-
International Journal of Urology :... Jun 2020Urinary tract infection is a bacterial infection that commonly occurs in children. Vesicoureteral reflux is a major underlying precursor condition of urinary tract...
Urinary tract infection is a bacterial infection that commonly occurs in children. Vesicoureteral reflux is a major underlying precursor condition of urinary tract infection, and an important disorder in the field of pediatric urology. Vesicoureteral reflux is sometimes diagnosed postnatally in infants with fetal hydronephrosis diagnosed antenatally. Opinions vary regarding the diagnosis and treatment of vesicoureteral reflux, and diagnostic procedures remain debatable. In terms of medical interventions, options include either follow-up observation in the hope of possible spontaneous resolution of vesicoureteral reflux with growth/development or provision of continuous antibiotic prophylaxis based on patient characteristics (age, presence/absence of febrile urinary tract infection, lower urinary tract dysfunction and constipation). Furthermore, there are various surgical procedures with different indications and rationales. These guidelines, formulated and issued by the Japanese Society of Pediatric Urology to assist medical management of pediatric vesicoureteral reflux, cover the following: epidemiology, clinical practice algorithm for vesicoureteral reflux, syndromes (dysuria with vesicoureteral reflux, and bladder and rectal dysfunction with vesicoureteral reflux), diagnosis, treatment (medical and surgical), secondary vesicoureteral reflux, long-term prognosis and reflux nephropathy. They also provide the definition of bladder and bowel dysfunction, previously unavailable despite their close association with vesicoureteral reflux, and show the usefulness of diagnostic tests, continuous antibiotic prophylaxis and surgical intervention using site markings.
Topics: Antibiotic Prophylaxis; Child; Humans; Hydronephrosis; Infant; Retrospective Studies; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 32239562
DOI: 10.1111/iju.14223 -
Journal of the American Society of... Feb 2022Untargeted plasma metabolomic profiling combined with machine learning (ML) may lead to discovery of metabolic profiles that inform our understanding of pediatric CKD...
BACKGROUND
Untargeted plasma metabolomic profiling combined with machine learning (ML) may lead to discovery of metabolic profiles that inform our understanding of pediatric CKD causes. We sought to identify metabolomic signatures in pediatric CKD based on diagnosis: FSGS, obstructive uropathy (OU), aplasia/dysplasia/hypoplasia (A/D/H), and reflux nephropathy (RN).
METHODS
Untargeted metabolomic quantification (GC-MS/LC-MS, Metabolon) was performed on plasma from 702 Chronic Kidney Disease in Children study participants (: FSGS=63, OU=122, A/D/H=109, and RN=86). Lasso regression was used for feature selection, adjusting for clinical covariates. Four methods were then applied to stratify significance: logistic regression, support vector machine, random forest, and extreme gradient boosting. ML training was performed on 80% total cohort subsets and validated on 20% holdout subsets. Important features were selected based on being significant in at least two of the four modeling approaches. We additionally performed pathway enrichment analysis to identify metabolic subpathways associated with CKD cause.
RESULTS
ML models were evaluated on holdout subsets with receiver-operator and precision-recall area-under-the-curve, F1 score, and Matthews correlation coefficient. ML models outperformed no-skill prediction. Metabolomic profiles were identified based on cause. FSGS was associated with the sphingomyelin-ceramide axis. FSGS was also associated with individual plasmalogen metabolites and the subpathway. OU was associated with gut microbiome-derived histidine metabolites.
CONCLUSION
ML models identified metabolomic signatures based on CKD cause. Using ML techniques in conjunction with traditional biostatistics, we demonstrated that sphingomyelin-ceramide and plasmalogen dysmetabolism are associated with FSGS and that gut microbiome-derived histidine metabolites are associated with OU.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Female; Glomerulosclerosis, Focal Segmental; Humans; Infant; Kidney; Logistic Models; Machine Learning; Male; Metabolic Networks and Pathways; Metabolome; Metabolomics; Prospective Studies; Renal Insufficiency, Chronic; Support Vector Machine
PubMed: 35017168
DOI: 10.1681/ASN.2021040538 -
Pediatric Nephrology (Berlin, Germany) Sep 2022Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children.
METHODS
Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed.
RESULTS
Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (β = 0.648, p = 0.023) and procalcitonin values (β = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p = 0.054), but dexamethasone treatment showed no effect.
