Abstract
Background and Objective
Urinary pH is an important factor in the preventative management of kidney stones. A variety of options are available for modulating urinary pH, including pharmaceuticals, over the counter (OTC) formulations [such as stone specific OTCs, complementary and alternative medicines (CAMs), and home remedies], and dietary modifications. These options can be overwhelming for both providers and patients and vary with regards to cost, convenience, and efficacy. In the absence of a consolidated central source of information for patients and physicians to reference, our study aims to summarize and analyze the effectiveness of these various treatment approaches to provide a more comprehensive understanding of how common interventions alter urinary pH.
Methods
The PubMed database was used to identify human clinical trials related to pharmacologic and dietary interventions to modify urinary pH. Eligible studies were selected based on the following criteria: (I) observational or interventional study; (II) urinary pH as a reported outcome of the study intervention; (III) inclusion baseline or control urinary pH data; (IV) sufficient presentation of data for analytical purposes. Data was abstracted, and the mean changes in urinary pH for each intervention were compiled and grouped.
Key Content and Findings
A total of 86 studies met inclusion criteria: 61 were randomized clinical trials, 20 were crossover or prospective studies, and 5 were observational cohort reports. In total, 150 individual experiments with a combined sample size of 2,895 were included. For urinary alkalinization, the most effective pharmaceutical, OTC formulation, and dietary change were sodium bicarbonate, Citro-Soda®, and lacto-ovo-vegetarian diet, respectively. For urinary acidification, the most effective interventions were ammonium chloride, methionine, and high protein diet, respectively.
Conclusions
Our study found that pharmaceuticals are not the only effective options for altering urine pH; select dietary changes and OTC options are also viable for patients. When considering cost, accessibility and side effects, these alternative options may be more appealing to some patients, potentially improving adherence compared to pharmaceuticals.
Keywords: Nephrolithiasis, urine, hydrogen-ion concentration, drug effects, therapy
Introduction
Modulation of urinary pH is an important tool for clinicians in the management of recurrent nephrolithiasis. Precipitation of calcium phosphate and magnesium ammonium phosphate (struvite) crystals occur at alkaline pH, while uric acid and cystine crystals precipitate at acidic pH. Calcium oxalate, the most common stone type, can crystalize at both pH extremes (1,2). Alkalinization of urine is readily achievable though a variety of modalities and is utilized in the prevention of many stone types including uric acid, cystine, or recurrent idiopathic stone formers (3). While calcium phosphate and struvite stones precipitate at a higher pH, urinary acidification is not widely utilized, primarily due to side effects associated with available therapies (4).
Urinary pH has a wide physiologic range from 4.5 to 8.0, with many causes of alterations in urinary pH, both physiologic and pathologic. Low urinary pH can result from high protein diets, metabolic acidosis, and volume depletion, while a high urinary pH may be caused by postprandial alkaline tide, vegetarian diet, urinary tract infection caused by urease-positive organisms, renal tubular acidosis (RTA), and medications such as citrate, bicarbonate, and acetazolamide (5).
Several options for altering urinary pH are available, including pharmaceuticals, over the counter (OTC) formulations [stone specific OTCs, complementary and alternative medicines (CAMs), and home remedies], and dietary modifications. These options can be overwhelming for both providers and patients, as they vary in terms of cost, convenience, and effectiveness. For example, the most common pharmacologic management for urinary alkalinization is potassium citrate, which is recommended by the American Urological Association (AUA) to raise urinary pH and increase the levels of lithoprotective urinary citrate (3). Sodium bicarbonate, as well as other citrate salts, are also used as alkalinizing agents. While these treatments can be effective, long-term adherence is poor due to side effects or cost, leading patients to seek out OTC options for managing their stone disease (6). Therefore, it is important for both patients and physicians to have a thorough understanding of the various methods for altering urinary pH. In the absence of a central source of information, we investigate the options available for urinary pH modulation and systematically outline their effectiveness. We present this article in accordance with the Narrative Review reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-275/rc).
Methods
Literature search
The PubMed database was used to identify studies related to changes in urinary pH. Our primary search criteria focused on identifying human clinical trials related to pharmacological and dietary interventions. The search strategy summary can be found in Table 1.
