively. A high prevalence of short stature (101 of 432 patients, 23.4%) and underweight (61 of 432 patients, 14.1%) was observed. In multivariable logistic regression analysis, CKD stages 4 and 5 (adjusted odds ratio (aOR) 2.700, p = 0.001), onset before age 2 (aOR 2.928, p < 0.0001), underweight (aOR 2.353, p = 0.013), premature birth (aOR 3.484, p < 0.0001), LBW (aOR 3.496, p = 0.001), and low household income (aOR 1.935, p = 0.030) were independent risk factors associated with short stature in children with CKD. CONCLUSIONS: Children with CKD in Korea were shorter and had lower body weight and BMI than the general population. Short stature in children with CKD was most independently associated with low birth weight, followed by premature birth, onset before age 2, CKD stages 4 and 5, underweight, and low household income. Among these, underweight is the only modifiable factor. Therefore, we suggest children with CKD should be carefully monitored for weight, nutritional status, and body composition to achieve optimal growth.

Lower albumin level and longer disease duration are risk factors of acute kidney injury in hospitalized children with nephrotic syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study. METHODS: This retrospective multicenter study included 14 pediatric nephrology centers in Korea. From 2013 to 2017, a total of 814 patients with idiopathic NS were cared for at participating centers. Among them, 363 patients were hospitalized for NS and investigated in this study. RESULTS: A total of 363 children with NS were hospitalized 574 times. AKI occurred in 93 admissions (16.2%) of 89 patients: 30 (32.3%) stage 1; 24 (25.8%) stage 2; and 39 (41.9%) stage 3. Multivariate logistic regression analysis showed that longer disease duration, lower albumin level, and methylprednisolone pulse treatment were significantly associated with AKI development in hospitalized children with NS. AKI was associated with a longer hospital stay than non-AKI (median 10 vs. 7 days, P = 0.001). Among 93 admissions, 85 (91.4%) episodes recovered from AKI without complication, whereas 6 (6.5%) progressed to advanced chronic kidney disease (CKD). CONCLUSIONS: AKI is not uncommon in hospitalized children with NS, and its incidence in this nationwide study was 16.2%. Risk factors for AKI in hospitalized children with NS include longer disease duration, lower albumin level, and methylprednisolone pulse therapy. Pediatric NS patients with these characteristics should be under more strict scrutiny for the occurrence of AKI. Graphical abstract.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD.

BACKGROUND: Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. METHODS: Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6-16 years), or Wechsler Adult Intelligence Scale (> 16 years). RESULTS: The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < -1.88), failure to thrive (weight Z scores < -1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. CONCLUSION: On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02165878.

Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE.

EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield.

Dyslipidemia in pediatric CKD patients: results from KNOW-PedCKD (KoreaN cohort study for Outcomes in patients With Pediatric CKD).

BACKGROUND: Pediatric as well as adult patients with chronic kidney disease (CKD) are susceptible to cardiovascular disease (CVD) events, which increase their mortality. Dyslipidemia is thought to be one of the most important contributing risk factors for developing CVD. This study aimed to evaluate the prevalence of dyslipidemia and assess clinical and laboratory risk factors associated with dyslipidemia in East Asian pediatric patients with CKD. METHODS: From April 2011 to April 2016, 469 patients with CKD aged < 20 years were enrolled in KNOW-PedCKD (the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease); 356 patients were included in the final analysis. Using the baseline data of the cohort cross-sectionally, a multivariable logistic regression analysis was performed to assess the risk factors for dyslipidemia; a subanalysis for each lipid abnormality was also done. RESULTS: The prevalence of dyslipidemia was 61.5% (n = 219). For dyslipidemia, nephrotic range proteinuria and 25-hydroxyvitamin D deficiency significantly increased the adjusted odds ratio. In the subanalysis, glomerulonephropathy as the origin of CKD and nephrotic range proteinuria significantly increased the risks for high total cholesterol and high low-density lipoprotein cholesterol. Overweight or obese body mass index z-score, elevated proteinuria, hypocalcemia, and 1,25-dihydroxyvitamin D deficiency were significantly associated with low high-density lipoprotein cholesterol. Glomerular filtration rate stage 3b or higher and hyperphosphatemia significantly increased the risk for high triglycerides. CONCLUSIONS: Long-term data accumulation and prospective analysis are needed to clarify the relationship between CKD progression and dyslipidemia and to find additional risk factors for dyslipidemia.

