Causes and Risk Factors
One of the most important risk factors for all types of kidney stones is dehydration (Wong 2015; Curhan 2012; Antonelli 2015). When there is too little water in the urine, stone-forming molecules are more concentrated and more likely to form crystals (Aggarwal 2013). In general, a urine flow rate of less than 1 L per day increases the risk of stone formation (Curhan 2012), and guidelines for people with a history of kidney stones include the recommendation to maintain their urine output above 2 L per day (Antonelli 2015).
In addition to the concentration or diluteness of the urine, other urinary factors are associated with kidney stone risk (Sakhaee, Maalouf 2012).
Urine pH. The pH of urine is largely determined by diet (Adeva 2011). For example, a diet high in animal protein tends to promote acidic conditions and lower urine pH (Fenton 2011; Friedlander 2015; Schwalfenberg 2012). The most common types of kidney stones, calcium oxalate and uric acid, usually form in acidic urine—as do cystine stones, which are uncommon. On the other hand, urine alkalinity may increase the risk of calcium phosphate and struvite stones (Frassetto 2011). Since varying urine composition and pH can give rise to different types of stones, it is critical that patients undergo urine analysis and have their stone type determined before treatment is initiated. Different types of stones require different treatment approaches (UCKSETP 2015).
Hypercalciuria. Hypercalciuria is excessive calcium in the urine; sometimes this occurs even when calcium intake is not excessive and blood calcium level is normal (Chines 1995). Hypercalciuria may be related to problems in the digestive tract that lead to increased calcium absorption, or dysfunctional renal calcium handling, but often no underlying cause is identified (Aliotta 2015). Excess urine calcium increases the risk of calcium oxalate and calcium phosphate kidney stones (Escribano 2014).
Hyperoxaluria. Hyperoxaluria refers to high oxalate concentration in the urine and is seen in 10‒40% of people with calcium oxalate stones, though it can also be present in individuals without kidney stone disease (Curhan 2012). One important determinant of the amount of oxalate in the urine is the amount absorbed from the intestines from food (Xu 2013). High oxalate concentrations are present in several foods, including nuts and nut butters and some vegetables and fruits, and can be made in the body from other compounds including vitamin C (Pena de la Vega 2004; UMICH 2015). Allegations that vitamin C supplementation might be associated with increased calcium oxalate kidney stone risk appear to overstate this risk, and no intervention studies have shown that vitamin C supplementation causally contributes to increased kidney stone risk (Traxer, Pearle 2003; Gerster 1997; Traxer, Huet 2003; Tiselius 2001).
Hypocitraturia. Hypocitraturia is too little citrate in the urine. Citrate is an alkalinizing molecule that raises urine pH, binds calcium in the urine, and blocks calcium oxalate and calcium phosphate crystallization. Thus, urinary citrate protects against calcium oxalate and uric acid kidney stones. Low intake of dietary citrate from vegetables and fruits and high animal protein intake may contribute to hypocitraturia, though often the cause is unknown (Curhan 2012; Zuckerman 2009; Pak 1986).
Hyperuricosuria. Hyperuricosuria is excessive uric acid concentration in the urine, which increases the risk of uric acid and calcium oxalate kidney stones. Hyperuricosuria commonly occurs in gout, but has many other possible causes, such as certain medications or excess purine intake (purines are organic compounds common in organ meats, some fish, and beer) (Zwolinska 2000; Ngo 2007; Halabe 1994; Maalouf 2011). Uric acid stones are more common in people with metabolic syndrome and in those with gout. About 20% of people with gout develop uric acid kidney stones (Grassi 2011; Xu 2013).
Dietary Risk Factors
High salt intake. A high-salt diet contributes to kidney stone risk, at least in part, because high sodium intake raises urine calcium concentration (Sakhaee, Maalouf 2012; Friedlander 2015).
High sugar intake. A high-sugar diet appears to raise the risk of kidney stones, which may relate in part to the ability of refined sugar and large quantities of carbohydrate to elevate urine calcium (Thom 1978; Garg 1990). In a 12-year study of 91 731 women, those who ate the most refined sugar were 52% more likely to develop kidney stones than those who ate the least (Curhan 1997). Similarly, in a study of nearly 200 000 individuals over an average of eight years, those who consumed the most sugar-sweetened soft drinks were 23% more likely to develop kidney stones compared with those who consumed the least (Ferraro 2013).
Low calcium intake. Although dietary calcium restriction was previously thought to lower urine calcium and calcium-containing stone risk, evidence from multiple large observational studies and a randomized controlled trial has shown that calcium restriction does not prevent stone formation (Friedlander 2015). In fact, calcium actually binds to oxalate in the digestive tract, preventing oxalate from entering the bloodstream. This then lowers urinary oxalate, and may help prevent calcium oxalate kidney stones. This possibility has received support from epidemiologic studies that have found that lower dietary calcium intake actually increases kidney stone risk (Sakhaee, Maalouf 2012; Sorensen, Eisner 2012).
