Thursday, July 29, 2010

Just a spoon full of (bicarbonate) makes the medicine go down..

Partly because I like the idea of my patients taking spoonfuls of household remedies for their kidney disease, and partly because I like the elegant simplicity of the remedy, I was pleased to see another study touting the renoprotective benefits of sodium bicarbonate. In this month’s issue of KI, Mahajan et al evaluated the effect of daily Na bicarbonate supplementation on patients with *mild CKD and *normal serum bicarbonate levels.

120 nondiabetic patients with eGFR between 60 and 90 mL/min, and macroalbuminuria (Ualb 200-2000 mg/d) were randomized to receive tablets containing 0.5 mg/kg Na bicarbonate, NaCl, or sucrose (placebo). Over the course of five years, eGFR (measured via creatinine and cystatin methods) and urinary albumin were followed.

The NaHCO3 group showed a statistically significant decrease in the rate of eGFR decline, as well as progression of albuminuria, compared to the two control groups. Interestingly, these results were observed in the absence of a significant difference in serum bicarbonate levels. The authors postulate that perhaps bicarbonate supplementation lessens the degree of tubulointerstitial injury by decreasing urinary endothelin-1 production. Excretion of endothelin-1 and N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular injury, were decreased in the bicarbonate group, lending support to this hypothesis.


The study does have some limitations, notably the restriction of study eligibility to only patients with presumptive hypertensive nephropathy. None underwent kidney biopsy before or after the study. The mechanism of renal injury in these patients may be markedly different from other forms of renal disease; and the diagnosis category of hypertensive nephropathy itself may include several different mechanisms of disease. The study population was made up of >60% African Americans, and 25% Hispanics, so it may not be applicable to patients of other races. Also, the issue of increased salt intake was not addressed (interestingly, urinary Na excretion did not increase in the NaCl and NaHCO3 groups). Still: the data are compelling, and the treatment is easy and cheap. When taken together with the results from de Brito-Ashurst et al’s finding last year showing slowing of CKD stage IV progression with bicarbonate supplementation, it is becoming easy to argue that maybe all of our patients ought to take a spoonful (or two, or three) of baking soda with their daily meds.

3 comments:

Anonymous said...

Very interesting stuff. Btw, the bicarb dosing was 0.5mEq/kg, not mg/kg, was it not? 1mEq = 84mg bicarb

lisajcohen said...

Yes, you are right. Sorry about my unit mistake!

Anonymous said...

Lisa: Also worth noting: Large associational studies (Raphael, n=1092, African-Americans), Kidney Int. 2010 Oct 2; Shah, 2009 n=5422 [Am J Kidney Dis] 2009 Aug; Vol. 54 (2), pp. 270-7, and previous sodium citrate work by Donald Wesson's Texas group (culminating in Mahajan study you mentioned.)

IN SUMMARY:
1. Long duration studies, early CKD, small cohorts but substantial statistical power because effect so dramatic. (44% slope reduction)

2. Benefit found for both very early and very late CKD (Brito-Ashurst).

3. Large associational studies with similar conclusions.

4. Nearly complete absence of the sodium complications "everyone expected" (conventional wisdom was wrong). EVEN in near-dialysis IV/V CKD (Brito-Ashurst). Arguably, risk considerably lower in Mahajan early CKD cohort.)

5. Animal studies dating back all the way to the 1980's regarding alkali therapy.

6. Statistically independent effect with comparable potency to all other strategies COMBINED.


Allowing CKD to progress to IV/V has known consequence of increasing mortality risk on order of 1000%. Realistically, can 600 mg/day net of sodium be even remotely comparable risk compared to CKD progression?

Put another way, what's the downside? (lets assume responsible level of patient monitoring.)

It might be a waste of time, but it might also delay dialysis by 10 years. Regardless it probably ISN'T particularly dangerous (toxicity lower than the overwhelming majority of prescription drugs, actually quite modest total sodium. If you really care that much perhaps consider K-bicarb instead for relatively intact GFR populations)

So, what the hell is everyone waiting for?