The urine sediment should be examined for crystals. A 24-hour urine collection should be performed to measure urine calcium, oxalate, uric acid, pH, volume, creatinine and citrate. Some laboratories calculate supersaturation values for calcium oxalate, calcium phosphate and uric acid and these are particularly helpful [124243].

The best way to evaluate stone risk is a 24-hour urine collection and analysis [812]. Two 24-hour urine collections are recommended for the initial evaluation for an accurate analysis and to determine variability [44]. The 24-hour urine collection should be several weeks after any procedures (i.e. 6-8 weeks after lithotripsy) in order to minimize the risk of result be being influenced by infection or presence of blood due to these causes. Infection can change the pH and citrate levels. It is very important that patients continue with their usual diet and activities during the collection period. The 24-hour urine creatinine excretion can give information about the adequacy of the urine collection. In general, adult males produce 18-24 mg creatinine/kg/d and females 15-20 mg/kg/d [912]. 24-hour urine collection is not accurate as the urinary creatinine levels will be higher than normal for over collection and lower than normal for under-collection [44].

Table 2 provides a summary of the normal values for the 24-hour urine collection and likely causes of abnormal values. The 24-hour urine sample should include volume, and the solutes calcium, phosphorus, oxalate, citrate, pH, and uric acid to provide an estimate of supersaturation and the risk of stone formation. Creatinine is tested to ensure full collection and to normalize solute excretion to the more constant amount of creatinine. Dietary factors include sulfates which are mostly from animal protein and sodium since they are related to calcium, potassium, and magnesium excretion. Urea nitrogen is used to estimate protein catabolic rate (PCR). The PCR is usually indicative of dietary protein intake in an individual who is not in a catabolic state. The relationship between urinary nitrogen appearance rate and estimated dietary protein intake is then calculated. The value of the 24-hour urine is to evaluate dietary nutrients and fluid intakes and to provide guidance for the patient's management. For example, normal urinary calcium levels are <250 mg/d for men and <200 mg/d for women. High urinary calcium may be caused by idiopathic hypercalciuria, or diet high in sodium or protein. Low urinary calcium is often due to malabsorption or underlying bone disease. A normal urinary oxalate level is 20-40 mg/d. High levels are due to high oxalate diet, increased endogenous production, high vitamin C consumption and irritable bowel disease. Normal urinary citrate levels are >450 mg/d for men and >550 mg/d for women. High animal protein diets and renal tubular acidosis (RTA) can increase acid production affecting urinary pH so that it declines citrate levels.

Urine must be supersaturated with solutes to form a crystal, the first step to form a stone. Low fluid intake will lead to low urine output. When urine volume is low, the urine can theoretically be easily supersaturated with various solutes, such as calcium, oxalate, phosphorus, and uric acid. However, there are several inhibitors normally present in the urine to prevent crystallization of these solutes [52535455]. Only if the supersaturation is very high does the crystallization start. The most direct way for patients to decrease risks of supersaturation is to increase the urine volume with oral fluids to above 2.5 L/d of urine volume [56].

Figure 2 shows a model of how idiopathic hypercalciuria occurs. Normal urine calcium excretion is less than 200-250 mg/d. If urine calcium excretion is higher than this, stone risk increases. To evaluate the stone risk, it is necessary to measure serum calcium, urinary calcium, oxalate, urine urea nitrogen (UUN), citrate, magnesium, creatinine, and volume (Table 5). In idiopathic hypercalciuria, the serum calcium level is normal but urinary calcium is high because of increased absorption of calcium from the gastrointestinal tract. The increased absorption of calcium increases the ionized calcium level, decreases parathyroid hormone (PTH) secretion and decreases renal tubular reabsorption of calcium. The increased intestinal calcium absorption can be treated with 1, 25-dihydroxy vitamin D3. There is also evidence of reduced proximal tubular reabsorption of sodium and calcium in patients with idiopathic hypercalciuria, which leads to a negative calcium balance [57]. The combination of a low sodium diet and thiazide diuretics may lower urinary calcium excretion by increasing reabsorption of calcium.

The most common type of stones are CaOx (75%) and a high urinary excretion of oxalate is a risk factor for them. Dietary sources of oxalate include spinach, rhubarb, beets and some berries. Oxalate is also created from endogenous metabolism of glycine, hydroxyproline and ascorbic acid. A low oxalate diet is recommended for the prevention of CaOx stones; however, a recent study showed that dietary oxalate had little effect on urinary oxalate excretion although vitamin C intake was highly correlated with urinary oxalate excretion [58].