CONCLUSION
Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."
Topics: Acute Disease; Child; Cicatrix; Dexamethasone; Glomerulonephritis; Humans; Infant; Kidney; Pyelonephritis; Technetium Tc 99m Dimercaptosuccinic Acid; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 35041042
DOI: 10.1007/s00467-021-05398-w -
Anales de Pediatria Jul 2022Reflux nephropathy is a radiologic condition commonly used to express the existence of renal morphological lesions in patients who have or had vesicoureteral reflux...
OBJECTIVES
Reflux nephropathy is a radiologic condition commonly used to express the existence of renal morphological lesions in patients who have or had vesicoureteral reflux (VUR). This morphological concept is used based on the image data collected, without conducting basic complementary renal function studies. The present study was designed to demonstrate that patients with active VUR present different functional renal alterations from those shown by patients with disappeared VUR.
METHODS
Longitudinal descriptive retrospective analysis including 89 children (46M, 43F) with VUR diagnosis through a standard voiding cystourethrogram (VCUG). The basic renal function tests collected were the maximum urinary osmolality (UOsm) and the urinary albumin/creatinine and NAG/creatinine ratios. The data collected corresponded to two moments, when VUR was diagnosed and when it had already disappeared.
RESULTS
Quantitative differences were verified in the three functional parameters when comparing those corresponding to both moments of the study. In the qualitative analysis, in relation to the intensity of the VUR, differences were observed in UOsm at diagnosis and in the albumin/creatinine ratio once the VUR had cured. At this last moment, a significant increase in the albumin/creatinine ratio was observed in patients with loss of renal parenchyma in relation to those without residual morphological lesions.
CONCLUSIONS
Concentrating ability defect is the most frequent finding in children with active reflux (true reflux nephropathy), whereas the most frequent functional disturbance found, once VUR has cured, is an increase in urinary albumin excretion, related to parenchymal damage. The term dysplastic-scarring nephropathy, could be more appropriate for patients with residual morphological lesions and impaired renal function, once VUR is cured.
Topics: Albumins; Child; Chronic Disease; Cicatrix; Creatinine; Humans; Pyelonephritis; Retrospective Studies; Vesico-Ureteral Reflux
PubMed: 35788336
DOI: 10.1016/j.anpede.2021.08.008 -
Annals of the Royal College of Surgeons... Sep 1977It is essential to distinguish between an obstructed and an unobstructed hydronephrosis as the management of the two types is quite different. Some of the radiographic...
It is essential to distinguish between an obstructed and an unobstructed hydronephrosis as the management of the two types is quite different. Some of the radiographic and isotopic methods of distinguishing these two leave much to be desired and the place of dynamic studies is discussed. The aetiology of pelviureteric junction obstruction remains uncertain, but it is probable that one or more of several factors may be involved and these are discussed. The types of hydroenphrosis are classified as chronic, intermittent, unsuspected, equivocal, and reflux-induced.
Topics: Adolescent; Adult; Chronic Disease; Female; Humans; Hydronephrosis; Male; Ureteral Obstruction; Urography
PubMed: 900795
DOI: No ID Found -
Advances in Chronic Kidney Disease Sep 2011Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract... (Review)
Review
Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract infection (UTI) and renal scarring, also called reflux nephropathy (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital RN). The acquired RN is more common in female children, whereas the congenital RN is more common in male children. This observation in children might help explain the differences in the clinical presentation of RN in adults, with males presenting mostly with hypertension, proteinuria, and progressive renal failure as compared with females who present mostly with recurrent UTI and have a better outcome. Known risk factors for RN include the severity of VUR, recurrent UTI, and bladder-bowel dysfunction; younger age and delay in treatment of UTI are believed to be other risk factors. Management of VUR is controversial and includes antimicrobial prophylaxis, surgical intervention, or surveillance only. No evidence-based guidelines exist for appropriate follow-up of patients with RN.
