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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 328-331
Xanthine urolithiasis

1 Department of Pediatrics, Charles Nicolle Hospital, Bab Saadoun, Tunisia
2 Department of Pediatric Surgery, University Children's Hospital, Bab Saadoun, Tunisia

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Date of Web Publication9-Mar-2010


Hereditary xanthinuria type I, a defect of purine matabolism, results from a genetic deficiency of xanthine oxidase. It is an uncommon cause of stone formation in children. We report here two children with xanthine urolithiasis. The first patient was an 8-year-old boy who presented with repeated episodes of hematuria evaluated with excretory urography, which demonstrated radio­lucent pelvic stone in the right kidney, causing hydronephrosis. He had pyelolithotomy, and the extracted stone consisted of pure xanthine. Family study revealed an asymptomatic xanthinuria in younger brother. The second patient was a 5-year-old boy who had a 2-week history of abdominal pain and gross hematuria. Conventional excretory intravenous urography showed a non-functioning right kidney. Nephrectomy was performed, and histology revealed end-stage pyelonephritis. The calculi consisted of pure xanthine. In both patients, plasma and urinary concentrations of uric acid were low but xanthine and hypoxanthine concentrations were markedly elevated. Xanthine uroli­thiasis is usually a benign condition, easy to prevent or cure by appropriate alkalinization, forced hydration and restriction of dietary purines. However asymptomatic, and therefore undiagnosed, stones may invade the kidney and urinary tract, resulting in destruction of parenchyma, nephrec­tomy and renal failure.

How to cite this article:
Gargah T, Essid A, Labassi A, Hamzaoui M, Lakhoua MR. Xanthine urolithiasis. Saudi J Kidney Dis Transpl 2010;21:328-31

How to cite this URL:
Gargah T, Essid A, Labassi A, Hamzaoui M, Lakhoua MR. Xanthine urolithiasis. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2023 Feb 9];21:328-31. Available from: https://www.sjkdt.org/text.asp?2010/21/2/328/60205

   Introduction Top

Xanthinuria type I, a rare hereditary disorder, is characterized by a marked and isolated defi­ciency of xanthine oxidase activity in the ti­ssues, resulting in hypouricemia and hypourico­suria. [1] Total urinary purine excretion is not in­creased, whereas excretion of xanthine and hy­poxanthine is considerably increased as a res­ponse to the elevated serum levels of these oxy­purines. [2] Clinical symptoms may include crystal­luric urolithiasis and acute renal failure. When unrecognized, xanthinuria can lead to nephrec­tomy or end-stage renal failure. [3],[4] The following cases illustrate the interest of earlier recognition to prevent stone formation and to avoid neph­rectomy.

   Case Reports Top

Case 1

An 8-year-old boy was referred to our center for evaluation of urolithiasis. He was born at term from apparently healthy consanguineous parents (first cousins), and he had no familial history of renal stone disease. His psychomotor develop­ment and physical growth were normal. The pa­tient presented with a 2-year history of intermi­ttent left flank associated with macroscopic hematuria explored by ultrasonography at 7 years of age, which was reported as normal. He su­ffered from repeated episodes of hematuria 12 months later, evaluated with excretory urogra­phy, which demonstrated radiolucent pelvic stone in the right kidney, causing distension of the intra-renal collecting system. The patient under­went pyelolithotomy and was referred to our department for further investigation of his renal stone disease.

Stone analysis demonstrated 100% xanthine composition. Serum concentration and urinary excretion of xanthine and hypoxanthine were massively increased. Screening for metabolic disorders detected markedly decreased uric acid concentrations in the urine and plasma. Other biochemical tests included serum creatinine, calcium, phosphorus, alkaline phosphatase and bicarbonate, and all were within normal limits. Urinary calcium/creatinine ratio was normal in a 24-hour urine specimen. Urinary citrate and oxalate excretion was normal. Accordingly, we diagnosed the patient to have hereditary xan­thinuria.

An increase in fluid intake as supplement free water and a low-purine diet were recommend­ded. Oral sodium bicarbonate therapy was ini­tiated, and the dose was adjusted to maintain the urine pH at 7. The repeated ultrasound exa­mination revealed no recurrence of stones. At his present age of 15 years, the patient remains free of nephrolithiasis.

