Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome.

BACKGROUND: We aimed to investigate the efficacy and safety of repeated use of rituximab (RTX) in pediatric patients with nephrotic syndrome (NS). METHODS: Retrospective review of 50 patients with steroid-dependent NS (SDNS) who had received more than three cycles of RTX was conducted; each consisted of one to four infusions until B lymphocytes were depleted. RESULTS: The median age of starting the first RTX cycle was 12.4 years (interquartile ranges (IQR) 10.2-14.6). During a median follow-up period of 6.3 (IQR 3.6-8.6) years, patients received a median of 5.0 RTX cycles (IQR 4.0-7.3). The number of relapses decreased from a median of 2.0 relapses per year (IQR 1.0-3.0) to 0.2 relapses per year (IQR 0.0-0.5) after long-term RTX treatments (P < 0.001). Longer relapse-free periods were associated with more than four RTX cycles, longer B-cell depletion, older age at each RTX treatment, and lower cholesterol levels. B lymphocytes recovered to 1% at a median of 5.9 months (95% confidence interval 5.7-6.1) after RTX administration. Factors related to a longer period of B-cell depletion included more than five RTX cycles, a higher dose of RTX, older age at treatment, and concurrent use of antimetabolites. During repeated RTX treatments, 8.0%, 6.0%, and 2.0% of patients developed hypogammaglobulinemia, severe infection, and severe neutropenia, respectively. CONCLUSIONS: Long-term repeated use of RTX may be effective and safe in pediatric NS patients. Furthermore, the redosing of RTX could be chosen by considering predictive factors for relapse-free and B-cell depletion periods.

Safety of BNT162b2 mRNA COVID-19 vaccine in children with chronic kidney disease: a national population study from South Korea.

BACKGROUND: In South Korea, COVID-19 vaccination has been recommended to adolescents aged 12 - 17 since October, 2021. We aimed to assess the rate of adverse events following COVID-19 vaccination in adolescents with chronic kidney disease (CKD) in South Korea, using national cohort data. METHODS: We retrieved the clinical information of adolescents 12 - 17 years old from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (K-COV-N) database, to calculate incidence rates of purpura and other hemorrhagic conditions, Guillain-Barré syndrome (GBS), Kawasaki disease/multisystem inflammatory syndrome in children (MIS-C), myocarditis and/or pericarditis, and anaphylaxis in adolescents with CKD, after BNT162b2 vaccination. RESULTS: Among the 2306 adolescents with CKD, 62.7% (n = 1446) had received the BNT-162b2 vaccine. GBS, Kawasaki disease/MIS-C, and anaphylaxis or anaphylactic shock did not occur during the observation period. Purpura and hemorrhagic conditions were more frequent in the unvaccinated group (7/860 vs. 1/1446), while myocarditis/pericarditis was observed only in the vaccinated group (0/860 vs. 1/1446). Adjusted odds ratio for any of the two adverse events was lower in vaccinated adolescents than in the unvaccinated group which did not reach statistical significance (adjusted odds ratio = 0.14, 95% confidence interval: 0.02, 1.16, P = 0.068). CONCLUSIONS: In this national cohort study of adolescents with CKD in South Korea, we observed no evidence of increased risk of adverse events following BNT162b2 vaccination. Our finding offers insights into the safety of COVID-19 vaccines, empowering adolescent patients with CKD and their caregivers to make informed decisions.

Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract.

BACKGROUND: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). METHODS: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. RESULTS: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. CONCLUSIONS: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.

Genotype-phenotype correlations in children with Gitelman syndrome.

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.

Gastrointestinal involvement of passenger lymphocyte syndrome followed by minor ABO-incompatible renal transplantation: A case report.

BACKGROUND: People with group O blood are considered universal organ donors compatible with any other blood group. However, in the case of minor ABO-incompatible transplantation, immune-mediated hemolysis may occur due to concomitant transfer of donor B lymphocytes together with the allograft. These passenger lymphocytes can produce antibodies in the recipients erythrocytes, causing hemolytic anemia known as passenger lymphocyte syndrome (PLS). METHODS: A retrospective chart review was performed. RESULTS: A 6-year-old boy (A+) underwent transplantation of a kidney from his father (O+). On postoperative day (POD) 6, the patient developed fever with no explainable causes. On POD 11, he presented with abdominal pain, hematochezia, and severe diarrhea, with sudden hemolytic anemia. Since then, GI symptoms have continued. On POD 20, direct antiglobulin test (DAT) was positive, and the anti-A IgM/G titer was 2/32. The results of the anti-A antibody elution test were strongly positive (3+). These findings highly suggested PLS. On the same day, the GI symptoms suddenly worsened, and laboratory findings showed hemolysis and thrombocytopenia with disseminated intravascular coagulation (DIC). Abdominal computed tomography (CT) scans suggested ischemic colitis of venous origin, and the patient underwent segmental colectomy with ileostomy formation on POD 23. To remove the anti-A antibodies, the patient underwent therapeutic plasma exchange (TPE) five times until the DAT and anti-A elution test were negative. CONCLUSIONS: We report a case of gastrointestinal involvement of PLS that occurred after minor ABO-incompatible kidney transplantation. This is the first report of ischemic colitis as an atypical manifestation of PLS.