Table 1. The search strategy summary.
| Items | Specification |
|---|---|
| Date of search | 9/14/2023 |
| Databases searched | PubMed database |
| Search terms used | Table S1 |
| Timeframe | 1979–2023 |
| Inclusion and exclusion criteria | Inclusion criteria: (I) observational or interventional study; (II) urinary pH as a reported outcome of the study intervention; (III) inclusion of baseline or control urinary pH data; (IV) sufficient presentation of data for analytical purposes |
| Exclusion criteria: patients with renal tubular acidosis | |
| Selection process | C.C., independently screened titles and abstracts of all identified literature for initial eligibility which was reviewed by W.S., and M.S. A full-text review was then conducted for further assessment |
Selection criteria
Eligible studies were selected based on the following criteria: (I) observational or interventional study; (II) urinary pH as a reported outcome of the study intervention; (III) inclusion of baseline or control urinary pH data; (IV) sufficient presentation of data for analytical purposes. Both stone formers and non-stone formers were included, while patients with RTA were excluded. Studies in all languages were included. Titles and abstracts of all identified literature were initially screened for eligibility. A full-text review was then conducted for further assessment.
Data extraction and analysis
Data was independently extracted from all eligible studies. The extracted data included the year of publication, intervention details (route and dose), study duration, sample size, patient age, stone former status, method of urinary pH analysis, and urinary pH data (baseline, intervention, control, and statistical significance). The mean pH change was calculated using baseline and intervention data or control and intervention data. Statistical significance was categorized as either significant (P<0.05), non-significant (P>0.05), or unknown (not reported). Each unique intervention was compiled, and the mean pH change was calculated using all available data. To categorize the significance of the calculated mean pH changes for use in Figure 1, significance was noted if >50% of the pH data per intervention was statistically significant.
Figure 1.
Mean urinary pH change by intervention.
Results
Study characteristics
A total of 288 articles were initially identified from the database search. After screening titles and abstracts, 98 articles were retained, of which, 12 were excluded due to insufficient data. Ultimately, 86 articles met the eligibility criteria, including 61 randomized clinical trials, 20 crossover or prospective studies, and 5 observational cohort reports. Within these 86 studies, there were a total of 150 individual interventional experiments, with 74 having a placebo/control group and 76 comparing outcomes to baseline data. These studies were published between 1979 and 2023, with a total sample size of 2,895. The sample sizes per experiment ranged from 4 to 353, and patient ages ranged from 6.5 to 76.5 years. The overall baseline pH per experiment ranged from 5.17 to 7.40. The included studies used various methods for pH measurement, including 24-hour urine collection (48% of studies), pH meter (14%), pH strips (12%), urinalysis (6%), and unspecified methods (20%). A full list of studies, including interventions and methods of pH analysis, can be found in Table S2.
Results for urinary alkalinization
Results for urinary alkalinization are shown in Figure 1, and all data, organized by category and effectiveness, can be found in Table 2. The highest increase in mean pH changes for pharmaceuticals included intravenous (IV) acetazolamide, oral high-dose bicarbonate loading (0.3 gm/kg), the trial drug ADV7103, and oral sodium bicarbonate. Citro-Soda® had the largest change in the OTC category with the second highest change overall, followed by orange juice, mineral water, and MoonstoneTM. Among dietary interventions, the lacto-ovo-vegetarian diet showed the largest increase in pH, followed by the mixed western/vegetarian diet and the high vegetables and fruits diet.
Table 2. Urinary pH modulators separated into alkalinizing agents and acidifying agents with each intervention organized first by category (pharm, OTC, diet) and then by change in mean urinary pH.
