{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:35:59Z","timestamp":1792121759224,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis-associated acute kidney injury (S-AKI) represents a significant health problem associated with adverse outcomes. Our study aimed to assess the value of serum cystatin-C (sCysC) and TNF-\u03b1 (rs361525) in combination for diagnosing S-AKI patients and predicting their adverse outcomes. The study included 100 critically ill neonates and 100 controls. Patients were categorized into an S-AKI group and a non-AKI group. TNF-\u03b1 (\u2212238, rs361525) genotyping was performed using RT-PCR, and sCysC was assessed using ELISA. Our study showed a fundamental difference in the genotype frequencies of TNF-\u03b1 (\u2212238, rs361525) and SNP between S-AKI and non-AKI patients. Furthermore, there was a significant relationship between cystatin C and TNF-\u03b1 (\u2212238, rs361525), where cystatin C was higher in patients with AA alleles than in patients with GA and GG alleles. Combining GA + AA genotypes with elevated serum cystatin-C levels can serve as a potential diagnostic and prognostic biomarker for AKI development in this population. The GA\/AA genotypes independently predicted S-AKI risk (OR = 6.64, p &lt; 0.001). At the same time, elevated sCysC (&gt;9.4 mg\/L) emerged as a sensitive biomarker (AUC = 0.848) and independent predictor of adverse outcomes. Collectively, these findings contribute to the growing field of personalized medicine and represent a strategic advantage, enabling prevention-focused care rather than the treatment of established disease.<\/jats:p>","DOI":"10.3390\/ijms26146738","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genotype\u2013Phenotype Correlation of TNF-\u03b1 (\u2212238, rs361525) and Cystatin C for Early Detection of Sepsis-Associated AKI and Its Severity in Critically Ill Neonates"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3993-5378","authenticated-orcid":false,"given":"Shimaa","family":"Abdelsattar","sequence":"first","affiliation":[{"name":"Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menofia University, Menofia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-0004","authenticated-orcid":false,"given":"Hiba S.","family":"Al-Amodi","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Nazih","sequence":"additional","affiliation":[{"name":"Al Ryada University for Science and Technology (RST), ElMehwar ElMarkazy-2, Cairo\u2014Alex Desert RD K92, Sadat City 16504, Egypt"},{"name":"Scientific Office, Egyptian Society of Pharmacogenomics and Personalized Medicine (ESPM), Cairo 11562, Egypt"},{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Ahram Canadian University (ACU), 6th of October City, Giza 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman H. M.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menofia University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha G.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menofia University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shymaa S.","family":"Menshawy","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1425","authenticated-orcid":false,"given":"Amany A.","family":"El-Banna","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma M.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Menoufia National University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia S.","family":"Nabih","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Mohsen","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaf","family":"Abozeid","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai El-Sayad","family":"Abd El-Hamid","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2817-645X","authenticated-orcid":false,"given":"Nabil A.","family":"Shoman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Ahram Canadian University, Giza 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-263X","authenticated-orcid":false,"given":"Naglaa Abdelmawgoud","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Community Health Nursing Department, Faculty of Nursing, Menoufia University, Shebin El-Kom 32511, Egypt"},{"name":"Faculty of Nursing, Al Ryada University for Science and Technology, Sadat City 16504, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-5427","authenticated-orcid":false,"given":"Mai Mohamed","family":"Nabil","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia Abdel-Wahab","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/clinids\/22.3.407","article-title":"Current Understanding of Sepsis","volume":"22","author":"Wenzel","year":"1996","journal-title":"Clin. 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