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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 [greater than or equal to] 4 mm in the second trimester and/or [greater than or equal to] 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., Author(s): Maria Herthelius [sup.1] [sup.2] Author Affiliations: (1) grid.24381.3c, 0000 0000 9241 5705, Astrid Lindgren Children's Hospital, K88, Karolinska University Hospital, , 141 86, Stockholm, Sweden (2) grid.4714.6, 0000 0004 [...]

Background Antenatally diagnosed urinary tract dilatation (UTD) still burdens healthcare providers and parents. This study was conducted to establish long-term outcome in an unselected group of children with antenatally detected UTD. Methods Seventy-one out of 103 children born in 2003-2005 and diagnosed with antenatal UTD agreed to participate in a 12-15-year follow-up including blood and urine samples, a kidney ultrasound exam, and kidney scintigraphy. The records were searched for previous urinary tract infections. Results Among children with an anteroposterior diameter (APD) [less than or equal to] 7 mm and no calyceal, kidney, ureteral, or bladder pathology in the early postnatal period, no one tested had reduced estimated glomerular filtration rate (eGFR), albuminuria, or UTD at the follow-up at a mean age of 13.6 years. One child had kidney damage not affecting kidney function. Among children with postnatal APD > 7 mm and/or kidney, calyceal, ureteral, or bladder pathology, 15% had persistent UTD and 32-39% (depending on the method used) had kidney damage. Major postnatal urinary tract ultrasound abnormalities and a congenital anomalies of the kidney and urinary tract (CAKUT) diagnosis were factors associated with an increased risk for permanent kidney damage (odds ratios 8.9, p = 0.016; and 14.0, p = 0.002, respectively). No one had reduced eGFR. One child (1/71, 1%) had a febrile urinary tract infection after the age of 2. Conclusions We conclude that in children with postnatal APD [less than or equal to] 7 mm, no calyceal dilatation, normal bladder, ureters, and kidney parenchyma, the outcome is excellent. There is no need for long-term follow-up in these patients., Author(s): Maria Herthelius [sup.1] [sup.2] , Rimma Axelsson [sup.3] [sup.4] , Karl-Johan Lidefelt [sup.1] [sup.2] Author Affiliations: (1) grid.24381.3c, 0000 0000 9241 5705, Astrid Lindgren Children's Hospital, Karolinska University Hospital, [...]

Background Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. Methods This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m.sup.2) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m.sup.2) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI). Results The prevalence of high FGF23 levels ([greater than or equal to]95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients ([beta] = -0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients ([beta] = 1.8, p = 0.06). In addition, high log FGF23 ([beta] = -0.43, p = 0.01) and low log Klotho ([beta] = 0.44, p = 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e'/a') in CKD-T patients. Conclusions In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation., Author(s): Ylva Tranæus Lindblad [sup.1] [sup.2] [sup.3] , Hannes Olauson [sup.4] , Georgios Vavilis [sup.5] , Ulf Hammar [sup.6] , Maria Herthelius [sup.1] [sup.3] , Jonas Axelsson [sup.7] [sup.8] , [...]

Background Left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac disease in pediatric chronic kidney disease (CKD), but few studies have analyzed longitudinal trends. We conducted a prospective 3-year follow-up study in pediatric CKD and kidney transplant (CKD-T) patients. Methods The patient cohort comprised 30 CKD and 42 CKD-T patients. The results of annual clinical and echocardiographic analyses using tissue Doppler imaging (TDI) and pulse wave Doppler (PWD) were assessed, and associations to predictive risk factors were studied using multivariate modeling. Results The mean age of CKD and CKD-T patients at inclusion was 9.8 ± 4.4 and 11.8 ± 4.3 years, respectively; the glomerular filtration rate was 35.3 ± 18.3 and 60.3 ± 18.8 mL/min/1.73 m.sup.2, respectively. The prevalence of left ventricular diastolic dysfunction (LVDD), as assessed using TDI (lateral z-score e') was 7.1 and 12.5 % in CKD and CKD-T patients, respectively; the corresponding values with PWD E were 3.3 and 2.4 %, respectively. In unadjusted analyses, both TDI and PWD markers of diastolic function worsened over the follow-up period; following adjustments, an elevated systolic ambulatory blood pressure was the most important predictor of cardiac disease. Conclusions Children with CKD show early signs of LVDD, with TDI being more sensitive than PWD in terms of diagnostic potential. An increased ambulatory systolic blood pressure predicted progression in diastolic function, suggesting opportunities for future interventions., Author(s): Ylva Tranæus Lindblad[sup.1] [sup.2] , Georgios Vavilis[sup.3] , Jonas Axelsson[sup.4] [sup.5] , Maria Herthelius[sup.1] [sup.2] , Peter Barany[sup.6] [sup.7] Author Affiliations: (1) Division of Pediatrics, Department of Clinical Sciences, [...]

