ArticleIranian journal of pharmaceutical research : IJPR
KIM-1 as an Early Diagnostic Biomarker of Cisplatin-Induced Acute Kidney Injury.
Article in Iranian journal of pharmaceutical research : IJPR. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Acute kidney injury (AKI) is a frequent complication of cisplatin chemotherapy, largely due to its toxic accumulation in renal proximal tubules. Current biomarkers show limited sensitivity in early detection, underscoring the need for more specific indicators. Kidney Injury Molecule-1 (KIM-1), upregulated in damaged tubular cells, shows promise as an early and accurate AKI biomarker. Objectives: This multimodal study integrates bioinformatic analyses, in vitro experiments, and a systematic review with meta-analysis to comprehensively evaluate KIM-1 expression, function, and early diagnostic performance. Methods: We analyzed single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data to assess HAVCR1 expression and co-regulated genes in kidney tissue and cisplatin-treated HK-2 cells. Protein interactions were mapped using STRING and Cytoscape. In vitro assays, including quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and Cell Counting Kit-8 (CCK-8), were conducted on cisplatin-treated HK-2 cells. For the systematic review and meta-analysis, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, and CNKI to identify studies evaluating urinary KIM-1 for early (≤ 24 h) detection of cisplatin-induced AKI. Study eligibility was based on clinical AKI defined by serum creatinine criteria, early KIM-1 measurement, and extractable 2 × 2 diagnostic data. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, and pooled estimates were generated using a bivariate model. Results: Single-cell and bulk RNA-seq analyses revealed that HAVCR1 (KIM-1) is specifically expressed in proximal tubular cells and is upregulated following cisplatin-induced injury. Gene enrichment and protein interaction analyses confirmed its association with epithelial transport and injury response pathways. In vitro, cisplatin treatment led to dose-dependent increases in KIM-1 mRNA and protein levels. Meta-analysis showed that urinary KIM-1 has acceptable diagnostic accuracy (AUC = 0.76; 95% CI: 0.65 - 0.86) as an early biomarker for cisplatin-induced AKI. Conclusions: KIM-1 is a proximal tubule-specific, injury-responsive biomarker that is upregulated early during cisplatin-induced kidney damage. Integrative bioinformatic and experimental analyses underscore its potential for early AKI detection, and the meta-analysis further supports its emerging clinical utility.
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