Clinical course of post-kidney transplant Schimke immuno-osseous dysplasia.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare systemic disease characterized by short stature, proteinuria, and recurrent infections. Patients usually have spondyloepiphyseal dysplasia, and progressive steroid-resistant nephropathy that leads to kidney failure. However, their clinical course after kidney transplantation (KT) is not yet well known. Here, we present our experience with cases of SIOD treated at our institute. CASE PRESENTATION: Since 2014, three children have been diagnosed with nephropathy resulting from SIOD. They presented with proteinuria in the nephrotic range at 7, 5, and 3 years of age. Focal segmental glomerulosclerosis was confirmed and progressed to kidney failure approximately 2 years after proteinuria was detected. These patients underwent living-donor KT from their parents. After KT, Case 1 lost his graft within 7 months due to multi-organ failure caused by disseminated adenovirus infection and died. Case 2 experienced graft failure 5 years after KT due to acute rejection from poor compliance. In Case 3, the allograft was still functioning 6 years after KT with low-dose tacrolimus single medication (trough level < 5 ng/mL). Extra-renal manifestations progressed regardless of KT, namely, right renal vein thrombosis and pulmonary hypertension in Case 1, severe bilateral hip dysplasia and Moyamoya syndrome in Case 2, and neutropenia and thrombocytopenia in Case 3, in addition to recurrent infection. CONCLUSION: In SIOD patients, KT is complicated with recurrent infections due to their inherent immune dysfunction. Additionally, extra-renal symptoms may render the patients morbid despite the recovery of kidney function.

Posttransplant renal replacement therapy is an alarm signal for survival outcomes in pediatric liver transplantation.

BACKGROUND: The impact of renal replacement therapy (RRT) on the long-term survival outcomes of pediatric liver recipients remains controversial. METHODS: A total of 224 patients aged <18 years, who underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n = 25, 11.2%) and those who did not (group N, n = 199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end-point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 [early: <6 months after LT (n = 5, 20.0%) and late: ≥6 months after LT (n = 8, 32.0%)]. The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%). RESULTS: The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end-stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p < .05). The number of patients (60.0% vs. 93.0%; p < .001) and graft survival rates (68.0% vs. 93.0%; p < .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation. CONCLUSION: The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post-LT RRT.

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.

Maternal antibiotic exposure during pregnancy is a risk factor for community-acquired urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in infants.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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."

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.

Genetic identification of inherited cystic kidney diseases for implementing precision medicine: a study protocol for a 3-year prospective multicenter cohort study.

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.

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.

Cystic dysplasia of the kidneys in extremely preterm infants following acute kidney injury.

BACKGROUND: Various perinatal morbidities may adversely affect postnatal nephrogenesis in preterm infants. Kidney ultrasonographic findings following acute kidney injury (AKI) have not been well described in preterm infants. Herein, we describe three cases of extremely preterm infants who showed abnormal kidney ultrasonographic findings resembling dysplasia of the kidneys following AKI. CASE-DIAGNOSIS/TREATMENT: Their median gestational age and birth weight were 25+6 (range 23+3-26+6) weeks and 620 (480-840) g, respectively. All infants suffered severe AKI during their third to seventh week of life. Their kidney function recovered with conventional management. Kidney ultrasonographies performed after AKI revealed increased kidney echogenicity, loss of corticomedullary differentiation, and multiple cortical cysts, which were similar to cystic dysplasia of the kidneys and were absent in previous kidney imaging. Three infants eventually developed at least one of the long-term kidney sequelae following AKI, including proteinuria, hypertension, and elevated levels of serum creatinine or cystatin C as determined during the last follow-up at the corrected age of 9-18 months. CONCLUSIONS: Based on these cases, we can infer that AKI occurring during the early postnatal period may result in dysplasia of the kidneys with cortical cysts in extremely preterm infants, which may lead to chronic kidney disease in their later life. It is useful to follow up not only laboratory parameters but also kidney ultrasonographic findings in extremely preterm infants who suffered AKI during their early postnatal periods.

Rasburicase improves the outcome of acute kidney injury from typical hemolytic uremic syndrome.

BACKGROUND: Typical hemolytic uremic syndrome (HUS) causes acute kidney injury (AKI) and serious sequelae of chronic kidney disease (CKD) in some. Hyperuricemia is a common finding in typical HUS that may contribute to kidney damage. We explored whether aggressive management of hyperuricemia with rasburicase could improve outcomes in AKI patients with typical HUS. METHODS: We retrospectively analyzed medical records of children with typical HUS admitted to a tertiary center between 2005 and 2017. We compared clinical outcomes of hospitalization and 1-year post-discharge between those with rasburicase treatment (n = 13) and those without (controls, n = 29). RESULTS: With rasburicase treatment, hyperuricemia corrected more rapidly (median 36 vs. 120 h, p < 0.001), and hospital stays were shorter (median 9 vs. 12 days, p = 0.003) than in the controls. There was no difference in dialysis requirement. At 1-year post-discharge, the proportion of patients with impaired kidney function (estimated glomerular filtration rate < 90 mL/min/1.73 m2) was lower in the rasburicase group (7.7% vs. 41.4%, p = 0.036) than in the controls. Hypertension and proteinuria tended to be more common in the controls than in the rasburicase group. Collectively, long-term renal sequelae of impaired kidney function, proteinuria, or hypertension at a 1-year follow-up was less common in the rasburicase group than in the controls (7.7% vs. 62.1%; p = 0.001). CONCLUSIONS: Children with typical HUS treated with rasburicase had shorter hospital stays and less long-term sequelae at 1-year post-discharge than those who were not treated with rasburicase. These results support the use of rasburicase to prevent CKD in pediatric patients with typical HUS-associated AKI. Graphical Abstract.

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.

Case of catastrophic antiphospholipid syndrome presenting as neuroretinitis and vaso-occlusive retinopathy.

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.

Renal Syndromic Hearing Loss Is Common in Childhood-onset Chronic Kidney Disease.

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.