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Purpose: This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG).Methods: Thirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR.Results: Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016).Conclusion: ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

Objectives: Gordon syndrome (GS), also known as pseudohypoaldosteronism type II, is a rare tubular disease characterized by hypertension, hyperkalemia, and metabolic acidosis. Its causative genes are CUL3, KLHL3, WNK1, and WNK4, and they are associated with varying severity of the disease. Herein, we report the first case of GS caused by a CUL3 mutation in a patient with short stature in Korea.Case presentation: A 7-year-old boy had hypertension, metabolic acidosis, and persistent hyperkalemia, which were initially detected during the evaluation of short stature. He was born small for gestational age at late preterm gestation. Laboratory test findings showed hyperkalemia with low trans-tubular potassium gradient, hyperchloremic metabolic acidosis with a normal anion gap, and low plasma renin levels. Genetic analysis revealed a heterozygous de novo mutation in the CUL3 gene (c.1377+1G > C in intron 9). Thus, a diagnosis of GS was made. The results of the endocrine function test (including growth hormone stimulation tests) were normal. After thiazide treatment, the patient’s electrolyte levels were normalized. However, he presented with persistent hypertension and short stature.Conclusions: GS should be considered in children with short stature, hypertension, and hyperkalemia, and early treatment may reduce complications.

This study aimed to investigate the risk factors for community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-positive bacteria in infants. We retrospectively reviewed the medical records of infants aged < 1 year with first UTI from 2018 to 2019 at two tertiary centers in Korea. Data analyzed included clinical findings, birth history, delivery mode, milk type, use of postpartum care center, and previous use of antibiotics both in the patient and mother. Of 265 patients, 62 (23.4%) were diagnosed with first UTI caused by ESBL-positive bacteria at the median age of 3.6 (interquartile range (IQR) 2.3–5.4) months. Maternal use of antibiotics during pregnancy (29.0 vs. 10.3%, p < 0.001) and Klebsiella species (19.4% vs. 4.9%, p < 0.001) were significantly associated with ESBL-positive UTIs and remained valid in the multivariate analysis (odds ratio [OR], 3.40; 95% confidence interval [CI] 1.61–7.19, p = 0.001, and OR 5.26; 95% CI 2.03–13.13, p = 0.001, respectively). Previous antibiotic exposure of patients, previous hospitalization, prematurity, delivery mode, milk type, and use of postpartum care center were not significantly different between ESBL-positive and ESBL-negative groups. With respect to the clinical course of UTI, the ESBL-positive group presented a higher number of blood leukocytes (p = 0.041) and longer hospital stay (p < 0.001) than the ESBL-negative group. About one-fourth of infantile UTI cases were ESBL-positive. Prenatal antibiotic exposure of mothers and Klebsiella species were associated with community-acquired UTI caused by ESBL-positive bacteria.

Background We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends. Methods We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979–2003, 2004–9 and 2010–17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis. Results We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin–angiotensin–aldosterone system (RAAS) blockers increased from 57.7% in 1979–2003 to 80.0% in 2010–17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010–17 compared with that of 1979–2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523–0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk. Conclusions Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.

Background Ocular involvement in catastrophic antiphospholipid syndrome (CAPS), a rare, life-threatening form of antiphospholipid syndrome (APS) that results in multiorgan failure and a high mortality rate, has rarely been reported. Case presentation A 15-year-old girl presented with sudden vision blurring in both eyes. She had marked optic disc swelling and macular exudates in the right eye and intra-arterial white plaques, a few retinal blot hemorrhages, and a white ischemic retina in the left eye. Systemic examination revealed she had acute kidney injury with thrombotic microangiopathy (TMA), multiple cerebral infarcts, valvular dysfunction, and a high titer of triple aPL. Thus, she was diagnosed with CAPS involving the brain, eyes, heart, and kidneys. Plasma exchange and the administration of glucocorticoids, immunoglobulin, warfarin, and rituximab brought a sustained recovery of the TMA, visual symptoms, and echocardiographic findings. Conclusions Ocular involvement of both vaso-occlusive retinopathy, an APS-related thrombotic microangiopathy, and neuroretinitis, a non-thrombotic microangiopathy, can occur as an initial presentation of CAPS.

