End-stage Renal Disease In Children Research Articles

Особенности CAKUT-синдрома (врожденных аномалий развития мочевыделительной системы): клинический случай

A clinical observation of a child with a severe combined defect of the reproductive system and reproductive system (cAKuT syndrome) is presented. cAKuT syndrome accounts for more than 20% of birth defects. congenital anomalies of the urinary system account for 40–50% of cases of end-stage renal disease in children and 7% in adults worldwide. early diagnosis and treatment of cAKuT syndrome in children is one of the most important tasks of pediatric nephrology at present. It is necessary to monitor the course of the disease and assess the rate of development of unfavorable outcomes of chronic kidney disease. clinical observation of cAKuT syndrome is to optimize the therapeutic tactics of the underlying disease and reduce the disability of the child population.

Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta-analysis.

Focal segmental glomerulosclerosis is the most prevalent acquired kidney disease leading to end-stage renal disease in children and has a propensity for recurring in the transplanted kidney. The recurrence of FSGS after kidney transplantation in children varies greatly. In addition, the risk factors and outcomes of recurrence of FSGS remain controversial. This study evaluated the recurrence rate, risk factors, and prognosis of FSGS after kidney transplantation in order to provide advice and assistance in clinical decision-making for pediatric kidney transplantation. PubMed, Embase, Web of Science, CNKI, and other databases were searched from the establishment of the repository to March 2022. We extracted data on incidence, risk factors, and outcomes. The results showed that the recurrence rate of primary FSGS in children after renal transplantation was 48% (95% CI 36%-59%) and the recurrence rate of FSGS (all forms) was 35% (95% CI 17%-52%). The graft loss rate of primary FSGS in children after kidney transplantation was 29% (95% CI 17%-42%) and the graft loss rate of FSGS (all forms) was 29% (95% CI 4%-62%). 57% (95% CI 42%-73%) of pediatric patients with recurrent primary FSGS showed complete remission. Risk factor analyses showed that age of onset (SMD .69, 95% CI .20-1.19, p=.006) was related to the recurrence of primary FSGS, whereas the living related donor was not a risk factor for recurrent primary FSGS in pediatrics after kidney transplantation (OR 1.22, 95% CI .48-3.10, p=.674). The recurrence rate and graft loss rate of FSGS in children after kidney transplantation were relatively high. Age at onset was associated with a risk for recurrent primary FSGS, whereas the living related donor was not a risk factor for recurrent FSGS in pediatric kidney recipients.

Analysis of the operational status of the three-level referral system for urologic ultrasound screening and risk factors for renal pelvic dilatation in high-risk children.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are the primary cause of end-stage renal disease in children, early diagnosis and treatment can significantly improve the kidney function. Among CAKUT, renal pelvis dilatation (RPD) due to various causes has the highest detection rate, which can be detected early by postnatal ultrasound screening. Since 2010, the Children's Hospital of Fudan University (CHFU), together with the Minhang District Maternal and Child Health Hospital (MCH) and Community Health Centres (CHCs) of Minhang District has created a three-level referral system for urological ultrasound screening. This study aims to describe the operation of a three-level referral system for ultrasound screening of CAKUT and to select risk factors of RPD in high-risk children. The operation of the three-level referral system was assessed by analyzing the screening volume, screening rate, referral rate, and follow-up rate; risk factors of RPD in high-risk children were selected by chi-square test and multivariate logistic regression. A total of 16,468 high-risk children were screened in ten years, and the screening volume was maintained at about 1,500 cases per year; the screening rate showed a linear increase, from 36.8% in 2010 to 98.2% in 2019; the referral rate from the CHCs to the MCH was 89.9% significantly higher after 2015 than that of 84.7% from 2010 to 2015; the follow-up rate after 2015 was 71.0% significantly higher than that of 46.3% from 2010 to 2015. Multivariate logistic regression analysis showed that the risk of RPD was 1.966 times higher in males than in females, and the risk of moderate to severe RPD was 2.570 times higher in males than in females; the risk of RPD in preterm children was 1.228 times higher than that of full-term children; and the risk of RPD was 1.218 times higher in twins than in singles. The screening volume of the three-level referral system has remained stable over a decade, with significantly higher screening, referral, and follow-up rates. Males, preterm, and twins are risk factors of RPD in high-risk children; males are also risk factors for moderate to severe RPD in high-risk children.

