The kidneys excrete 1 meq/kg/day of noncarbonic H+ ion on a normal diet. To do this, all of the filtered HCO32– needs to be reabsorbed proximally so that H+ pumps in the intercalated cells of the collecting duct can secrete H+ ions that are subsequently trapped by urinary buffers, particularly phosphates and ammonia (see Chap. 277). While remaining nephrons increase their solute load with loss of renal mass, the ability to maintain total body H+ excretion is often impaired by the gradual loss of H+ pumps or with reductions in ammoniagenesis leading to development of a non-delta acidosis. Although hypertrophy of the proximal tubules initially increases their ability to reabsorb filtered HCO32– and increases ammoniagenesis, with progressive loss of nephrons this compensation is eventually overwhelmed. In addition, with advancing renal failure, ammoniagenesis is further inhibited by elevation in levels of serum K+, producing type IV renal tubular acidosis. Once the glomerular filtration rate falls below 25 mL/min, noncarbonic organic acids accumulate, producing a delta metabolic acidosis. Hyperkalemia can also inhibit tubular HCO32– reabsorption, as can extracellular volume expansion and elevated levels of parathyroid hormone. Eventually, as the kidneys fail, the level of serum HCO32– falls severely, reflecting the exhaustion of all body buffer systems, including bone.