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. 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. 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). 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.

The burden of disease of X-linked hypophosphatemia (XLH) in East Asia is poorly understood. This was a cross-sectional study using an online questionnaire to evaluate health-related quality of life (HRQOL) and disease complications in Japanese and Korean patients with XLH. Adults with XLH and the caregivers of children

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. From April 2011 to April 2016, 469 patients with CKD aged

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

Background : Yersinia pseudotuberculosis is known to cause fever, gastroenteritis, or acute kidney injury (AKI). There have been several Y. pseudotuberculosis infection outbreaks to date associated with ingestion of contaminated food or unsterile water. While this disease was considered to have practically been eradicated with the improvement in public health, we encountered several cases of AKI associated with Yersinia infection. Methods : We retrospectively collected data from medical records of patients with suspected Y. pseudotuberculosis infection who visited Seoul National University Children's Hospital in 2017. Results : There were nine suspected cases of Yersinia infection (six males and three females; age range 2.99-12.18 years). Among them, five cases occurred in May, and seven patients were residing in the metropolitan Seoul area. Three patients had history of drinking mountain water. Every patient first presented with fever for a median of 13 days, followed by gastrointestinal symptoms and oliguria. Imaging studies revealed mesenteric lymphadenitis, terminal ileum wall thickening, and increased renal parenchymal echogenicity. Creatinine levels increased to 5.72 ± 2.18 mg/dL. Urinalysis revealed sterile pyuria, proteinuria, and glycosuria. Oliguria continued for 4 to 17 days, and two patients required dialysis; however, all of them recovered from AKI. Mucocutaneous manifestations developed later. In the diagnostic work-up, Yersinia was isolated from the stool culture in one patient. Anti-Yersinia immunoglobulin (Ig) A and IgG were positive in 6 patients. Conclusion : Y. pseudotuberculosis infection is an infrequent cause of interstitial nephritis presenting with AKI. When a patient presents with fever, gastroenteritis, and AKI not resolving despite hydration, the clinician should suspect Y. pseudotuberculosis infection.

Introduction. Matrix metalloproteinase (MMP) is an emerging disease marker in rheumatic diseases. This is a meta-analysis aimed at systematically reviewing association between serum MMP-3 levels and systematic lupus erythematosus (SLE) activity, which sought to raise interest in MMP-3 as a putative biomarker. Methods. We conducted a meta-analysis of serum MMP-3 levels in patients with SLE and controls. We performed a PubMed search, EMBASE search, and forward search of the retrieved articles published until Oct. 1, 2018. In addition to this, we included data from a case-control study on a national pediatric SLE cohort, in which serum MMP-3 levels were measured in 11 SLE patients and 9 controls (unpublished). Subgroup analyses based on gender and disease activity were performed. Results. A total of 662 cases and 771 controls including 651 patients and 762 controls from 11 publications were studied. We observed significantly higher MMP-3 levels in SLE patients compared to healthy controls (P<0.001, Hedges’ g: 2.104, 95% CI 1.426-2.782). In subgroup analyses, we found a significant elevation of MMP-3 in the patients with nephritis compared to those without (P=0.006, Hedges’ g: 0.611, 95% CI 0.611-1.704). This finding was consistent between patients with persistent proteinuria and those without (P=0.023, Hedges’ g: 1.535, 95% CI 0.207-2.862). Meta-analysis showed no association between MMP-3 levels and gender or anti-double strand DNA antibody titer. Conclusions. Our meta-analysis demonstrated significantly higher MMP-3 levels in SLE patients than in controls and in patients with renal involvement than in those without.

