PURPOSE OF REVIEW: We review the growing clinical evidence that metabolic acidosis mediates chronic kidney disease (CKD) progression and that treatment to increase the associated low serum bicarbonate (HCO3) in CKD is disease-modifying. RECENT FINDINGS: Seven prospective studies of patients with wide ranges of estimated glomerular filtration rates (eGFRs) and serum HCO3 examined the effect on CKD of increasing serum HCO3 using dietary acid reduction with either oral alkali (sodium bicarbonate or sodium citrate), a vegetarian diet very low in acid-producing protein (0.3 g/kg/day) supplemented with ketoanalogues or added base-producing fruits and vegetables. Clinical outcomes included slower kidney function decline (using eGFR measurements) and fewer patients progressing to end-stage kidney disease. Post hoc analyses demonstrated that: treatment of metabolic acidosis for 2 years decreased the number of patients with at least a 40% eGFR decline, a validated surrogate for progression to end-stage kidney disease and across four studies, treatment to increase serum HCO3 by 4-6.8 mEq/l in acidotic patients with CKD was associated with a ∼4 ml/min/1.73 m reduction in the rate of eGFR decline over 6-24 months compared with controls. SUMMARY: Metabolic acidosis appears to enhance CKD progression and its treatment should be studied further as a potential disease-modifying intervention.