Effect of hypertension on the long-term prognosis of children with primary focal segmental glomerulosclerosis-a retrospective cohort study.

Primary focal segmental glomerulosclerosis is a common clinicopathologic syndrome. More than 50% of the patients may have hypertension, which can further deteriorate the renal function of patients. However, the impact of hypertension on the development of end-stage renal disease in children with primary focal segmental glomerulosclerosis is still unclear. The end-stage renal disease greatly increases medical costs and mortality. Studying the related factors of end-stage renal disease is helpful to prevent and treat end-stage renal disease. This study aimed to explore the impact of hypertension on the long-term prognosis of children with primary focal segmental glomerulosclerosis. The data of 118 children with primary focal segmental glomerulosclerosis admitted to the Nursing Department of West China Second Hospital from January 2012 to January 2017 were retrospectively collected. The children were divided into a hypertension group (n=48) and a control group (n=70) according to whether they had hypertension. The children were followed up (by clinic visit and telephone interviews) for 5 years to compare the differences in the incidence of end-stage renal disease between the two groups. Compared with the control group, the proportion of patients with severe renal tubulointerstitial damage in the hypertension group was significantly higher (18.75% vs. 5.71%, P=0.026). Moreover, the incidence of end-stage renal disease was markedly higher (33.33% vs. 5.71%, P<0.001). Both systolic and diastolic blood pressure had a certain value in predicting the development of end-stage renal disease in children with primary focal segmental glomerulosclerosis (P<0.001 and P=0.025, respectively), and the predictive value of systolic blood pressure was relatively higher. Multivariate logistic regression analysis showed that hypertension was risk factors for end-stage renal disease in children with primary focal segmental glomerulosclerosis (P=0.009, relative risk: 17.022, 95% CI: 2.045-141.723). Hypertension was a risk factor for poor long-term prognosis in children with primary focal segmental glomerulosclerosis. For primary focal segmental glomerulosclerosis children with hypertension, blood pressure should be actively controlled to prevent the development of end-stage renal disease. Moreover, due to the high incidence of end-stage renal disease, we should monitor the end-stage renal disease during follow-up.

Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.

Posterior urethral valves (PUV) are the commonest cause of end-stage renal disease in children, but the genetic architecture of this rare disorder remains unknown. We performed a sequencing-based genome-wide association study (seqGWAS) in 132 unrelated male PUV cases and 23,727 controls of diverse ancestry, identifying statistically significant associations with common variants at 12q24.21 (p=7.8 × 10-12; OR 0.4) and rare variants at 6p21.1 (p=2.0 × 10-8; OR 7.2), that were replicated in an independent European cohort of 395 cases and 4151 controls. Fine mapping and functional genomic data mapped these loci to the transcription factor TBX5 and planar cell polarity gene PTK7, respectively, the encoded proteins of which were detected in the developing urinary tract of human embryos. We also observed enrichment of rare structural variation intersecting with candidate cis-regulatory elements, particularly inversions predicted to affect chromatin looping (p=3.1 × 10-5). These findings represent the first robust genetic associations of PUV, providing novel insights into the underlying biology of this poorly understood disorder and demonstrate how a diverse ancestry seqGWAS can be used for disease locus discovery in a rare disease.

