Review

Authors: Maria Herthelius

This review provides updated knowledge on the long-term outcomes among children with antenatally diagnosed urinary tract dilatation (UTD), previously often referred to as antenatal hydronephrosis. Different definitions of UTD exist, which makes comparison between studies and generalized conclusions difficult. Roughly, one-third of antenatally diagnosed UTD, defined as a renal pelvis anterior posterior diameter (APD) of ≥ 4 mm in the second trimester and/or ≥ 7 mm in the third trimester, will resolve before birth, another third will resolve within the first years of life, and in the remaining cases, UTD will persist or a congenital abnormality (CAKUT) will be diagnosed postnatally. The risk of a postnatal CAKUT diagnosis increases with the degree of prenatal and postnatal dilatation, except for vesicoureteral reflux (VUR), which cannot be predicted from the degree of UTD. Urinary tract infections (UTIs) occur in 7-14% of children with UTD during the first years of life. The risk of UTI is higher in children with traditional risk factors for UTI, such as dilated VUR, hydroureteronephrosis, female gender, and intact foreskin. Continuous antibiotic prophylaxis may be considered in selected patients during the first years of life. In long-term follow-ups, permanent kidney damage is diagnosed in approximately 40% of children with moderate or severe UTD, but hypertension, proteinuria, and/or reduced eGFR are uncommon (0-5%). In children with mild UTD, the long-term outcome is excellent, and these children should not be subjected to unnecessary examinations and/or follow-up.

Topics: Dilatation; Dilatation, Pathologic; Child; Female; Urinary Tract Infections; Pregnancy; Humans; Urinary Tract; Urogenital Abnormalities; Hydronephrosis; Vesico-Ureteral Reflux; Kidney Pelvis

PubMed: 36920569
DOI: 10.1007/s00467-023-05907-z

Authors: Hideshi Miyakita, Yutaro Hayashi, Takahiko Mitsui...

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

Authors: Víctor M García Nieto, Margarita Monge Zamorano, Luis Antón Hernández...

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

Authors: Arthur M Lee, Jian Hu, Yunwen Xu...

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

Randomized Controlled Trial

Authors: Neus Rius-Gordillo, Natàlia Ferré, Juan David González...

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

Review

Authors: Tej K Mattoo

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

Authors: R H Whitaker

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

Review

Authors: Lisa A Schimmenti

Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, frequently called optic nerve coloboma or morning glory anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst and pigmentary macular dysplasia. The kidney abnormalities consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than the normal number of glomeruli and these glomeruli are enlarged, a finding called oligomeganephronia. Consequences of the ocular malformations include decreased visual acuity and retinal detachment. Consequences of the renal hypodysplasia include hypertension, proteinuria and renal insufficiency that frequently progresses to end-stage kidney disease. High frequency hearing loss has been reported. Autosomal dominant mutations in PAX2 can be identified in nearly half of all patients with clinical findings suggestive of RCS, however, the majority of published cases have mutations in PAX2, thus biasing the known information about the phenotype.

Topics: Animals; Coloboma; Disease Models, Animal; Genetic Counseling; Genetic Testing; Humans; Mutation; PAX2 Transcription Factor; Renal Insufficiency; Vesico-Ureteral Reflux

PubMed: 21654726
DOI: 10.1038/ejhg.2011.102

Authors: R R Bailey, K L Lynn, R A Robson...

Forty-two of 371 patients (11.3%) entering a dialysis-transplant program had end-stage reflux nephropathy. Thirteen of these 371 patients were under 16 years of age, with 6 of them having reflux nephropathy. Most patients presented with severely impaired renal function, hypertension, and proteinuria. Documented urinary tract infections occurred in only 4 of the 18 male and 14 of the 24 female patients. Thirty-five patients had hypertension, which in 22 had not been detected before presentation. Five presented with accelerated hypertension. Eight of the 24 women presented during a pregnancy. Twenty-nine patients are still alive, 20 with a functioning renal transplant. Reflux nephropathy is an important cause of end-stage renal failure, particularly in younger people. All patients presenting with renal insufficiency and proteinuria, with or without urinary tract infections or hypertension, should have reflux nephropathy excluded.

Topics: Adolescent; Adult; Australia; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; New Zealand; Registries; Renal Dialysis; Vesico-Ureteral Reflux

PubMed: 8184143
DOI: 10.3109/08860229409044845

Authors: Hillary L Copp

Topics: Female; Humans; Male; Pyelonephritis; Urinary Bladder; Urinary Tract Infections; Vesico-Ureteral Reflux

PubMed: 25549568
DOI: 10.1016/j.juro.2014.10.125