Thread by @medrants

1/ #KashlakChief spends more than #5goodminutes exploring normal anion gap metabolic acidosis (NAGMA) due to CKD.

We see many CKD patients on sodium bicarbonate tablets or sodium citrate. This tweetorial will start with why we treat NAGMA. @thecurbsiders

2/ Following we will explain the physiologic causes of NAGMA. Finally, we will discuss treatment dosing.

3/ Current guidelines recommend treating NAGMA with a goal bicarbonate of 22. Three benefits - decrease bone disease, improve nutritional status, delay progression of CKD to ESRD.

4/ Now for a physiology lesson! Our diets include approximately 1 mEq/kg of acid that we need to excrete each day. We accomplish this through 2 urinary buffering mechanisms - phosphates and ammonia. We have no significant metabolic ability to modify phosphate excretion.

5/ Ammonium (NH4+) excretion is under metabolic control if we have normal renal function. We produce ammonia (NH3) in proximal tubular cells through the well known equation glutamine -> glutarate + NH3. The enzyme glutaminase stimulates this conversion.

6/ The NH3 enters the proximal tubule and quickly gets converted to NH4+. These molecules persist until the famous NaK-2Cl co-transporter. As a small cation, the NH4+ is transported in the counter current mechanism and quickly reverts to NH3.

7/ The NH3 concentration is high in the medulla and low in the cortex. When we acidify the distal tubule, NH3 passively crosses and again becomes NH4+. As classic buffer system we excrete mEq of NH4+ using microequivalents of H+.

8/ As renal function decreases we both lose proximal tubular cells and thus we produce less NH3. We also steadily "wash out" the counter current stratification, so we have less NH3 and concentrate is less well. Thus, we progressively have less NH3 available for buffering.

9/ Generally we do not see a decrease in serum bicarbonate until the patient reaches Stage 3B or 4.

10/ As an aside, if the pt also has hyporenin/hypoaldo & develops hyperkalemia, they will develop NAGMA w/ better renal function. The reason is fascinating. Hyperkalemia inhibits glutaminase, so we produce less NH3.

11/ (The contrary is true explaining why hypokalemia is risk for hepatic encephalopathy)

12/ The treatment adds buffering capacity using sodium bicarbonate or sodium citrate (Bicitra or Shohl's). We initially assume that approximately high the daily acid is successfully buffered, therefore we need to give up to 1/2 mEq/Kg of buffer. Now let's discuss amounts.

13/ Let's assume an 80 kg man. Thus we need to give approximately 40 mEq of buffer daily. NaHCO3 tablets have either 650 mg or 1300 mg. Given a molecular weight of 84 mg/mEq, that means 7.7 mEq / 650 mg tab - 15.4 mEq / 1300 mg tab. Na citrate converts to 1 mEq/ cc.

14/ Thus, patients will be getting either four or five 650 mg tabs or two 1300 mg tabs. If we give Bicitra or Shohl's it will be 30-40 cc/day.

15/ The initial dose then needs adjustment (titration) to reach a bicarbonate level of approximately 22 mEq/L. Hopefully you better understand why patients are taking NaHCO3 or Na citrate. Please ask clarifying questions.

16/ Addendum:

Of interest, there are some data on a diet emphasizing fruits and vegetables can delay the acidosis and progression of CKD.