**3.1. Alkalizing agents**

Animal proteins increase the acid load, the excretion of calcium, and decrease the excretion of citrate [25]. In addition, purine metabolism increases uric acid [25], which increases the risk of calcium stones through epistaxis [31]. Despite all this, the protein restrictions recommended for adults are not suitable as part of stone metaphylaxis in children and adolescents, except in

56 Updates and Advances in Nephrolithiasis - Pathophysiology, Genetics, and Treatment Modalities

Urinary excretion of citrate is affected by the system's acid‐base balance. Although acidosis decreases renal excretion of citrate and increases its reabsorption, the opposite is true in alka‐ losis [32]. A Western‐type diet that includes decreased consumption of fruits and vegetables and increased consumption of animal products causes metabolic acidosis, resulting in lower urine pH and hypocitraturia [33]. Hypokalemia also lowers urine pH, and low potassium intake decreases urine potassium and citrate in hypokalemia and increases urinary excretion of calcium [32, 34]. Systemic alkalization increases excretion of citrate, decreases excretion of calcium, and raises urine pH [35]. Oranges, lemons, limes, and some types of mandarins are natural sources of citrate [35]. Alkaline fruits, including melons, cause urinary alkalization [36]. Grapefruits increase excretion of both citrate and oxalate [37]. The lithogenic effects of

Metaphylaxis benefits may be provided by increasing hydration and citrus intake and decreasing intake of sodium, oxalate, animal protein, and fructose [32]. Cranberry juice is high in oxalate and, therefore, increases urinary calcium and oxalate and decreases uric acid concentration. However, cranberry juice acidifies the urine, resulting in increased formation of calcium‐oxalate and urate stones but decreased formation of calcium‐phosphate stones [40]. Since cranberry juice acidifies the urine, it may be useful for infection stones that have

A study of 42,859 adults showed that high coffee and tea intake decreased the risk of symp‐ tomatic stone formation [39]. A more recent study of 6033 adults suggested that coffee intake decreased urine oxalate and uric acid, increased urine calcium and potassium, and also decreased the supersaturation of calcium oxalate by increasing urine volume [42]. However, dietary intake of coffee and tea cannot be recommended for pediatric patients because of the

Potential renal acid load (PRAL) is used to calculate the acid load of foods in adults. However, renal net acid excretion (NAE), which is based on body area, is recommended for use in pediat‐ ric patients [43]. PRAL is calculated by the formula (mEq/d) = 0.49 × protein (g/d) + 0.037 × phos‐ phorus (mg/d) − 0.021 × potassium (mg/d) − 0.026 × magnesium (mg/d) − 0.013 × calcium (mg/d) [43]. As the formula indicates, dietary protein and phosphorus have acidic effects, whereas

When dietary modification is insufficient for metaphylaxis of urinary stones, medical treat‐

cases of definite indications [6].

grapefruit juice and apple juice are controversial [38, 39].

limited options for medical treatment [41].

lack of studies of these substances in children.

**3. Medical treatment**

ment must be a part of the plan.

potassium, magnesium, and calcium have alkaline effects.

Urine alkalization is used to reduce recurrence of calcium oxalate, uric acid, and cysteine stones, and urine acidification is used to reduce recurrence of infection and calcium‐phos‐ phate stones. For urine alkalization, potassium citrate is chosen instead of sodium citrate because sodium causes hypercalciuria. Potassium citrate directly dissolves calcium‐oxalate crystals [44]. Therefore, it has a protective effect, even on calcium‐oxalate stones that have normal citrate levels. Potassium‐citrate tablets are available in 5 and 10‐mEq doses, and Shohl's citrate‐containing solution, which contains 1 mEq of base per millimeter, may be used for infants and children who cannot use tablets.

For calcium‐oxalate stones, the targeted urine pH is 6.5, because uric acid cannot dissolve urine pH lower than 5.5, as it needs more alkalinity to dissolve. In metaphylaxis for hyperuri‐ cosuria, the targeted pH is also 6.5; however, to dissolve small uric‐acid stones, the targeted pH range is 7–7.2 [7]. The daily dose may include 1–3 mEq/kg, depending on the urine pH and the primary disease, and the dose may be as high as 5–8 mEq/kg for infants with distal RTA [45]. Ideally, three doses a day should be administered, and if only one dose is possible, it should be administered in the evening [46].

Alkalization with hydration and potassium citrate has effectively decreased the risk of stones in children who are on a ketogenic diet, but these children should be referred to pediatric neu‐ rology for treatment of their primary diseases before beginning alkalization treatment [47]. Because cysteine has poor solubility and precipitates when urine pH is between 5 and 7, in alkalization therapy, the targeted value of urine pH must be higher than 7.0 [6, 48]. Alkalization accompanied by hydration has effectively prevented the recurrence of cysteine stones [49, 50].

Acetazolamide, a carbonic anhydrase inhibitor, inhibits the reabsorption of sodium bicarbon‐ ate through the proximal tubules, thus raising urine pH and potentially resulting in metabolic acidosis with prolonged use. Including acetazolamide in citrate therapy at night significantly raises urine pH in patients with cysteine and uric‐acid stones, but half of these patients dis‐ continue the drug due to side effects [51]. In addition, high urine pH may lead to calcium‐ phosphate stones [52, 53].