Increased urinary oxalate excretion has also been noted in patients with diabetes [5759]. Patients with IBD have a high prevalence of CaOx stones with hypocalciuria due probably to their negative calcium balance. Negative calcium balance can also cause secondary hyperparathyroidism to maintain normal calcium levels in blood, and a calcium supplement may be effective for preventing CaOx stone risk by decreasing the hyperparathyroidism. The timing of calcium supplements is important and patients should take supplements at the meal time to bind oxalate from dietary sources. Individuals who have had restrictive bariatric surgery have a high risk of hyperoxaluria due to malabsorption and increased reabsorption of oxalate, which may increase hyperoxaluria [2960]. Recent studies by Jiang et al. suggest that enteric colonization with Oxalobacter formigenes, which uses oxalate as a main energy source, reduces the risk of CaOx stone recurrence among individuals whose intakes of calcium were low [61]. In contrast, there is insufficient evidence to support the use of probiotics to reduce stone risk at this time [62].

The urine is usually supersaturated with solutes, especially CaOx; however, the level tends to be less than the 10 times the level of concentration to form the CaOx crystals due to the presence of citrate in the urine. Citrate in the urine binds with urinary calcium to form a soluble compound and this increases the urine pH. CaOx stone formation is favored by a low urine pH; therefore, citrate can help prevent CaOx stone formation. The most common form of citrate prescribed is potassium citrate. The normal value of urinary citrate for males is >450 mg/d and for females >550 mg/d. Renal tubular acidosis and chronic diarrhea can also cause decreased citrate in the urine. However calcium, oxalate and urine pH should be checked before initiation of citrate treatment [63]. If urine pH increases later with citrate treatment, the risk of CaP stone formation rises. In patients who have IBD with high urinary oxalate, and low urinary sodium levels because of malabsorption and gastrointestinal loss of sodium, sodium citrate is more beneficial than potassium citrate, and it should be used. However, sodium citrate can increase urinary calcium excretion and therefore it may increase the risk of CaOx stones.

Urine pH is an important factor in the formation of kidney stones. A low urine pH can promote CaOx and uric acid stones, and a high urine pH can increase the risk of CaP stones. Urine pH is affected by the acid and alkaline ash from the diet, and before the advent of effective urinary acidifying and alkalinizing agents, it was necessary to rely on diet to alter urinary pH, although this could rarely be accomplished effectively. The practice has been largely outdated by the advent of better acidifying and alkalinizing agents. The mineral salt that predominates in foods determines whether the residue or 'ash' is acidic or alkaline. The minerals producing alkaline ash are sodium, potassium, magnesium, and calcium. Acid-forming minerals are sulfur, chlorine, and phosphorus. High animal protein diets which have high purine content and sulfur containing amino acids can reduce urine pH and will lead to an increased risk of uric acid stones. An alkaline ash diet which is high in citrate, mostly from fruits and vegetables, can increase urine pH and citrate excretion. Today alkali therapy is preferable because an alkaline ash diet is difficult to follow for most patients although an alkaline ash urine is preferable for the certain type of stone risk. However, for other stones, the reverse may be true. A high pH without alkali therapy may increase the risk of struvite stones from a UTI.

The prevalence of uric acid stones is about 5% of total kidney stone disease. The main determinant of uric acid stones is urine pH. A low urine pH has more insoluble uric acids concentration; therefore, the risk of uric acid stone is higher. Measurements of urinary calcium, uric acid, and post-prandial urine pH are used to assess the uric acid stone. The average adult consumes about 2 mg of purine/kg/d, which produces 200-300 mg of uric acid daily. Endogenous production of uric acid is about 300 mg/d. In some studies, uric acid excretion is 5.6 mg/kg/d [32] and total excretion of uric acid is less than 800 mg/d. Dietary consumption of purine varies daily among individuals. Kessler et al. conducted a cross-sessional study by using bicarbonate-rich mineral water and various types of juices on uric acid stone formation and found that black current juice decreased uric acid stone risk the most, by increasing the urine pH [6465]. Ingestion of alcohol can also affect urinary uric acid excretion, and excesses should be avoided. If patients have gout, allopurinol is usually prescribed along with low purine diet to reduce blood uric acid and uricosuria [3234].

