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Prediction of End-Stage Renal Disease in Children with Chronic Kidney Disease and Obstructive Uropathy
Yuri Sebastião, PhD, Jennifer Cooper, PhD, Christina Ching, MD, Brian Becknell, MD PhD, Daryl J. McLeod, MD MPH.
Nationwide Children's Hospital, Columbus, OH, USA.

BACKGROUND: Chronic kidney disease (CKD) in children, though rare, is associated with decreased quality of life and shorter life expectancy. Due to the progressive and often irreversible nature of CKD, there is a need for research to identify clinical prognostic factors. We examined the accuracy and usefulness of a validated kidney failure risk equation (KFRE), previously developed in adults, to predict the risk of end-stage renal disease (ESRD) in children with obstructive uropathy, the most frequent non-glomerular cause of pediatric CKD.
METHODS: This retrospective cohort study included 118 children diagnosed with obstructive uropathy and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73m2 in the Chronic Kidney Disease in Children (CKiD) study. CKiD is a longitudinal, observational sample of children with mild to moderate CKD recruited from 48 North American Pediatric Nephrology Centers. Only children with a GFR less than 60 ml/min/1.73m2 (CKD stage 3 or greater) were included, as this represented the same range used for initial KFRE validation in adults. Using study baseline data and published parameters for the 4-variable (age, sex, bedside Schwartz eGFR, and ratio of albumin to creatinine levels) and 8-variable (4 variables plus serum calcium, phosphate, bicarbonate, and albumin levels) KFREs, we estimated the 5-year risk (probability) of ESRD for each patient. The ability of the KFRE to discriminate between patients who did and did not progress to ESRD was examined using the C index for time-to-event analysis. The proportion of true-positives among patients who progressed to ESRD (sensitivity), and the proportion of true-negatives among patients who did not reach ESRD (specificity), were evaluated over a range of different cut-offs for the estimated 5-year risk.
RESULTS: Among 118 children in the study, 100 (85%) were boys, and the median age at study entry was 10 years (interquartile range (IQR): 6-14). Median eGFR was 42 mL/min/1.73m2 (IQR: 32-53), and median follow-up time was 4.5 years (IQR: 2.7-7.2); 23 patients (19.5%) developed ESRD within 5 years of enrollment. The 4- and 8-variable KFREs discriminated risk of ESRD with C statistics of 0.75 (95% CI: 0.68-0.82) and 0.78 (0.70-0.86), respectively. A cut-off of ≥30% for the estimated 5-year risk of ESRD based on the 4-variable KFRE yielded the best combination of sensitivity (82.6%) and specificity (74.7%), with similar results for the 8-variable KFRE.
CONCLUSIONS: The 4- and 8-variable KFRE provide similar discrimination for the 5-year risk of ESRD among children with CKD due to obstructive uropathy. Classifying patients as likely to progress to ESRD within 5 years if their KFRE value was ≥30% allowed accurate prediction of the 5-year risk of ESRD with 82.6% sensitivity and 74.7% specificity. To our knowledge, this is the first application of such a tool for children with obstructive uropathy. These results support inclusion of the KFRE for risk stratification and patient counseling in children with obstructive uropathy and CKD stages 3 and above. Research is ongoing to identify novel biomarkers that can be added to such a predictive tool to allow earlier and more accurate risk stratification.


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