{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:18:29Z","timestamp":1775110709667,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A robust and sustained correlation was identified between Cr levels and all motor function metrics\u2014both at baseline and during follow-up (Spearman\u2019s\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u202f\u2265\u202f0.711,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Routinely measured Cr is a more reliable dynamic biomarker than CCR and CMI for assessing therapeutic response in pediatric SMA patients undergoing nusinersen treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnhum.2026.1764456","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:24:23Z","timestamp":1775107463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum creatinine outperforms the creatinine to cystatin C ratio and creatinine muscle index as biomarkers in Chinese pediatric spinal muscular atrophy"],"prefix":"10.3389","volume":"20","author":[{"given":"Zixi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolesents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingshuang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolesents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolesents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolesents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolesents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1002\/mus.27187","article-title":"Safety and efficacy of nusinersen in spinal muscular atrophy: the EMBRACE study","volume":"63","author":"Acsadi","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e921","DOI":"10.1212\/wnl.0000000000008762","article-title":"Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy","volume":"94","author":"Alves","year":"2020","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1681\/ASN.0000000000000037","article-title":"A novel creatinine muscle index based on creatinine filtration: associations with frailty and mortality","volume":"34","author":"Ballew","year":"2023","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s13023-025-03730-3","article-title":"Serum creatinine to cystatin C ratio as monitoring biomarker in Chinese adult spinal muscular atrophy: a prospective cohort study","volume":"20","author":"Chen","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e70268","DOI":"10.1111\/ene.70268","article-title":"Longitudinal assessment of 4-year HFMSE changes in SMA II and III patients treated with Nusinersen","volume":"32","author":"Coratti","year":"2025","journal-title":"Eur. J. Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e2492","DOI":"10.1212\/wnl.0000000000007527","article-title":"Nusinersen in later-onset spinal muscular atrophy","volume":"92","author":"Darras","year":"2019","journal-title":"Neurology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus sham control in infantile-onset spinal muscular atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1002\/acn3.51340","article-title":"Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment","volume":"8","author":"Freigang","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"6887","DOI":"10.3390\/ijms26146887","article-title":"Application of biomarkers in spinal muscular atrophy","volume":"26","author":"Gao","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/jcsm.13511","article-title":"Creatinine, cystatin C, muscle mass, and mortality: findings from a primary and replication population-based cohort","volume":"15","author":"Groothof","year":"2024","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1373\/clinchem.2013.220707","article-title":"Generation of a new cystatin C\u2013based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator","volume":"60","author":"Grubb","year":"2014","journal-title":"Clin. Chem."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s40265-017-0711-7","article-title":"Nusinersen: First Global Approval","volume":"77","author":"Hoy","year":"2017","journal-title":"Drugs"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1111\/j.1523-1755.2004.00517.x","article-title":"Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement","volume":"65","author":"Knight","year":"2004","journal-title":"Kidney Int."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"905","DOI":"10.12372\/jcp.2022.21e1353","article-title":"Comparison of different estimation formulas of glomerular filtration rate in children aged 15-18 years with chronic kidney disease","volume":"40","author":"Kuang","year":"2022","journal-title":"J. Clin. Pediatr."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/jcla.20504","article-title":"Reference intervals and factors contributing to serum cystatin C levels in a Chinese population","volume":"26","author":"Li","year":"2012","journal-title":"J. Clin. Lab. Anal."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1097\/MNH.0000000000001022","article-title":"Serum creatinine and serum cystatin C as an index of muscle mass in adults","volume":"33","author":"Liu","year":"2024","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1177\/0300060519855575","article-title":"Age- and sex-specific reference intervals for the serum cystatin C\/creatinine ratio in healthy children (0\u201318 years old)","volume":"47","author":"Liu","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/jcsm.12361","article-title":"Skeletal muscle reference for Chinese children and adolescents","volume":"10","author":"Liu","year":"2019","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1055\/s-0037-1603517","article-title":"Diagnosis and new treatment avenues in spinal muscular atrophy","volume":"48","author":"Pechmann","year":"2017","journal-title":"Neuropediatrics"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3760\/cma.j.cn101070-20220124-00092","article-title":"Consensus statement for standard of pulmonary management in spinal muscular atrophy (2022 version)","volume":"37","author":"Cao","year":"2022","journal-title":"Chin. J. Appl. Clin. Pediatr."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1055\/s-0042-1750719","article-title":"The effect of nusinersen therapy on laboratory parameters of patients with spinal muscular atrophy","volume":"53","author":"Uzan","year":"2022","journal-title":"Neuropediatrics"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","article-title":"Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study","volume":"29","author":"Vivo","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"6004","DOI":"10.1007\/s00415-024-12567-y","article-title":"Long-term impact of nusinersen on motor and electrophysiological outcomes in adolescent and adult spinal muscular atrophy: insights from a multicenter retrospective study","volume":"271","author":"Wang","year":"2024","journal-title":"J. Neurol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"61","DOI":"10.12372\/jcp.2025.23e0998","article-title":"Advances in real-world research on disease-modifying treatments for spinal muscular atrophy","volume":"43","author":"Wu","year":"2025","journal-title":"J. Clin. Pediatr."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.4103\/NRR.NRR-D-24-00067","article-title":"Insights into spinal muscular atrophy from molecular biomarkers","volume":"20","author":"Xing","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"923","DOI":"10.3969\/j.issn.1006-9771.2020.08.010","article-title":"Advance in clinical functional assessment of neuromuscular disease (review)","volume":"26","author":"Yang","year":"2020","journal-title":"Chin. J. Rehabil. Theory Pract."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"5378","DOI":"10.1007\/s00415-024-12442-w","article-title":"Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China","volume":"271","author":"Yao","year":"2024","journal-title":"J. Neurol."}],"container-title":["Frontiers in Human Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2026.1764456\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:24:29Z","timestamp":1775107469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2026.1764456\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":27,"alternative-id":["10.3389\/fnhum.2026.1764456"],"URL":"https:\/\/doi.org\/10.3389\/fnhum.2026.1764456","relation":{},"ISSN":["1662-5161"],"issn-type":[{"value":"1662-5161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"article-number":"1764456"}}