Chronic Kidney Disease In Children Research Articles

POS-301 EARLY CHRONIC KIDNEY DISEASE IN SCHOOL CHILDREN IN KANO, NIGERIA

The benefits of chronic kidney disease (CKD) screening as it relates to cost effectiveness and absolute relevance is of concern to many. However, screening for CKD in children will make a huge impact in resource limited countries. This study aimed to determine the burden of early CKD among school children in Kano, Nigeria.

Glomerular Filtration Rate Abnormalities in Children With Type 1 Diabetes

ObjectivesType 1 diabetes (T1D) increases the risk of chronic kidney disease (CKD) development. The primary objective of this study was to assess the prevalence of abnormalities in estimated glomerular filtration rate (eGFR) in children with T1D. As a secondary objective, we sought to explore the relationship between clinical characteristics and abnormalities in eGFR. MethodsThis cross-sectional study involved children ≤18 years of age with T1D followed in the diabetes clinic at a pediatric tertiary care centre. Data were collected from health records between 2016 and 2020. Using the Bedside Schwartz, Chronic Kidney Disease in Children Under 25 (CKiD U25) and European Kidney Function Consortium (EKFC) equations, eGFR was categorized as CKD (<60 mL/min/1.73 m2), mildly decreased (60 to <90 mL/min/1.73 m2), normal (90 to <158 mL/min/1.73 m2) and hyperfiltration (≥158 mL/min/1.73 m2). Linear regression analysis was used to describe the relationship between eGFR and clinical characteristics. ResultsOf the 420 participants, 225 were male (54%); the median age at diagnosis and duration of T1D were 6.1 and 4.8 years, respectively. The proportion of participants with mildly decreased eGFR was similar regardless of eGFR equation, with 11% to 14% of participants with an eGFR <90 mL/min/1.73 m2. When analyzed as a function of duration of T1D, eGFR was 1.4 mL/min/1.73 m2 lower per year duration of T1D. ConclusionsA notable proportion of children with T1D demonstrates eGFR abnormalities early in their T1D course. This finding along with evidence of lower eGFR in adolescence is concerning for long-term risk of CKD and warrants systematic serum creatinine monitoring at diagnosis and regular intervals thereafter in children with T1D.

The Relationship Between Neighborhood Disadvantage and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Cohort

To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD. Observational cohort study. Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data. Neighborhood poverty and neighborhood disadvantage. Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy [KRT] or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis. Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income. There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 [95% CI, 1.08-2.71]) and ED use (OR, 1.56 [95% CI, 1.02-2.40]) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 [95% CI, 1.02-1.87]). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 [95% CI, 0.24-0.96]) and higher neighborhood deprivation (OR, 0.31 [95% CI, 0.10-0.97]), but these associations did not persist after controlling for participant characteristics. Limited generalizability, as only those with consistent longitudinal nephrology care were studied. Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.

Evaluation of the creatinine-based chronic kidney disease in children (under 25years) equation in healthy children and adolescents.

The Chronic Kidney Disease in children (CKiD) equation to estimate glomerular filtration rate eGFR = k × Ht / SCr (Ht = height in cm, SCr = serum creatinine in mg/dL), with fixed k = 0.413, has recently been optimized by introducing age/sex dependent k-values valid for young children up to young adults (the CKiD Under 25years (CKiDU25) equation). Although the CKiD equation was designed for children with chronic kidney disease (CKD), this equation found common use both clinically and in research, and also in children without CKD. This report aims to evaluate properties of CKiD and CKiDU25 in healthy children and adolescents. Sex-specific metadata (height and creatinine) for healthy children were obtained from national growth curves and creatinine versus age curves. These data were used to calculate average CKiD and CKiDU25 values for each year of age and compare them against age-independent measured GFR of 107mL/min/1.73 m2. The CKiD estimations show a steep decline with age (1.5mL/min/1.73 m2/year in females and 2.0mL/min/1.73 m2/year in males) over the entire age range (2-20years) and large differences between adolescent males and females. Due to the age/sex specific k-values, the CKiDU25 equation solves this age-decline artifact of the CKiD equation. However, CKiDU25 still shows a systematic higher estimation of about 10% in healthy males compared to females over the entire age range. Although the CKiDU25 shows major improvements compared to the CKiD equation, as the unexpected age decline has been removed, a systematic difference is still observed between healthy males and females.

