Nomograms for Predicting Annual Resolution Rate of Primary Vesicoureteral Reflux: Results From 2,462 Children Carlos R. Estrada, Jr.,* Carlo C. Passerotti, Dionne A. Graham, Craig A. Peters, Stuart B. Bauer, David A. Diamond, Bartley G. Cilento, Jr., Joseph G. Borer, Marc Cendron, Caleb P. Nelson, Richard S. Lee, Jing Zhou, Alan B. Retik and Hiep T. Nguyen From the Department of Urology (CRE, CCP, CAP, SBB, DAD, BGC, JGB, MC, CPN, RSL, ABR, HTN) and Clinical Research Program, Department of Biostatistics (DAG, JZ), Children’s Hospital Boston, Boston, Massachusetts Purpose: We determined the resolution rate of vesicoureteral reflux and the factors that influence it to formulate nomograms to predict the probability of annual resolution for individual cases of reflux. Materials and Methods: We studied 2,462 children with primary vesicoureteral reflux diagnosed between 1998 and 2006. Cox proportional hazards regression was used to model time to resolution as a function of statistically significant demographic and clinical variables. The resulting model was used to construct nomograms predicting the annual cumulative probability of reflux resolution. Results: Multivariate analysis showed that all cases of unilateral reflux resolved earlier than female bilateral reflux (HR 1.42, p 0.001). Additionally age less than 1 year at presentation (HR 1.31, p 0.001), lower reflux grade (2.96, p 0.001 for grade I; 2.28, p 0.001 for grade II; 1.63, p 0.001 for grade III), reflux diagnosed on postnatal evaluation for prenatal hydronephrosis or sibling screening (1.24, p = 0.002) and single ureter (1.55, p 0.001) were associated with significantly earlier resolution of reflux. Specific predicted cumulative prob- abilities of reflux resolution at annual intervals from diagnosis (1 to 5 years) were calculated for every possible combination of the significant variables. Conclusions: Our analyses demonstrate that resolution of vesicoureteral reflux is dependent on age at presentation, gender, grade, laterality, mode of clinical presentation and ureteral anatomy. We constructed nomogram tables containing estimates of annual reflux resolution rate as a function of these variables. This information is valuable for clinical counseling and management decisions. Key Words: nomograms, treatment outcome, vesico-ureteral reflux Abbreviations and Acronyms PNH = prenatal hydronephrosis RNC = radionuclide cystogram UDS = urodynamics US = ultrasound UTI = urinary tract infection VCUG = voiding cystourethrogram VUR = vesicoureteral reflux Submitted for publication January 27, 2009. Study received institutional review board ap- proval. * Correspondence: Department of Urology, Children’s Hospital Boston, 300 Longwood Ave., HU-370, Boston, Massachusetts 02115 (tele- phone: 617-355-7796; FAX: 617-730-0474; e-mail: carlos.estrada@childrens.harvard.edu). See Editorial on page 000. MANAGEMENT of vesicoureteral reflux is challenging, and the debate regard- ing its clinical significance underpins the lack of consensus on whom, when and how to treat. 1 Reflux is routinely managed by prophylactic antibiotics and watchful waiting, although the efficacy of antibiotics has recently been challenged in randomized controlled trials. 1,2 Following diagnosis repeat radiological assessments of reflux are performed at an interval of 1 to sev- eral years between studies. 3,4 This ap- proach is based on the assumption that most cases resolve spontaneously with time. 5–7 Three studies from 1987 to 1992 were used to formulate the 1997 Pe- diatric Vesicoureteral Reflux Guide- lines. 4,6,8,9 While these guidelines have 0022-5347/09/1824-1535/0 Vol. 182, 1535-1541, October 2009 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2009.06.053 www.jurology.com 1535 ARTICLE IN PRESS