Abstract Background and Aims Chronic kidney disease (CKD) remains a major health problem, till now, diagnosis of CKD depends on radiology and estimated glomerular filtration rate (eGFR). Therefore, there is an ultimate need for new sensitive prognostic and diagnostic biomarkers for diagnosis and progression of CKD. CKD is accompanied by increased levels of circulating fibroblast growth factor 23 (FGF23) and aldosterone levels. In the current study, we aim to evaluate the association between circulating FGF23 and serum aldosterone levels in CKD patients and to test the hypothesis that aldosterone may be a direct driving factor of increased FGF23 secretion in CKD patients. Method This cross section observational study was carried out at Kafr El Sheikh University Hospital's internal medicine department which enrolled 140 subjects that were divided into two groups: group I: 70 patients with various stages of newly diagnosed chronic kidney disease who did not receive renin-angiotensin-aldosterone system (RAAS) blocker yet (CKD stage 1 –5) & group II: 70 apparently healthy subjects (of corresponding age and sex as a control group). We detected serum FGF-23 and Serum aldosterone using enzyme-linked immunosorbent assay (ELISA). Results A strong correlation was identified between FGF-23 and serum aldosterone in group I (p = < 0.001), there was remarkably stage dependent strong associations in CKD patients. High FGF-23 and serum aldosterone significantly independently increase risk of CKD by 1.15 and 1.043 folds respectively. The best cutoff of FGF-23 in prediction of kidney injury is ≥59.735 with area under curve 0.977, sensitivity 91.4%, specificity 90%, positive predictive value 90.1%, negative predictive value 91.3% and overall accuracy 90.7% (p < 0.001). The best cutoff of aldosterone in prediction of kidney injury is ≥117.59 with area under curve 0.978, sensitivity 92.9%, specificity 88.6%, positive predictive value 89%, negative predictive value 92.5% and overall accuracy 90.7% (p < 0.001). Conclusion FGF23 and aldosterone may be used as markers in CKD progression. aldosterone may be a direct driving factor of increased FGF23 secretion in CKD patients.