© 2016 Elsevier Inc. Objective To asses if cystatin c-calculated glomerular filtration rate (GFR) can reveal chronic kidney disease (CKD) not detected by creatinine-based calculations in a larger prospective cohort of children with myelomeningocele (MMC). Wheelchair-bound MMC patients frequently have low muscle mass, and assessing renal deterioration based on creatinine-based GFR is imprecise. MMC patients are also at risk for end-stage renal disease. Methods Prospectively enrolled patients with MMC underwent annual serum creatinine and cystatin c testing. Anthropometric measurements were obtained from clinic visit. The modified (bedside) Schwartz formula for creatinine-based GFR and the Zappitelli cystatin C formula were utilized for calculation. The exclusion criteria were patients with reduced GFR (CKD stage 2) or chronic CKD (CKD stage 3 and greater); these patients were excluded from analysis on the premise that they had already been identified for closer renal monitoring. Results A total of 131 patients were included in the analysis. The median creatinine-based estimated GFR was 126.5 mL/min/1.73 m2 (range: 22-310). The median cystatin C-based estimated rate was 98.5 mL/min/1.73 m2 (range: 16-171), yielding an absolute median rate reduction of 30.2%. Using cystatin c-calculated GFR, CKD stage was upgraded from stage 1 to ≥2 in 34 patients (26%). Conclusion In MMC patients with poor muscle mass, cystatin C-based GFR is more sensitive than creatinine-based GFR in detecting early CKD. In this high-risk population, serial cystatin C estimation is a valuable tool in identifying children who may benefit from early nephrology referral and intervention.