Background
Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric ...cohort to delineate the clinical characteristics and genotypes.
Methods
A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti‐complement‐factor‐H autoantibody (anti‐CFH) titers were measured. Multiplex ligation‐dependent probe amplification assay was performed to detect deletions in the complement factor‐H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann–Whitney U‐test and chi‐squared test.
Results
Fifteen patients (group A, 29.7%) had anti‐CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti‐CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively.
Conclusions
The incidence of anti‐CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.
Purpose: This article was to investigate the association between urinary tract infections (UTIs) and high weight status in infancy.Methods: We conducted a nationwide matched cohort study from January ...2018 to December 2020 using data from the Korean National Health Insurance System and the Korean National Health Screening Program for Infants and Children. We analyzed the association between UTI diagnosis codes and high weight status (which was defined as being in the 90th percentile or higher of weight-for-age).Results: We found that 22.8% of infants with UTIs exhibited high weight status, compared to 20.0% of non-UTI infants (P<0.001). Per our multivariable analyses, the adjusted odds ratio for high weight status was 1.09 (95% confidence interval, 1.06–1.13).Conclusions: UTI in the first 12 months of life was associated with a weight-for-age percentile of ≥90. Our findings corroborate those of previous single-center studies and emphasize the importance of careful monitoring for this at-risk group.
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.
Adequate fluid management is an important therapeutic goal of dialysis. Recently, bioelectrical impedance methods have been used to determine body fluid status, but pediatric reports are rare. To ...determine the accuracy of bioelectrical impedance methods in the assessment of body fluid statusof children undergoing hemodialysis (HD), 12 children on HD were studied. A multi-frequency bioimpedance analysis device (Inbody S10) and bioimpedance spectroscopy device (BCM) were used to evaluate fluid status. Fluid removal during a HD session (assessed as body-weight change, ΔBWt) was compared with the difference in total body water determined by each device (measured fluid difference, ΔMF), which showed strong correlation using either method (Pearson's coefficient, r = 0.772 with Inbody S10 vs. 0.799 with BCM). Bioimpedance measurement indicated fluid overload (FO; ΔHS greater than 7%) in 34.8% with Inbody S10 and 56.5% with BCM, and only about 60% of children with FO by bioimpedance methods showed clinical symptoms such as hypertension and edema. In some patients with larger weight gain Inbody S10-assessed overhydration (OH) was much smaller than BCM-assessed OH, suggesting that BCM is more relevant in estimating fluid accumulation amount than Inbody S10. To our knowledge, this is the first report on the use of body composition monitors to assess fluid status in Korean children receiving HD.
Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. ...However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria.Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks.Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period.Conclusions: Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)
This study aimed to use whole-exome sequencing (WES) to diagnose ultra-rare renal diseases and the clinical impact of such an approach on patient care.
Clinical, radiological, pathological, and ...genetic findings were reviewed in the patients and their family members.
Nine patients from nine unrelated Korean families were included in the study and evaluated. WES identified eight different conditions in these patients, i.e., autosomal dominant tubulointerstitial kidney disease associated with UMOD mutation; recurrent urinary stones associated with APRT deficiency; Ayme-Gripp syndrome associated with MAF mutation; short rib-thoracic dysplasia associated with IFT140 mutation; renal coloboma syndrome associated with PAX2 mutations; idiopathic infantile hypercalcemia associated with CYP24A1 mutation; and hypomagnesemia associated with TRPM mutation. Eleven different mutations, including seven novel mutations, were identified, i.e., four truncating mutations, six missense mutations, and one splice-acceptor variant. After genetic confirmation, strategies for the management of the following: medications, donor selection for renal transplantation, and surveillance for extra-renal manifestations were altered. In addition, genetic counseling was provided for the patients and their family members with respect to family member screening for affected but yet unidentified patients and future reproductive planning.
As WES can effectively identify ultra-rare genetic renal diseases, facilitate the diagnosis process, and improve patient care, it is a good approach to enable a better understanding of ultra-rare conditions and for the establishment of appropriate counseling, surveillance, and management strategies.
Purpose Hematuria and proteinuria have various causes and consequential outcomes in children. Immunosuppressants are needed in some children with biopsy-proven glomerulonephropathy but have many ...adverse effects. Since the clinical practice patterns of Korean pediatric nephrologists are diverse, we surveyed their opinions. Methods Using a clinical vignette, the survey was emailed to all Korean Society of Pediatric Nephrology members. The questionnaires included diagnosis, examination, medications, and dietary recommendations for patients with hematuria and proteinuria. Results A total of 32 clinicians (5.48%, 22 pediatric certificated nephrologists) responded to the survey. Most responders (87.5%) suspected immunoglobulin A nephropathy, and 68.8% replied that kidney biopsies were a diagnostic tool. Renin-angiotensin system inhibition (62.5%) or steroids (18.8%) were selected as the treatment. Salt and protein intakes were usually encouraged as dietary reference intakes (34.4% and 65.6%, respectively). Conclusions Children with abnormal urinalysis have various causes, treatments, and prognoses. As treatments such as immunosuppressants can have many adverse effects, it is necessary to confirm an accurate diagnosis and indications of treatments before starting the treatment. Recommendations for a diet should not hinder growth.
BackgroundWhether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to ...breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients. MethodsIn total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded. ResultsAfter the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range IQR 7.2-402.8) to 1,612.1 (IQR 153.9-5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels (<400 AU/mL) post-third vaccination were a risk factor for symptomatic breakthrough infection (hazard ratio HR=3.46, P<0.001). Anti-RBD IgG levels <200 AU/mL were a critical risk factor for hospitalization (HR=36.4, P=0.007). ConclusionsLow anti-spike IgG levels after third vaccination in kidney transplant recipients were associated with symptomatic breakthrough infection and, particularly, with hospitalization during the Omicron surge. These data can be used to identify patients requiring additional protective measures, such as passive immunization using monoclonal antibodies.
BACKGROUNDChronic 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. METHODSEighty-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). RESULTSThe 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. CONCLUSIONOn 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 REGISTRATIONClinicalTrials.gov Identifier: NCT02165878.
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