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Abstract This study presents a rapid and non-invasive method to screen high renin hypertension using serum Raman spectroscopy combined with different classification algorithms. The serum samples taken from 24 high renin hypertension patients and 22 non-high renin hypertension samples were measured in this experiment. Tentative assignments of the Raman peaks in the measured serum spectra suggested specific biomolecular changes between the groups. Principal component analysis (PCA) was first used for feature extraction and reduced the dimension of high-dimension spectral data. Then, support vector machine (SVM), linear discriminant analysis (LDA) and k-nearest neighbor (KNN) algorithms were employed to establish the discriminant diagnostic models. The accuracies of 93.5%, 93.5% and 89.1% were obtained from PCA-SVM, PCA-LDA and PCA-KNN models, respectively. The results from our study demonstrate that the serum Raman spectroscopy technique combined with multivariate statistical methods have great potential for the screening of high renin hypertension. This technique could be used to develop a portable, rapid, and non-invasive device for screening high renin hypertension. Graphical abstract Raman spectroscopy technique combined with multivariate statistical methods for the screening of high renin hypertension. Unlabelled Image Highlights • Raman spectroscopy has the potential to screen high renin hypertension patients. • The high accuracy of 93.5% is obtained from multivariate statistical method. • Our method is expected to develop a clinical diagnostic tool. [ABSTRACT FROM AUTHOR]