Renal deterioration in children and adults with spina bifida: fact, fiction or both?
Konrad M. Szymanski, MD, MPH, Arthur J. Szymanski, BSc, Amr Salama, MD, Mark P. Cain, MD, Rosalia Misseri, MD.
Riley Hospital for Children, Indianapolis, IN, USA.
BACKGROUND: Estimated glomerular filtration rate (eGFR) in the general population is stable in children after the age of 2. In the first 3 decades after age 18, eGFR decreases by 0.3-0.8ml/min/1.73m2 annually. It is unclear if eGFR changes similarly in the spina bifida (SB) population. In the absence of a validated SB-specific eGFR formula it is also unclear if these changes vary when different eGFR formulas are used. We performed a cross-sectional study (1) to determine trends in eGFR over time in children and adults with SB and (2) to compare eGFRs calculated using different formulas.
METHODS: We retrospectively reviewed records of patients 2-50 years old with SB followed at our institution (2014-2019) with serum Cr, Cystatin C and height measurements (children only). We determined eGFR using 4 pediatric formulas (2-17 years: Schwartz Cr, Schwartz CysC, CKiD CysC-Cr and Zappitelli) and 5 adult formulas (18+ years: CKD-EPI Cr, CKD-EPI Cr-CysC, CKD-EPI CysC, NEJM and Modification of Diet in Renal Disease Study [MDRD]). The analysis included a single eGFR per patient, the last eGFR for those with serial measurements. When categorizing eGFR, chronic kidney disease (CKD) stage 2 (eGFR 60-89ml/min/1.73m2) and Stage 3+ (<60) were used. Non-parametric tests, linear regression and Spearman's correlation were used for analysis.
RESULTS: Among 209 children with SB (median age 10.3 years), depending on the formula, eGFR decreased by 0.7-1.8ml/min/1.73m2/year (Schwartz CysC, Schwartz Cr, p<=0.001), remained stable (CKiD CysC-Cr, p=0.41) or increased by 2.7/year (Zappitelli, p<0.001) (Figure). The proportion of children with CKD 2+ varied with the formula used: (11.5-58.9%, p<0.001). Correlations between pediatric formulas were low to moderate. Comparing any two different eGFR formulas, 12.0-65.5% of children were assigned a different CKD stage. Among 164 adults (median age 26.3), eGFR decreased regardless of the formula used (range: 1.3-2.2/year, p<=0.01) (Figure). The proportion of adults with CKD 2+ varied with the formula used (9.2-30.5%, p<0.001). Correlations between adult formulas were moderate to very high. Comparing any two different eGFR formulas, 0.6-26.8% of adults were assigned a different CKD stage. CONCLUSIONS: Renal function may be deteriorating in the SB population at a higher rate than in the general population. This may be a real phenomenon, an artifact of inaccurate eGFR formulas, or both. Our results indicate that existing eGFR formulas lack precision in the SB population. A validated SB-specific eGFR formula is needed. 
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