Chronic metabolic acidosis occurs commonly in patients with diseased kidneys.Metabolic acidosis leads to significant morbidity and mortality with adverse effects on nitrogen balance, protein degradation, proximal renal tubular metabolism and loss of bone and muscle mass.Data strongly indicate that oral bicarbonate has a renoprotective effect at the level of the renal proximal tubular cell level (reducing polypeptide catabolism in patients) and delaying progression.This presentation focuses on novel mechanisms in conditions mimicking chronic acidosis HK-2 cells and determines effects on oxidative stress and PAI-1, a potent pro-fibrogenic molecule important in promoting glomerular and renal tubular fibrosis.