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BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment. RESULTS: We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats. CONCLUSION: The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens.
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BACKGROUND: The standard rate of sodium removal in adult anuric patients on continuous ambulatory peritoneal dialysis (CAPD) is 7.5 g/L of ultrafiltration volume (UFV). Although automated PD (APD) is widely used in pediatric patients, no attempt has yet been made to estimate sodium removal in APD. METHODS: The present, retrospective cohort study included pediatric patients with APD who were managed at Tokyo Metropolitan Children's Medical Center between July 2010 and November 2017. The patients underwent a peritoneal equilibrium test (PET) at our hospital. Sodium removal per UFV was calculated by peritoneal function and dwell time using samples from patients on APD with 1- and 2-h dwell effluent within three months of PET and 4- and 10-h dwell effluent at PET. RESULTS: In total, 217 samples from 18 patients were included, with 63, 81, and 73 of the samples corresponding to the High [H], High-average [HA], and Low-average [LA] PET category, respectively. Sodium removal per UFV (g/L in salt equivalent) for dwell times of one, two, four, and ten hours was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively. CONCLUSIONS: Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, leading to sodium accumulation. Therefore, salt intake should be restricted in combination with one or more long daytime dwells, especially in anuric patients.
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Sodio , Ultrafiltración , Humanos , Masculino , Estudios Retrospectivos , Femenino , Niño , Adolescente , Sodio/análisis , Ultrafiltración/métodos , Preescolar , Diálisis Peritoneal/métodos , Diálisis Peritoneal Ambulatoria Continua/métodos , Fallo Renal Crónico/terapia , Anuria/terapiaRESUMEN
OBJECTIVE: To evaluate whether antibiotic treatment of febrile urinary tract infection (UTI) is delayed in febrile infants with respiratory symptoms compared with those without. STUDY DESIGN: Data of infants 2-24 months of age diagnosed with UTI from March 1, 2012 to May 31, 2023 were collected from our hospital's medical charts and triage records. Patients with known congenital anomalies of the kidney and urinary tract or a history of febrile UTI were excluded. Patients were classified as having respiratory symptoms if they had any of the following symptoms or clinical signs: cough, rhinorrhea, pharyngeal hyperemia and otitis media. Time to first antibiotic treatment from fever onset was compared between patients with and without respiratory symptoms. A Cox regression model was constructed to adjust for potential confounders. RESULTS: A total of 214 patients were eligible for analysis. The median age of the eligible patients was 5.0 months (interquartile range: 3.0-8.8) and 118 (55%) were male. There were 104 and 110 patients in the respiratory symptom and no respiratory symptom groups, respectively. The time to first antibiotic treatment was significantly longer in the group with respiratory symptoms (51 hours vs. 21 hours). Respiratory symptoms were significantly associated with a longer time to first treatment after adjustment for age and sex in the Cox regression model (hazard ratio = 0.63, 95% confidence interval: 0.47-0.84). CONCLUSIONS: Treatment of febrile UTI infants with respiratory symptoms tends to be delayed. Pediatricians should not exclude febrile UTI even in the presence of respiratory symptoms.
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Infecciones Urinarias , Sistema Urinario , Lactante , Humanos , Masculino , Femenino , Retraso del Tratamiento , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/complicaciones , Antibacterianos/uso terapéutico , Fiebre/tratamiento farmacológicoRESUMEN
The repeated-dose liver micronucleus (RDLMN) assay is a widely accepted method for detecting genotoxic substances. We investigated the effect of animal age on this assay. Proliferation activity in the liver tissue of untreated rats at age = 3.5, 6, 8, 10, or 12 weeks was measured via immunohistochemical expression of Ki-67 protein. The percentage of Ki-67-positive hepatocytes decreased markedly with age, reaching very low levels after 10 weeks, indicating decline with age of proliferative capacities in the liver. We calculated the area under the curve (AUC) of the approximate curve generated from the percentage of Ki-67-positive cells, to estimate the hepatocyte proliferation activity over the dosing period in the two regimens of the 4-week RDLMN assay: dosing initiated at age = 6 or 8 weeks. Hepatocyte proliferation activity of the former regimen was approximately double that of the latter. We also calculated the AUC for the juvenile-rat method, in which rats are treated for two days at age = 3.5 weeks. The AUC calculated for that method was approximately half of that for the 4-week repeated-dosing regimen initiated at 6 weeks of age. These findings suggest that the 4-week RDLMN assay with dosing initiated at age = 6 weeks could be approximately twice as sensitive as the other two methods.