Dietary sodium restriction alone decreases urinary calcium excretion [5467]. Proximal tubular calcium reabsorption is increased on a low sodium diet (2,000-3,000 mg/d) and this in turn decreases the SSCaOx. In addition of thiazide diuretics, calcium reabsorption is enhanced and further decreases hypercalciuria. However, addition of thiazide can lead to volume depletion; although ion exchange and volume status will come to the steady state in a few days. If the patient continues to consume a high sodium diet, sodium will reach the distal nephron and increase the excretion of calcium and potassium along with citrate, resulting in a change in the urinary pH that will eventually increase the risk of stone formation. Therefore, after analyzing the 24-hour urine, stone risk is high, prescribing a low sodium diet will help avoid inappropriate thiazide use for patients with CaOx stones. Patients with IBD usually have low urinary sodium levels and low urinary citrate, and so use of sodium citrate instead of potassium is beneficial to improve fluid status from gastrointestinal losses and increase urine volume.

Potassium is abundant in most fruits and vegetables. However, if the patient has low urinary citrate and low urine pH, potassium citrate is commonly used along with such a diet to further improve hypocitruria. Monitoring 24-hour urinary excretion of potassium is important to evaluate compliance to diet and medications. Taylor et al. analyzed the 24-hour urine with the Diet Approaches to Stop Hypertension (DASH) diet and found that diets conforming more closely to DASH had decreased risk of stone formation [6869]. Because high DASH score foods are high in potassium, magnesium, and phosphorus, these may increase urine pH, resulting in a decrease in SSCaOx and uric acid in the urine as well as increased urine volume and citrate [6869]. If patients have chronic kidney disease and take angiotensin converting enzyme inhibitors (ACEI) as antihypertensive medications, serum potassium level should be monitored closely.

There are few markers of 24-hour urine to evaluate dietary protein intake, production and excretion. Urea nitrogen appearance (UNA) and PCR are measurements of daily protein intake that are calculated per kg body weight. In normal healthy steady state, intake of protein can be equivalent to protein catabolism; therefore, PCR determines the nitrogen balance from 24-hour urine urea concentration:

Patients who have acute, or chronic infection are usually malnourished and experience catabolism, and have more nitrogen in the urine. Therefore, this formula should not be used to evaluate protein intake. For patients without active stress of illness, the PCR can guide protein recommendations for patients to prevent further stone risks.

The ammonium (NH₄) level should be low in patients who are prescribed alkali therapy or who present with RTA. Monitoring citrate, an indicator of urine acidity, can identify these problems. Patients who take alkali therapy especially with low citrate levels have low urinary ammonium levels with higher pHs and therefore the risk of uric acids or CaOx can be substantially decreased.

High ammonium and sulfate are indicators of a high protein diet, especially one which is high in animal protein [3070]. A high protein diet (>2.0 g/kg/d) can reduce urine pH; therefore, a moderate to low protein diet should be advised (0.8-1.4 g/kg/d). Currently most common and popular weight loss diets promote consumption of large amounts of protein but such a reducing diet is not recommended for the patients who have a history of kidney stones. This high protein diet regimen increases hypercalciuria, lowers pH of urine and increases uric acid levels, which increase kidney stone risk [14]. Massey et al. conducted a study to monitor the effect of stone risk in beef vs. plant protein and concluded that a moderate amount of protein intake of either type had the same effects in reducing CaOx stone risk [71]. The amount of protein seemed to be a more important factor in that study. Recently, an epidemiological study showed that animal protein intake was not independently associated with the incidence of nephrolithiasis among a large cohort of postmenopausal women [72]. However, the evaluation of stone risk varies by individuals and is complicated. Therefore, the recommendation of a usual protein intake remains until the scientific evidence to change this recommendation is provided.

Approximately 20% of dietary calcium is absorbed under normal conditions. There is substantial evidence that a higher calcium diet is associated with lower kidney stone formation, because the higher calcium intake will bind oxalate in the gut if it is consumed with meals thereby reducing oxalate absorption. Patients who consumed a diet with a normal calcium intake (i.e., 1,200 mg/d) plus a low animal protein intake had a 51% lower incidence of recurrent stones than patients who consumed low (400 mg/d) calcium diets [20]. Although data to date on taking calcium supplements does not show that they are theoretically effective in reducing stone risk, taking a calcium supplement with meals is beneficial because calcium can bind with the dietary oxalate and thus it is not absorbed.