Left-ventricular diastolic dysfunction in Korean children with chronic kidney disease: data from the KNOW-Ped CKD study.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in pediatric chronic kidney disease (CKD) patients. Left ventricular (LV) hypertrophy (LVH) is associated with LV diastolic dysfunction (LVDD) development and is used as an early marker of CVD in pediatric CKD. This study aimed to assess the prevalence and risk factors of LVDD and the association between LVH and LVDD in Korean pediatric CKD patients. METHODS: Data were collected using the baseline data of the Korean cohort study for outcome in patients with pediatric chronic kidney disease, a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 244 patients were included in the final analysis. Two-dimensional echocardiography and tissue Doppler images were used to evaluate LVH and LVDD. LVH was defined as an LV mass index (LVMI) ≥38 g/m2.7 and LV-wall thickness z-score > 1.64. LVDD was defined as a mitral peak velocity of early filling to early diastolic mitral annular velocity (E/E') > 14. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors of LVDD. RESULTS: In this study, the male-to-female ratio was 2.2 (168:76) and median age was 11.2 years. The average estimated glomerular filtration rate was 57.4 ml/min/1.73 m2, and no patients received renal replacement therapy. The mean value of LVMI and E/E' was 37.0 g/m2.7 and 7.4, respectively. The prevalence of LVH was 40.1 and 17.4% by LVMI ≥38 g/m2.7 and LV-wall thickness z-score, respectively. The prevalence of LVDD was 4.5%, and patients with LVH showed greater risk of LVDD (odds ratio 7.3, p = 0.012). In the univariate analysis, young age, low hemoglobin level, higher LVMI, and higher LV-wall thickness z-score were associated with LVDD. In the multivariate analysis, young age, low hemoglobin level, and higher LV-wall thickness z-score were independently associated with LVDD. CONCLUSION: This study shows that LVH patients have a greater risk of LVDD and that anemia is the only modifiable risk factor for LVDD in Korean pediatric CKD patients.

Mental health and psychosocial adjustment in pediatric chronic kidney disease derived from the KNOW-Ped CKD study.

BACKGROUND: Psychosocial development of pediatric chronic kidney disease (CKD) patients is substantially affected due to growth retardation, frequent school absences, and difficulties engaging in normal peer relationship activities. While many studies focus on specific issues such as depression, anxiety, or neurocognitive function, few evaluate prevalence of various types of mental health and psychosocial adjustment problems among children with CKD. This study aimed to investigate these within the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). METHODS: One hundred sixty-six subjects who completed the Korean-Child Behavioral Checklist (K-CBCL) were included. The clinical group comprised subjects with scores indicating psychosocial adjustment or mental health problems using the T scores for the 14 subscales of the K-CBCL. We analyzed associations between mental health or adjustment problems in pediatric CKD and each variable. RESULTS: Mean age was 11.1 (± 3.9) years, number of males was 117 (70.5%), and 20.5% and 22.3% of children had significant mental health problems and psychosocial adjustment problems, respectively. Overall, 33.1% were assigned to the clinical group, and exhibited short stature and higher rates of preterm birth history compared to the non-clinical group. Subjects with adjustment problems had higher comorbidities such as CNS disease, developmental delay, cardiovascular disease, and multi-organ involvement. Logistic regression analysis revealed preterm birth and developmental delay correlated highly with clinical group. CONCLUSIONS: A significant proportion of children and adolescents with CKD experience mental health and adjustment problems. In particular, patients with developmental delay or preterm birth history require screening and targeted follow-up.

Susceptibility of the Index Urinary Tract Infection to Prophylactic Antibiotics Is a Predictive Factor of Breakthrough Urinary Tract Infection in Children with Primary Vesicoureteral Reflux Receiving Continuous Antibiotic Prophylaxis.

BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.

Impact of end-stage renal disease in children on their parents.

AIM: This study was designed to investigate the impact of paediatric end-stage renal disease (ESRD) on parents, based on the PedsQL Family Impact Module (FIM), and the relationship to the quality of life (QOL) of paediatric ESRD patients measured by PedsQL 3.0 ESRD module. METHODS: We performed a cross-sectional study using Korean translations of the PedsQL FIM and the PedsQL 3.0 ESRD module. In all, 79 patients were enrolled, including 47 children receiving dialysis and 32 children who underwent renal transplant. RESULTS: FIM scores, analyzed for every category according to treatment modality, were significantly lower in haemodialysis (HD) than in peritoneal dialysis (PD) or renal transplant patients. Mother's age, duration since diagnosis of ESRD and the existence of comorbidity were variables to have significant effects on FIM scores. The correlation between total FIM and QOL scores of paediatric patients were significant, in both parent-proxy and child-self report. CONCLUSIONS: The PedsQL FIM appears to be a useful tool for the assessment of family impact on children with ESRD. Further prospective studies focused on the QOL of parents and caregivers should be performed with the goal of improving clinical outcomes for paediatric ESRD patients.