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Médula Ósea , Carcinógenos , Ratas , Animales , Antígeno Ki-67 , Pruebas de Micronúcleos/métodos , Ratas Sprague-Dawley , Carcinógenos/toxicidad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Administración Oral , Aberraciones Cromosómicas , Conducta Cooperativa , Sociedades Farmacéuticas , Hígado , Hepatocitos , Proliferación CelularRESUMEN
BACKGROUND: Icodextrin has a lower absorption rate, and icodextrin peritoneal dialysate contributes to more water removal than glucose dialysate in patients with high peritoneal permeability. There are limited data on icodextrin dialysate use in children. METHODS: This study included all pediatric patients who received peritoneal equilibration tests and peritoneal dialysis with icodextrin dialysate at the study center. The factors related to ultrafiltration volume with icodextrin dialysate with long dwell time were statistically analyzed. Then the ultrafiltration volume with icodextrin and medium-concentration glucose dialysate was compared in individual cycles in the same patients. RESULTS: Thirty-six samples were included in the icodextrin group, and nine samples were used to compare the ultrafiltration volume with icodextrin and glucose dialysate. Dwell time, D/P-creatinine, D/D0-glucose, age, height, and weight correlated significantly with the ultrafiltration volume of icodextrin dialysate (p < 0.05). A dwell volume equal to or more than 550 mL/m2 was associated with a significantly higher ultrafiltration volume than a lower dwell volume (p = 0.039). Multiple regression analysis revealed that dwell time (p = 0.038) and height (p < 0.01) correlated with ultrafiltration volume significantly. In addition, the ultrafiltration volume was superior (p < 0.01), and dwell time was longer (p = 0.02), with icodextrin dialysate than with medium-concentration glucose dialysate. CONCLUSIONS: The ultrafiltration volume with icodextrin dialysate decreases in patients with small stature. Providing sufficient dwell time and volume is important for maximal water removal even in children. Ultrafiltration volume is superior with icodextrin than medium-concentration glucose dialysate for long dwell times. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Soluciones para Diálisis , Ultrafiltración , Humanos , Niño , Icodextrina , Glucanos , GlucosaRESUMEN
BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Insuficiencia Renal Crónica , Sistema Urinario , Recién Nacido , Embarazo , Femenino , Humanos , Lactante , Creatinina , Estudios Retrospectivos , Diálisis Renal , Riñón , Sistema Urinario/anomalíasRESUMEN
BACKGROUND: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants. METHODS: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis. RESULTS: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]". CONCLUSION: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established.
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Estatura , Riñón , Niño , Femenino , Humanos , Japón , Riñón/diagnóstico por imagen , Masculino , Valores de Referencia , Estudios Retrospectivos , UltrasonografíaRESUMEN
BACKGROUND: The clinical spectrum of Henoch-Schönlein purpura nephritis (HSPN), now known as IgA vasculitis-associated nephritis (IgAVN), ranges from isolated microscopic haematuria to nephrotic syndrome, progressive glomerulonephritis, and kidney failure. The outcome also varies, and the management of IgAVN is controversial. The presence of nephrotic state at disease onset is thought to be a risk factor of a poor prognosis. However, not all patients with nephrotic state have a poor prognosis, and it is unclear whether they need early treatment. METHODS: We herein retrospectively examined the clinical course of paediatric IgAVN cases with nephrotic state (serum albumin [sAlb]<3.0 g/dL and urine protein-creatinine ratio of >2.0 g/ gCr) without kidney injury treated at our hospital between 2010 and 2018. RESULTS: Of the 216 patients with IgAVN identified, 17 met the inclusion criteria. The median follow-up period from disease onset to the last observation was 40.5 months (IQR:31.0-74.2). Eleven patients were male, the median age at onset was 5 years, the minimum serum Alb level was 1.9 g/dL, the maximum proteinuria value was 12.3 g/gCr, and the median minimum eGFR was 86.0 mL/min/1.73 m2 in the acute phase. Eight patients (47%) achieved resolution of nephrotic state within 3 months and complete remission without treatment by the last observation. The patients with spontaneous resolution of nephrotic state had less severe hypoalbuminaemia (Alb<2.0 g/dL) and tended to show a quick increase in the serum albumin level. CONCLUSIONS: Our study found that half of paediatric patients with IgAVN with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short-term outcome. Consideration of the duration of nephrotic state and trends in the serum albumin level in children with IgAVN may allow unnecessary kidney biopsies and immunosuppressive therapy to be avoided.