Background Acute kidney injury (AKI) is a critical issue in cancer patients because it is not only a morbid complication but also able to interrupt timely diagnostic evaluation or planned optimal treatment. However, the impact of AKI on overall mortality in cancer patients remains unclear. Methods We conducted a retrospective cohort study of 67 986 cancer patients, from 2004 to 2013 to evaluate the relationship between AKI and all‐cause mortality. We used KDIGO AKI definition and grading system. Results During 3.9 ± 3.1 years of follow‐up, 33.8% of the patients experienced AKI at least once. Among AKI events, stage 1, 2, and 3 was 71.0%, 13.8%, and 15.1%, respectively. AKI incidence was highest in hematologic malignancies, followed by urinary tract cancer, and hepatocellular carcinoma. Male sex, older age, underlying diabetes and hypertension, lower serum albumin and plasma hemoglobin, more frequent radio‐contrast exposure, entrance of clinical trials, and receiving chemotherapy were associated with AKI occurrence. AKI development was an independent risk factor for elevated mortality in cancer patients with dose‐responsive manner (Stage 1, hazard ratio [HR] 1.183, 95% confidence interval [CI] 1.145‐1.221, P

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations.Methods:PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019).Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.

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, Graphical Abstract

Background Inherited cystic kidney disease is a spectrum of disorders in which clusters of renal cysts develop as the result of genetic mutation. The exact methods and pipelines for defining genetic mutations of inherited cystic kidney disease are not clear at this point. This 3-year, prospective, multicenter, cohort study was designed to set up a cohort of Korean patients with inherited cystic kidney disease, establish a customized genetic analysis pipeline for each disease subtype, and identify modifying genes associated with the severity of the disease phenotype. Methods/design From May 2020 to May 2022, we aim to recruit 800 patients and their family members to identify pathogenic mutations. Patients with more than 3 renal cysts in both kidneys are eligible to be enrolled. Cases of simple renal cysts and acquired cystic kidney disease that involve cyst formation as the result of renal failure will be excluded from this study. Demographic, laboratory, and imaging data as well as family pedigree will be collected at baseline. Renal function and changes in total kidney volume will be monitored during the follow-up period. Genetic identification of each case of inherited cystic kidney disease will be performed using a targeted gene panel of cystogenesis-related genes, whole exome sequencing (WES) and/or family segregation studies. Genotype-phenotype correlation analysis will be performed to elucidate the genetic effect on the severity of the disease phenotype. Discussion This is the first nationwide cohort study on patients with inherited cystic kidney disease in Korea. We will build a multicenter cohort to describe the clinical characteristics of Korean patients with inherited cystic kidney disease, elucidate the genotype of each disease, and demonstrate the genetic effects on the severity of the disease phenotype. Trial registration This cohort study was retrospectively registered at the Clinical Research Information Service (KCT0005580) operated by the Korean Center for Disease Control and Prevention on November 5th, 2020.

Bioimpedance spectroscopy (BIS) is a noninvasive method used to evaluate body fluid volume status in dialysis patients, but reports on its effectiveness in pediatrics are scarce. We investigated the correlation between BIS and clinical characteristics and identified the changes in patients whose dialysis prescription was modified based on BIS. The medical records of children on maintenance dialysis who had undergone BIS between 2017 and 2019 were reviewed. Of the 49 patients, 14 were overhydrated, based on the &gt, 15% proportion of overhydration relative to extracellular water (OH/ECW) measured by BIS. Intake of &ge, two antihypertensive medications was noted in the majority (85.7%) of children with fluid overload and only in 48.6% of those without fluid overload (p = 0.017). Elevated blood pressure despite medication use was significantly more common in patients with fluid overload than in those without fluid overload (78.6% vs. 45.7%, p = 0.037). Of the 14 overhydrated children, 13 (92.9%) had significant changes in body weight, OH/ECW, the number of antihypertensive drugs, left ventricular end-diastolic diameter, and cardiothoracic ratio after the change in dialysis prescription. BIS is a useful and noninvasive method to assess fluid status in dialysis children. Long-term follow-up and correlation with a more objective clinical indicator of fluid overload is necessary to verify the clinical effectiveness of BIS.

