From Saliva to Diagnosis: A Scoping Review of Conventional and Biosensor-Based Methods for Salivary Biomarkers in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a progressive global health burden often diagnosed in late stages due to reliance on invasive and centralized blood and urine tests. Saliva, as a non-invasive diagnostic fluid, has emerged as a promising alternative for assessing renal function. This scoping review aims to evaluate the diagnostic accuracy of salivary biomarkers compared to traditional methods, and to explore the potential of emerging biosensing technologies for CKD detection and monitoring. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library up to 1 July 2025, following the PRISMA-ScR guidelines. Studies involving adult CKD patients and healthy controls that assessed the diagnostic performance of salivary biomarkers against validated reference standards (e.g., serum creatinine, eGFR) were included. A total of 29 eligible studies were selected after applying predefined inclusion and exclusion criteria. RESULTS: Salivary creatinine and urea were the most frequently assessed biomarkers and demonstrated strong correlations with serum levels (AUCs up to 1.00; sensitivity and specificity frequently >85%). Several studies reported high diagnostic potential for novel salivary markers such as Trimethylamine N-oxide (TMAO), cystatin C, and amino acids. Technological innovations, including electrochemical biosensors and ATR-FTIR spectroscopy, showed promise for enhancing sensitivity and enabling point-of-care testing. However, heterogeneity in sampling protocols and limited data for early-stage CKD were notable limitations. CONCLUSIONS: Salivary diagnostics, supported by biosensor technologies, offer a feasible and non-invasive alternative for CKD screening and monitoring. Standardization, broader clinical validation, and integration into dental workflows are key to clinical implementation.