The Role of the Nephrologist in the Treatment and Prevention of Nephrolithiasis

Adequate daily drinking is one of the basic preventive measures of recurrent nephrolithiasis; it recommends at least 2500 to 3000 ml of fluids per day, with a regulation according to current diuresis (optimal daily diuresis of 2000–2500 ml per day), requirements, and extrarenal fluid losses. (13). In practice, this means that the patient needs to take fluids regularly, not abruptly, and should increase their standard fluid intake during periods of sweating, increased physical activity, vomiting, or diarrhea. We can practically verify fluid intake by the value of the specific gravity of urine, the adequate value of which should be lower than 1.010 (13).

In the context of dietary measures, it is important to consider not only the quantity of fluids consumed, but also the quality or type of drinks consumed.

From the point of view of drinking coffee and other caffeinated drinks, the idea that plant-based foods like coffee and tea have a higher risk of calcium oxalate nephroliths was shown to be false. A meta-analysis by Ferraro and colleagues (2014) confirmed reciprocal results: coffee intake reduced the risk of kidney stones (14). The Mendelian randomization study by Yuan and Larsson (2022) also confirmed this, concluding that caffeine and coffee intake reduce the incidence of kidney stones (15). For healthy individuals, except for pregnant women, the European Food Safety Authority considers a daily intake of caffeine up to 400 mg, or around four cups of brewed coffee, to be safe (16). Other possible causes of tea consumption's protective effect include increased overall fluid intake and the antioxidant activity of phytochemicals such as polyphenols (17, 18). In the study by Ferraro et al. (2013), the authors confirmed an increased risk of kidney stones with an increased consumption of cola and non-cola-sweetened beverages. On the other hand, drinking beer reduced the risk of developing nephroliths by up to 41%, wine by 31–33%, and orange juice by up to 13% (19). Interesting results were obtained by a study by Finnish authors (1999) who concluded that each bottle of beer drunk daily reduced the risk of kidney stones by 40% (RR = 0.60, 95% CI 0.47–0.76). Caution is in order, especially in the case of urate kidney stones, as alcohol increases the risk of urinary excretion of urates (20).

The water's hardness is another indicator of the quality of the fluids received. Studies indicate that a calcium ion concentration exceeding 120 mg/l, a sign of water hardness, enhances the overall daily calcium intake. Consuming bicarbonate is a powerful alkalizing agent and enhances the body's ability to function as a buffer. By raising urine pH and citrate excretion, bicarbonate-rich mineral water can assist alkalinization therapy and enhance urine's inhibitory potential (21). In one study the likelihood of calcium oxalate and uric acid stones in the urine was examined in healthy individuals who were randomly assigned to receive either potassium citrate or an equal amount of bicarbonate-rich mineral water (22). Urine pH and citrate excretion were raised, significantly, and oxalate excretion was reduced when 2 litres per day of mineral water containing 1715 mg/l bicarbonate, or 2.55 g/day potassium citrate were consumed. The relative supersaturation of uric acid and calcium oxalate dropped dramatically in both groups. A study of healthy people under controlled dietary settings revealed that bicarbonate, calcium, and magnesium-rich mineral water raised urine pH and enhanced the excretion of citrate, magnesium, and the urinary inhibitors of calcium oxalate stone formation (23).

Dietary citrate converts to bicarbonate, and may elevate urine pH and citrate excretion (24). Citrus juices from oranges, lemons, and grapefruits contain large amounts of citrates. These juices may be consumed instead of medication that contains alkalizing agents. There are conflicting results from research on how drinking orange juice affects urinary risk factors for kidney stones. Three cohort studies have linked orange juice consumption to a lower chance of the development of kidney stones (19). Interventional studies done under a controlled eating regimen found that orange juice increased the pH and citrate levels in urine (25,26,27). The nutritional advice is to choose the whole fruit over the juice, to limit daily consumption of fruit juice to one serving, and to dilute the juice with water due to concerns over the high sugar and energy content as well as the lack of dietary fibre in orange juice (28). A study conducted on healthy individuals revealed that drinking nearly 2 litres of coconut water daily greatly increased the excretion of potassium, chloride, and citrate in the urine while having no effect on the pH (29).

From the perspective of soft drinks, one study demonstrated a considerable increase in the risk of recurring stone development associated with the consumption of soft drinks, particularly those acidified by phosphoric acid. Consequently, cohort studies also showed a highly favourable correlation between risk of developing gout and soft beverages with added sugar (30, 31). The fructose content of sugar-sweetened soft drinks has been linked to an elevated incidence of incident kidney stone formation, which could account for at least some of these results (32, 33).

To prevent recurring nephrolithiasis, another general preventative approach is to reduce protein intake, with a daily limit of 0.8 to 1.0 g/kg of animal protein. Research suggests that a high-protein diet could negatively affect the urinary risk factors for the development of kidney stones. A high-protein diet can cause an acid load that can lower urine pH and citrate excretion, as well as raise urinary calcium (34, 35). A systematic review linked high-protein diets to increased urinary calcium excretion, a risk factor for the development of calcium stones (36).