Quantitative Evaluation of Real-Time Shear-Wave Elastography under Deep Learning in Children with Chronic Kidney Disease

Objective. This research was to study the application value of real-time shear wave elastography (SWE) quantitative evaluation based on deep learning (DL) in the diagnosis of chronic kidney disease (CKD) in children. Methods. 60 children with pathological diagnoses of CKD were selected as a CKD group. During the same period, 45 healthy children for physical examination were selected as the control group. The application value of real-time shear-wave elastography based on DL in the evaluation of CKD in children was explored by comparing the differences between the two groups. Results. It was found that the elastic modulus values of the middle and lower parenchyma of the left kidney and right kidney in the case group were (22.02 ± 10.98) kPa and (21.99 ± 11.87) kPa, respectively, which were substantially higher compared with (4.61 ± 0.47) kPa and (4.50 ± 0.59) kPa in the control group. Young’s modulus (YM) of the middle and lower parenchyma of the left kidney in patients with CKD stages 3 to 5 was 13.27 ± 0.83, 24.21 ± 5.69, and 31.67 ± 3.82, respectively, and that of the right kidney was 17.26 ± 0.98, 26.76 ± 7.22, and 32.37 ± 4.27, respectively, and the difference was significant ( P &lt; 0.05). In patients with moderate and severe CKD, the YM values of the middle and lower parenchyma of the left kidney were 17.27 ± 0.83, 27.93 ± 6.49, and those of the right kidney were 17.26 ± 0.98, 29.56 ± 6.49, respectively, and the difference was statistically significant ( P &lt; 0.05). The serum creatinine (Scr) of the CKD group was substantially higher than that of the control group, and the estimated glomerular filtration rate (eGFR) level of the former was lower than that of the latter. However, there was no statistical difference between the YM values of the middle and lower parts of the left and right kidneys of the CKD group and the control group. Conclusion. The DL-based SWE is a new noninvasive, real-time, and quantitative detection method, which can effectively evaluate the stiffness of the kidney and help to better detect the progress of CKD as a clinical reference.

Ранняя диагностика хронической болезни почек у детей: проблемы и решения

The urgency of the problem of searching for sensitive and specific biomarkers of nephron damage in various pathological conditions is due to the increasing prevalence of chronic kidney disease in children. Currently, chronic kidney disease is determined by a decrease in the glomerular filtration rate, however, this indicator is quite variable, and its fluctuations depend on many factors, such as age, features of the disease, nutrition, and physical activity. The article presents an overview of research on the problem of early diagnosis of chronic kidney disease in children. The advantages and disadvantages of early biomarkers of kidney damage are described, which include NGAL, KIM-1, VEGF, TIMP-1, Type IV collagen, serum creatinine, cystatin C. The conducted studies demonstrate the high diagnostic value of cystatin C in the initial stages of chronic kidney disease.

A study of improvement of prevention of kidney disease in children of preschool and school age

In the complex treatment of acute and chronic kidney diseases in children, diet therapy plays an important role. High requirements are imposed on therapeutic nutrition, since the kidney is the main organ for the excretion of metabolic products that come with food and are formed as a result of the breakdown of body tissues, as well as the organ responsible for maintaining the constancy of the internal environment. Under certain conditions, it becomes necessary to correct in the diet of nutrients such as animal protein, gluten, oxalates, urates, phosphates, the metabolic products of which are excreted through the kidneys and affect not only the pathogenetic mechanisms of the development of the disease, but also participate in the formation of non-immune processes of progression disease to the stage of renal failure.

