Increased animal protein consumption is associated with a higher renal stone incidence [8–10]. High protein intake causes an increase in calciuria and uricosuria, with a decrease in urine citrate and urine pH [11, 12]. Studies reveal that in both stone formers and non-stone formers, high animal protein intake results not only in higher urinary excretion of calcium, oxalate, and uric acid but also lower excretion of urinary citrate [13, 14]. Animal flesh protein contains sulfur-containing amino acids which produce sulfate as they are metabolized, causing a metabolic acidosis. In this state, calcium resorption from bone is increased, and with the increased urine acidity, calcium reabsorption in the renal tubules is decreased, which combine to increase urinary calcium. In addition to decreasing the tubular calcium reabsorption, the acid load increases reabsorption of urinary citrate, concurrently lowering the urinary citrate level. For every 25 g increase in animal protein intake, the urinary calcium will rise by approximately 32 mg [15]. This holds true for all animal flesh proteins. When compared directly to red meat, fish and poultry have been shown to increase the acid load by similar amounts, leading to similar changes in urine [14].

Studies of populations with particularly high or low protein intake further support these findings. In oil-rich Middle Eastern countries, people generally eat animal protein (red meat, fish, poultry) at all three daily meals, with a higher average protein intake even than Americans. This high level of animal protein intake results in high levels of urinary uric acid, acidic urine pH, and low urinary citrate. These factors contribute to an increase stone formation, and lifetime prevalence of stone formation in this population is >20%, compared to 8–15% in Western industrialized nations [16–18]. Another well-characterized population with increased animal protein intake includes patients on the “Atkin’s diet .” This is an obese population who eat a diet rich in protein and fat, but very low in carbohydrates. One study evaluated a cohort whose animal protein intake was increased to 170 g/day; after 6 weeks the urinary calcium increased by 90 mg/day and the urine uric acid increased by 130 mg/day. Simultaneously, the urine citrate decreased by 180 mg/day and the pH fell from 6.09 to 5.67 [19]. Vegetarian diets have the opposite effects. A study compared the effects of different proteins on urinary risk factors by starting with 75 g animal protein, which was first replaced with ovo-vegetable protein, and finally with solely vegetable protein. The vegetarian-only diet resulted in urine with decreased calcium, decreased acid excretion, and increased citrate, indicating that decreasing animal protein lowers the urinary risk factors for stone formation [20].

Currently, no recommendation exists for specific quantity of protein to be considered an upper limit or a safe range for daily intake. Consider that the studies cited above had protein intake ranging from 75 to 170 g (or 2.6–6 oz), which in many industrialized nations may be less than a serving of meat at only one meal. For hypercalciuric patients, rather than focusing on a specific upper limit of animal protein intake, perhaps efforts should be focused on significantly reducing their current intake, which should reduce urinary calcium excretion .

Excess sodium intake can increase urinary calcium levels. A high sodium intake increases the amount of sodium traveling through the distal tubule, where sodium and calcium compete for a reabsorptive transport mechanism. This competition inhibits the reabsorption of calcium, leading to increased urinary calcium levels. Additionally, high sodium intake decreases the effectiveness of thiazides for lowering the urinary calcium levels in hypercalciuric patients [21]. Current AUA guidelines suggest that daily sodium intake should not exceed 100 mEq (2,300 mg) [17].

A review of salt loading studies found that in normal subjects, urinary calcium excretion rose approximately 40 mg for each 100 mEq (2,300 mg) increase in dietary sodium, but subjects who are calcium stone formers with hypercalciuria appeared to have even more significant increases in urinary calcium (approximately 80 g) per 100 mEq increase in salt intake [23].

The primary dietary source for sodium source is not the added salt via the salt shaker. Penniston et al. evaluated diet records from stone-forming patients and found the source of salt was spread out across numerous foods, including processed meats, bread and baked, added salt and spices containing salt, canned vegetables/soups/pickles, condiments, salty snacks, cheese, pizza and fast food, and meal starters such as rice and pasta mixes. The aforementioned foods range in their contribution to the daily sodium from 14% to 7% in a descending manner [24, 26]. Some foods that may not be particularly high in sodium may contribute more to the overall sodium intake load if they are eaten regularly or in high quantities. The sodium content in bread, for example, may add up since bread is commonly eaten several times a day as breakfast toast, breakfast bagel, part of a sandwich, or dinner rolls. Sodium-containing foods must be recognized for the amount of sodium content as well as the pattern of intake to properly counsel a patient on decreasing sodium intake.

Additionally, although the mechanism is unknown, increased dietary sodium intake is associated with decreased urinary citrate [25].

Keeping daily sodium intake below 100 mEq (2,300 mg) will allow better control of urinary calcium levels.

Previously, calcium restriction was prescribed as a method to decrease stone episodes. Unfortunately, a low calcium diet decreases oxalate binding by calcium in the gut resulting in increased intestinal absorption of oxalate and subsequent increased levels of urinary oxalate [27]. Calcium restriction in patients can cause a negative calcium balance in patients who excrete more calcium than normal (hypercalciuria), which in the long term may result in osteoporosis [28–30]. Current guidelines recommend calcium intake of 1,000–1,200 mg in hypercalciuric patients with calcium stones [22].

