A possible explanation for these different observations is that, in people from the general population who do not have CKD or diabetes, a chronic low grade metabolic acidosis, for which a low serum bicarbonate is a surrogate, has pathophysiological consequences including accelerated renal damage [26], protein catabolism [27], systemic inflammation [28] and activation of the renin-angiotensin system [29]. Here, REN is linked to diabetes mellitus.