Agonists of prostaglandin E2 receptors as potential first in class treatment for nephronophthisis and related ciliopathies

Nephronophthisis (NPH) is an autosomal recessive tubulointerstitial nephropathy belonging to the ciliopathy disorders and known as the most common cause of hereditary end-stage renal disease in children. Yet, no curative treatment is available. The major gene, NPHP1, encodes a protein playing key functions at the primary cilium and cellular junctions. Using a medium-throughput drug-screen in NPHP1 knockdown cells, we identified 51 Food and Drug Administration-approved compounds by their ability to alleviate the cellular phenotypes associated with the loss of NPHP1; 11 compounds were further selected for their physicochemical properties. Among those compounds, prostaglandin E1 (PGE1) rescued ciliogenesis defects in immortalized patient NPHP1 urine-derived renal tubular cells, and improved ciliary and kidney phenotypes in our NPH zebrafish and Nphp1 knockout mouse models. Furthermore, Taprenepag, a nonprostanoid prostaglandin E2 receptor agonist, alleviated the severe retinopathy observed in Nphp1−/− mice. Finally, comparative transcriptomics allowed identification of key signaling pathways downstream PGE1, including cell cycle progression, extracellular matrix, adhesion, or actin cytoskeleton organization. In conclusion, using in vitro and in vivo models, we showed that prostaglandin E2 receptor agonists can ameliorate several of the pleotropic phenotypes caused by the absence of NPHP1; this opens their potential as a first therapeutic option for juvenile NPH-associated ciliopathies.

End Stage Renal Disease in Children in Bahrain: Etiology and Outcome

Background: End-stage renal is an overwhelming illness associated with high morbidity and mortality worldwide. Identifying the risk factors in children and planning preventive strategies is of great significance. The aim of the present study is to assess the etiology and outcome of end-stage renal disease in children in Bahrain. Methods: As a part of the retrospective analysis, all children with end-stage renal disease were below 16 years and were on renal replacement therapies between 2008 and 2018. Data were collected from patients' chart and electronic medical records. Results: Out of the total 50 children (with end-stage renal disease) who enrolled for the study, the subjects were 37 (74%) and 13 (26%) were boys and girls, respectively. Among the subjects, 19 patients (38%) were diagnosed with congenital anomalies of the kidneys and urinary tract as the main cause of end-stage renal disease. Posterior uretheral valve was the main abnormality seen in 12 (24%) patients. Inherited renal diseases were the second leading cause of end-stage renal disease in children 15 (30%) patients. Glomerulopathies accounted for 12% of the total patients, focal segmental glomerulosclerosis was the most common glomerulopathy seen in 5 (10%) patients. 28 patients (56%) received hemodialysis; 18 patients (36%) received peritoneal dialysis. 24 (48%) children had renal transplantation, 4 children (8%) underwent preemptive kidney transplantation, while 3 (6%) children died. Conclusions: Congenital anomalies of the kidneys and urinary tract is the leading cause of end-stage renal disease in children followed by hereditary diseases. Thus, planning preventive strategies and counselling support for the children and their families are of great importance. Keywords: Bahrain, Chronic kidney disease, kidney transplantation, peritoneal dialysis, renal dialysis, urogenital abnormalities

Early Evidence on Genetic Polymorphisms in Conferring A "Two-Hit" Propensity to Renal Injury in Asian Indian Children.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of end-stage renal disease in children. While certain nephrogenic genes have been incriminated in these malformations, data to identify the frequency of gene polymorphisms in Asian Indian children with CAKUT are scarce. This study was done to identify the effect of polymorphisms in paired-box gene 2 (PAX2), bone morphogenetic protein (BMP)-4, angiotensin-converting enzyme (ACE), and angiotensin II receptor Type 2 (AGTR2) nephrogenic genes on the development of CAKUT. In this prospective cohort study, 158 children <12 years old (86 cases with CAKUT and 72 age-matched controls) were analyzed. DNA from both sets was extracted from peripheral blood using the Keygen DNA extraction kit, and single-nucleotide gene polymorphisms (SNPs) in PAX2, BMP-4, ACE, and AGTR2 nephrogenic genes were detected by polymerase chain reaction (PCR) using previously published primers and PCR conditions. The presence of A allele SNP for AGTR2 gene at rs3736556 was found to be significantly correlated with the development of ureteropelvic junction obstruction and vesicoureteral reflux (VUR) with the TT allelic genotype having a lower incidence of pelviureteric junction obstruction (odds ratio [OR] 0.18 [95% confidence interval [CI], 0.06-0.55], P = 0.01) and VUR (OR 0.31 [95% CI, 0.11-0.91], P = 0.03). Furthermore, on substratification of the patients with the presence of the A allele of AGTR2, 24 out of 27 patients with scarring were found to harbor the D allele of the ACE gene, thus predisposing them to further renal damage. This study points to early evidence in the implication of nephrogenic genes in development as well as predisposition to renal injury in Asian Indian patients with CAKUT.