Normalizing calcium intake to 1,200 g is based on a randomized clinical trial in which hypercalciuric men were placed on a diet of either low calcium (400 mg) or normal calcium (1,200 mg) daily. Both groups were told to limit oxalate, drink proper fluids, and were placed on an animal protein restriction of 52 g and a sodium restriction of 2,900 mg. After 5 years, the low calcium group formed 23 stones in 60 subjects, while the normal calcium group formed only 12 stones. Compared to the low calcium diet cohort, the relative risk for forming a stone for the normal calcium intake group was 0.49 [12].

If patients are unable to take adequate amounts of daily calcium (food allergies, intolerances, etc.) calcium supplements may be beneficial, and conflicting reports exist throughout the literature. The Women’s Health Initiative study looked at a large population of subjects randomized to 100 mg Ca carbonate or placebo, and the calcium supplement cohort had a higher risk of stone formation; however, the calcium supplement cohort had a daily calcium intake higher than recommended, which may have affected the findings [31]. Other studies suggest that calcium supplementation can also be safe. Studies in postmenopausal women that were placed on calcium and estrogen for osteoporosis showed no significant increase in urinary calcium or oxalate [32]. The type of calcium preparation may be important. Over-the-counter calcium citrate (950 mg calcium citrate – 200 mg elemental calcium/tablet) did not have a significant impact on kidney stone episode [14, 33]. Additionally, the timing of calcium supplement intake may also have a role. Domrongkitchaiporn et al. reported that calcium supplements in any preparation are not associated with an increase in urinary calcium if taken with meals [34]. Breaking the calcium tablet into two to three portions to be taken with each meal may be further beneficial. In summary, the risk of calcium supplements is not conclusively characterized. For patient safety, the AUA guidelines suggest obtaining a 24-h urine sample before and after beginning calcium supplements to insure that no increase in urinary calcium risk occurs [22].

Hypercalciuric patients should be counseled to have a goal of taking in 1,000–1,200 mg of calcium daily, preferably split up so that calcium-containing foods are taken with each meal.

As dietary acid load increases, urinary calcium and uric acid increases while urinary citrate decreases. This concept was discussed in the Animal Protein section above since animal flesh protein also raises the acid load. A scale has been developed to estimate the potential renal acid load (PRAL) effect of diet on renal net acid excretion [35].

Acid load in diet is believed to increase the risk of kidney stones by inhibiting tubular calcium reabsorption and increasing bone mineral mobilization to buffer the acid load [35]. In addition to animal protein, foods that increase the net acid load due to their sulfur-containing amino acids include cheese, eggs, and grains and grain products (flour, pasta) [36]. Notably, fats are neutral; milk and yogurt have minimal acid effect. Vegetables and fruits and their juices give an alkali load and should usually be increased to lower stone risk.

By altering the intake of high PRAL foods such as animal flesh protein, eggs, cheese, and grain products so that they are eaten in moderation and increasing low PRAL foods such as fruit, vegetables, milk, and yogurt, hypercalciuric patients will decrease their renal net acid excretion and consequently lower their urinary calcium levels.

Fiber intake reduces gastrointestinal calcium absorption if at the recommended levels (25–30 g/day) [36]. However, oxalate levels may rise, so one may choose not to utilize this therapy in patients with hyperoxaluria.

Fifteen healthy women were given a standardized calcium-rich diet (1,800 mg calcium/day) with or without 36 g bran for 5 days. A similar study was also carried out with rice, soy, and wheat bran. Urine samples were also collected 24 h. With all brans renal calcium excretion decreased slightly and renal oxalic acid excretion increased slightly. However, the effect of rice bran was statistically significant. After 5 days of consuming 36 g rice bran/day, 14 of 15 subjects showed significant decreases in calcium excretion, but concomitant increases in oxalic acid excretion. Relative supersaturation with calcium oxalate, as a measure for the risk of calcium stone formation, increased after addition of all forms of bran [36].

For the purpose of decreasing calcium excretion, increased fiber may be an effective option in patients with normal urinary oxalate.

Carbohydrate , alcohol , and caffeine may slightly increase urinary calcium excretion. However, the effect is transient and does not necessitate limitation or restriction and should be assessed on case to case basis [37–39].

Citrate is a potent natural inhibitor of calcium stone formation [40]. Citrate binds to calcium in the renal tubule, resulting in a complex with increased solubility [41]. Additionally, citrate binds to existing stone crystals, preventing further crystal growth. For calcium stone formers with 24-h urine testing that reveals low citrate, current AUA guidelines recommend supplementation by increasing the consumption of fruits and vegetables [22]. A study including both stone formers and non-stone formers clearly reinforces this recommendation. In the group of non-stone-forming subjects, the removal of all fruits and vegetables from the diet resulted in significant decreases in urinary citrate (44%) and potassium (62%). Conversely, in a cohort of calcium stone formers with hypocitraturia, supplementing the diet with fruits and vegetables (100 g orange juice, 400 g fresh fruit, 300 g fresh vegetables) caused a significant increase in urinary citrate (68%) and potassium (68%) and additionally raised urine volume from 1,231 to 2,024 ml/day, a 64% increase [42].