Magnesium forms a complex with oxalate and decreases SSCaOx in the urine, which can reduce the risk of stone formation [6869]. The DASH diet, which is high in magnesium, showed a decrease in stone risk by increasing pH and lowering SSCaOx [13686973]. Magnesium can also bind with oxalate in the gastrointestinal tract to reduce oxalate absorption; however, a magnesium supplement is not recommended especially patients with chronic kidney disease because magnesium is accumulated in the blood in advanced kidney disease. Decreased urinary magnesium may be a sign of malabsorption, malnutrition, small bowel disease or laxative abuse. Hypomagnesemia is not a risk factor for stone formation.

Vitamin C is metabolized to dehydroascorbic acid and then converted to oxalate which is then excreted in the urine; therefore, a high vitamin C intake can be a risk for stone formation by increasing endogenous oxalate. A recent observational study showed that consumption of more than 1,000 mg/d vitamin C was associated with a 40% higher risk of stone formation in men than in those who consumed the Dietary Reference Intake (DRI) for vitamin C [74].

Citrate consumption can increase urine pH, and also increases citrate concentration in the urine. Citrate also decreases SSCaOx due to its capacity to form a complex with calcium ions and inhibit crystallization of CaOx [63]. However, citrate may increase the risk of CaP stones. A clinical trial conducted by Koff et al. used potassium citrate and lemonade for 21 stone patients, and showed that potassium citrate increased urine pH with increased urinary citrate level but lemonade did not have an effect on urinary pH or citrate levels except for increasing urine volume [75].

Phytates are present in whole grains and legumes and they can inhibit CaOx stone formation. Some studies have shown an inverse correlation with phytate intake and the risk of kidney stone formation in women [74767778].

Dietary sodium restriction is important as it is associated with a reduction in urine calcium excretion. Thiazide diuretics lead to increased serum calcium levels and reduced urine calcium levels and are therefore used in therapy for patients with hypercalciuria. Oxalate reabsorption in the colon is reduced by the formation of insoluble calcium oxalate. This is very important in therapy because restricting dietary calcium results in less calcium being available in the intestinal lumen to bind oxalate. This leads to increased oxalate absorption and therefore increased urinary oxalate excretion [25]. Table 9 shows the list of high oxalate foods.

The high oxalate foods are considered to be healthy, with high fiber and nutrient dense in vitamins and minerals. Patients who have diabetes, hypertension and high blood cholesterol are often instructed to consume high oxalate foods such as fruits and vegetables. When patients develop kidney stones, they are instructed to change the diet to lower oxalate contents and therefore most patients are confused. The clinical dietitian should be able to advise the patients individualized diet to prevent kidney stone but to keep healthy diet.

As uric acid is more soluble in an alkaline urine, urine alkalinization is an important part of the treatment of uric acid stones. Patients should decrease their intake of animal proteins which helps decrease uric acid generation. Allopurinol, a xanthine oxidase inhibitor, is used to decrease the formation of uric acid.

Low purine diet is recommended if patient has elevated blood uric acid level [3234]. A high protein diet (>2.0 g/kg) can cause a decrease in urine pH which can increase risk of uric acid stone therefore moderate amount of protein (0.8-1.4 g/kg/day) is recommended.

There are no specific diet recommendations for cysteine stones except increasing fluid intake. Cystine solubility can be increased by alkalinization of the urine, although solubility only increases when the pH reaches 7-7.5. Thiol containing drugs like Penicillamine and Tiopronin may be given to patients who are unable to comply with increased fluid intake and urinary alkalinization or fail despite it. These drugs increase the solubility of cystine. Tiopronin is better tolerated than penicillamine which is associated with multiple side effects including rash, fever, serum sickness, epidermolysis and membranous nephropathy. Captopril is used because of its sulfhydryl group forms a thiol-cysteine disulfide bond that is more soluble than cysteine. However its efficacy is unclear. Low animal protein diet can lower the stone risk by lowering methionine which is precursor of cystine [84].

The preferred treatment of struvite stones is surgical removal because they are large. Antibiotic therapy is important and may slow stone growth. It is important to culture stone material to help direct antibiotic therapy. However low sodium diet can help prevention of struvite stone [84].