PurposeAcute kidney injury (AKI) in cancer patients is associated with increased morbidity and mortality. The incidence of AKI in lung cancer seems to be relatively higher compared with other solid organ malignancies, although its impact on patient outcomes remains unclear.Materials and MethodsThe patients newly diagnosed with lung cancer from 2004 to 2013 were enrolled in this retrospective cohort study. The patients were categorized according to the presence and severity of AKI. We compared all-cause mortality and long-term renal outcome according to AKI stage.ResultsA total of 3,202 patients were included in the final analysis. AKI occurred in 1,783 (55.7%) patients during the follow-up period, with the majority having mild AKI stage 1 (75.8%). During the follow-up of 2.6±2.2 years, total 1,251 patients (53.7%) were died and 5-year survival rate was 46.9%. We found that both AKI development and severity were independent risk factors for all-cause mortality in lung cancer patients, even after adjustment for lung cancer-specific variables including the stage or pathological type. In addition, patients suffered from more severe AKI tend to encounter de novo chronic kidney disease development, worsening kidney function, and end-stage kidney disease progression.ConclusionIn this study, more than half of the lung cancer patients experienced AKI during their diagnosis and treatment period. Moreover, AKI occurrence and more advanced AKI were associated with a higher mortality risk and adverse kidney outcomes.

Backgrounds Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887.

Renal tubular dysgenesis (RTD) is a rare fatal disorder in which there is poor development of proximal tubules, leading to oligohydramnios and the Potter sequences. RTD occurs secondary to renin-angiotensin system (RAS) blockade during the early stages of fetal development or due to autosomal recessive mutation of genes in the RAS pathway. A boy born at 33+1 weeks due to cord prolapse was found to be anuric and hypotensive. Pregnancy was complicated by severe oligohydramnios from gestational age 28+4 weeks. Abdominal sonography revealed diffuse globular enlargement of both kidneys with increased cortical parenchymal echogenicity. Infantogram showed a narrow thoracic cage and skull X-ray showed large fontanelles and wide sutures suggestive of ossification delay. Basal plasma renin activity was markedly elevated and angiotensin-converting enzyme was undetectable. Despite adequate use of medications, peritoneal dialysis, and respiratory support, he did not recover and expired on the 23rd day of life. At first, autosomal recessive polycystic kidney disease was suspected, but severe oligohydramnios along with refractory hypotension, anuria, skull ossification delay and high renin levels made RTD suspicious. ACE gene analysis revealed compound heterozygous pathogenic variations of c.1454.dupC in exon 9 and c.2141dupA in exon 14, confirming RTD. Based on our findings, we propose that, although rare, RTD should be suspected in patients with severe oligohydramnios and refractory hypotension., Graphical Abstract

HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in six patients (43%). All patients had bilateral renal abnormalities, primarily multiple renal cysts. Twelve patients exhibited progressive renal functional deterioration, and six of them progressed to kidney failure. The annual reduction in estimated glomerular filtration rate was&minus, 2.1 mL/min/1.73 m2. Diabetes developed in five patients (36%), including one patient with new-onset diabetes after transplantation. Neurological deficits were noted in three patients (21%), one with total gene deletion and two with missense mutations. Pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations. Genotype showed no significant correlation with renal outcomes or other extrarenal manifestations. The HNF1B scores at the times of onset and genetic diagnosis were &lt, 8 in two patients and one patient, respectively. Diagnosis of HNF1B mutations is clinically difficult because of extreme phenotypic variability and incomplete penetrance. Furthermore, some phenotypes develop with age. Therefore, patient age should be taken into consideration to increase the diagnostic rate, because some phenotypes develop with age.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage renal disease (ESRD) in childhood and is mostly associated with focal segmental glomerulosclerosis (FSGS). More than 50 monogenic causes of SRNS or FSGS have been identified. Recently, the mutation detection rate in pediatric patients with SRNS has been reported to be approximately 30%. In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (9.4%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). Mutations in COQ6, NUP107, and COQ8B were more frequently detected, and mutations in NPHS2 were less commonly detected in this cohort than in study cohorts from Western countries. The mutation detection rate was higher in patients with congenital onset, those who presented with proteinuria or chronic kidney disease/ESRD, and those who did not receive steroid treatment. Genetic diagnosis in patients with SRNS provides not only definitive diagnosis but also valuable information for decisions on treatment policy and prediction of prognosis. Therefore, further genotype-phenotype correlation studies are required.

