Alkalinizing agents reduce the recurrence risk for multiple stone types, but they are the gold standard treatment for the management of uric acid stones, where the most common cause is acidic urine. Thankfully, >90% of uric acid in the urine is soluble or “dissolved” at a pH of 6.5 or higher, which is clinically achievable in most patients.

The mainstay of urinary alkalinization has been potassium citrate (KCit). KCit is highly effective at achieving urinary alkalinization, but there are barriers to compliance. The medication can be quite expensive, especially for patients without prescription insurance coverage, and the pills themselves can be difficult to swallow for some patients. Perhaps more than we realize, some patients experience bothersome stomach upset that may limit compliance, including up to 48% of patients leaving KCit studies early due to gastrointestinal (GI) side effects in a review by Mattle and Hess.¹ Finally, some stone formers are intolerant of the potassium load associated with KCit, such as those with significant renal insufficiency and those on potassium-sparing medications like ACE inhibitors. Thus, in many patients an alternative to KCit is desirable.

Figure. Patient 24-hour urinary values before and after starting NaHCO₃ therapy. Patients experienced significant rise in urine pH, citrate and sodium, without change in urine calcium levels. Figure reflects update of data originally reported by Penniston et al.⁷ Illustration courtesy of Kristina Penniston.

Sodium bicarbonate (NaHCO₃), also known as baking soda, has a long track record in the treatment of metabolic acidosis in patients with chronic kidney disease. Di Iorio et al reported improved survival as well as lower progression to dialysis in patients treated with NaHCO₃, without any increase in hypertension or admissions for fluid retention.² NaHCO₃ also has equivalent benefits to urinary risk factors for stone formation to KCit, both in rise in urine pH and citrate levels. In a randomized, double-blind, crossover study by Pinheiro et al, both KCit and NaHCO₃ resulted in a significant increase in urine pH from an average baseline of 6.1 to 7.3 and 7.4, respectively.³ Both treatments also resulted in a significant increase in urine citrate, from a mean baseline of 287 mg/day to 491 mg/day for KCit and 495 mg/day for NaHCO₃. While that study was of calcium stone formers, a smaller study by Sakhaee et al of 5 uric acid stone formers reported similar findings when participants were prescribed 60 mEq a day of either KCit or NaHCO₃.⁴ These uric acid stone formers had a mean urine pH of 5.4 at baseline but achieved a mean urine pH of 6.7 on either type of alkalinizing agent, well within the target range for uric acid stone formers.

Sodium bicarbonate is inexpensive and readily available, whether purchased as a box of baking soda at the grocery store or as prescription tablets. Each half teaspoon of baking soda powder provides 25 mEq alkali. We often advise patients to mix one-quarter teaspoon of baking soda in a liquid of their choice and drink it on an empty stomach twice a day, but the dose could be adjusted if patients are converting from a known dose of KCit by matching the milliequivalents prescribed (20 mEq KCit converted to baking soda would be about one-half teaspoon).

All of this sounds great: NaHCO₃ is cheap, is well tolerated, and improves both urine pH and citrate. So why hasn’t it “taken off” in clinical practice the way KCit has? Part of the reason is the “bad reputation” sodium has developed in modern medicine. Sodium chloride (NaCl), or salt, has been blamed for hypertension, and while even that is up for debate in the modern cardiovascular literature, there does appear to be a proportion of hypertensive patients who are so-called “salt sensitive.” Whether it is the sodium or the chloride in salt causing this blood pressure effect was considered largely irrelevant, as more than 85% of the sodium consumed in modern diets is from NaCl. Recent studies, however, have suggested that the chloride component may play an even larger role in hypertensive response than the sodium, and that perhaps chloride restriction rather than sodium should be advised.⁵ Due to this concern for hypertension, the study by Di Iorio et al measured patient blood pressures and found no significant effect of NaHCO₃ on hypertension.²

Another explanation for the hesitation in adoption of NaHCO₃ therapy by urologists is a concern that the increased sodium load will result in hypercalciuria. Classically, we have taught that there is a mathematical relationship between dietary sodium consumption and urine calcium levels such that for every 100 mEq/day that sodium consumption is reduced, urine calcium levels may be expected to drop by 40 to 50 mg/day. However, both older and more recent studies suggest that this might not be the entire story, and that perhaps it is the pairing of Na and Cl in table salt that may promote the excretion of calcium in the urine. Lemann et al administered loads of KCl, NaCl, KHCO³ and NaHCO₃ to patients on a controlled study diet and found that only NaCl resulted in an increase in urine calcium.⁶ Sodium when paired with bicarbonate as an anion did not appear to cause hypercalciuria. The previously discussed study by Pinheiro et al also reported that patients receiving NaHCO₃ did not experience a rise in their urine calcium levels.³ A more recent clinical study by Penniston et al prescribed baking soda to 33 stone formers for whom alkali citrate therapy was indicated.⁷ With a mean of 9 months between 24-hour urine collections, they found that both urine pH and citrate significantly increased, as did the amount of sodium in the urine, but that urine calcium levels were unchanged (p=0.92, see figure).

These studies suggest that sodium bicarbonate/baking soda may represent an inexpensive, safe and well tolerated form of alkali citrate with which to treat uric acid stone formers, with alkalinizing and citraturic responses similar to KCit. However, it is important to note that only 1 of these studies specifically reported outcomes in uric acid stone formers,⁴ and none reported stone-specific outcomes such as stone growth rates or need for surgery. Future studies should seek to address this. Additionally, some stone patients, particularly those with concomitant hypercalciuria, may benefit more from KCit than NaHCO₃, since KCit has been shown to independently reduce urine calcium levels. It is beneficial, however, to have more options available for the treatment of our kidney stone patients, and sodium bicarbonate certainly merits a place in our toolbox.