Urinary Acidification

Speakers: L. Lee Hamm, Thomas DuBose, Eric Simon
[twitter transcript]

This set of lectures started out with Dr. Hamm reviewing the basic processes of acid excretion along different portions of the nephron. In the proximal tubule (PCT), acid excretion primarily occurs through bicarbonate reabsorption (i.e., for every 1 bicarbonate anion that is reabsorbed, one proton is excreted). Bicarbonate absorption in the PCT heavily depends upon carbonic anhydrase (isoforms II and IV). Isoform II is intracellular and isoform IV is found on the brush border (luminal side). CA II is needed to convert carbon dioxide back to proton + bicarbonate anion; the latter is then reabsorbed back into the blood stream through a sodium-bicarbonate antiporter on the basolateral surface of the principal cell.

In the distal nephron, the main transport proteins that facilitate acid excretion are: 1) the H+-ATPase and 2) the H+/K+-exchanger (an antiporter).

Net acid excretion (NAE) can be defined by this simple mathematical equation:

NAE = urine TA + urine NH4+ — urine bicarbonate

The greater the titratable acid, more the NH4+, and the more bicarbonate reabsorbed, the greater the net acid excretion. In this equation, only 3 variables determine NAE, with NH4+ actually representing 2/3 of NAE.

Now we turn to the renal tubular acidoses (RTAs). Dr. DuBose spent about 1 minute explaining the “delta-delta” equation to identify an superimposed non-anion gap acidosis in the presence of an an anion-gap acidosis. [See our 10-Minute Rounds video to understand this concept (video 1 and video 2]. It is important to try to calculate the amount of urinary NH4+ that is excreted, since the kidney relies on this mechanism to “defend the body” against acidemia. While it is possible to directly measure urinary NH4+ levels, it is still cumbersome. Thus, we continue to use the urine anion gap (link) and the urine osmolar gap to estimate NH4+ excretion (UOSM gap /2 = ~ urinary NH4+ excretion).

A final note about RTAs: there has been recent talk disfavoring the use of the TTKG. Dr. DuBose did not dwell on the subject too much but was unequivocal in his statement that he continues to use the TTKG and teaches it to his residents and fellows. [See this 10-Minute Rounds video on why the TTKG was developed (link) and how to interpret its value (link)]

Dr. Simon concluded the session with a discussion of acidosis in CKD. It seems that in many studies, a bicarbonate level of < 22 leads to faster progression towards ESRD (in Wesson KI 2010, the higher bicarbonate group had a decline in GFR of -1.8 ml/min/year versus -4.8 ml/min/year in the lower bicarbonate group; link), greater damage to bone and muscle, and higher mortality (in one study whose reference I could not get, a 2.5x greater mortality for those patients with bicarbonate < 22).