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3&ndash, 5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.

Background and Aims Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Method The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every one year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Disussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Conclusion In conclusion, we describe the objectives and clinical protocol for the KORNERSTONE. As the first large-scale glomerulonephropathy cohort study with the integration of clinical data, biospecimens and digital pathologic images in Korea, the KORNERSTONE will help to clarify the natural course, complication profiles, and novel treatment targets of the Asian population with glomerular disease.

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.

Background Hearing loss (HL) in children may adversely affect their development. HL is more prevalent in patients with chronic kidney disease (CKD) than in the general population. This study evaluated the prevalence of HL and its underlying diseases in patients with childhood-onset in CKD. Methods In this retrospective study of a tertiary referral center, childhood-onset CKD patients (stage 2–5, age at onset of renal symptom < 18 years) were recruited. We referred to the “renal” syndromic HL as cases with genetic or syndromic diseases, or extra-renal anomalies in addition to HL and CKD. Results A total of 421 patients (male:female = 279:142) were reviewed according to the causes of CKD: congenital anomalies of the kidney and urinary tract (CAKUT; n = 184, 43.7%), glomerulopathies (GP; n = 105, 24.9%), cystic kidney diseases (CYST; n = 39, 9.3%), perinatal problems (PP; n = 29, 6.9%), and others (n = 64, 15.2%). HL was detected in 82 (19.5%) patients, including 51 (12.1%) patients with sensorineural hearing loss (SNHL), 30 (7.1%) with conductive hearing loss (CHL), and 1 patient with mixed HL. The prevalence of HL in each group was as follows: 16.8% in the CAKUT group, 28.6% in the GP group, 12.8% in the CYST group, 24.1% in the PP group, and 14.1% in the others group. HL was more common in higher CKD stages, especially CHL in end-stage renal disease. SNHL was more prevalent in CKD from GP. Of the 82 patients with HL, 50% had renal syndromic HL: 58.8% of SNHL and one-third of CHL were renal syndromic HL. Conclusion One-fifth of the childhood-onset CKD had HL. Collectively, renal syndromic HL comprised half of the HL in this study. To improve the quality of life in patients with childhood-onset CKD, we suggest that HL should be considered, requiring surveillance, and if necessary, early intervention., Graphical Abstract

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., Schematic diagram showing the number of patients with and without variant identification and family member testing and the proportion of variant classification.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment caused by uncontrolled activation of the complement system. About 20% of patients show extrarenal manifestations, with central nervous system involvement being the most frequent. We described the clinical course and management of aHUS in an infant, that was caused by a complement 3 (C3) gene mutation with severe extrarenal manifestations. Case Presentation: A 4-month-old girl visited our hospital for jaundice and petechiae. Laboratory tests revealed microangiopathic hemolytic anemia, thrombocytopenia, and hyperazotemia. She was diagnosed with aHUS with a C3 p.E1160K mutation. Daily fresh-frozen plasma (FFP) therapy was administered; however, she experienced the severe extrarenal manifestations of pulmonary hemorrhage and gastrointestinal bleeding. With aggressive treatment, supportive care, and daily FFP transfusion, the patient recovered and was discharged after 72 days of hospital stay, on a regular FFP transfusion. Four months after diagnosis, she was switched to eculizumab treatment. Twenty months have passed since then and she has been relapse-free until now. Conclusion: aHUS is rare but has a devastating course if not properly treated. Severe extrarenal manifestations, such as pulmonary hemorrhage and gastrointestinal bleeding, can develop in aHUS caused by a C3 mutation. In our case, long-term management with eculizumab resulted in relapse-free survival.

