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Vesicoureteral reflux in newborn boys with Posterior Urethral Valves is associated with lower serum creatinine nadir in the first year of life, suggesting decreased baseline functional renal mass
Alexandra Rehfuss, MD1, Yuri Sebastião, PhD1, Edward Gong, MD2, Candace Granberg, MD3, Pramod Reddy, MD4, Konrad Szymanski, MD MPH5, Brian VanderBrink, MD4, Benjamin Whittam, MD5, Daryl J. McLeod, MD MPH1.
1Nationwide Children's Hospital, Columbus, OH, USA, 2Lurie Children's Hospital, Chicago, IL, USA, 3Mayo Clinic Children's Center, Rochester, MN, USA, 4Cincinnati Children's Hospital, Cincinnati, OH, USA, 5Riley Children's Hospital, Indianapolis, IN, USA.

BACKGROUND: Posterior Urethral Valves (PUV) remains a frequent cause of pediatric End Stage Renal Disease (ESRD). Progression to ESRD is multifactorial, comprising of decreased functional renal mass at birth compounded by serial renal insults throughout childhood. Prior research identified serum nadir creatinine in the first year of life (SNC1) as a leading predictor of early and late progression to ESRD. Given that SNC1 represents the lowest value of creatinine a child experiences in early life, it is thought to reflect baseline functional renal mass. Vesicoureteral Reflux (VUR) on initial Voiding Cystourethrogram (VCUG) has also been identified as a possible indicator for increased risk for ESRD. However, it is unknown if any potential risk associated with VUR and ESRD is due to its relationship with initial functional renal mass or increased risk of serial infectious insults during childhood. We aimed to investigate the association between VUR status, pre- and post-valve ablation in newborns with PUV and functional renal mass, estimated by SNC1.
METHODS: Clinical data was extracted from the Pediatric Urology Midwest Alliance (PUMA) multi-institutional PUV cohort, for which details have been previously published. The total cohort is comprised of 274 patients born between 1995 and 2015 with the diagnosis of PUV confirmed on VCUG or cystoscopy in the first 3 months of life. For the current study, only boys initially treated with cystoscopic valve ablation, who underwent pre- and post-valve ablation VCUG and for which SNC1 data was available were included.
RESULTS:In total 177 patients met study inclusion criteria with 107 (60.5%) having VUR on pre-valve ablation VCUG. VUR was unilateral in 51 (47.7%), bilateral in 52 (48.6%) and unknown in 4 (3.7%). In patients with reflux, 98 (91.6%) were grades 3-5 (higher grade reported if bilateral). Median time from valve ablation to follow-up VCUG was 84 days (Interquartile Range; 43-213 days). On post-valve ablation VCUG, VUR resolved in 22 (20.6%) and improved from high grade (3-5) to low grade (1-2) in an additional 7 (6.5%). The presence of VUR on pre-valve ablation VCUG was associated with higher SNC1 (mean SCN1 0.5 vs 0.3; p=0.002). SNC1 was also higher in bilateral VUR compared to unilateral (mean SNC1 0.6 vs. 0.5, respectively), however this did not reach statistical significance (p=0.881). VUR grades 3-5 were associated with higher SNC1 (p=0.011), however the presence of VUR grades 1-2 showed no statistical difference compared to the no VUR group (p=0.605). Lastly, on post-valve ablation VCUG, if VUR resolved or was downgraded, this was not associated with lower SNC1 (p=0.842 and 0.699 respectively).
CONCLUSIONS: This study confirms the relationship between grades 3-5 VUR on pre-valve ablation VCUG in children with PUV and increased SNC1. SNC1 is a surrogate for functional renal mass at birth, and has shown to be highly predictive of ESRD progression risk. Further research is necessary to investigate the mechanism by which early high grade VUR influences functional renal mass development and determine if continued VUR throughout childhood provides additive risk for ESRD.


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