Topics: Female; Glomerulosclerosis, Focal Segmental; Humans; Hydronephrosis; Hypertension; Incidence; Kidney Failure, Chronic; Male; Prognosis; Proteinuria; Risk Factors; Severity of Illness Index; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 21896376
DOI: 10.1053/j.ackd.2011.07.006 -
Pediatric Nephrology (Berlin, Germany) Mar 2021Urinary tract infections (UTIs) are generally considered a disease of women. However, UTIs affect females throughout the lifespan, and certain male populations... (Review)
Review
Urinary tract infections (UTIs) are generally considered a disease of women. However, UTIs affect females throughout the lifespan, and certain male populations (including infants and elderly men) are also susceptible. Epidemiologically, pyelonephritis is more common in women but carries increased morbidity when it does occur in men. Among children, high-grade vesicoureteral reflux is a primary risk factor for upper-tract UTI in both sexes. However, among young infants with UTI, girls are outnumbered by boys; risk factors include posterior urethral valves and lack of circumcision. Recent advances in mouse models of UTI reveal sex differences in innate responses to UTI, which vary somewhat depending on the system used. Moreover, male mice and androgenized female mice suffer worse outcomes in experimental pyelonephritis; evidence suggests that androgen exposure may suppress innate control of infection in the urinary tract, but additional androgen effects, as well as non-hormonal sex effects, may yet be specified. Among other intriguing directions, recent experiments raise the hypothesis that the postnatal testosterone surge that occurs in male infants may represent an additional factor driving the higher incidence of UTI in males under 6 months of age. Ongoing work in contemporary models will further illuminate sex- and sex-hormone-specific effects on UTI pathogenesis and immune responses.
Topics: Animals; Female; Humans; Male; Pyelonephritis; Risk Factors; Testosterone; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 32040629
DOI: 10.1007/s00467-020-04492-9 -
Pediatric Nephrology (Berlin, Germany) Apr 2022Over the years, hyaluronic acid (HA) has emerged as an important molecule in nephrological and urological studies involving extracellular matrix (ECM) organization,... (Review)
Review
Over the years, hyaluronic acid (HA) has emerged as an important molecule in nephrological and urological studies involving extracellular matrix (ECM) organization, inflammation, tissue regeneration, and viral sensing. During this time, many have noted the perplexing double-edged nature of the molecule, at times promoting pro-fibrotic events and at other times promoting anti-fibrotic events. Different molecular weights of HA can be attributed to these disparities, though most studies have yet to focus on this subtlety. With regard to the kidney, HA is induced in the initial response phase of injury and is subsequently decreased during disease progression of AKI, CKD, and diabetic nephropathy. These and other kidney diseases force patients, particularly pediatric patients, to face dialysis, surgical procedures, and ultimately, transplant. To summarize the current literature for researchers and pediatric nephrologists, this review aims to expound HA and elucidate its paradoxical effects in multiple kidney diseases using studies that emphasize HA molecular weight when available.
Topics: Child; Diabetic Nephropathies; Fibrosis; Humans; Hyaluronic Acid; Kidney; Renal Dialysis
PubMed: 34009465
DOI: 10.1007/s00467-021-05113-9 -
Advances in Chronic Kidney Disease May 2022Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney... (Review)
Review
Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney and urinary tract (CAKUT), affecting approximately 30% of children with CKD. These structural anomalies often require coordinated care with the pediatric urology team to address voiding issues, bladder involvement, and the potential need for surgical intervention. For pediatric nephrologists and urologists, common CAKUT that are encountered include antenatal hydronephrosis, obstructive uropathies (eg, posterior urethral valves), and vesicoureteral reflux. As more pediatric patients with CAKUT, CKD, and ESRD transition to adult care, it is important for receiving adult nephrologists to understand the clinical presentation, natural history, and prognosis for these diagnoses. This review outlines the diagnosis and potential interventions for these conditions, including strategies to address bladder dysfunction that is often seen in children with CAKUT. A discussion of these management decisions (including surgical intervention) for CAKUT, which are quite common to pediatric nephrology and urology practices, may provide unique learning opportunities for adult nephrologists who lack familiarity with these pediatric conditions.
Topics: Adult; Child; Female; Humans; Kidney Failure, Chronic; Pregnancy; Renal Insufficiency, Chronic; Urogenital Abnormalities; Urology; Vesico-Ureteral Reflux
PubMed: 36084977
DOI: 10.1053/j.ackd.2022.02.006 -
The Journal of Urology Apr 2015
Topics: Female; Humans; Male; Pyelonephritis; Urinary Bladder; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 25549568
DOI: 10.1016/j.juro.2014.10.125