Serum and urine periostin and cytokeratin-18 in children with congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is one of the most common causes of chronic kidney disease in children. The aim of the study was to investigate serum and urine periostin and cytokeratin-18 (CK-18) in children with CON in relation to CON etiology, treatment, and kidney injury. We evaluated 81 children with CON secondary to ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), posterior urethral valves (PUV) and 60 controls. Neither biomarker demonstrated any relation to CON etiology. However, all patients showed significantly higher urine periostin (uPeriostin) and uPeriostin/Cr levels than the controls. Also, UVJO patients showed higher sCK-18 and uCK-18/Cr levels, and PUV patients showed higher uCK-18/Cr levels than the controls. Neither biomarker was found to have any relation to CON treatment. However, conservatively treated children and those before and after surgery showed significantly higher uPeriostin and uPeriostin/Cr levels than the controls. uPeriostin strongly correlated with differential renal function (DRF) < 40%. The ROC analysis demonstrated the best area under the curve (AUC) for uPeriostin (0.831) and uPeriostin/Cr (0.768), and low for sPeriostin (0.656) and uCK-18 (0.615) for detecting renal injury. In conclusion, although serum and urine periostin and CK-18 did not display any relation to etiology or the type of CON treatment, uPeriostin seems to be a useful tool for detecting renal injury in children with CON, especially due to its strong negative correlation with DRF < 40%.

A Global Perspective on Impact of Chronic Kidney Disease in Children

A Global Perspective on Impact of Chronic Kidney Disease in Children

Left Ventricular Mass and Functions in Egyptian Children with Chronic Kidney Disease in Comparison to Normal Subjects.

Left ventricular hypertrophy (LVH) and cardiac fibrosis are common accompaniments of chronic kidney disease (CKD). They can be rather easily assessed by conventional cardiac imaging modalities, most practically by M-mode or two-dimensional (2D) echocardiography, with adequate recognition of pitfalls. This study uncovers the impact of impaired renal function on left ventricular mass (LVM) and LVM index (LVMI) in children with CKD on regular hemodialysis (HD) attending the Zagazig University Hospital for Children. A total of 80 Egyptian children, out of which 40 subjects having a mean age of 11.2 ± 3.12 years were cases with CKD in stage 5 on regular HD and the other 40 healthy subjects as controls, with a mean age of 12.2 ± 2.54 years, were included in the study and assessed for LVH and LVMI by 2D echocardiography. HD children had a significantly higher mean LVMI (102.3 ± 19.1 vs. 49.6 ± 4.11 g/m2, P <0.001) than controls. Relative wall thickness was significantly higher in the patients with CKD patients on HD compared with controls (P <0.001) with a mean value of 0.46 indicating concentric LVH in renal patients. Comparing mitral inflow velocities between both the groups revealed that the patient group had a significant decrease in mitral E-wave velocity (0.88 ± 0.2 vs. 1.1 ± 0.1 m/sec, P <0.001) and E/A velocity ratio (1.3 ± 0.3 vs. 1.7 ± 0.3, P <0.001) in comparison with the control group, but there was no statistically significant difference in A-wave velocity. This indicates early diastolic dysfunction in CKD patients. LV mass changes in CKD children were strongly related to hypocalcemia and Vitamin D deficiency. Children with CKD are prone to the development of cardiac diastolic dysfunction and LVH, so early and regular echocardiographic studies of all children with CKD are recommended to detect early cardiac changes and institute interventions.

Role of Hepcidin in Pediatric Chronic Kidney Disease with Anemia

Introduction: Anemia is a frequent complication of chronic kidney disease (CKD) in children and it causes an increase in morbidity, mortality and accelerates the rate of progression of CKD. Inflammation and impaired kidney clearance increase plasma hepcidin, inhibiting duodenal iron absorption and sequestering iron in macrophages. However, the role of hepcidin in increasing the risk of anemia in children with CKD is still uncertain. This study aimed to investigate the association between hepcidin levels and anemia in children with pre-dialysis CKD. Methods: A cross-sectional study was conducted at Dr. Soetomo Academic Hospital from December 2018 to February 2019. Children with pre-dialysis CKD were enrolled in this study. The subject had no history of erythropoietin administration and blood transfusion 3 months before the blood sample were withdrawn. A complete blood count, ferritin serum, transferrin saturation (TSAT) and hepcidin serum were performed. The correlations between Hepcidin and ferritin level, between ferritin level and anemia, and between TSAT and anemia were analyzed using Spearman correlation and the Mann-Whitney test.&#x0D; Results: A total of 47 children, 27 boys and 20 girls, ranged in age from 3 months to 18 years old. There was a significant correlation between hepcidin and ferritin levels (p=0.006) and the value of the Spearman correlation was r=0.392. While the correlation between ferritin level and anemia showed a significant result, p=0.001. However, TSAT did not show any significant correlation with anemia (p=0.230).&#x0D; Conclusion: There was an indirect association between hepcidin level and anemia by increasing ferritin level that induces anemia in pre-dialysis CKD children.

Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study

Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD. Observational cohort study. Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively. Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status. mGFR based on iohexol clearance. Linear regression with generalized estimating equations, stratified by age (<6, 6-12, 12-18, and≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations. Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups. Small number of children< 6 years; lean body mass was estimated. Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Hyperuricemia and Associated Factors in Children with Chronic Kidney Disease: A Cross-Sectional Study.

Background: Hyperuricemia is increasingly recognized as a risk factor for chronic kidney disease (CKD) just in adults. The purpose of this study was to investigate the clinical characteristics of hyperuricemia and its associated factors in Chinese children with CKD at a single center. Methods: A cross-sectional study of 170 CKD children collected from the Department of Nephrology, The Zhejiang University Children’s Hospital was conducted. The clinical data, including anthropometric data, blood pressure measurements, and biochemical parameters, were recorded and analyzed retrospectively. The factors associated with hyperuricemia in CKD children were evaluated by Pearson and Spearman correlation analysis and multiple logistic regression analysis. Results: The mean age was 9.79 ± 4.10 years, and 72 (42.35%) were girls. Higher blood urea nitrogen (BUN), serum creatinine, cystatin C, D-dimer, lower hemoglobin, albumin, and estimated glomerular filtration rate (eGFR) were significantly associated with higher serum uric acid (SUA). In multiple logistic regression analysis, anemia and higher BUN were both positively associated factors, whereas eGFR ≥ 90 mL/min/1.73 m2 was a negatively associated factor for subjects with SUA ≥ 390 µmol/L (6.5 mg/dL). Conclusions: SUA was significantly associated with kidney risk factors in CKD children. Monitoring and controlling SUA, Hb, BUN, and Scr levels in CKD children may help to prevent the progression of CKD.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Echocardiographic Findings in Children of Chronic Kidney Disease

Background: Patients with Chronic Kidney Disease (CKD) are at significantly increased risk for both morbidity and mortality from cardiovascular disease (CVD). Determining the spectrum of echocardiographic abnormalities in these patients can help in reduction of morbidity and mortality from CKD.&#x0D; Materials and Methods: This cross-sectional study was held on department of Pediatric Nephrology, Dhaka Shishu Hospital, Dhaka, during July 2018 to December 2018 (Six months). A total of thirty-six children with chronic kidney disease with creatinine clearance &lt;60ml/min/1.73 m2 and age ranged from 2 to 16 years on supportive treatment and hemodialysis were included. In control group equal number of age and sex matched healthy children without any preexisting renal or cardiovascular diseases were included. Both study group and control group were assessed for cardiovascular findings by echocardiography.&#x0D; Results: The mean age was 9.09±3.01 years (mean±SD) in case group and 7.85±3.69 years (mean±SD) in control group. Regarding sex, 22 patients (61.1%) in the case group were male and 14 (38.9%) were female. In this study, in CKD patients significant (p&lt;0.001) difference was observed in following cardiac parameters, left ventricular end diastolic diameter (LVEDD) (38.34 vs 34.52), left ventricular end systolic diameter LVESD (26.64 vs 20.75), interventricular septal thickness (IVS) (9.34 vs 7.27), left ventricular posterior wall thickness (LVPWT) (8.36 vs 7.46), ejection fraction (EF) (56.68% vs 70.36%), fractional shortening (FS) (31.88% vs 38.30%) and peak early diastole velocity/peak atrial filling velocity (E/A ratio) (1.15 vs 1.45) when compared to control group. Most common cardiac abnormality in children with chronic kidney disease were left ventricular systolic dysfunction (44.4%), mild pulmonary hypertension (30.6%) and left atrial dilatation (27. 8%).&#x0D; Conclusion: Left ventricular systolic dysfunction was the commonest echocardiographic findings in CKD children. There was also significant difference in diastolic function between study and control group.

