Background: The course of chronic kidney disease (CKD) is highly connected with the Klotho gene through multiple pathways, including renal fibrosis, vascular calcification, inflammation, and mineral bone abnormalities. Objectives: This study aimed to assess the impact of oral sodium bicarbonate supplementation on blood levels of soluble α-Klotho in patients suffering from chronic renal disease (stage 3b:4) at Ain Shams Specialized Hospital in Cairo, Egypt, using the CKD-EPI formula. Patients and Methods: 45 CKD patients were recruited for this interventional, prospective, open-label clinical trial from the Inpatient and Outpatient Clinics at Ain Shams Specialized Hospital in Cairo, Egypt. Results: The cohort study had an average age of 48.13 ± 6.96 years. Serum bicarbonate (HCO₃) improved from mean 19.74 ± 1.43 mmol/L pre-study to 23.63 ± 3.23 mmol/L post-study, with a p-value of 0.000. Additionally, eGFR significantly improved with a p-value of 0.000 following the study. Serum alpha Klotho level was 596.30 ± 148.58 pg/mL before the study and 696.16 ± 172.99 pg/mL after the study, with a statistically significant difference of 0.006. Serum alpha Klotho after the study did not show a statistically significant link with serum creatinine, eGFR, potassium and phosphorus, or parathyroid. However, serum bicarbonate level and serum Klotho after the study showed a statistically significant positive correlation. Conclusion: Serumsoluble α klotho level was significantly higher post-study compared to pre-study after oral sodium bicarbonate supplementation and improved acidosis.