| Intervention (route/formulation) | Category | Number of papers | Number of reported results | Mean duration (days) | Mean intervention sample size | Number of trials with stone formers | Number of significant results (%)† | Total mean pH change |
|---|---|---|---|---|---|---|---|---|
| Urinary alkalinizing agents | ||||||||
| Acetazolamide (IV) | Pharm | 1 | 1 | 0.3 | 13.0 | 0 | 1 (100%) | 2.00 |
| Bicarbonate loading (oral) | Pharm | 1 | 1 | 0.0 | 65.0 | 0 | 1 (100%) | 1.44 |
| ADV7103 (Citrate + Bicarb) (oral) | Pharm | 3 | 3 | 5.0 | 4.0 | 0 | 3 (100%) | 1.27 |
| Sodium bicarbonate (oral) | Pharm | 10 | 13 | 30.1 | 22.2 | 2 | 8 (62%) | 1.19 |
| Sodium bicarbonate (IV) | Pharm | 9 | 15 | 0.4 | 84.2 | 0 | 12 (80%) | 1.12 |
| Citrate + bicarbonate (oral) | Pharm | 1 | 1 | 42.0 | 8.0 | 1 | 1 (100%) | 1.07 |
| Indomethacin (oral) | Pharm | 1 | 1 | 7.0 | 11.0 | 0 | 1 (100%) | 1.00 |
| Potassium bicarbonate (oral) | Pharm | 3 | 5 | 63.0 | 54.0 | 0 | 5 (100%) | 0.89 |
| Citrate (oral) | Pharm | 37 | 49 | 137.8 | 33.8 | 18 | 37 (76%) | 0.61 |
| Exenatide (IV) | Pharm | 1 | 1 | 0.1 | 10.0 | 0 | 1 (100%) | 0.51 |
| Potassium gluconate (oral) | Pharm | 1 | 1 | 16.0 | 30.0 | 0 | 1 (100%) | 0.46 |
| Topiramate (oral) | Pharm | 2 | 3 | 228.0 | 19.5 | 0 | 2 (67%) | 0.45 |
| Sulfonylurea gliclazide (oral) | Pharm | 1 | 1 | 84.0 | 20.0 | 0 | 1 (100%) | 0.40 |
| Acetazolamide (oral) | Pharm | 2 | 2 | 14.1 | 57.5 | 0 | 2 (100%) | 0.39 |
| Glycine, L-tryptophan (oral) | Pharm | 1 | 2 | 42.0 | 31.0 | 0 | 1 (50%) | 0.20 |
| Neutra-phos (oral) | Pharm | 1 | 1 | 14.0 | 7.0 | 0 | 0 (0%) | 0.04 |
| Citro-soda (oral) | OTC | 2 | 2 | 31.5 | 20.0 | 0 | 2 (100%) | 1.56 |
| Orange juice (oral) | OTC | 7 | 7 | 12.0 | 9.4 | 3 | 5 (71%) | 0.68 |
| Mineral water (oral) | OTC | 4 | 6 | 28.8 | 40.3 | 1 | 6 (100%) | 0.56 |
| Lime powder (oral) | OTC | 2 | 4 | 135.0 | 24.5 | 2 | 2 (50%) | 0.52 |
| Milk (oral) | OTC | 2 | 2 | 28.0 | 6.0 | 0 | 2 (100%) | 0.36 |
| Cantaloupe Juice (oral) | OTC | 1 | 1 | 0.3 | 10.0 | 1 | 1 (100%) | 0.36 |
| Moonstone (oral) | OTC | 1 | 1 | 7.0 | 10.0 | 1 | 1 (100%) | 0.33 |
| Performance drink (oral) | OTC | 1 | 1 | 3.0 | 10.0 | 0 | 1 (100%) | 0.31 |
| Lime Juice (oral) | OTC | 1 | 1 | 0.3 | 10.0 | 1 | 0 (0%) | 0.25 |
| Pickles (oral) | OTC | 1 | 1 | 84.0 | 9.0 | 0 | 0 (0%) | 0.17 |
| Omeprazole (oral) | OTC | 1 | 1 | 10.0 | 10.0 | 0 | 0 (0%) | 0.10 |
| Vitamin C (oral) | OTC | 5 | 7 | 104.8 | 17.2 | 3 | 0 (0%) | 0.03 |
| Gatorade drink (oral) | OTC | 1 | 1 | 3.0 | 10.0 | 0 | 0 (0%) | 0.19 |
| Lacto-ovo-vegetarian diet (oral) | Diet | 1 | 1 | 5.0 | 10.0 | 1 | 1 (100%) | 0.85 |
| Mixed western/vegetarian diet (oral) | Diet | 1 | 1 | 5.0 | 10.0 | 1 | 1 (100%) | 0.56 |
| DASH diet (oral) | Diet | 1 | 1 | 56.0 | 21.0 | 1 | 0 (0%) | 0.50 |
| High vegetables and fruits diet (oral) | Diet | 5 | 8 | 50.0 | 43.2 | 0 | 6 (75%) | 0.35 |