Serum uric acid levels in the patient's mother and father were normal. His younger brother, with age of 4 years, showed a significant hypo­uricosuria and hypo-uricemia without nephroli­thiasis or nephrocalcinosis on an ultrasound exa­mination, and his creatinine clearance was nor­mal. Oral sodium bicarbonate, high fluid intake and low-purine diet were initiated too. No renal stone was detected later with the yearly ultra­sound examination.

Case 2

A 5-year-old boy was admitted to another lo­cal hospital mainly for renal colic and gross he­maturia. The parents, who were first cousins, denied having health problems or familial his­tory of renal stone. Two weeks before hospita­lization, the patient had abdominal pain and vo­mited frequently, and later presented with gross hematuria. A plain abdominal radiography sho­wed the absence of radiopaque stones, and he was treated at the local hospital with intrave­nous antispasmotic.

Ten days later, the patient was transferred to our hospital for further evaluation of his repea­ted episodes of gross hematuria and renal colic. Physical examination on arrival, revealed a healthy appearing child. Mental and motor develop­ment was appropriate for age. We confirmed the presence of macroscopic hematuria with no hypertension or renal failure. Ultrasonography evaluation of the urinary tract revealed the presence of multiple calculi in the right kidney with moderate distention of the left pyelocaly­ceal system. An excretory urogram demonstra­ted a well-functioning left kidney and a non­functioning right kidney [Figure 1]. All the fin­dings were also documented by Tc-99m diethyl­enetriamine pentaacetic acid and Tc-99m dimer­captosuccinic acidscintigraphy. At operation, many calculi were impacted in the right kidney with dilatation of the pylocalyceal system. Neph­rectomy was performed, and the histologic exa­mination revealed end-stage chronic pyeloneph­ritis [Figure 2]. The examination of the extrac­ted stones with infrared spectrophotometry re­vealed pure xanthine content. The serum uric acid level was particulary low at 22 µmol/L. After right nephrectomy, the renal function re­mained normal. The patient was treated with oral sodium bicarbonate to maintain his urinary pH at 7 and was encouraged to drink more fluids. He had no stone in the left kidney during the next 40 months of follow-up.

   Discussion Top

The defect of this xanthine oxidase is uncom­mon causes of pediatric stone formation. [5] Du­ring the last decade, in the pediatric nephrology department of Charles Nicolle hospital in Tu­nisia, we noted that less than 3% of the enfants referred for renal stone had xanthinuria. Arik­yants [6] and Sarkissian [7] reported a low frequency of xanthine stone around 0.1%, but Al-Aissa [8] found a very high proportion about 13%.

A minority of patients with hereditary xanthi­nuria have renal calculi or nephrocalcinosis du­ring childhood. More than 50% of all children do not develop calculi. [1] The younger brother of the first patient was asymptomatic and did not have calculi. Xanthinuric children who have stones during childhood excrete higher amounts of xanthine and consume few fluids than those who do not. The low urinary citrate excretion noted in the first patient may be another impor­tant factor of stone formation in xanthinuria.

The severity of the nephrolithiasis resulting in kidney destruction and nephrectomy is uncom­mon in children. [9] It may be explained by late diagnosis, recurrent urinary tract infection, and staghorn urolithiasis. The progression of renal disease resulting in dialysis, transplantation, and even death has been observed. [10]

Many symptoms have been reported in xanthi­nuria such as hematuria, urinary tract infection, and renal colic cristalluria. Moreover, exercise­induced acute renal failure was described in both adults and children. [11],[12] However, most cases of xanthinuria have been discovered acci­dentally in patients being investigated for other disorders. [13]

The plasma uric acid in xanthinuria type I is very low and even undetectable and is replaced by xanthine and hypoxanthine. In fact, there is complete absence of uric acid in body fluids and its replacement predominantly by xanthine. [14] Confirmation of the enzyme defect is rarely made because it needs invasive techniques such as intestinal or liver biopsy. [1] Differential diagnosis for xanthinuria type I includes mainly xanthi­nuria type II with combined xanthine dehydro­genase and aldehyde oxidase deficiency. Both types of defects are clinically similar, but can be distinguished by urinary screening. [15]

The management of xanthinuria type I includes high fluid intake and a low-purine diet. Alkali­nization of the urine elevates modestly the solu­bility of xanthine. Increased citrate excretion in­duced by oral potassium citrate administration prevents the stone formation. [16] The treatment modality of xanthine stones depends on their size and location. Surgical stone removal should be reserved for urinary obstruction when lithotripsy has failed to relieve it. [17]

