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Variation in Definitions of Kidney Dysfunction in Patients with Spina Bifida: A Systematic Scoping Review
James Rague, MD1, Jeremy Lai, MD, MBA2, Peggy Murphy, MLIS1, Andrea Fawcett, MLIS1, Ryan Walton, BS1, Ilina Rosoklija, MPH1, Diana Bowen, MD1, Earl Cheng, MD1, Elizabeth Yerkes, MD1, Jonathan Routh, MD, MPH3, Tamara Isakova, MD, MMSc2, David Chu, MD, MSCE1.
1Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA, 2Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 3Duke University School of Medicine, Durham, NC, USA.

Background: Kidney dysfunction (KD) is known to occur in individuals with spina bifida (SB) secondary to neurogenic bladder, with a reported increased lifetime risk of advanced KD compared to healthy controls. However, inconsistent measures of KD in the literature may skew the true incidence, and current guidelines lack granular details on how to best assess kidney health in this population. We evaluated the literature involving patients with SB for criteria used by authors to define and report KD.Methods: A systematic literature search was conducted using MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO, Web of Science, and clinicaltrials.gov for articles from time of database inception to September 2020. No language or age restrictions were applied. Primary research articles involving individuals with SB where KD was assessed as an outcome were included. Two researchers independently reviewed abstracts and full-text articles, with a third arbitrating conflicts. Means of identifying KD and defining KD severity were abstracted and summarized using descriptive statistics. KD outcomes used were compared by type of publishing journal (urology versus non-urology) and age group of study participants included in each article (0-18, >18, both, or not stated).Results: Of 2,034 articles found, 274 were included in the review (Figure). Most articles (63.5%) were published after 1990, in urology journals (65.3%), and included pediatric populations only (0-18yo) (60.5%). KD outcomes were identified by imaging-based anatomic outcomes (84.7%), serum-based outcomes (44.9%), imaging-based functional outcomes (5.5%), urine-based outcomes (3.3%), and diagnoses of end-stage kidney disease (2.6%) or chronic kidney disease otherwise unspecified (1.8%). Hydronephrosis was the most commonly used specific outcome (177/274, 64.6%), but hydronephrosis severity was documented in only 19.8% (35/177) of articles (Table). Hydronephrosis was used more commonly in studies of pediatric patients only compared to studies including adults >18yo. Renal scarring was used in 24.1% (66/174) of articles, with the number of scars or differential functional loss consistent with KD reported in only 33.3% (22/66) of articles. Creatinine and cystatin-C were used in 82.1% (101/123) and 17.9% (22/123) of articles reporting serum-based outcomes, respectively, but estimated glomerular filtration rate (eGFR) severity was only used in 32.7% and 50.0% of articles. Serum-based outcomes were more commonly used in articles including patients >18yo. Measured GFR was assessed by imaging or serum radioisotope tests in 9.9% (27/274) of articles, with a GFR cut-off to define KD reported by 44.4% (12/27) of articles. Conclusion: Among primary research articles reporting KD outcomes in patients with SB, broad variability exists in how authors define KD with few specifically defining KD severity. Consensus and consistency in defining KD outcomes and identifying and using the most accurate and reliable tests for this population may assist in identifying the true incidence of KD in patients with SB.


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