Impacto en la competitividad de las firmas contratantes

All uric acid and ammonium urate stone formers are considered to be at high risk of recurrence (1). Uric acid nephrolithiasis is responsible for approximately 10% of kidney stones (2). They are associated with hyperuricosuria or low urinary pH. Hyperuricosuria may be a result of dietary excess, endogenous overproduction (enzyme defects), myeloproliferative disorders, tumour lysis syndrome, drugs, gout or catabolism (3). Low urinary pH may be caused by decreased urinary ammonium excretion (insulin resistance or gout), increased endogenous acid production (insulin resistance, metabolic syndrome, or exercise-induced lactic acidosis), increased acid intake (high animal protein intake), or increased base loss (diarrhoea) (3). Ammonium urate stones are extremely rare, comprising < 1% of all types of urinary stones. They are associated with UTI, malabsorption (inflammatory bowel disease and ileostomy diversion or laxative abuse), potassium deficiency, hypokalemia and malnutrition.

Suggestions on uric acid and ammonium urate nephrolithiasis are based on level 3 and 4 evidence.

11.7.1 Diagnosis

Figure 11.5 shows the diagnostic and therapeutic algorithm for uric acid and ammonium urate stones. Blood analysis requires measurement of creatinine, potassium and uric acid levels. Urinalysis requires measurement of urine volume, urine pH profile, specific weight of urine, and uric acid level. Urine culture is needed in case of ammonium urate stones.

11.7.2 Interpretation of results

Uric acid and ammonium urate stones form under completely different biochemical conditions. Acidic arrest (urine pH constantly < 5.8) promotes uric acid crystallisation.

Hyperuricosuria is defined as uric acid excretion > 4 mmol/day in adults or > 0.12 mmol/kg/day in children. Hyperuricaemia may be present, but there is only weak evidence for its association with stone formation.

Hyperuricosuric calcium oxalate stone formation can be distinguished from uric acid stone formation by: urinary pH, which is usually > 5.5 in calcium oxalate stone formation and < 5.5 in uric acid stone formation and occasional absence of hyperuricosuria in patients with pure uric acid stones (4,5).

Ammonium urate crystals form in urine at pH > 6.5, at high uric acid concentration and ammonium being present to serve as cation (6-8).

11.7.3 Specific treatment

General preventive measures are recommended for fluid intake and diet. Hyperuricosuric stone formers benefit from purine reduction of their daily diet. Figure 11.5 describes pharmacological treatment (1-15). For uric acid

stones, allopurinol may change the stone composition distribution in patients with gout to a pattern similar to that in stone formers without gout (16).

Figure 11.5: Diagnostic and therapeutic algorithm for uric acid and ammonium urate stones

tid = three times a day. 1 d: day (24h)

* A higher pH may lead to calcium phosphate stone formation.

11.7.4 References

1. Hesse AT, Tiselius H-G. Siener R, Hoppe B. (Eds). Urinary Stones, Diagnosis, Treatment and Prevention of Recurrence, 3rd edn. Basel, S.Karger AG; 2009. ISBN 978-3-8055-9149-2. 2. Mandel NS, Mandel GS. Urinary tract stone disease in the United States veteran population. II.

Geographical analysis of variations in composition. J Urol 1989 Dec;142(6):1516-21. http://www.ncbi.nlm.nih.gov/pubmed/2585627

3. Cameron MA, Sakhaee K. Uric acid nephrolithiasis. Urol Clin North Am 2007 Aug;34(3):335-46. http://www.ncbi.nlm.nih.gov/pubmed/17678984

4. Millman S, Strauss AL, Parks JH, et al. Pathogenesis and clinical course of mixed calcium oxalate and uric acid nephrolithiasis. Kidney Int 1982 Oct;22(4):366-70.

http://www.ncbi.nlm.nih.gov/pubmed/7176335

5. Pak CY, Poindexter JR, Peterson RD, et al. Biochemical distinction between hyperuricosuric calcium urolithiasis and gouty diathesis. Urology 2002 Nov;60(5):789-94.

http://www.ncbi.nlm.nih.gov/pubmed/12429297

6. Chou YH, Huang CN, Li WM, et al. Clinical study of ammonium acid urate urolithiasis. Kaohsiung J Med Sci 2012 May;28(5):259-64.

http://www.ncbi.nlm.nih.gov/pubmed/22531304

7. Wagner CA, Mohebbi N. Urinary pH and stone formation. J Nephrol 2010 Nov-Dec;23 Suppl 16: S165-9.

http://www.ncbi.nlm.nih.gov/pubmed/21170875

Urate containing stones

Ammonium urate stone Urid acid stone

Basic evaluation Basic evaluation

Urine pH > 6.5 “Uric acid arrest”

Urine pH < 6 Alcaline citrate 9-12 g/d2 Or Sodium bicarbonate 1.5 g tid L-methionine 200-500 mg tid Target urine-pH 5.8-6.2 Correction of factors predisposing amm.urate stone formation Dose depends on targeted urine pH Prevention

urine pH 6.2-6.8 urine pH 6.5-7.2*Chemolytholisis

Allopurinol 100-300 mg/d UTI Antibiotics > 4.0 mmol/d _{> 4.0 mmol/d} and Hyperuricemia > 380 µmol Allopurinol 100 mg/d Hyperuricosuria

8. Miano R, Germani S, Vespasiani G. Stones and urinary tract infections. Urol Int 2007;79 (Suppl 1): 32-6.

http://www.ncbi.nlm.nih.gov/pubmed/17726350

9. Rodman JS, Sosa E, Lopez ML. Diagnosis and treatment of uric acid calculi. In: Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger GM, eds. Kidney Stones. Medical and Surgical Management. Philadelphia: Lippincott-Raven, 1996, pp. 973-989.

10. Low RK, Stoller ML. Uric acid-related nephrolithiasis. Urol Clin North Am 1997 Feb;24(1):135-48. http://www.ncbi.nlm.nih.gov/pubmed/9048857

11. Shekarriz B, Stoller ML. Uric acid nephrolithiasis: current concepts and controversies. J Urol 2002 Oct;168(4 Pt 1):1307-14.

http://www.ncbi.nlm.nih.gov/pubmed/12352383

12. Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest 2005 Oct;115(10):2598-608. http://www.ncbi.nlm.nih.gov/pubmed/16200192

13. Pak CY, Waters O, Arnold L, et al. Mechanism for calcium urolithiasis among patients with

hyperuricosuria: supersaturation of urine with respect to monosodium urate. J Clin Invest 1977 Mar; 59(3):426-31.

http://www.ncbi.nlm.nih.gov/pubmed/14173

14. Wilcox WR, Khalaf A, Weinberger A, et al. Solubility of uric acid and monosodium urate. Med BiolEng 1972 Jul;10(4):522-31.

http://www.ncbi.nlm.nih.gov/pubmed/5074854

15. Mattle D, Hess B. Preventive treatment of nephrolithiasis with alkali citrate--a critical review. Urol Res 2005 May;33(2):73-9.

http://www.ncbi.nlm.nih.gov/pubmed/15875173

16. Marchini GS, Sarkissian C, Tian D, et al. Gout, stone composition and urinary stone risk: a matched case comparative study. Urol 2013 Apr;189(4):1334-9.

http://www.ncbi.nlm.nih.gov/pubmed/23022002