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Glomerulonefritis , Vasculitis por IgA , Nefritis , Niño , Femenino , Glomerulonefritis/patología , Humanos , Vasculitis por IgA/complicaciones , Vasculitis por IgA/diagnóstico , Riñón/patología , Masculino , Nefritis/complicaciones , Estudios Retrospectivos , Albúmina SéricaRESUMEN
BACKGROUND: Malignancy after kidney transplantation (KT) is one of the most serious post-transplant complications. This study aimed to investigate the incidence, type, and outcomes of malignancy after pediatric KT. METHODS: We performed a retrospective cohort study on pediatric kidney transplant recipients aged 18 years or younger who received their first transplant between 1975 and 2009. RESULTS: Among the 375 children who underwent KT, 212 were male (56.5%) and 163 were female (43.5%) (median age at KT, 9.6 years [interquartile range {IQR}] 5.8-12.9 years). The incidence of malignancy was 5.6% (n = 21). The cumulative incidences of cancer were 0.8%, 2.5%, 2.8%, 4.2%, 5.5%, and 15.6% at 1, 5, 10, 15, 20, and 30 years post-transplantation, respectively. Of 375 patients, 12 (3.2%) had solid cancer and nine (2.4%) had lymphoproliferative malignancy. The median age at the first malignancy was 21.3 years (IQR 11.5-33.3 years). The median times from transplant to diagnosis were 22.3 years (IQR 12.3-26.6 years) for solid cancer and 2.2 years (IQR 0.6-2.8) for lymphoproliferative malignancies. During follow-up, five recipients died due to malignancy. The causes of death were hepatocellular carcinoma in one patient, squamous cell carcinoma in the transplanted kidney in one patient, malignant schwannoma in one patient, and Epstein-Barr virus-related lymphoma in two patients. The mortality rate was 0.79 per 1000 person-years (95% confidence interval 0.38, 1.85). CONCLUSIONS: Early diagnosis and treatment of malignancies in transplant recipients is an important challenge. Therefore, enhanced surveillance and continued vigilance for malignancy following KT are necessary.
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Infecciones por Virus de Epstein-Barr , Trasplante de Riñón , Neoplasias , Adolescente , Niño , Preescolar , Detección Precoz del Cáncer/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Herpesvirus Humano 4 , Humanos , Incidencia , Japón/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Neoplasias/epidemiología , Neoplasias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Although the concept of chronic kidney disease (CKD) in children is similar to that in adults, pediatric CKD has some peculiarities, and there is less evidence and many factors that are not clearly understood. The past decade has witnessed several additional registry and cohort studies of pediatric CKD and kidney failure. The most common underlying disease in pediatric CKD and kidney failure is congenital anomalies of the kidney and urinary tract (CAKUT), which is one of the major characteristics of CKD in children. The incidence/prevalence of CKD in children varies worldwide. Hypertension and proteinuria are independent risk factors for CKD progression; other factors that may affect CKD progression are primary disease, age, sex, racial/genetic factors, urological problems, low birth weight, and social background. Many studies based on registry data revealed that the risk factors for mortality among children with kidney failure who are receiving kidney replacement therapy are younger age, female sex, non-White race, non-CAKUT etiologies, anemia, hypoalbuminemia, and high estimated glomerular filtration rate at dialysis initiation. The evidence has contributed to clinical practice. The results of these registry-based studies are expected to lead to new improvements in pediatric CKD care.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Adulto , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/terapia , Sistema de Registros , Diálisis Renal , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/terapia , Factores de RiesgoRESUMEN
BACKGROUND: In typical cases of Bartter syndrome (BS), assessing response to diuretics (furosemide and thiazide), hereinafter referred to as diuretic loading test, may be used to diagnose the type by detecting which part of the kidney tubule is not functioning correctly. However, the diuretic loading test may not always agree with the results of genetic analyses. CASE PRESENTATION: A 5-year-old boy was admitted due to lower extremity weakness and abnormal gait. He had a recurrent episode of muscle weakness and laboratory results showed severe hypokalemia. The direct genomic sequencing of the case revealed a new mutation in the SLC12A1 gene, which is associated with type I Bartter syndrome. Because there was the difference between the phenotype and genotype, we conducted a diuretic loading test to confirm the diagnosis. However, the results showed a clear increase in urine excretion of Na and Cl. These results were not consistent with typical type I BS, but consistent with the patient's phenotype. CONCLUSION: The diuretic loading test has limited utility for diagnosis especially in atypical cases. On the other hand, this test, which allows assessment of channel function, is useful for better understanding of the genotype-phenotype correlation.
