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.

Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. METHODS: A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. RESULTS: The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p = .003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p < .001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p = .003). Overall, the graft survival rate was inferior in the high IPV group (p < .001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p < .001). CONCLUSION: The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.

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."

Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry.

RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. OUTCOME: All-cause MPD mortality. ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias. CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

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

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

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

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

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

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

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (Pmeta=6.71E-28, OR=1.88) and TNFSF15 (Pmeta=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).

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.

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

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

A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis.

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.

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.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

This corrects the article on e203 in vol. 34, PMID: 31373185.

Acute Kidney Injury in Pediatric Cancer Patients.

OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria. STUDY DESIGN: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria. Impaired renal function of estimated glomerular filtration rate less than 90 mL/minute/1.73 m2 and development of proteinuria of cancer survivors were also assessed. RESULTS: This study included 1868 patients who were diagnosed with cancer at a median age of 7.9 years. During the course of treatment, 983 patients (52.6%) developed 1864 episodes of AKI, and the cumulative incidence at 2 weeks, 3 months, and 1 year after diagnosis was 28.9%, 39.6%, and 53.6%, respectively. The 1-year cumulative incidence was the highest in patients with acute myeloid leukemias (88.4%). In all, 6.1% of patients had more than 4 episodes of AKI and 11.8% of patients had stage 3 AKI. Among the 1096 childhood cancer survivors, 22.6% were found to have impaired renal function. A greater number of AKI episodes (≥4 times) and nephrectomy were independent risk factors of impaired renal function. Also, 8.2% of the survivors developed proteinuria among 742 childhood cancer survivors. CONCLUSIONS: A large percentage of children with cancer experience AKI during the course of treatment, and AKI is associated with impaired long-term renal function.

Life-Threatening Extrarenal Manifestations in an Infant with Atypical Hemolytic Uremic Syndrome Caused by a Complement 3-Gene Mutation.

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.

Low relapse rate of urinary tract infections from extended-spectrum beta-lactamase-producing bacteria in young children.

BACKGROUND: Extended-spectrum-beta-lactamase (ESBL)-producing bacteria are an increasingly important cause of urinary tract infections (UTIs) worldwide. We evaluated clinical characteristics and associated risk factors of UTIs in young children according to ESBL-producing status and relapse rates. METHODS: All urinary culture results in patients younger than 2 years old were assessed, and only children with febrile UTIs from gram-negative bacterial infections were reviewed. RESULTS: Of 845 episodes evaluated, 146 (17.3%) were caused by ESBL-positive bacteria. Significant differences were observed in previous UTIs, use of antibiotics or history of hospitalization within previous 3 months, and underlying urinary abnormalities between the ESBL UTI and non-ESBL UTI groups. After 2 weeks of treatment completion, UTI relapse occurred in 2.7% of children in the ESBL group and 1.1% of children in the non-ESBL group (P = 0.13). In the ESBL UTI group, relapse rate was not significantly different between patients treated with susceptible antibiotics and those treated with non-susceptible but clinically effective antibiotics. CONCLUSIONS: Previous history of UTI, antibiotic treatment, or hospitalization within previous 3 months and underlying disease are risk factors for ESBL UTI in children under 24 months of age. However, relapse rate was < 3% regardless of in vitro susceptibility of the treating antibiotics, as long as the antibiotics were clinically effective. We cautiously propose that we may continue the use of initial empirical antibiotics when a definite clinical response is observed, although further study is necessary to confirm the findings of this study.

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

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

Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.