ACE and chronic kidney disease: In CKD patients, there are several factors that can positively or negatively influence the onset of metabolic acidosis; among these, we find [192]: (i) decrease of GFR, which doubles the risk of metabolic acidosis in CKD stage III and increases the risk seven-fold in CKD stage IV; (ii) smoking increases the risk by 43%; (iii) normochromic and normocytic anemia increases the risk by 40%; (iv) the use of diuretics reduces the risk by 30%; (v) the use of ACE inhibitors increases the risk by 30%.