Current Opinions in nephrology and hypertension has an excellent review this month on the rationale for bicarbonate treatment to slow the progression of CKD. The original data animal data was derived from the 5/6 nephrectomy model where rats fed with an acid chow developed metabolic acidosis and had relatively rapid GFR decline that could be ameliorated by giving the rats sodium bicarbonate. Interestingly, switching them to a low-acid, soy-based diet had a similar effect suggesting that simply reducing net acid intake is just as effective. The same group developed a 2/3 nephrectomy model in rats where they did not develop acidosis but the decline in renal function could still be slowed by treatment with bicarbonate. Current guidelines in humans suggest that patients should be prescribed bicarbonate when the TCO2 is less than 22 but recent studies have suggested that even above this level, patients with a reduced GFR may have net acid retention in the kidney with a potential for consequent renal injury that could be prevented by alkali treatment. This, of course is balanced by the fact that we do not want to give large quantities of sodium to patients with CKD.
More Fruit Please
One suggestion is to look closer at the diet of patients with CKD. The biggest source of dietary acid is animal protein and reducing meat intake will reduce overall acid intake (in contrast, we all see elderly malnourished patients on dialysis with high pre-dialysis bicarbonate levels that is actually a negative prognostic sign). The DASH diet is high in fruits and vegetables and is already a first line treatment for hypertension. Because it has a high component of fruits and vegetables, it has a high alkali content and could substitute for exogenous bicarbonate treatment in some patients. The trade-off is that it is also high in potassium and this would need to be carefully monitored in patients with a low GFR. The take home for me is that this explains, at least in part, the deleterious effects of a diet high in animal protein in patients with CKD and that we can potentially treat acidosis in these patients without resorting to large quantities of oral sodium bicarbonate. See this previous post on the benefits of bicarbonate therapy in patients with mild CKD.
It's interesting that the article by Wesson does not mention ammoniagenesis or ammonium excretion at all. It cites Hostetter's JCI paper from 1985 but suggests the mechanism of benefit is related to what Wesson himself has shown: effect on endothelin and aldosterone. That's a bit peculiar given the history of this, as Dr. Rondon suggests. I have thought that perhaps the effect of alkali would be predicted by urinary ammonium levels as normal serum HCO3 does not preclude benefit.
In my clinical practice with CKD patients, assessment of daily urinary sodium excretion is the first step on the very first visit. I use the Moroni-Mitch formula and a one-week dietary diary to estimate daily dietary protein intake. I made an attempt in reducing sodium and protein intake in almost every patient. If the patient is well intructed, sodium bicarbonate at a dose of 1-2g/day (or even more if needed) may be prescribed without a clinically significant increase in sodium balance. Do not forget: 1 g of Bicarb is equal to about 12 mEq of sodium, whereas 1 g of NaCl contains about 17 mEq of sodium. My personal target for sodium restriction in CKD range from 80 to 100 mEq/day. A common Western diet may include 250 mEq/day of sodium.
In normal Italian kidney function teenagers and young adults evalueted because of kidney stones, I have seen a sodium intake of 500 mEq/day or even more as a very common feature. Interestingly, this finding is uncommon among older normal function patients (median sodium intake of about 180-200 mEq/die). I think this difference may be related to different dietetic habits, particularly to the popularity of an American-style diet among the youngest Italians.
The work by Wesson and others before him has REPEATEDLY failed to show the sodium-driven volume issues everyone "expects" to occur. Sodium bicarbonate is NOT the same as salt, and the preponderance of what little evidence we have suggests it is the CHLORIDE ion that actually matters.
A more thorough literature review will show that the fears regarding sodium bicarbonate are unfounded. In fact, there is on the order of 95% chance there WON'T be a measurable impact on fluid or hypertension, even suggestions in crossover studies that overall, blood pressure is actually REDUCED modestly on bicarb therapy. This doesn't mean that there are NEVER issues, just that they USUALLY don't happen.
Get over it. What everyone was taught is just plain wrong.
That's a good point about sodium bicarbonate but even if there is no significant volume issue, there may still be a benefit to avoiding sodium in general in these patients. Our (western) diets are too high in salt as it is and having another reason to impress on our patients the real benefits of healthy eating can't be a bad thing.
Great post ! One of the main mechanisms for progression is the production of large amounts of ammonia in response to acidosis. There is evidence that ammonia activates the alternative pathway of complement causing inflammation and aggravating interstitial fibrosis. This same mechanism is playing a role in hypokalemic nephropathy. I, however disagree with your suggestion that sodium bicarbonate could result in significant fluid overload. It is well established that the kidneys handle sodium bicarbonate in a different way than sodium chloride . The answer to this probably lies in the interaction between Pendrin and ENaC. I have a post about this sometime ago.