Disseminated adenovirus infection can result in high mortality and morbidity in immunocompromised patients. Here, we report the case of a 10-year-old renal allograft recipient who presented with hematuria and dysuria. Adenovirus was isolated from his urine. His urinary symptoms decreased after intravenous hydration and reduction of immunosuppressants. However, 2 weeks later he presented with general weakness and laboratory tests indicated renal failure necessitating emergency hemodialysis. Adenovirus was detected in his sputum; therefore, intravenous ganciclovir and immunoglobulin therapy were initiated. Renal biopsy revealed diffuse necrotizing granulomatous tubulointerstitial nephritis compatible with renal involvement of the viral infection. Adenovirus was detected in his serum. Despite cidofovir administration for 2 weeks, adenovirus was also detected in the cerebrospinal fluid, resulting in generalized tonic-clonic seizure. The patient died 7 weeks after the onset of urinary symptoms. Adenovirus should be considered in screening tests for post-renal transplantation patients who present with hemorrhagic cystitis.

Background : Nephrotic syndrome (NS) is the most common glomerulopathy in children. Acute kidney injury (AKI) is a common complication of NS, caused by severe intravascular volume depletion, acute tubular necrosis, interstitial nephritis, or progression of NS. However, the incidence and risk factors of childhood-onset NS in Korea are unclear. Therefore, we studied the incidence, causes, and risk factors of AKI in hospitalized Korean patients with childhood-onset NS. Methods : We conducted a retrospective review of patients with childhood-onset NS who were admitted to our center from January 2015 to July 2017. Patients with decreased renal function or hereditary/secondary NS, as well as those admitted for management of other conditions unrelated to NS, were excluded. Results : During the study period, 65 patients with idiopathic, childhood-onset NS were hospitalized 90 times for management of NS or its complications. Of these 90 cases, 29 met the Kidney Disease Improving Global Outcomes criteria for AKI (32.2%). They developed AKI in association with infection (n = 12), NS aggravation (n = 11), dehydration (n = 3), and intravenous methylprednisolone administration (n = 3). Age ≥ 9 years at admission and combined use of cyclosporine and renin-angiotensin system inhibitors were risk factors for AKI. Conclusion : AKI occurred in one-third of the total hospitalizations related to childhood-onset NS, owing to infection, aggravation of NS, dehydration, and possibly high-dose methylprednisolone treatment. Age at admission and use of nephrotoxic agents were associated with AKI. As the AKI incidence is high, AKI should be considered during management of high-risk patients.

Acute kidney injury (AKI) is characterized by abrupt deterioration of renal function, and its diagnosis relies on creatinine measurements and urine output. AKI is associated with higher morbidity and mortality, and is a risk factor for development of chronic kidney disease. There is no proven medication for AKI. Therefore, prevention and early detection are important. Physicians should be aware of the risk factors for AKI and should monitor renal function in high-risk patients. Management of AKI includes optimization of volume status and renal perfusion, avoidance of nephrotoxic agents, and sufficient nutritional support. Continuous renal replacement therapy is widely available for critically ill children, and this review provides basic information regarding this therapy. Long-term follow-up of patients with AKI for renal function, blood pressure, and proteinuria is recommended.

Objective The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6–17 years, with or without chronic kidney disease (CKD). Methods This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram. Results Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (− 14.9 mmHg and − 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients. Conclusions Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.

Aim This study was designed to investigate the impact of pediatric 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 pediatric ESRD patients measured by PedsQLTM 3.0 ESRD module. Methods We performed a cross-sectional study using Korean translations of the PedsQLTM FIM and the PedsQLTM 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 hemodialysis (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 pediatric 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 pediatric ESRD patients.

Background/Aims: Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. Methods: A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Results: Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype–phenotype correlation. Conclusions: SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA.