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Síndrome de Bartter/diagnóstico , Diuresis/efectos de los fármacos , Diuréticos/farmacología , Pruebas Genéticas , Síndrome de Bartter/complicaciones , Síndrome de Bartter/genética , Preescolar , Furosemida/farmacología , Genotipo , Humanos , Hipopotasemia/etiología , Masculino , Inhibidores de los Simportadores del Cloruro de Sodio/farmacologíaRESUMEN
INTRODUCTION: Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease in children. OBJECTIVES: We aimed to compare the long-term outcomes and surgical complications of the intraperitoneal approach (IPA) and extraperitoneal approach (EPA) for KTx in children weighing <15 kg. STUDY DESIGN: We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing <15 kg, who received their first living-related kidney transplant between January 1987 and December 2015. Patients were divided into two groups based on the surgical approach (IPA or EPA) during transplant, and clinical data were extracted from the medical records. RESULTS: The median follow-up duration was 14.1 years (interquartile range, 9.0-19.2). Comparing the two groups (IPA group, n = 62; EPA group, n = 38), the median age and body weight were significantly lower in the IPA group (4.2 vs. 4.8 years, P = 0.03; 11.7 vs. 13.0 kg, P < 0.01). There were 26 surgical complications (26%) in 19 patients during the follow-up period. The surgical complication rate was higher in the IPA group (39% vs. 6%). DISCUSSION: We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing <15 kg who underwent KTx and received a size-mismatched adult donor kidney. There was no significant difference in renal transplantation prognosis using the surgical approach, but IPA-related complications were more frequent in the long term. Therefore, our data suggest that in cases of donor-recipient size mismatch in pediatric KTx, the EPA, associated with fewer surgical complications, is preferable to the IPA if the patient's body size has sufficient space for allograft placement. CONCLUSION: The transplant approach did not influence the long-term outcomes in children weighing <15 kg, but EPA had fewer surgical complications and was technically safe.
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Fallo Renal Crónico , Trasplante de Riñón , Niño , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/cirugía , Donadores Vivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: Accurate and precise estimation of glomerular filtration rate (GFR) is essential in kidney disease. We evaluated the usefulness of the mean of creatinine clearance (CCr ) and urea clearance (CUN ) examined over a 1-h urine collection period (1-h (CCr + CUN )/2) in a retrospective, cross-sectional study across two centres, as a relatively simple method for estimating GFR in children. METHODS: Children aged ≤18 years who underwent inulin clearance (CIn ) tests were eligible. Two clearance values were obtained during a 2-h test consisting of two periods of 1 h each. The mean clearance in two periods was defined as 1-h clearance. 1-h (CCr + CUN )/2, 1-h CCr , 1-h CUN and GFR estimated by Cr-based and cystatin C (CysC)-based formulas for Japanese children were compared with CIn . Bland-Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1-h (CCr + CUN )/2 and CIn . RESULTS: Fifty-three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3-14.2) years, and median CIn and 1-h (CCr + CUN )/2 were 77.0 (IQR: 51.5-95.1) and 81.0 (IQR: 64.1-97.7) ml/min/1.73 m2 , respectively. Percentage difference of CIn and 1-h (CCr + CUN )/2 in the Bland-Altman plot was -11.2% (95% confidence interval - 15.3% - -7.1%), with 95% lower and upper limits of agreement of -40.3% and 18.0%, respectively. Thus, 1-h (CCr + CUN )/2 was 1.12 times CIn . CONCLUSION: 1 h (CCr + CUN )/2 was almost concordant with CIn . 1-h (CCr + CUN )/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice.
