#4671 estimated glomerular filtration rate using cystatin c and creatinine in children with neurogenic bladder – impact of demographics and proteinuria

Abstract Background and Aims There is a high-risk of progressive chronic kidney disease (CKD) in patients with neurogenic bladder (NB) and early detection of estimated glomerular filtration rate (eGFR) reduction is essential, preventing delayed diagnosis. Creatinine-based formulas can overestimate eGFR in these patients due to decreased muscle mass. This study aims to compare eGFR calculated by different equations using serum creatinine (Cr) and/or cystatin C (CysC), in children with NB, and analyse the influence of demographic variables and proteinuria. Methods Data on pediatric patients with NB and CKD stage 1 and 2, based on eGFR calculated by the CKiD-Cr formula, were collected from January 2009 to December 2022, in a Pediatric Nephrology Unit from a tertiary hospital. The eGFR was calculated using CKiD CysC, Schwartz combined Cr/CysC, Zapitelli-CysC and Zapitelli combined Cr/CysC formulas. Proteinuria was defined by urine protein-to-creatinine ratio greater than 0.2 (mg/mg). Results Fifty patients were evaluated, with a median (25th-75th percentile) age of 14.2 (9.0-16.7) years, 48% (n = 24) female, with a median height of 142 (119.8-154.3) cm, mostly below to 5th percentile (64%, n = 32) and a median body mass index of 20.5 (15.5-26.7) kg/m2, 58% (n = 29) of patients had lipo/myelomeningocele and 76% (n = 38) were classified as stage 1 CKD. The median eGFR (ml/min/1.73m2) calculated by different formulas was: CKiD-Cr 108.1 (89.2-129.6); CKiD-CysC 77.1 (59.7-87.7), CKiD- Cr/CysC 86.6 (67.4-98.1); Zapitelli-CysC 83.3 (63.3-95.7) and Zapitelli combined- Cr/CysC 101.4 (75.5-121.2). When compared to CKiD-Cr, all the CysC-based formulas showed significantly lower values of eGFR (p<0.01). No statistical differences were obtained in eGFR calculated by CKiD-Cr and CKiD-CysC equations regarding age, sex, percentile of height or body mass index. In patients without independent gait (wheelchair or orthosis), with more muscle atrophy and underdeveloped lower limbs (54%, n = 27), the eGFR calculated by CKiD- Cr equation was higher than in the patients who are ambulatory (119.0 (102.8-150.0) vs 91.6 (64.5-111.8); p<0.01). On the other hand, there were no differences regarding eGFR obtained by CKiD-CysC in those two groups of patients (p = 0.640). Proteinuria was detected in 39% (n = 15) of the patients with stage 1 CKD and of these 87% (n = 13) had CKD upstaging using CKiD-CysC equation. In addition, the difference between the median Cr-eGFR and CysC-eGFR was significantly higher in the group of patients with proteinuria (53.0 (36.2-59.7) vs 32.6 (13.4-45.9); p = 0.007). Proteinuria was significantly higher in the group of children with more muscle atrophy, without independent gait (wheelchair or orthosis) compared to ambulatory (0.30 (0.12-0.43) vs 0.12 (0.06-0.20); p = 0.021). Conclusions In pediatric patients with NB and poor muscle mass Cr-based formulas can overestimate eGFR and delay the diagnosis and correct staging of CKD. In these patients CysC-based equations seem to be more reliable in assessing kidney function. In children with NB proteinuria appears to be a possible early and sensitive marker of CKD progression, mostly in those with more muscle depletion.