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Estimated glomerular filtration rate and hydronephrosis in patients with spina bifida: are we missing silent chronic kidney disease?
David I. Chu, MD, MSCE1, Lauren C. Balmert, PhD2, Liqi Chen, MS2, Cameron M. Arkin, BA1, Theresa Meyer, RN, MSN1, Ilina Rosoklija, MPH1, Diana K. Bowen, MD1, Kavita S. Hodgkins, MD, MSCI1, Earl Y. Cheng, MD1, Tamara Isakova, MD, MMSc2, Elizabeth B. Yerkes, MD1.
1Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA, 2Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background:
Preservation of kidney function is a top priority in children born with spina bifida (SB). Kidney health is usually assessed through laboratory tests, such as creatinine and/or cystatin-C, which are used to calculate estimated glomerular filtration rate (eGFR), or through imaging tests, such as renal ultrasound (RUS), which can identify abnormalities including hydronephrosis. However, low eGFR may occur "silently" in the absence of hydronephrosis. We examined the association between eGFR and abnormal RUS findings to test the hypothesis that although lower eGFR would be associated with presence of hydronephrosis on RUS, certain individuals with "normal" RUS findings could still have reduced eGFR.
Methods:
We conducted a retrospective, cross-sectional cohort study at a single institution from 2012-2017. We included patients who had complete required data measurements, such as creatinine, cystatin-C, and height, that were needed to calculate eGFR via 6 different pediatric or 5 different adult estimating equations. Patients with a solitary kidney were excluded. We stratified the study sample by age (pediatric equations for 1-18 year olds, adult equations for >18 year olds). We used RUS findings that corresponded to the eGFR data timepoints and dichotomized results into presence or absence of any hydronephrosis. Median eGFR values and frequencies of patients with eGFR <90 mL/min/1.73m2 were reported for each estimating equation by hydronephrosis status. We used logistic regression models to investigate the associations between eGFR and RUS findings.
Results:
248 patients with two kidneys met eligibility criteria, including 177 children and 71 adults. Mean (standard deviation) age was 13.7 (6.6) years, 58% were female, 81% had myelomeningocele, 83% were dependent on clean intermittent catheterization, 18% had prior bladder augmentation, and 32% were non-ambulatory. Hydronephrosis was found in 35/177 (20%) children and 18/71 (25%) of adults, with 41/53 (77%) being Society for Fetal Urology grade I or II hydronephrosis. Across pediatric equations, eGFR <90 mL/min/1.73m2 was found in 1-66% of children without hydronephrosis and 14-86% of children with hydronephrosis (Table). Across adult equations, eGFR <90 mL/min/1.73m2 was found in 0-17% of adults without hydronephrosis and 11-33% of adults with hydronephrosis. Logistic regression models showed statistically significant associations between eGFR and hydronephrosis for all 6 pediatric equations and 3 of the 5 adult equations, no matter whether incorporating creatinine-only, cystatin-C-only, or both. In these equations, for every 10-unit decrease in eGFR, the odds of hydronephrosis increased by 1.1-to-2.3-fold.
Conclusion:
Using RUS only to monitor kidney health may miss low eGFR, as 1-66% of children and 0-17% of adults without hydronephrosis had eGFR<90 mL/min/1.73m2, depending on the estimating equation. Lower eGFR, whether derived from equations incorporating creatinine-only, cystatin-C-only, or both, was associated with higher odds of hydronephrosis. These results support the recommendation to use both periodic RUS and eGFR values for kidney health surveillance in patients with SB.


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