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Creatinina/orina , Tasa de Filtración Glomerular , Enfermedades Renales/diagnóstico , Riñón/fisiopatología , Modelos Biológicos , Urea/orina , Adolescente , Factores de Edad , Biomarcadores/orina , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Enfermedades Renales/fisiopatología , Enfermedades Renales/orina , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , TokioRESUMEN
No reports describe high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (auto-PBSCT) in pediatric patients with neuroblastoma and end-stage renal disease. Here, we report the case of a patient with high-risk neuroblastoma who developed anuria during treatment. HDCT with auto-PBSCT under hemodialysis, with strict attention to the ultrafiltration volume and dose modification of alkylating agents, was performed. Although the first auto-PBSCT led to engraftment failure, the second auto-PBSCT resulted in successful myeloid engraftment 8 months after anuria. This case demonstrated that HDCT with auto-PBSCT can be safely performed in children with renal failure under hemodialysis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anuria/terapia , Fallo Renal Crónico/terapia , Neuroblastoma/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Diálisis Renal/métodos , Anuria/etiología , Anuria/patología , Preescolar , Terapia Combinada , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Masculino , Neuroblastoma/complicaciones , Neuroblastoma/patología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Pronóstico , Trasplante AutólogoRESUMEN
OBJECTIVES: To investigate the frequency of vesicoureteral reflux, and the relationship of pretransplant decreased bladder capacity and post-transplant vesicoureteral reflux in children undergoing kidney transplantation. METHODS: A voiding cystourethrography was carried out in 172 pediatric kidney transplantation recipients before, and 4 months after, transplantation to evaluate bladder capacity and vesicoureteral reflux. The correlation of post-transplant vesicoureteral reflux with pretransplant bladder capacity, vesicoureteral reflux in the native kidney and the method of ureteral reimplantation (intravesical/extravesical) was analyzed. Atrophic bladder was defined as having ≤50% functional bladder capacity (age in years + 2) × 25 (mL) or ≤150 mL in patients aged >10 years. RESULTS: Bladder capacity increased remarkably after transplantation in both post-transplant vesicoureteral reflux- group (from 180 to 253 mL) and vesicoureteral reflux+ group (from 82 to 171 mL). Voiding cystourethrography showed vesicoureteral reflux in 12 cases of kidney transplantation (7%; grade 1: 2, grade 2: 3, grade 3: 7). Pretransplant atrophic bladder was an independent risk factor of post-transplant vesicoureteral reflux (P = 0.004, hazard ratio 9.5). There was no difference in renal function between the vesicoureteral reflux- group and vesicoureteral reflux+ group at 4 months to 5 years post-transplantation. CONCLUSIONS: Pretransplant atrophic bladder is a risk factor of post-transplant vesicoureteral reflux in pediatric patients. However, bladder capacity can remarkably increase after transplantation, and kidney function in the post-transplant vesicoureteral reflux+ group is stable.
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Trasplante de Riñón , Uréter , Reflujo Vesicoureteral , Anciano , Niño , Humanos , Trasplante de Riñón/efectos adversos , Reimplantación , Estudios Retrospectivos , Reflujo Vesicoureteral/diagnóstico por imagen , Reflujo Vesicoureteral/epidemiología , Reflujo Vesicoureteral/etiologíaRESUMEN
BACKGROUND: Despite advances in non-invasive vascular imaging, detection of renal artery stenosis via catheter angiography is the criterion standard for the diagnosis of renovascular hypertension (RVH). However, because of lack of evidence, the utility of various blood tests and imaging modalities remains unclear. METHODS: We retrospectively analyzed the utility of blood tests (plasma renin activity [PRA], aldosterone, and renal vein renin [RVR] values) and imaging studies (computed tomography angiography [CTA], kidney ultrasonography [US]) by comparing them with catheter angiography. Ten pediatric patients with RVH at two institutions from January 2008 to December 2017 were recruited. The sensitivities for diagnosing RVH via imaging and blood tests (kidney [US], PRA, and aldosterone) were derived by examining patient records. Furthermore, the sensitivity and specificity of CT angiography were calculated by considering both the affected and non-affected renal arteries of the patients. RESULTS: A high sensitivity for diagnosing RVH via kidney US (89%) and PRA (80%) was observed. The sensitivity and specificity of CTA were 100%, each. RVR sampling did not aid in the diagnosis of RVH; only two of six patients with unilateral RVH showed significant laterality of RVR boundary ratios. Renal scintigraphy facilitated detection of a non-functional kidney (split renal function <5%). CONCLUSIONS: RVH in children could be diagnosed utilizing non-invasive blood and imaging tests, without catheter angiography. We recommend kidney length measurement along with measurement of PRA level, as a simple and highly useful screening test, followed by CTA as a diagnostic test.
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Hipertensión Renovascular/diagnóstico , Aldosterona/sangre , Cateterismo/métodos , Niño , Preescolar , Angiografía por Tomografía Computarizada/métodos , Femenino , Humanos , Hipertensión Renovascular/sangre , Hipertensión Renovascular/diagnóstico por imagen , Riñón/diagnóstico por imagen , Masculino , Obstrucción de la Arteria Renal/diagnóstico , Venas Renales , Renina/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía/métodosRESUMEN
Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin ß2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin ß2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.