   References Top

1.Raivio KO, Saksela M, Lapatto R. Xanthine oxidoreductase: role in human pathophysiology and in hereditary xanthinuria. In: Scriver CR, Beaudet AL, Sly WS, Valle D(eds) The meta­bolic and molecular bases of inherited diseases,8 th edn. New York. McGraw-Hill., 2001,2639-52.  Back to cited text no. 1      
2.Mateos FA, Puig JG, Jimenez ML, Fox IH. Hereditary xanthinuria: Evidence for enhanced hypoxanthine salvage. J Clin Invest 1987;79: 847-52.  Back to cited text no. 2      
3.Carpenter TO, Lebowitz RL, Nelson D, Bauer S. Hereditary xanthinuria presenting in infancy nephrolithiasis. J Pediatr 1986;109:309-9.  Back to cited text no. 3      
4.Pais VM, Lowe G, Lallas C, Preminger GM, Assimos DG. Xanthine urolithiasis. Urology 2006;67:1084e9-11.  Back to cited text no. 4      
5.Fildes RD. Hereditary xanthinuria with severe orolithiasisoccurring in infancy as renal tubular acidosis and hypercalciuria. J Pediatr 1989;115: 277-80.  Back to cited text no. 5  [PUBMED]    
6.Arikyants N, Sarkissian A, Hesse A, Eggermann T, Leumann E, Steinman B. Xanthinuria type I: A rare case of urolithiasis. Pediatric Nephrol 2007;22:310-4.  Back to cited text no. 6      
7.Sarkissian A, Babloyan A, Arikyants N, Hesse A, Blau N, Leumann E. Pediatric urolithiasis in armenia: A study of 198 patients observed from 1991 to 1999. Pediatr Nephrol 2001;16:728-32.  Back to cited text no. 7  [PUBMED]    
8.Al-Issa AA, Al-Hunayyan A, Gupta R. Pediatric urolithiasis in Kuwait. Int Urol Nephrol 2002; 33:3-6.  Back to cited text no. 8      
9.Badertscher E, Robson WL, Leung AK, Trevenen CL. Xanthine calculi presenting at 1 month of age. Eur J Pediatr 1993;152:252-4.  Back to cited text no. 9  [PUBMED]    
10.Gofrit O, verstanding AG, Pode P. Bilateral obstructing ureteral uric acid stones in an infant with hereditary renal hypouricemia. J Urol 1993;149:1506-7.  Back to cited text no. 10      
11.Tanaka M, Itoh K, Matsushita K, et al. Two male siblings with hereditary renal hypouricemia and exercise-induced acute renal failure. Am J Kidney Dis 2003;42:1287-92.  Back to cited text no. 11  [PUBMED]    
12.Bradbury MG, Hendersen M, Brocklebank JT, Simmonds HA. Acute renal failure due to xanthine stone. Pediatr Nephrol 1995;9:476-7.  Back to cited text no. 12      
13.Bennett MJ, Carpenter KH, Hill PG. Asymp­tomatic xanthinuria detected as a result of rou­tine analysis of serum for urate. Clin Chem 1985;31:492.  Back to cited text no. 13  [PUBMED]    
14.Bory C, Chantin C, Boulieu R. Comparison of capillary electrophoretic and liquid chromato­graphic determination of hypoxanthine and xan­thine for the diagnosis of xanthinuria. Prenat Diag 1999;19:386-8.  Back to cited text no. 14      
15.Reiter S, Simmonds HA, Zollner N, et al. De­monstration of combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol. Clin Chim Acta 1990;187:221-34.  Back to cited text no. 15      
16.Hisatome I, Tanaka Y, Kotake H, et al. Renal hypouricemia due to enhanced tubular secretion of urate associated with urolithiasis: successful treatment of urolithiasis by alkalization of urine K + , Na + -citrate. Nephron 1993;65:578-82.  Back to cited text no. 16  [PUBMED]    
17.Nicoletta JA, Lande MB. Medical evaluation and treatment of urolithiasis. Pediatr Clin North Am 2006;53:479-91.  Back to cited text no. 17  [PUBMED]    

Correspondence Address:
Tahar Gargah
Department of Pediatrics, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

PMID: 20228523

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