Influence of the Method of Definition on the Prevalence of Left-Ventricular Hypertrophy in Children with Chronic Kidney Disease: Data from the Know-Ped CKD Study.

BACKGROUND/AIMS: Children with chronic kidney disease (CKD) have a high risk of cardiovascular disease. Left-ventricular (LV) hypertrophy (LVH) is an early marker of cardiovascular disease in pediatric CKD, and the prevalence of LVH in pediatric CKD is approximately 20-30% in pre-dialysis CKD patients. However, there is no consensus on the ideal method of defining LVH in pediatric CKD patients. Previous studies have typically used the LV mass index (LVMI), which is calculated as LV mass in grams divided by height in meters to the 2.7th power ≥ 38 g/m2.7, to diagnose LVH in children with CKD. Recently, age-specific reference values for LVMI ≥ 95th percentile and LV wall-thickness z-score > 1.64 in children were addressed. The aim of this study was to assess the prevalence and contributing factors of LVH in pediatric CKD patients according to each measurement and evaluate the concordance between each measurement. METHODS: We used the baseline data of the KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD), which is a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 469 patients were enrolled, and 458 patients were included in the final analysis. Univariate and multiple logistic regression analysis were performed to evaluate the association of the variables with LVH. Kappa statistics were used to analyze the concordance. RESULTS: According to an LVH diagnosis of LVMI ≥ 38 g/m2.7, 188 patients (41.0%) were diagnosed with LVH, and the prevalence of LVH was high in younger patients (< 2 years of age). Using the age-specific reference values, 116 patients (25.3%) were diagnosed with LVH, and there was no difference in the prevalence of LVH according to age. Thirty-one patients (6.8%) were diagnosed with LVH using an LV wall-thickness z-score > 1.64. There is poor concordance between the diagnosis of LVH using the LV wall-thickness z-score and the LVMI method. CONCLUSIONS: The results of this study show that there is poor concordance between the diagnosis of LVH using the wall-thickness z-score and the LVMI2.7 criteria. Further investigation is needed to estimate the correlation between LVH and cardiac dysfunction and to find a better method for defining LVH in the pediatric CKD cohort and thereby predicting cardiac dysfunction.

Health-related quality of life of children with pre-dialysis chronic kidney disease.

BACKGROUND: The goal of this study was to evaluate the quality of life (QOL) of Asian children with pre-dialysis chronic kidney disease (CKD) and to reveal the factors influencing the QOL of children with CKD. METHODS: We performed a cross-sectional study of the PedsQL 4.0 Generic Core Scale Module in the KNOW-PedCKD (KoreaN cohort study for Outcome in patients with Pediatric Chronic Kidney Disease) cohort, and compared the child self-reported and parent proxy-reported QOL of the pediatric cohort. From 2011 through 2016, a total of 376 children with CKD were enrolled after informed consent was obtained from parents or caregivers in seven pediatric nephrology centers. RESULTS: In parent proxy-reports, male patients had a better QOL than female patients in the Physical Functioning category. In child self-reports, male patients had better QOL than female patients in the Physical, Emotional, and School Functioning categories. According to CKD stage, there were significant differences in the QOL score in all categories of parent proxy-reports, and patients with higher CKD stage (lower glomerular filtration rate) had a worse QOL. Growth parameters showed a significantly positive correlation with the QOL score in all categories. CONCLUSIONS: The QOL of children with predialysis CKD is affected by various factors, including sex, glomerular filtration rate (GFR), socio-economic status, existence of co-morbidities, anemia, growth retardation, and behavioral disorders. To improve their QOL, it is important to objectively understand the respective effects of these factors and attempt early intervention.

KNOW-Ped CKD (KoreaN cohort study for outcomes in patients with pediatric CKD): Design and methods.

BACKGROUND: The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on children's growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. METHODS/DESIGN: From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. DISCUSSION: With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. TRIAL REGISTRATION: NCT02165878 (ClinicalTrials.gov), submitted on June 11, 2014.

Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

BACKGROUND: Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. CASE PRESENTATION: We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule was detected on chest CT. The patient was scheduled for adjuvant gemcitabine-cisplatin chemotherapy. CONCLUSIONS: The present case was interesting because we cannot be sure if the SUC chondrosarcoma originated from the 12-year-ago proximal ureter tumor, the 2-year-ago contralateral distal ureter tumor, or a new primary bladder tumor. Genetic profiling might have been useful to determine the origin of the SUC chondrosarcoma.

Atypical hemolytic uremic syndrome: Korean pediatric series.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. METHODS: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. RESULTS: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. CONCLUSIONS: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.