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Membrana Basal Glomerular , Laminina , Mutación Missense , Síndromes Miasténicos Congénitos , Síndrome Nefrótico , Trastornos de la Pupila , Empalme del ARN , Sustitución de Aminoácidos , Niño , Preescolar , Femenino , Membrana Basal Glomerular/metabolismo , Membrana Basal Glomerular/patología , Humanos , Lactante , Laminina/biosíntesis , Laminina/genética , Masculino , Síndromes Miasténicos Congénitos/genética , Síndromes Miasténicos Congénitos/metabolismo , Síndromes Miasténicos Congénitos/patología , Síndrome Nefrótico/genética , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Dominios Proteicos , Trastornos de la Pupila/genética , Trastornos de la Pupila/metabolismo , Trastornos de la Pupila/patologíaRESUMEN
OBJECTIVES: To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period. METHODS: We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era 1: methylprednisolone and azathioprine; era 2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era 3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). RESULTS: The median age and bodyweight at transplantation were 9.7 years and 20.6 kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1 year post-transplant decreased significantly from 61.0% in era 1 to 14.5% in era 3 (P < 0.001). For transplant eras 1-3, 1-year graft survival was 81%, 93% and 95%; 5-year graft survival was 66%, 86% and 93%; and 10-year graft survival was 47%, 79% and 89%, respectively. The overall 5-, 10- and 20-year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251-1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547-3.842), re-transplant (hazard ratio 2.680, 95% confidence interval 1.759-3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754-4.691) as independent risk factors for graft loss at 10 years post-transplant. CONCLUSIONS: The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30 years of pediatric transplantation.
Asunto(s)
Trasplante de Riñón , Niño , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Japón/epidemiología , Trasplante de Riñón/efectos adversos , Donadores Vivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Hepatocyte nuclear factor 1ß (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. METHODS: We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. RESULTS: Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m2; p = 0.0091). CONCLUSION: We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.
Asunto(s)
Síndrome de Bartter/genética , Enfermedades del Sistema Nervioso Central/genética , Deleción Cromosómica , Cromosomas Humanos Par 17 , Esmalte Dental/anomalías , Diabetes Mellitus Tipo 2/genética , Eliminación de Gen , Factor Nuclear 1-beta del Hepatocito/genética , Enfermedades Renales Quísticas/genética , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/genética , Adolescente , Adulto , Síndrome de Bartter/diagnóstico , Enfermedades del Sistema Nervioso Central/diagnóstico , Niño , Preescolar , Hibridación Genómica Comparativa , Diabetes Mellitus Tipo 2/diagnóstico , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Herencia , Humanos , Lactante , Japón , Enfermedades Renales Quísticas/diagnóstico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Linaje , Fenotipo , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Anomalías Urogenitales/diagnóstico , Reflujo Vesicoureteral/diagnósticoRESUMEN
BACKGROUND: In pediatric patients, due to variations in baseline serum creatinine (Cr) reference values, renal dysfunctions sometimes go unnoticed. In addition, renally excreted drugs need dose adjustment while nephrotoxic drugs should be avoided altogether in patients with impaired renal function. However, most physicians are apparently unaware of these facts and may administer these drugs to vulnerable patients. METHODS: We administered a questionnaire to all physicians and pharmacists specializing in pediatric medical care at six Tokyo metropolitan government-run hospitals in Japan. RESULTS: 276 (59%) of 470 physicians and pharmacists participated. The rate of correct answers given by physicians who were asked to state the serum Cr reference range for 4-year-olds and 8-year-olds was 83 and 74%, respectively. On the other hand, the rate of correct answers given by pharmacists to the same question was only 27 and 24%, respectively. Only about 50% of physicians were aware that histamine H2-receptor antagonists and oseltamivir are renally excreted or that acyclovir and angiotensin II receptor blocker are nephrotoxic. However, most of the pharmacists recognized that histamine H2-receptor antagonists and oseltamivir are renally excreted drugs. CONCLUSIONS: For the majority of the investigated drugs, the awareness that we need to reduce dosages for patients with renal dysfunction was insufficient. To ensure safe drug administration, communication between physicians and pharmacists is paramount. There is an urgent need for the creation of a safe drug administration protocol for pediatric patients with renal dysfunction.