Immunoglobulin A nephropathy in paediatrics: An up‐to‐date

Immunoglobulin A nephropathy is the main cause of glomerulonephritis globally and an important aetiology of end-stage renal disease in children. It has been considered an autoimmune disease that can lead to the production of autoantibodies against abnormal IgA1 and formation of immune complexes. These autoantibodies and immune complexes deposit in the glomeruli, resulting in renal injury. At the beginning of IgA nephropathy course, most patients are asymptomatic and the first clinical manifestations in children are macroscopic hematuria and proteinuria. The diagnosis is defined by the detection of IgA mesangial deposits in kidney biopsy using immunofluorescence techniques. The Oxford MEST-C score is the most used classification to associate histological findings and clinical outcomes, being validated for application in children. Recommended treatment options are antihypertensive and antiproteinuric therapy, corticosteroids, immunosuppressive agents, and other non-pharmacological approaches. There is no ideal prognosis indicator but new perspectives are in science's scope to find possible biomarkers of the disease through OMICS's research. This review aims to summarize and to up-to-date the scientific literature on paediatric IgA nephropathy, focusing on pathophysiology, clinical findings, histopathology, current treatment, prognosis, and future perspectives.

Association of nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study

Abstract Background Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown. Purpose To examine whether NPHP4 gene variability is related to CRS and cardiovascular events in general population. Methods and results This prospective cohort study included 2,946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor. Conclusion Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events. Funding Acknowledgement Type of funding sources: None.

Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study.

Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single-nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown. This prospective cohort study included 2946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor. Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events.

Treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis

Objectives: To analyze the clinical characteristics, treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis (LN), and to explore the risk factors for progression to end-stage renal disease (ESRD). Methods: In this retrospective study, the clinical data including general conditions, clinical manifestations, laboratory examinations, treatment, following up (till December 31st, 2020) and prognosis of 343 children with LN who were treated and followed up in the First Affiliated Hospital of Sun Yat-sen University from January 1, 2003 to December 31, 2019 were analyzed. Complete remission rates were compared between different pathological types according to renal biopsies and flare rates were compared between complete remission group and partial remission group according to the treatment effectiveness after 6 months of induction treatment. To investigate the risk factors of ESRD, the prognosis of flare and non-flare cases, and of cases with normal and elevated serum creatinine levels at baseline, was compared. Chi-squared tests were used for comparison between groups, and cumulative survival rate and renal survival rates were calculated by Kaplan-Meier survival analysis. Risk factors for ESRD were analyzed by COX regression model. Results: Among the 343 children, 68 were males (19.8%) and 275 were females (80.2%) with a median age of 13.0 (11.0, 16.0) years. Regarding the renal symptoms, 305 (88.9%) children had proteinuria and 245 (71.4%) had hematuria; while for extra-renal manifestations, 273 (79.6%) had anemia, 183 (53.4%) had rashes and 165 (48.1%) had fever. A total of 212 (61.8%) children had severely active SLE at initial presentation. After 6 months of induction treatment, the complete remission rate was 63.8% (219/343) and the partial remission rate was 27.1% (93/343). The complete remission rate was significantly higher in type Ⅰ and type Ⅱ LN compared to type Ⅳ LN (10/12 vs. 82/135 (60.7%), χ²=3.936, P=0.047). One hundred and ten children who achieved remission, including complete remission and partial remission, experienced renal flare with a flare rate of 35.3% and a mean time to flare was (43.2±28.4) months. There was no significant difference in flare rates between complete and partial remission group (36.1% (79/219) vs. 33.3% (31/93), χ²=3.394, P=0.065). The follow-up time of all the children was 60.4 (32.3, 100.9) months. During the follow-up period, 15 children died and the cumulative survival rates at 3, 5 and 10 years were 97.2%, 96.4% and 93.3%, respectively; 14 children progressed to ESRD and the cumulative renal survival rates at 3, 5, and 10 years were 99.2%, 97.1%, and 93.4%, respectively. COX multivariate analysis demonstrated that elevated serum creatinine at baseline, nephritic flare and nephrotic flare were independent risk factors for progression of ESRD (hazard ratio (HR)=3.575, 21.550 and 8.590, 95%CI 1.127-11.341, 2.394-194.027 and 1.042-70.823, P=0.031, 0.006, and 0.046, respectively). Conclusions: Children with LN are characterized by high SLE disease activity and multi-system involvement at onset. After 6 months of induction treatment, most of LN children could achieve clinical remission but some would experience renal flare. Nephritic flare, nephrotic flare and elevated serum creatinine at onset are independent risk factors for the progression of ESRD in children with LN.

