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• Plasma melatonin diagnoses early CKD patients with over 95% accuracy. • Plasma melatonin and tryptophan diagnose early CKD patients with 100% accuracy; • Plasma markers predict patients with early IgA nephropathy with over 85% accuracy. Chronic kidney disease (CKD) causes low quality of life and alarming morbidity and mortality. The crucial to retard CKD progression is to diagnose early for timely treatment. IgA nephropathy (IgAN) is a typical CKD and the most common glomerulonephritis. Both CKD and IgAN lack accurate and sensitive blood biomarkers for early diagnosis. Here we report the potential of plasma biomarkers for early diagnosis of CKD and IgAN. Plasma levels of metabolites derived from tryptophan were quantified with an LC-MS/MS-based metabolomics for two cohorts. Based on the predictive probability of each metabolite, multivariate models including logistic regression and random forest were used to establish the early diagnostic biomarkers for CKD and IgAN. The plasma melatonin diagnosed early CKD (stages Ⅰ−Ⅱ) with an accuracy exceeding 95%, and a panel of melatonin and tryptophan achieved a remarkable 100% accuracy in diagnosing early CKD. Furthermore, indole-3-lactic acid had an excellent ability to distinguish IgAN among CKD patients. Based on the CKD screening and IgAN diagnosis primarily contributed by melatonin and indole-3-lactic acid, early IgAN could be diagnosed with an accuracy of over 85%. This study provides promising plasma biomarkers for early diagnosis of CKD and IgAN. [ABSTRACT FROM AUTHOR]