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Background Obstructive uropathy (OU) is a leading cause of pediatric kidney injury. Accurate prediction of kidney disease progression may improve clinical outcomes. We aimed to examine discrimination and accuracy of a validated kidney failure risk equation (KFRE), previously developed in adults, in children with OU. Methods We identified 118 children with OU and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m.sup.2 in the Chronic Kidney Disease in Children study, a national, longitudinal, observational cohort. Each patient's 5-year risk of kidney failure was estimated using baseline data and published parameters for the 4- and 8-variable KFREs. Discriminative ability of the KFRE was estimated using the C statistic for time-to-event analysis. Sensitivity and specificity were evaluated across varying risk thresholds. Results Among the 118 children, 100 (85%) were boys, with median baseline age of 10 years (interquartile range, 6-14). Median eGFR was 42 mL/min/1.73m .sup.2 (32-53), with a median follow-up duration of 4.5 years (2.7-7.2); 23 patients (19.5%) developed kidney failure within 5 years. The 4-variable KFRE discriminated kidney failure risk with a C statistic of 0.75 (95% CI, 0.68-0.82). A 4-variable risk threshold of [greater than or equal to] 30% yielded 82.6% sensitivity and 75.0% specificity. Results were similar using the 8-variable KFRE. Conclusions In children with OU, the KFRE discriminated the 5-year risk of kidney failure at C statistic values lower than previously published in adults but comparable with suboptimal values reported in the overall CKiD population. The 8-variable equation did not improve model discrimination or accuracy, suggesting the need for continued research into additional, disease-specific markers., Author(s): Yuri V. Sebastião [sup.1] , Jennifer N. Cooper [sup.1] [sup.2] [sup.3] , Brian Becknell [sup.4] [sup.5] , Christina B. Ching [sup.4] [sup.6] , Daryl J. McLeod [sup.1] [sup.6] Author [...]

Background Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Methods Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. 'Cases' were defined as individuals receiving any kidney replacement therapy (KRT), while 'controls' were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. Results In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). Conclusions In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors., Author(s): Daryl J. McLeod [sup.1] [sup.2] , Yuri V. Sebastião [sup.2] , Christina B. Ching [sup.1] [sup.3] , Jason H. Greenberg [sup.4] , Susan L. Furth [sup.5] , Brian Becknell [...]

Background Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. Methods Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. Results In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m.sup.2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO.sub.2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m.sup.2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p [less than or equal to] 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). Conclusions Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU., Author(s): Daryl J. McLeod [sup.1] [sup.2] , Christina B. Ching [sup.1] [sup.3] , Yuri V. Sebastião [sup.2] , Jason H. Greenberg [sup.4] , Susan L. Furth [sup.5] , Kirk M. [...]