Increasing fruit and vegetable consumption is another dietary suggestion. Extensive observational studies linked an increased risk of stone formation to a larger dietary net acid load (37). These findings suggest that, rather than total protein consumption, the ratio of fruits and vegetables consumed to ingested protein may be a more accurate predictor of urinary stone development. Vegetables and fruits improved urine pH and citrate excretion while decreasing the relative supersaturation of uric acid and calcium oxalate in hypocitraturic stone patients (38). High nutritional proton load or high dietary acidity can lead to a reduced urine pH and citrate excretion, which can increase the risk of numerous types of urinary stones, especially the most frequent ones, which are calcium oxalate and uric acid. The capacity to bind calcium and excrete citrate, which inhibits the formation of stones, increases with urine pH, while the excretion of calcium in the urine decreases (39).

The relationship between carbohydrates and the risk of kidney stone production is not conclusive. Many studies have identified a positive correlation between the consumption of sucrose and the likelihood of stone formation in women but not in men (40,41,42,43). The increase in calcium excretion following the consumption of glucose orally has been attributed to an augmented absorption of calcium in the intestines and a decrease in the reabsorption of calcium in the renal tubules (44). In recent decades, fructose consumption has significantly increased due to its use as a sweetener in beverages and food, often replacing sucrose or glucose. A comprehensive analysis found a direct correlation between the consumption of fructose and the likelihood of developing kidney stones (32). A study on a group of males found a direct correlation between fructose consumption and the risk of developing gout (31).

There is a lack of data on the relationship between dietary fat consumption and the risk of recurrent nephrolithiasis. The composition of fatty acids in one's diet, particularly the ratio of n-6 to n-3 polyunsaturated fatty acids, can affect the likelihood of developing calcium oxalate stones. Researchers have shown that idiopathic calcium oxalate stone patients have an unusually high level of arachidonic acid (C20:4n-6) in their plasma and erythrocyte membrane phospholipids compared to healthy individuals (45, 46). An increased prostaglandin E2 synthesis is believed to cause hypercalciuria by enhancing calcium absorption in the intestines and promoting bone tissue breakdown (47). The elevated amounts of arachidonic acid in phospholipids can lead to hyperoxaluria, which in turn enhances the transport of oxalate in the intestines and kidneys (48, 49). Urinary oxalate is considered a crucial risk factor for the development of calcium-oxalate stones. Modifications in the concentration of oxalate in urine can greatly enhance the degree of urinary supersaturation of calcium oxalate (50). It originates from the synthesis of oxalate inside the body and the consumption of oxalate through diet (51). Precursors like ascorbic acid and hydroxyproline primarily influence the liver's endogenous oxalate metabolism (52). Plant-based foods predominantly serve as the primary source of dietary oxalate. Dietary oxalate intake estimates vary significantly based on the consumption of foods that are high in oxalate. A precise understanding of the oxalate levels in foods is crucial for the dietary treatment of individuals with calcium oxalate stones. Spinach, rhubarb, white beans, sesame, and liquorice are examples of foods that have a high oxalate content. Food processing and preparation methods have a crucial role in determining the oxalate level due to the potential loss of oxalate into the cooking water during boiling (53). For instance, researchers discovered that the oxalate concentration in raw spinach is over five times greater than that in cooked spinach, with raw spinach containing 1959 mg/100 g and cooked spinach containing 364 mg/100 g (54, 55). Intestinal colonisation by the Gram-negative anaerobic bacterium Oxalobacter formigenes, which degrades oxalate, can be inversely linked to the production of calcium oxalate stones (56).

Hypercalciuria is a significant predisposing factor for calcium stone development. Evidence has shown that consuming an appropriate amount of calcium from both dairy and non-dairy sources can help reduce the formation of urinary stones (57). To prevent bone loss and excessive oxalate absorption and excretion, dietary calcium limitations must be avoided. Restricting dietary calcium decreases the amount of calcium in the intestines, which increases the absorption of unbound oxalate and thus leads to higher levels of oxalate in the urine (58).

The consumption of dietary sodium chloride increases the risk of stone formation because it tends to increase the excretion of calcium in urine (59). An increased consumption of sodium chloride can lead to the excretion of calcium by preventing the reabsorption of calcium in the renal tubules due to the expansion of extracellular fluid volume caused by sodium. Interventional investigations conducted on healthy persons have demonstrated that for every 100 mmol (equivalent to 2300 mg) increase in daily sodium consumption there is an approximate rise of 1 mmol in daily calcium excretion (60).

General preventive measures to reduce the risk of the urolithiasis recurrence as well as pharmacological agents to prevent stone formation are summarized in Tables 1 and 2 (61).