Background Ravulizumab, a humanized anti-complement C5 monoclonal antibody designed by targeted modification of eculizumab to achieve an extended half-life, is approved to treat aHUS in the USA (2019), EU and Japan (2020). Data at 26 weeks (wk) and 1 year (yr) from the phase 3 studies of ravulizumab in adults and children with aHUS have been published. Here we report 2-yr data from these trials. Methods Efficacy and safety data from ravulizumab clinical trials in adults naïve to complement inhibitor treatment (NCT02949128), and in children either naïve to (naïve) or switched from (switch) eculizumab (NCT03131219), were assessed at 2 yr and presented alongside data from the initial 26-wk evaluation periods; patients were dosed every 8 wk (adult), or every 4 or 8 wk (children), according to body weight. Descriptive statistical analyses were conducted on these data. No statistical comparisons between data at 26 wk and 2 yr, or between trials, were conducted. Results Efficacy data in adults and treatment-naïve children are presented in the Table. Complete thrombotic microangiopathy (TMA) response (platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, met concurrently at 2 separate assessments, at least 4 wk apart) was achieved in more patients at 2 yr vs 26 wk in both studies (adult: 34 [61%) vs 30 [54%]; naïve: 18 [90%] vs 15 [75%]). All complete TMA response components were either numerically improved or maintained at 2 yr vs 26 wk. Kidney function continued to improve, with the median change in estimated glomerular filtration rate from baseline numerically increasing at 2 yr vs 26 wk in both adults (35 vs 29 mL/min/1.73m 2) and naïve children (82.5 vs 80 mL/min/1.73m 2). Most patients receiving dialysis at baseline were able to discontinue dialysis at 26 wk; this was sustained in adults (67% vs 67%) while all naïve children receiving dialysis at baseline had discontinued by 2 yr (83% vs 100%). No patients who discontinued dialysis by 26 wk subsequently restarted. Chronic kidney disease (CKD) stage improved in most patients through 26 wk in both studies (adult, 68%; naïve, 88%); improvements were sustained at 2 yr (adult, 71%; naïve, 94%). No naïve children experienced a worsening of CKD stage at 2 yr. Improvements from baseline in quality of life were seen at both 26 wk and 2 yr, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (adults: 20 vs 12; naïve: 10 vs 8), EQ-5D-3L visual analog scale (adults: 32 vs 33) and EQ-5D-3L time trade-off (adults: 0.32 vs 0.31). Most adverse events (AEs) and serious AEs (SAEs) occurring in these studies were reported during the initial 26-wk evaluation period, with a general reduction in the number of patients with any new S/AE events being reported at 2 yr. The most common AEs reported through 2 yr, which had not met the 15% reporting threshold through 26 wk, were (n, %): adults - constipation (9, 16%), fatigue (9, 16%) and nasopharyngitis (9, 16%); naïve children - abdominal pain (6, 25%), contusion (5, 21%), cough (5, 21%), nausea (4, 17%), myalgia (4, 17%), rash (4, 17%) and rhinorrhea (4, 17%); switch children - upper respiratory tract infections (URTI; 4, 40%), oropharyngeal pain (3, 30%), pharyngitis (3, 30%), cough (2, 20%), gastroenteritis (2, 20%), nasopharyngitis (2, 20%), otitis media (2, 20%), viral URTI (2, 20%) and dehydration (2, 20%). No patients discontinued either study due to treatment-emergent AEs after 26 wk. No meningococcal infections were recorded in either study at any timepoints. One adult patient, who had previously met complete TMA response criteria while receiving therapy, discontinued treatment by choice and subsequently experienced recurrent disease, as evidenced by an increase in serum creatinine (SCr). This patient then restarted therapy, leading to improvements in SCr levels. Conclusions In both treatment-naïve adults and children, ravulizumab was associated with numerically sustained or increased improvements in hematologic outcomes and kidney function at 2 yr vs 26 wk. Fewer S/AEs were reported during the extension period of these studies vs the initial 26-wk evaluation periods. Importantly, no meningococcal infections were reported in either study at any timepoint. The data suggest that long-term treatment with ravulizumab is well tolerated and may be associated with continuing improvements in TMA parameters and renal function in adults and children with aHUS. Figure 1 Figure 1. Disclosures Dixon: Apellis Pharmaceuticals: Consultancy; Horizon Pharmaceuticals: Consultancy; Alexion Pharmaceuticals: Consultancy. Kavanagh: Gyroscope Therapeutics: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Apellis: Honoraria, Speakers Bureau; Idorsia: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Kang: Alexion Pharmaceuticals: Honoraria, Research Funding; Handok: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Amgen: Research Funding; Bayer: Research Funding. Wang: Alexion, AstraZeneca Rare Disease Inc.: Current Employment. Garlo: Alexion: Current Employment; AstraZeneca: Current Employment. Greenbaum: Alexion Pharmaceuticals: Honoraria, Research Funding. Ogawa: Alexion Pharmaceuticals: Current Employment. Cataland: Ablynx/Sanofi: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Alexion: Consultancy, Research Funding; Takeda: Consultancy. Miyakawa: Sanofi: Consultancy; Zenyaku Kogyo: Consultancy; Sanofi: Research Funding; argenx: Consultancy, Research Funding.

