*3.2.5. Infection stones*

Furthermore, deficiency of adenosine phosphoribosyl transferase (APRT), a purine metabo‐ lism enzyme, converts adenine into 8‐hydroxyadenine and xanthine dehydrogenase enzyme into 2,8‐dihydroxyadenine (DHA) [76]. Transfer of DHA into the urine is high, and its solubil‐ ity is low, even in alkaline urine, so DHA stones form. Alkalization therapy is not useful in such cases, and therapy must consist of 5–10 mg/kg of allopurinol and sufficient hydration [77]. Xanthinuria has two types: type 1 develops with a deficiency of xanthine dehydrogenase enzyme and type 2 develops with a deficiency of aldehyde oxidase enzyme [78]. These two types are differentiated using an allopurinol test [78]. In addition, xanthinuria may develop after Lesh‐Nyhan syndrome is treated using allopurinol [79]. Xanthinuria has no specific treat‐ ment but responds well to hydration, urine alkalization, and reduction of dietary purine [80].

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

Cystinuria is a genetic disease in which reabsorption of cysteine and other dibasic amino acids, including ornithine, arginine, and lysine, through the proximal tubules is impaired [81]. Cystinuria has two genetic types: type 1, which is caused by the SLC3A1 gene on the 2nd chromosome and type 2, which is caused by the SLC7A9 gene on the 19th chromosome [82]. Cystinuria is more common in Eastern Mediterranean populations [83]. Cysteine higher

hydration and alkalization fail, use of thiol‐containing drugs is recommended [6]. Thiol forms a disulfide complex, which is soluble with cysteine and prevents formation of stones. Thiol‐ containing drugs are more effective on alkaline urine, and a study has demonstrated that dis‐ solution in urine incubated with cysteine was low for the first 60 minutes when the pH was 6, but it was optimal when the pH was 8 [84]. However, no difference was found between pH 7 and 8 after either 60 minutes or 48 hours [84]. This indicates the importance of alkalization even when using thiol‐containing drugs. However, a high urine pH may lead to phosphate

**D‐penicillamine** is a chelating agent that contains thiol and increases cysteine dissolution by as much as 50‐fold [85]. D‐penicillamine may cause bonemarrow suppression, proteinuria, skin eruptions on the neck and extremities, arthralgia, liver dysfunction, and febrile reaction [86]. Its use for metaphylaxis of cysteine stones is restricted by the fact that up to 86% of pedi‐ atric patients using it have developed side effects [87]. Although d‐penicillamine use is not recommended in children, if it must be used, close follow‐up for side effects is essential. In addition, to decrease side effects and increase tolerance, during the first week, the dose should be 5 mg/kg/day, and then it should be increased by 5 mg/kg/day, reaching 20 mg/kg/day at the end of four weeks [86]. Pyridoxine deficiency develops with long‐term d‐ penicillamine

**Alfa mercaptopropionylglycine (AMG, thiopronin)** has an effect similar to that of d‐penicil‐ lamine but with fewer side effects [85]. The daily dose is 10–15 mg/kg [6]. The rate of treat‐ ment discontinuation is lower than that for d‐penicillamine therapy [88]. Although thiopronin has fewer side effects than penicillamine, patients must be closely monitored for side effects, including fever, which often occurs during the first month, rash, bone marrow suppression,

crystallization; therefore, pH 7–7.5 appears to be the most appropriate target.

therapy, so therapy should include pyridoxine [85].

in 24‐hour urine is considered as a diagnostic for cystinuria [26]. Where

*3.2.4. Cystine stones*

than 50 mg/1.73 m2

*3.2.4.1. Drugs containing thiol*

Infection stones are stones of struvite, carbonate apatite, or ammonium urate. Urease‐positive bacteria increase urinary bicarbonate and ammonium, making urine basic [7]. Unlike acidic stones, ammonium‐urate stones form in basic environments and are associated with urinary tract infections [7]. In the case of infection stones, the carbonate‐apatite form of calcium phos‐ phate crystalizes at pH 6.8 or higher [7].

In metaphylaxis of infection stones, the primary objective is complete elimination of the stones. If a renal anomaly is causing stasis, it should be treated. Use of urease inhibitors is con‐ troversial, even in adult patients, due to their high rate of complications, and L‐methionine for urine acidification is not recommended in children [6, 7]. Intake of cranberry juice may be recommended for urine acidification in pediatric patients. Antibiotic therapy and prophylaxis may be begun if required, along with urinary‐culture follow‐up.