| High-carb diet (oral) | Diet | 1 | 1 | 4.0 | 16.0 | 0 | 0 (0%) | 0.30 |
| Potato (oral) | Diet | 1 | 1 | 16.0 | 30.0 | 0 | 1 (100%) | 0.28 |
| French fries (oral) | Diet | 1 | 1 | 16.0 | 30.0 | 0 | 1 (100%) | 0.25 |
| Urinary acidifying agents | ||||||||
| Ammonium chloride (oral) | Pharm | 1 | 1 | 0.3 | 10.0 | 0 | 0 (0%) | −1.63 |
| Furosemide (IV) | Pharm | 2 | 2 | 0.2 | 8.5 | 0 | 1 (50%) | −0.52 |
| Sodium chloride (IV) | Pharm | 2 | 2 | 1.0 | 113.0 | 0 | 1 (50%) | −0.48 |
| Dapagliflozin (oral) | Pharm | 1 | 1 | 84.0 | 24.0 | 0 | 0 (0%) | −0.10 |
| Methionine (oral) | OTC | 1 | 2 | 56.0 | 53.0 | 1 | 1 (50%) | −0.72 |
| Fructose (oral) | OTC | 1 | 1 | 14.0 | 33.0 | 0 | 1 (100%) | −0.26 |
| Apple cider vinegar (oral) | OTC | 2 | 2 | 84.0 | 8.5 | 0 | 1 (50%) | −0.21 |
| Cranberry (oral) | OTC | 11 | 14 | 35.4 | 16.4 | 1 | 8 (57%) | −0.16 |
| Citric acid (oral) | OTC | 1 | 2 | 7.0 | 13.0 | 1 | 0 (0%) | −0.05 |
| Lemonade (oral) | OTC | 5 | 5 | 5.8 | 13.6 | 2 | 0 (0%) | −0.02 |
| Sleep deprivation (NA) | OTC | 1 | 1 | 2.1 | 12.0 | 0 | 0 (0%) | 0.00 |
| Food deprivation (NA) | Diet | 1 | 1 | 2.8 | 12.0 | 0 | 1 (100%) | −1.20 |
| High protein diet (oral) | Diet | 3 | 3 | 9.3 | 25.7 | 0 | 3 (100%) | −0.65 |
| Keto diet (oral) | Diet | 1 | 1 | 4.0 | 16.0 | 0 | 0 (0%) | −0.55 |
| Low-oxalate diet (oral) | Diet | 1 | 1 | 56.0 | 20.0 | 1 | 0 (0%) | −0.10 |
†, number of reported results that the original authors found to be statistically significant (P<0.05). DASH, Dietary Approaches to Stop Hypertension; IV, intravenous; NA, not applicable; OTC, over the counter; pharm, pharmaceutical.
Results for urinary acidification
Results for urinary acidification are shown in Figure 1, and all data, organized by category and effectiveness, can be found in Table 2. The highest decrease in mean pH change for pharmaceuticals included oral ammonium chloride, followed by IV furosemide and IV 0.9% sodium chloride. Among the OTC interventions, oral methionine showed the greatest acidification, followed by oral fructose, apple cider vinegar, and cranberry juice. Of the dietary interventions, food deprivation showed the largest decrease in pH, followed by the high protein diet and the keto diet.
Discussion
Dietary methods
Dietary therapies are a critical component of stone prevention. The AUA guidelines include general dietary recommendations, such as increased fluid intake for all stone formers and avoiding or consuming certain foods based on stone type (3). We analyzed studies on more specific dietary eating patterns to determine their effect on urinary pH and to assess whether there is evidence for their impact on stone risk or prevention. Popular diets, such as plant-based, Dietary Approaches to Stop Hypertension (DASH), Mediterranean, flexitarian, and vegetarian diets, may protect against kidney stone development, while high protein and ketogenic diets may raise stone risk (7).