Association of GSTM1 Deletion With Progression of CKD in Children: Findings From the Chronic Kidney Disease in Children (CKiD) Study

Loss of function of the product of the GSTM1 gene has been implicated in rapid progression of adult chronic kidney disease (CKD). Its role in pediatric CKD has not been previously described. Secondary analysis of a prospective observational cohort examining the association between deletions in GSTM1 and progression of CKD. We used data and samples from the prospective Chronic Kidney Disease in Children (CKiD) cohort aged 1-16 years at enrollment with CKD. We defined the exposure as fewer than 2 GSTM1 alleles on real-time polymerase chain reaction amplification. The primary outcome was a composite of 50% decrease in estimated glomerular filtration rate (eGFR) or start of kidney replacement therapy. Secondary outcomes included remission of proteinuria in children with glomerular disease and cardiovascular complications. The primary analysis was by Cox proportional hazards model. Analysis was adjusted for age, sex, race, ethnicity, body mass index category, diagnosis category, and eGFR. The analysis included 674 children. Their mean age at most recent visit was 11.9 years; 61% were male, and 20% were Black. There were 241 occurrences of the primary outcome at the time of analysis. After adjustment for baseline characteristics, the risk of progression of CKD for exposed children was 1.94 (95% CI, 1.27-2.97). The effect size was similar with either 1 or 2 deletions (autosomal dominant inheritance). The relationships between number of functional GSTM1 alleles and prespecified secondary outcomes were not statistically significant after adjustment. Missing data, especially for secondary outcomes, and relatively small sample size compared to genetic studies in adults. GSTM1 deletion is associated with more rapid progression of pediatric CKD after adjustment in this large prospective cohort. No statistically significant associations were seen with secondary outcomes. If replicated, these findings may inform development of interventions for CKD in children.

The Relationship Between Chronic Kidney Disease and Weight Loss in Children

Background: Weight loss often occurs in children with Chronic Kidney Disease (CKD). Provision of proper nutrition is necessary for growth and development and weight gain of patients with chronic kidney disease in children. Objectve: To aimed the relationship between chronic kidney disease and weight loss in children Methods: An observational analytic study with a retrospective cohort design in outpatients and inpatients with chronic kidney disease aged 5 to 18 years at the H. Adam Malik Medan General Hospital and USU Hospital in December 2019 to March 2021. Results: This study was followed by 29 CKD children. Subjects who experienced weight loss were 16 (55.2%) children and 13 (44.8%) children who did not experience weight change after 3 months follow-up. There was a significant difference between the mean weight at baseline and after the 3-month follow-up period (p<0.001). There was no difference in the stage of CKD between initial examination and after 3-month follow-up (p = 0.877). There was no significance between the stage of chronic kidney disease and weight loss (p = 0.096). there was no significant relationship between chronic kidney disease stage and weight loss (p = 0.343), with the same nutritional status after 3 months follow-up. Other results showed that there was no difference in urea and creatinine levels between the start of the study and after 3 months of follow-up (p>0.05). The mean delta weight loss was 0.87 kg with the largest decrease being around 3 kg and 13 subjects did not show any weight loss. Conclusion: There was a significant association between initial weight loss and after 3 months of follow-up but not for height. There is no relationship between the initial examination stage of CKD and weight loss. There was no significant relationship between the initial examination of body weight, nutritional status, urea and creatinine levels and after 3 months of follow-up.

Multidisciplinary approach to screening and management of children with Fabry disease: practice at a Tertiary Children\u2019s Hospital in China

BackgroundFabry disease (FD) remains poorly recognized, especially in children in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children’s hospital in China.MethodsA multidisciplinary team (MDT) of pediatric FD experts was launched at Children’s Hospital of Fudan University. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team.ResultsBefore the establishment of the MDT, no case was diagnosed with FD in the hospital. However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Four of them started to receive enzyme replacement therapy.ConclusionScreening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach. We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.

Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT

PurposeCongenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. MethodsWe conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. ResultsIn 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype–phenotype correlation. ConclusionWe conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.