The Continuum of Acid Stress

Abstract

Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.

Keywords: chronic kidney disease; end stage kidney disease; nutrition; oxidative stress; progression of chronic renal failure.

Figure 1.

The body has multiple strategies to mitigatethe potential untowardeffects of added acid (H⁺). Alb⁻, albumin; AlbH, protonated albumin; Buf⁻, buffer; Ca⁺⁺, calcium; CO₃ ²⁻, carbonate; CO₂, carbon dioxide gas; ECF, extracellular fluid; H⁺, hydrogen; H₂CO₃, carbonic acid; Hb⁻, hemoglobin; HbH, protonated hemoglobin; HCO₃ ⁻, bicarbonate; HPO₄ ⁼/H₂PO₄ ⁻, phosphate; ICF, intracellular fluid; K⁺, potassium; Na⁺, sodium; NAD⁺/NADH, nicotinamide adenine dinucleotide; NH₄ ⁺, ammonium; PCO₂, partial pressure of carbon dioxide; PO₄ ³⁻, phosphate.

Figure 2.

In the setting of a high acid-producing diet, progressive decreases in glomerular filtration rate are associated with progressively increasing acid accumulation that initially decreases plasma bicarbonate concentration (HCO₃⁻]) within normal ranges but eventually decreases it below normal to manifest as metabolic acidosis. The top horizontal line of the boxes characterizes progressively decreasing levels GFR combined with either low or high dietary acid intake. The middle horizontal portion figuratively compares plasma bicarbonate concentration ([HCO₃ ⁻]) either within the brackets of the normal range or below it. The bottom horizontal figuratively compares H⁺ retention among the four stages. Adapted from ref. , with permission.