Alkylating agents
Our analysis found that diets high in fruits and vegetables significantly increase the urinary pH, which may be beneficial for stone prevention. Vegetarian diets, in particular, raise urinary pH due to high content of potassium, bicarbonate, and alkaline components (8). The lacto-ovo vegetarian diet showed the highest increase in urinary pH and may offer specific benefits in patients with cystinuria (9). In comparison, the mixed Western/vegetarian diet—which has a similar protein content but a higher proportion of animal proteins—was less effective at increasing urinary pH. Similarly, the DASH diet, which is notably high in fruits and vegetables, significantly increased urinary pH when compared to the low-oxalate diet in recurrent stone formers. Additionally, the DASH diet showed a possible trend of decreasing calcium oxalate supersaturation (10).
Acidifying agents
High protein diets decrease urinary pH due to a high content of sulfur-containing amino acid, such as methionine (4). The low-carbohydrate, ketogenic diet—which consists of high-fat and moderate protein intake—was found to decrease the urinary pH when compared to a high-carbohydrate diet, which slightly raised the urinary pH (11). Similarly, food deprivation significantly decreased urinary pH, likely due to an increase in ketogenesis, a mechanism shared with the ketogenic diet.
OTC therapies
In our study, the category of OTC treatments includes stone specific OTCs, CAMs, and home remedies such as orange juice, Gatorade, pickles, and others. Long-term adherence is critical to the success of metabolic stone management, which has led to the exploration and utilization of stone specific OTC treatment options (6). CAMs have gained popularity in recent years, with a survey showing 80% of patients are aware of CAMs and 56% of recurrent stone formers report using them (12). Many of these non-pharmaceutical therapies aim to increase urinary pH and citrate levels through the use of citrus fruits, non-citrus fruits, and citrate-supplemented drinks. Bicarbonate-rich mineral water has also been investigated as an alkylating agent. Additionally, various urinary acidifying agents such as cranberry, apple cider vinegar, pickles, and fructose, have been studied.
Alkylating agents
Our analysis found that orange juice was shown to increase urinary pH and citrate levels. However, one study found that orange juice was unable to decrease urinary saturation of calcium oxalate compared to potassium citrate (13). Additionally, compared to lemonade, orange juice has greater effects on pH and citrate levels, as many studies have shown lemonade does not alter urinary pH and has only a modest effect on citrate levels (14-17). Lime powder containing potassium and citrate was found to increase urinary pH and citrate in stone-forming patients, and one study found blended cantaloupe juice increases pH to a level equivalent to orange juice (18).
A study on sports drinks containing citrate showed that, compared to water, only Performance (Shaklee Corp., Pleasanton, CA, USA)—not Gatorade (Gatorade, Chicago, IL, USA)—caused an increase in urinary pH and citrate (19). Bicarbonate-rich mineral water directly provides an alkali load, leading to significant urinary alkalinization. Furthermore, bicarbonate-rich mineral water was found to decrease supersaturation of calcium oxalate and uric acid in both stone-forming and healthy subjects (20,21).
Drink supplements targeted for urinary alkalinization, such as Moonstone® (22) and Citro-Soda® (Abbott), contain various alkylating agents, including citrate and bicarbonate salts. These formulations are easily accessible to patients, using dissolvable packets or gummies, which may improve adherence. Both drinks have been shown to be well tolerated and effective at increasing urinary pH (22,23).
Acidifying agents
Vitamin C was first reported as an acidifying agent in the 1970s, however, more recent studies have been unable to replicate these findings. Excessive vitamin C supplementation may increase stone formation due to elevated urinary oxalate and increased risk of calcium oxalate crystallization (24).
L-methionine has been suggested as a possible preventative therapy by acidifying the urine, as demonstrated in long-term (25) and short-term studies (4). While an earlier study suggested an association with sulfur-containing amino acids and hypercalciuria (26), a recent study has shown that L-methionine does not cause hypercalciuria at physiologic doses (10 mmol/d) (4).
Omeprazole, a proton pump inhibitor (PPI), has not been shown to affect urinary pH; however, a recent report demonstrated an association between PPI use and incident stone formation, possibly due to its effects on urinary magnesium and citrate (27).