Normal levels of citrate are difficult to characterize, but since most non-stone-forming people excrete 600 or more mg of citrate daily, the AUA guidelines suggest 600 mg as a minimum goal for stone-forming patients.

In order to maintain high levels of urinary citrate, adequate potassium levels must be maintained. Hypocitraturia results in intracellular acidosis and decreases tubular pH [43]. Decreased tubular pH stimulates reabsorption of citrate, and intracellular acidosis has been shown to increase mitochondrial transport and metabolism of citrate. Consequently, low 24-h potassium levels must be supplemented to allow for adequate citrate excretion .

Hyperoxaluria presents a challenging scenario for both practitioners and patients. Treatment would be straightforward if we could simply give patients a simple, short list of high oxalate foods to avoid in order to bring their urinary oxalate levels down to within normal limits. And while dietary restriction of oxalate is a mainstay of treatment, other approaches exist that can be utilized in addition to dietary restriction to lower oxalate excretion. Evidence-based studies are lacking for treatment of hyperoxaluria, and the current AUA guidelines only have one statement for hyperoxaluria, with a strength of evidence only noted to be “expert opinion.”

Hyperoxaluria is defined as urinary oxalate higher than 40 mg/24 h, leading to increased urinary calcium oxalate supersaturation (SS) and subsequently formation of kidney stones. There are multiple causes of hyperoxaluria including primary hyperoxaluria (disorders in biosynthetic pathways), intestinal malabsorptive states associated with inflammatory bowel disease, celiac sprue, or intestinal resection (enteric hyperoxaluria), and excessive dietary intake or high substrate levels (vitamin C) (dietary hyperoxaluria) [44].

Primary hyperoxaluria comes from one of two different autosomal recessive genetic disorders , both of which are characterized by an endogenous overproduction of oxalate. These patients generally present in childhood with oxalosis, stone disease, and often renal failure.

Primary hyperoxaluria 1 (PH1) is caused by an autosomal recessive defect in the enzyme alanine glyoxylate aminotransferase (AGT) . This deficiency results in an inability to detoxify glyoxylate in the peroxisomes. PH1 patients with renal failure require a hepatectomy prior to a combined liver/kidney transplant. PH2 is caused by a defect in glyoxylate reductase , also an autosomal recessive defect. Urine parameters are characterized by high urine oxalate excretion [45]. Primary hyperoxaluria of either type should be referred to gastroenterology for management.

Enteric hyperoxaluria stems from an intestinal malabsorptive state such as bowel resection or inflammatory bowel disease. Enteric hyperoxaluria is characterized by high urine oxalate more than 50 mg/day and is often associated with chronic diarrheal states in which fat malabsorption causes saponification of calcium and magnesium with fatty acids. This decreases the calcium and magnesium available to bind oxalate, resulting in much more free oxalate which is easily absorbed. The chronic diarrhea also results in dehydration, bicarbonate fluid loss, low urine PH, and hypocitraturia, all of which further increase stone risk [46, 47].

Dietary hyperoxaluria is either due to the deficiency of Oxalobacter formigenes or an increased intake of oxalate-containing foods [48], [49]. Since a small increase in urinary oxalate affects calcium oxalate supersaturation, perhaps patients with only mild or borderline hyperoxaluria may benefit from low oxalate diet [60].

Commonly, patients are placed on some arbitrary dietary combination of “low green vegetables, no coffee/tea/soda, no nuts or nut butter” type of diet without regard for what the patient actually eats on a daily basis. Penniston et al. examined food diaries from patients in a metabolic stone clinic to evaluate oxalate intake in stone formers. This study revealed that nuts, seeds, and nut butters offer the highest contribution to the total oxalate intake by 26%; spinach and flours and baked goods come next with 12% share. Cereals, potatoes, and french fries offer 7% and other foods less [50]. Note that these are averages, and individual intake may be much different for unique stone patients. Only a thorough dietary assessment will identify which foods place different individual patients at risk. Additionally, practitioners must take care to avoid examining only the intake of high oxalate foods, as low oxalate-containing foods eaten regularly or in large amounts may add up to yield large quantities of oxaluria even though the food may not seem like a particularly high oxalate food type. Again, this type of information would be identified through a dietary assessment .

A conundrum exists when we wish to stringently restrict oxalate-containing foods. Since oxalates are obtained almost solely from plants, these foods are healthy fruits and vegetables. Indiscriminate restriction could decrease the health benefits derived from the variety of nutrients that come from these foods, as well as restrict some of the important stone-inhibiting food products such as citrate, magnesium, potassium, fiber, phytate, etc. [26].

A detailed list of oxalate-containing food can be found in many research articles, and excellent, detailed lists may be found on several websites, as well as through Internet search engines (Appendix 6) (Fig. 8.1). These lists are important for practitioners and patients to review, as they will not only guide meal planning but will also dispel certain myths about which foods may or may not be high in oxalate. For example, these show most leafy green vegetables (with the notable exceptions of spinach or collard greens) are not high in oxalate, and coffee is also shown to have low content.