Introduction

Kidney stones are prevalent. An estimated 1 out of 11 Americans will experience a stone event in their lifetime and approximately 50% of first-time stone formers will have a repeat stone event in the subsequent 10 years.¹ Therefore, for patients who are motivated or presenting with a recurrent stone episode, the AUA guidelines recommend metabolic testing for kidney stone prevention (statement 5).² Metabolic testing includes: 1 or 2, 24-hour urine collections and a stone analysis (statements 4 and 6).² Herein, we will focus on 2 aspects of the 24-hour urine collection—citrate and pH—and techniques and supplements to naturally improve these parameters.

Citrate is a urinary stone inhibitor that directly binds to calcium ions to form soluble calcium-citrate complexes and inhibits calcium-oxalate crystal aggregation.³ Citrate also increases urinary pH, which improves the solubility of calcium-oxalate and uric acid stones.⁴ Indeed, oral potassium citrate has been proven to increase urinary pH and citrate levels, resulting in reduced rates of stone formation/recurrence.⁵ However, potassium citrate can be cost-prohibitive and cause multiple gastrointestinal side effects, thus long-term compliance is low.⁶ Therefore, finding natural, tolerable alternatives to increase urinary citrate and pH is desirable.

AUA guidelines recommend that patients with low urinary citrate and calcium stones increase their intake of fruits/vegetables and limit nondairy protein (statement 11).² Similarly, patients with uric acid/calcium stones with high uricosuria should limit their intake of nondairy animal protein (statement 12).² Physiologically, systemic and urinary pH are closely linked to citrate as ingested citrate undergoes hepatic metabolism into bicarbonate leading to systemic alkalosis.⁷ Urinary citrate is increased during alkalotic states due to decreased proximal tubule reabsorption of citrate (resulting in hypercitraturia and alkaluria). However, the opposite is also true, during systemic acidosis, citrate is reabsorbed and incorporated into the Krebs cycle (resulting in hypocitraturia and aciduria). Thus, systemic alkalinization is actually the most important factor for increasing urinary citrate.⁷

Diet

Our main dietary source of alkali is from fruits/vegetables (stored as potassium citrate) and our main dietary source of acid is from nondairy animal proteins (from sulfur moieties on amino-acids). Thus, it’s no surprise that the Dietary Approaches to Stop Hypertension (DASH) diet (which has a high intake of fruits, vegetables, whole grains, and a low intake of salt, sugars, and red/processed meats) resulted in a reduced risk for kidney stones (HRs 0.55-0.60, P < .001).⁸ In another study of stone patients who ate no fruits/vegetables at baseline, the addition of fruits/vegetables resulted in a 68% increase in citrate, 64% increase in urine volume, and pH increase of 0.35, as well as a decrease in calcium and uric acid stone supersaturations.⁹ Similar benefits were seen with the Mediterranean diet (legumes, whole grains, fruits, nuts, vegetables, etc). Indeed, in a longitudinal study of 3 cohorts of health care workers (n = 193,627), the authors identified that patients who adhered more closely to the Mediterranean diet had higher urinary citrate, volume, and pH and were at lower risk of kidney stones than those who did not (HR 0.72, P < .001).¹⁰

Citrus Beverages

Citrus fruits contain high amounts of citrate so it’s been hypothesized they could improve urinary citrate and pH. Indeed, lemonade has been shown to increase urinary citrate by 204 mg/d¹¹ and others have also shown similar improvements (in citrate levels).¹² However, in a randomized cross-over study comparing orange juice (OJ) and lemonade, Odvina found that OJ increased urinary citrate and pH, whereas lemonade did not have any effect.¹³ The authors hypothesized that this was due to the citrate in OJ being complexed with potassium (providing alkali benefit), but the citrate in lemons is primarily citric acid—citrate complexed with a hydrogen ion—negating the bicarbonate produced by intrahepatic metabolism of citrate; ie, there is no alkali benefit with citric acid.¹³

Haleblian et al measured citrate concentrations of commercially available beverages.¹⁴ Grapefruit juice had the highest citrate content (197.5 mEq/L). OJ and Crystal Light lemonade (CLL) also had 144.6 and 117.2 mEq/L of citrate, respectively.¹⁴ Unexpectedly, several large epidemiologic studies identified an increased risk of stones with grapefruit juice and this could be due to an increase in urinary oxalate with grapefruit juice.¹⁵ CLL is an attractive option compared to OJ because CLL is a low-calorie beverage and sugar has an independent calciuric effect.¹⁶ Furthermore, excess calories from OJ could worsen obesity (another risk factor for stones). To avoid these negative effects, Large et al performed a randomized, cross-over study using low-calorie OJ and identified that Kroger low-calorie OJ and CLL both increased urinary citrate (177.9 and 155.6 mg/d, respectively) and pH (0.74 and 0.25, respectively) in nonstone-forming, healthy subjects.¹⁷ Thus, low-calorie OJ and CLL both may be effective options for improving urinary stone risk parameters.

Noncitrus Juices and Supplements

Noncitrus juices have also been tested. For example, melon juice was shown to increase urinary citrate and pH.¹⁸ The authors hypothesized that alkali citrate and malate within melon could be responsible for this effect. Malate also functions as a polycarboxylic anion to promote systemic alkalosis, which in turn increases citraturia.¹⁹ Coconut water has also been shown to increase urinary citrate by 29%, but no effect on urinary pH was identified.²⁰ This effect was also attributed to the malate content within coconut water.

Multiple supplements are also available over-the-counter that aim to improve urinary stone risk parameters. We will highlight only a few for brevity. Canvasser et al compared LithoLyte (2 packets BID) and KSPtabs (1 tablet BID) and found LithoLyte significantly increased urinary pH, but not citrate.²¹ KSPtabs increased urinary citrate and pH (200 mg/d and 0.40, respectively).²¹ Moonstone (1 packet BID) was also found to increase urinary citrate by 237.2 mg/d (P < .05) and urinary pH (P < .05).²² Thus, these supplements could also be feasible alternatives to potassium citrate therapy.

Conclusion

In conclusion, there are multiple natural strategies that can be utilized to increase urinary pH and citrate. In general, patients wanting to pursue natural strategies should eat a diet rich in fruits and vegetables, moderate nondairy animal protein, and drink citrus-containing beverages such as low-calorie OJ.