Cranberry juice has been shown to significantly decrease urinary pH in some studies, while others have found no effect. An assessment of urinary stone risk factors revealed significant increases in urinary calcium and oxalate, as well as decreases in urinary and serum uric acid (28).
Fructose has been associated with an increased risk of incident kidney stones (29) and, while it significantly decreases urinary pH, it also increases urinary oxalate and decreases urinary magnesium (30).
Apple cider vinegar may decrease urinary pH, though this effect has not been consistently reported (31). At the population level, apple cider vinegar has been associated with a decreased risk of kidney stone formation (32), with proposed mechanisms including epigenetic regulation influencing urinary citrate and calcium excretion (33) and alteration of the gut microbiome that promote oxalate degradation rather than absorption (34).
Pharmaceutical therapies
Alkylating agents
While many pharmaceutical therapies are available to alkalinize urine, the primary intervention used in stone management is oral citrate and bicarbonate salts. Citrate therapy is effective, with most studies finding significant increases in urinary pH. Additionally, citrate is lithoprotective by binding calcium and can be used for management of recurrent calcium stones. Although citrate is available bonded to several different cation formulations, potassium is preferred due to its tolerability and its independent ability to reduce urinary calcium excretion (35). However, inconsistent availability of potassium citrate, gastrointestinal side effects, and high costs, have contributed to the poor adherence rates.
Bicarbonate salts are another commonly used pharmacologic agent for urinary alkalinization in stone formers. We found that, in many studies, both oral and IV bicarbonate resulted in similar urinary alkalinization. Furthermore, increasing the oral dose to 0.3 gm/kg body weight in bicarbonate loading enhanced the mean pH change. A study using the trial medication ADV7103, a prolonged-release granule formulation containing a 1:2 combination of potassium citrate and potassium bicarbonate, demonstrated a more effective alkalinization than citrate or bicarbonate alone, or when taken together in a 2:1 ratio (36).
Medications such as acetazolamide and topiramate have been shown to increase urinary pH; however, their association with an increased risk of stone formation limits their potential use. IV acetazolamide demonstrated the largest increase in urinary pH, while its oral formulation only modestly raises pH. Long term acetazolamide treatment has been associated with an increased risk of urolithiasis (37), likely due to a decrease in urinary citrate and an increase in urinary oxalate (38). Similarly, topiramate has been linked to the development of kidney stones, as it inhibits carbonic anhydrase, a mechanism shared with acetazolamide (39,40).
Other medications that can increase urinary pH have not yet been extensively studied in the context of kidney stones. Non-steroidal anti-inflammatory drugs (NSAIDs) may increase urinary pH due to inhibition of prostaglandin synthesis (41); however, they are often avoided because of the risk of chronic kidney disease. Diabetes medications, such as exenatide and sulfonylureas, were found to slightly raise urinary pH, while dapagliflozin decreased urinary pH in mouse models (42) but increased urinary citrate and ketone excretion in humans (43). Glycine and tryptophan, investigated for their uric acid-lowering effects, were also found to significantly increase urinary pH (44).
Acidifying agents
Medical therapies used to acidify urine are more limited, particularly in the context of preventing struvite and calcium phosphate stones. Ammonium chloride has been used for urinary acidification; however, it is an impractical long-term strategy for struvite stones due to the risk of metabolic acidosis from hyperchloremia (45). The loop diuretic furosemide causes urinary acidification but is not commonly utilized because of side effects such as dehydration and hypokalemia. Sodium chloride infusions have also been shown to induce urinary acidification; however, this approach is unlikely to be useful in management of kidney stones. Phosphate salts, such as potassium acid phosphate, are used in the management of calcium stones by reducing urinary calcium excretion (46). Although phosphate supplementation is hypothesized to decrease urinary pH, a small study involving seven patients with neurogenic bladder found no significant change (47).