Background This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin). Methods A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m.sup.2). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates ±30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPA.sub.CYSC and Berg.sub.CYSC, for creatinine equations, Schwartz.sub.CREA and Gao.sub.CREA, the arithmetic mean of CAPA.sub.CYSC and Schwartz.sub.CREA (MEAN.sub.CAPA+Schwartz), Berg.sub.CYSC and Schwartz.sub.CREA (MEAN.sub.BERG+SCHWARTZ) and the composite equation Chehade.sub.CYSC+CREA. Results Overall results of CAPA.sub.CYSC, Berg.sub.CYSC, Schwartz.sub.CREA, Gao.sub.CREA, MEAN.sub.CAPA+Schwartz, MEAN.sub.BERG+SCHWARTZ and Chehade.sub.CYSC+CREA were: median bias -7.6/-4.9/-3.7/-2.3/-4.6/-4.0/-10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m.sup.2 and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEAN.sub.CAPA+Schwartz and MEAN.sub.BERG+SCHWARTZ had a more stable performance across subgroups compared with Schwartz.sub.CREA, Gao.sub.CREA and Chehade.sub.CYSC+CREA. Conclusions Cystatin C was the preferred filtration marker for GFR estimation in children, while the benefit of combining cystatin C and creatinine deserves further investigations., Author(s): Ulla B. Berg[sup.1] , Ulf Nyman[sup.2] , Rune Bäck[sup.3] , Magnus Hansson[sup.3] , Kajsa Åsling Monemi[sup.1] , Maria Herthelius[sup.1] , Jonas Bjork[sup.4] Author Affiliations: (1) Department of Clinical Science, [...]

Background: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. Methods: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI). Results: The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients (β = −0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (β = 1.8, p = 0.06). In addition, high log FGF23 (β = −0.43, p = 0.01) and low log Klotho (β = 0.44, p = 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e′/a′) in CKD-T patients. Conclusions: In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation. [ABSTRACT FROM AUTHOR]

Background/Objective: Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population. Patients/Methods: We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort. Results: In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient. Conclusions: The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance. [ABSTRACT FROM AUTHOR]

This study is aimed at a better understanding of the pathogenesis of urinary tract infection (UTI) by examining factors influencing the bacterial ecology of the genital tract. It comprises two sets of experiments in a monkey model. In the first the persistence and transmission between individuals of a P-fimbriated Escherichia coli (strain DS17) in faeces was examined and in the second we studied the influence of amoxicillin on the occurrence of this strain in the vagina. Orally administered E. coli DS17 was shown to spread to cage mates and to persist in the gut for at least 17-18 months. One of four monkeys so colonized developed three separate UTIs with the DS17 strain. The second set of expriments comprised four other monkeys, who either harboured the E. coli DS17 strain in the faeces and/or in small amounts in the vagina, probably through contamination during defaecation. Amoxicillin induced a persistent vaginal E. coli DS17 colonization in nine of ten experiments. The study thus shows that uropathogenic E. coli may persist for long time in the faeces and that, in this situation, amoxicillin may promote an abnormal, vaginal E. coli colonization similar to that characteristic of females prone to recurrent UTI and often preceding manifest urinary infections. [ABSTRACT FROM AUTHOR]

Background and Objectives: Data on recovery of kidney function in pediatric patients with presumed ESKD are scarce. We examined the occurrence of recovery of kidney function and its determinants in a large cohort of pediatric patients on maintenance dialysis in Europe., Design, Setting, Participants, & Measurements: Data for 6574 patients from 36 European countries commencing dialysis at an age below 15 years, between 1990 and 2014 were extracted from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Recovery of kidney function was defined as discontinuation of dialysis for at least 30 days. Time to recovery was studied using a cumulative incidence competing risk approach and adjusted Cox proportional hazard models., Results: Two years after dialysis initiation, 130 patients (2%) experienced recovery of their kidney function after a median of 5.0 (interquartile range, 2.0-9.6) months on dialysis. Compared with patients with congenital anomalies of the kidney and urinary tract, recovery more often occurred in patients with vasculitis (11% at 2 years; adjusted hazard ratio [HR], 20.4; 95% confidence interval [95% CI], 9.7 to 42.8), ischemic kidney failure (12%; adjusted HR, 11.4; 95% CI, 5.6 to 23.1), and hemolytic uremic syndrome (13%; adjusted HR, 15.6; 95% CI, 8.9 to 27.3). Younger age and initiation on hemodialysis instead of peritoneal dialysis were also associated with recovery. For 42 patients (32%), recovery was transient as they returned to kidney replacement therapy after a median recovery period of 19.7 (interquartile range, 9.0-41.3) months., Conclusions: We demonstrate a recovery rate of 2% within 2 years after dialysis initiation in a large cohort of pediatric patients on maintenance dialysis. There is a clinically important chance of recovery in patients on dialysis with vasculitis, ischemic kidney failure, and hemolytic uremic syndrome, which should be considered when planning kidney transplantation in these children., (Copyright © 2018 by the American Society of Nephrology.)