Background Decline in neurocognitive function is a reported complication in children with chronic illness. Concerns have been increasing that exposure to a major surgery or trauma may negatively impact cognitive performance in children. This study has evaluated cognitive function in 43 Korean children who received organ transplantation, and sought to identify associated clinical factors. Methods Pediatric recipients of kidney (KT) or liver transplantation (LT) from years 1999 to 2011 were recruited for cognitive tests. Cognitive function was evaluated by Intelligent Quotient (IQ), Social Quotient (SQ), and Continuous Performance Test using Advanced Test for Attention (ATA) scores which reflect the attention ability. Intellectual delay was graded as intellectual disability (ID, IQ

Background Rituximab (RTX) can be used as a rescue therapy for steroid-dependent nephrotic syndrome (SDNS). However, the efficacy and safety of long-term, repeated use of RTX are not established. This study was conducted to assess the efficacy and safety of long-term, repeated RTX treatment in children. Methods Eighteen consecutive child patients with SDNS who were treated with three or more cycles of RTX for one year or longer were recruited, and their medical records were retrospectively reviewed. Results The patients were followed for 4.7 ± 1.9 years and received 5.2 ± 2.3 cycles of RTX over 2.8 ± 1.1 years. Approximately 70% of the additional RTX cycles were administered due to recovery of B-cells without relapse. The relapse rate decreased from 3.4 ± 2.0 per year initially to 0.4 ± 0.8 per year at the third year after RTX treatment. Approximately 10% of the RTX infusions were accompanied by mild infusion reactions. Eight patients showed sustained remission without any oral medication after the last cycle of RTX, while 10 patients had one or more episodes of relapse after the last cycle of RTX. The relapse rate in the latter group decreased from 2.8 ± 1.5 per year before RTX treatment to 1.3 ± 0.8 per year after cessation of RTX treatment. No significant differences in clinical parameters were found between the two groups. Conclusion This retrospective study showed that pre-emptive and long-term, repeated RTX treatment is relatively effective and safe in children with SDNS. However, well-designed prospective studies are needed to confirm these findings.

Background/Aims: Renovascular hypertension (RVHT) is an important cause of childhood hypertension. This study evaluated the clinical characteristics and outcomes of Korean children with RVHT. Methods: Children treated for RVHT between 2000 and 2015 at our center were retrospectively reviewed. Results: Forty-six children were followed for a median of 6.5 (0.66-27.23) years. Forty-five percutaneous transluminal angioplasties (PTAs) were performed in 32 children. At the last visit, clinical benefit was observed in 53.3% of children. Patients with comorbid cerebrovascular disease (CVD) showed less favorable long-term outcomes after PTA (clinical benefit in 41.7% vs. 61.1% in others) and higher restenosis rates (50% vs. 31.6% in others). Surgical procedures (bypass or nephrectomy) were performed in 8 patients. After surgery, blood pressure was normalized in 2 patients, improved in 3 patients, and unchanged in the remaining patients. Between PTA group (n=21) and medication group (n=14), percentage of atrophic kidneys became higher after follow-up period in medication group than in PTA group (60.0% vs. 26.1%, P=0.037). Conclusion: Aggressive treatment of pediatric RVHT yielded fair outcomes in our cohort. CVD comorbidity was associated with relatively poor PTA outcomes. To confirm our findings, larger cohort studies with a longer follow-up period are warranted.