Urinary pH modulation: current landscape, gaps, and future work
The current landscape in urinary pH modulation includes urinary alkalinization for patients with uric acid and cystine stones, primarily using potassium citrate to raise the pH and urinary citrate to optimal levels (3). Sodium bicarbonate is another common pharmacologic therapy effective at increasing urinary pH. However, there are fewer reliable options for urinary acidification in stone formers. While the European Association of Urology (EAU) guidelines include L-methionine or ammonium chloride for the management of struvite and calcium phosphate stones, the recommendation is weak, and there remains limited alternatives for urinary acidification (48).
Dietary recommendations specifically targeting urinary pH modulation is scarce. The AUA recommends increased fluid intake for all stone formers, but specific dietary strategies primarily focus on addressing metabolic abnormalities related to urinary oxalate, calcium, citrate, and cystine. Our study found that many diets high in vegetables can increase urinary pH, which could be a useful in management of kidney stone disease. Future studies comparing specific diets and their direct relationship on urinary risk factors and kidney stone disease could provide valuable insight.
It is well known that patients explore alternatives therapies beyond pharmaceuticals to treat or prevent kidney stones. Common therapies include fruit juices, supplements, and various other drinks. In our study, we have found that orange juice, mineral water, vitamin C, cranberry, and lemonade have been the most extensively studied in the context of stone disease. Other therapies, such as apple cider vinegar, lime powder, cantaloupe juice, sports drinks, and drink supplements, show potential metabolic benefits; however, limited studies make these claims less reliable. Additionally, we were unable to identify studies on other popular CAMs, such as Lithobalance™ and KSPtabs®. Further investigation of these therapies regarding their metabolic effects and impact on stone recurrence could expand treatment options for patients.
Pharmaceuticals remain the most studied treatments for urinary pH modulation and stone disease in general, with many studies focusing citrate therapy. During our review, we found that the majority of these studies focused on potassium citrate or potassium magnesium citrate, as these are the most common and clinically favored. Other citrate formulations, such as sodium citrate, calcium citrate, potassium sodium citrate, and potassium calcium citrate, have been less studied. Few studies directly compare these formulations to potassium citrate, representing a potential area for future research. Additionally, our search did not find studies specifically testing for sodium potassium bicarbonate, another commonly used bicarbonate preparation. Lastly, newer pharmaceuticals, such as trial medication ADV7103 and the increasingly popular class of sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown promise for use in stone disease, highlighting another important area for future investigation.
Limitations
This study has several limitations that should be considered. The included studies varied in design and quality, with some relying on less accurate methods for measuring urinary pH, such as pH strips or spot urine samples, rather than the gold-standard 24-hour urine collection. The diversity of study populations, including healthy individuals and recurrent stone formers across a wide age range, may also limit the applicability of findings to specific subgroups. Additionally, the studies were conducted in various settings, including intensive care units and inpatient environments, which may limit their generalizability.
Furthermore, the number of studies per intervention varied significantly, with some interventions supported by multiple studies and others by only one. This variability, combined with the lack of direct comparisons between interventions, may affect the strength of our findings and limit the ability to draw definitive conclusions. Despite these limitations, this study provides a comprehensive overview of urinary pH modulation and highlights key areas for future research, particularly in understanding the tools for urinary pH modulation and their role in stone prevention.
Conclusions
There are a multitude of different therapies aimed at modifying urinary pH. Our study found that pharmaceuticals are not the only effective options for altering urine pH; select dietary changes and OTC options are also viable for patients. When considering cost, accessibility and side effects, these alternative options may be more appealing to some patients, potentially improving adherence compared to pharmaceuticals. While many of these methods have been shown to effectively increase or decrease urinary pH, their impact on stone recurrence requires further investigation. This study provides a valuable resource for understanding how common interventions influence urinary pH and highlights the need for future research to optimize stone prevention strategies.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Footnotes
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-275/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-275/coif). M.C.B. received consulting fee from Alnylam Advancing Care in PH1, Collective Acumen, SAI MedPartners LLC, and PeerView Institute for Medical Education; and lecture payment from Novo Nordisk. M.C.B. is also a participant of Nedosiran Nephrology Advisory Board and member of Oxalosis and Hyperoxaluria Foundation Scientific Advisory Council. M.S. is a cofounder in the development of Moonstone Stone Stopper® and has stock options in Moonstone Nutrition. The other authors have no conflicts of interest to declare.
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