Long-term outcomes of living-donor kidney transplant children weighing less than 15 kg: Comparison of the surgical approach

Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease in children. 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 <15kg. We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing <15kg, 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. 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. 13.0kg, 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%). We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing <15kg 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. The transplant approach did not influence the long-term outcomes in children weighing <15kg, but EPA had fewer surgical complications and was technically safe.

Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis.

Nephronophthisis (NPH) is an autosomal recessive ciliopathy and a major cause of end-stage renal disease in children. The main forms, juvenile and adult NPH, are characterized by tubulointerstitial fibrosis whereas the infantile form is more severe and characterized by cysts. NPH is caused by mutations in over 20 different genes, most of which encode components of the primary cilium, an organelle in which important cellular signaling pathways converge. Ciliary signal transduction plays a critical role in kidney development and tissue homeostasis, and disruption of ciliary signaling has been associated with cyst formation, epithelial cell dedifferentiation and kidney function decline. Drugs have been identified that target specific signaling pathways (for example cAMP/PKA, Hedgehog, and mTOR pathways) and rescue NPH phenotypes in in vitro and/or in vivo models. Despite identification of numerous candidate drugs in rodent models, there has been a lack of clinical trials and there is currently no therapy that halts disease progression in NPH patients. This review covers the most important findings of therapeutic approaches in NPH model systems to date, including hypothesis-driven therapies and untargeted drug screens, approached from the pathophysiology of NPH. Importantly, most animal models used in these studies represent the cystic infantile form of NPH, which is less prevalent than the juvenile form. It appears therefore important to develop new models relevant for juvenile/adult NPH. Alternative non-orthologous animal models and developments in patient-based in vitro model systems are discussed, as well as future directions in personalized therapy for NPH.

Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used the piggyBac (PB) transposon-based mutagenesis to construct a mouse with lncRNA 4933425B07Rik (Rik) PB insertion (RikPB/PB) and detected overexpression of Rik and a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in the RikPB/PB embryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated in RikPB/PB embryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression of Rik may cause a reduction in the UB branches by reducing the expression levels of the UB branching-related molecule Bmp4, thus leading to the development of CAKUT.

Anephric Neonate and Evolution of our Study on Intestinal Dialysis.

Purpose:Intestinal dialysis for end-stage renal disease (ESRD) is a proposed renal replacement therapy, and studies are going on worldwide to make it practicable. We are also doing the same study in our institution and would like to share our experience in managing an anephric neonate with intestinal dialysis in the perspective of our ongoing study of intestinal dialysis since 2010.Patients and Methods:We did double-ended jejunostomy in an isolated loop of the jejunum keeping the main tract intact with jejunojejunal anastomosis in this anephric neonate. Following that, we started irrigation with peritoneal dialysis fluid from the 3rd postoperative day (POD) in that jejunal loop through jejunostomy.Results:This patient had no uremic features since re-admission and showed better laboratory and clinical outcomes with combined jejunal loop and colonic dialysis for 7 days. However, the patient died on the 9th POD following severe hypoglycemia.Conclusions:From this study, it seems intestinal dialysis, with necessary modifications done in our subsequent patients, which might be recommended for ESRD in children as well as in adults.