Low fruit and vegetable intake. Several fruits and vegetables provide alkaline-forming substances including bicarbonate, citrate, and potassium, which alkalinize urine, reduce urinary calcium excretion, and raise urinary citrate, thus reducing kidney stone risk (Morris 1999).
Animal Protein Intake and Kidney Stones
Animal protein acidifies urine, decreases urinary citrate, and raises urinary calcium and uric acid, potentially increasing risk of calcium and uric acid kidney stones (Friedlander 2015; Gul 2014; Lambert 2012).
A small randomized study in healthy individuals found that beef, chicken, and fish have similar potential to promote kidney stone formation based on their impact on urinary uric acid and urine chemistry (Tracy 2014). Overall, vegetarians have a lower risk of stone development than meat eaters; and among meat eaters, studies suggest those who consume more fruits and vegetables are less likely to form kidney stones (Espinosa 2012).
The effectiveness of a diet low in animal protein, independent of other dietary changes, for preventing kidney stones has yet to be rigorously studied (Friedlander 2015), but several expert sources recommend restriction of animal protein in order to reduce the risk of calcium oxalate stone formation and recurrence (Curhan 2012; Trinchieri 2013; Heilberg 2013; UMMC 2013).
Some medications can affect urine chemistry and increase the likelihood of kidney stone formation. In general, these medications cause higher urinary levels of calcium, uric acid, or oxalate. Examples of such medications include (Antonelli 2015; Husain 2012):
- A class of antiviral drugs known as protease inhibitors
- A class of drugs known as carbonic anhydrase inhibitors, which includes some drugs used to treat glaucoma, epilepsy, and edema
- The decongestant ephedrine and the expectorant guaifenesin (Mucinex, Robitussin)
- Some diuretics such as triamterene (Dyrenium)
- The antibiotic sulfadiazine
Conditions Associated with Increased Kidney Stone Risk
Impaired kidney function. Kidney diseases and disorders that impair renal calcium handling cause high urinary calcium and thereby increase stone risk. Similarly, kidney diseases that cause increased phosphate in the urine also contribute to stone risk (Arrabal-Polo, Arrabal-Martin 2013; Aliotta 2015).
Hyperparathyroidism. In this condition, parathyroid hormone levels are elevated. This leads to increased intestinal calcium absorption and calcium removal from bones, raising blood calcium levels as well as urine calcium concentrations and kidney stone risk (Gasser 2013; Nussey 2001; Moe 2008).
Osteoporosis. Emerging evidence suggests a strong relationship between bone loss and kidney stones. This has led some researchers to recommend osteoporosis testing for recurrent kidney stone formers (Arrabal-Polo, Sierra Giron-Prieto 2013).
Digestive and intestinal disorders. People with chronic diarrhea or inflammatory bowel diseases like ulcerative colitis and Crohn’s disease absorb more dietary oxalate, leading to hyperoxaluria and thus an increased calcium oxalate stone risk (Aliotta 2015). Hyperoxaluria can also occur in people with fat malabsorption due to digestive disorders or after gastrointestinal surgery, including bariatric surgery for weight loss. In this condition, excess (unabsorbed) fat in the gut binds to calcium, which then cannot attach to and block absorption of oxalate (Arrabal-Polo, Arrabal-Martin 2013; Nazzal 2015).
Type 2 diabetes. People with diabetes have more acidic urine and higher urinary uric acid and oxalate than people without diabetes, increasing their risk of uric acid and calcium oxalate kidney stones (Eisner 2010; Torricelli 2014; Hartman 2015).
Kidney stones, insulin resistance, and metabolic syndrome. The American Heart Association defines metabolic syndrome by the presence of three or more of the following risk factors: abdominal obesity, high blood pressure, elevated fasting glucose, high triglycerides, and low HDL cholesterol. Metabolic syndrome is associated with increased kidney stone risk (Sakhaee 2008; Wong 2015; Kaur 2014; AHA 2014).
Insulin resistance, a central feature of impaired glucose metabolism and metabolic syndrome, may partly explain the link, because it increases urine acidity and has been associated with uric acid stone formation (Ahmed 2014). In fact, the American Urologic Association suggests people with recurrent uric acid kidney stones should be screened for insulin resistance and metabolic syndrome (Li 2014).
Risk Factors for Uncommon Stones
Cystinuria. Cystine stones occur only in people with a genetic condition called cystinuria, in which the kidneys excrete a large amount of cystine, an amino acid that has a high tendency to form stones (Xu 2013).Infection. Certain urinary tract infections increase the risk of struvite stones. These infections involve a type of bacteria known as urease-producing (or urea-splitting) bacteria. Some examples of urease-producing bacteria are Klebsiella, Proteus, Pseudomonas, and Enterococcus species. These bacteria can colonize the kidneys and increase risk of struvite precipitation, leading to stone formation (Xu 2013). Struvite stones are more common in women than men; infants and the elderly also have increased susceptibility (Curhan 2012; Kristensen 1987; Gettman 1999).