Serum creatinine outperforms the creatinine to cystatin C ratio and creatinine muscle index as biomarkers in Chinese pediatric spinal muscular atrophy

Background This study aimed to validate the utility of serum creatinine (Cr), creatinine-to-cystatin C ratio (CCR) and creatinine muscle index (CMI) as biomarkers in Chinese pediatric patients with spinal muscular atrophy (SMA). Methods A retrospective cohort of 21 pediatric patients with 5q-spinal muscular atrophy (5q-SMA) was followed over 18-month after initiating nusinersen therapy. Serum biomarkers (creatinine, cystatin C, and albumin) and multidimensional motor function scores were assessed at six predefined time points. Associations between serum markers and motor function outcomes were analyzed statistically. Results A robust and sustained correlation was identified between Cr levels and all motor function metrics—both at baseline and during follow-up (Spearman’s ρ ≥ 0.711, p < 0.001). This association remained statistically significant even after adjusting for confounders (age, SMA subtype, and albumin levels). In contrast, the baseline relationship between CCR and motor function was attenuated post-adjustment, suggesting confounding effects. CMI exhibited no significant associations in any analysis. Longitudinally, neither Cr nor CCR displayed marked changes over time, whereas CMI declined significantly at the V8 assessment ( p = 0.016). Conclusion Routinely measured Cr is a more reliable dynamic biomarker than CCR and CMI for assessing therapeutic response in pediatric SMA patients undergoing nusinersen treatment.