Challenges of long-term vascular access in pediatric hemodialysis: Recommendations for practitioners.

Kidney transplantation is the preferred treatment of end-stage renal disease in children. However, time to transplant varies, making a well-functioning long-term vascular access essential for performing hemodialysis efficiently and without disruption until a kidney becomes available. However, establishing long-term vascular access in pediatric patients can present distinct challenges due to this population's unique characteristics, such as smaller body size and lower-diameter blood vessels. There are three main pediatric long-term vascular access options, which include central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG). CVC are currently the most widely used modality, although various studies and guidelines recommend AVF or AVG as the preferred option. Although AVF should be used whenever possible, it is crucial that clinicians consider factors such as patient size, physical exam findings, comorbidities, predicted duration of treatment to decide on the most optimal long-term vascular access modality. This article reviews the three long-term vascular access methods in children and the benefits and complications of each.

Possible PKHD1 Hot-spot Mutations Related to Early Kidney Function Failure or Hepatofibrosis in Chinese Children with ARPKD: A Retrospective Single Center Cohort Study and Literature Review.

PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease (ARPKD). ARPKD is a rare disorder and one of the most severe conditions leading to end-stage renal disease in childhood. With the biallelic deletion mutation, patients have difficulty in surviving the perinatal period, resulting in perinatal or neonatal death. This study retrospectively analyzed patient characteristics, imaging characteristics, laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018. Of the 7 children, there were 3 males and 4 females. Eight missense mutations, two frameshift mutations, two deletion mutations, and two intronic slicing mutations were identified. Six of the mutations have not previously been identified. In the literature search, we identified a total of 29 Chinese children with PKHD1 mutations. The missense mutation c.2507T>C in exon 24 was found in one patient in our study, and five patients with liver fibrosis but normal renal function were reported in the literature. The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature. Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37. It was concluded that: (1) Kidney length more than 2-3 SDs above the mean and early-onset hypertension might be associated with PKHD1-associated ARPKD; (2) The more enlarged the kidney size is, the lower the renal function is likely to be; (3) c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations; (4) c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1.

Fetal bladder outflow obstruction: Interventions, outcomes and management uncertainties

Fetal lower urinary tract obstruction (LUTO) is classically based on prenatal ultrasound identification of a dilated/ thick-walled bladder, bilateral hydronephrosis, dilated ureters and a dilated posterior urethra (also known as the “keyhole sign”) in a male fetus. Although the most common underlying diagnosis is posterior urethral valves, the prenatal appearance may be similar with urethral atresia or stenosis, the Prune-Belly Syndrome, or even a cloacal anomaly in a female. These conditions form part of the Congenital Anomalies of Kidney and Urinary Tract (CAKUT) spectrum, which is the commonest cause of end-stage renal disease in children. Although it is difficult to predict postnatal renal function from the prenatal appearance, studies have recently identified predictive features (based on ultrasound findings and fetal biochemistry), and established staging systems to assist with counselling, and, where indicated, patient selection for in-utero intervention. Current in-utero therapy includes amnio-infusion, vesico-amniotic shunting, and fetal cystoscopy with valve ablation or urethral stenting. Postnatal survival and renal functional outcomes, complications and management uncertainties are described, highlighting areas of future development.

Re: Prenatal Renal Parenchymal Area as a Predictor of Early End-Stage Renal Disease in Children with Vesicoamniotic Shunting for Lower Urinary Tract Obstruction.

Re: Prenatal Renal Parenchymal Area as a Predictor of Early End-Stage Renal Disease in Children with Vesicoamniotic Shunting for Lower Urinary Tract Obstruction.