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Table 1: Differential Diagnosis of Uric Acid Stones Stone Type


Urinary pH UA stones Xanthine stones 2,8 dihydroxyadenine Mixed UA/CaOx stones


Hyperuricosuric calcium stones FE = fractional excretion; UA = uric acid.


Decreased Normal


Normal


Decreased to Normal Normal


Urinary UA Normal


Increased to Normal Normal


Increased to Normal


Increased Biochemical Profiles Urinary


FE Uric Acid Decreased


Normal Normal


Decreased to Normal Normal


Table 2: Comparison of Potassium Alkali Treatment versus Sodium Alkali Treatment in Uric Acid Nephrolithiasis


Urinary pH


Urinary citrate Urinary calcium Inhibitory effect


against CaOx Prevention of


UA stones Prevention of


calcium stones UA = uric acid.


Pharmacological Treatment


Treatment with alkali is the mainstay treatment for UA nephrolithiasis. This treatment has been shown to effectively raise urine pH and prevent the occurrence of stone disease.84–86


Potassium alkali is the preferred


mode of treatment since it is known to raise urinary pH and citrate while lowering urinary calcium excretion. Therefore the risk of calcium oxalate stone formation, a condition that has been shown to occur with sodium alkali treatment, diminishes with this preparation85,86


(see Table 2).


Sodium alkali may be used in patients with GI intolerance to potassium salt or impaired renal function. The recommended daily dosage of alkali depends upon body weight and estimated amount of dietary purine intake. The typically recommended dosage is 30–60 mEq/day. The effectiveness and compliance with treatment may be monitored by measurement of urinary pH and potassium. During the first year of treatment, these values should be monitored every six months and annually thereafter in order to avoid a rise in pH above 6.7, which may increase the risk of calcium phosphate stone formation.87


Alternatively,


one may use urinary NH4+ as a marker of sufficient alkalinization. A 50 % reduction in urinary NH4+ excretion following alkali treatment is


1. Mandel NS, Mandel GS, Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition, J Urol, 1989;142(6):1516–21.


2. Lieske JC, de la Vega LS, Gettman MT, et al., Diabetes mellitus and the risk of urinary tract stones: a population-based case-control study, Am J Kidney Dis, 2006;48(6):897–904.


3. Pak CY, Sakhaee K, Moe O, et al., Biochemical profile of stone-forming patients with diabetes mellitus, Urology, 2003;61(3):523–7.


4. Ekeruo WO, Tan YH, Young MD, et al., Metabolic risk factors and


Potassium Alkali Increase Increase Decrease


Significant increase Significant increase Significant increase


Sodium Alkali Increase Increase


No change or increase No change or increase


Significant increase Increase Urinary Calcium Serum UA


Normal Normal


Normal


Increased to Normal Normal


Increased Decreased


Normal


Increased to Normal Normal


Response to


Alkali Treatment Positive


Negative Negative Positive Positive


suggestive of sufficient acid neutralization. In rare instances, a carbonic anhydrase inhibitor (Diamox®) can be used to allow for urinary alkalinization. However, this treatment may pose a risk since the development of systemic metabolic acidosis, hypocitraturia, and highly alkaline urine may increase the risk of calcium phosphate stones.88–90


Allopurinol is necessary in patients with excessive urinary UA excretion, hyperuricosuirc calcium nephrolithiasis, gout, genetic disorders of UA metabolism, and in conditions associated with increased tissue catabolism. Although the side effects associated with this medication are minimal, it should be used with caution in patients with renal impairment.91


The effectiveness of a newly released purine analog


inhibitor of xanthine oxidase, febuxostat (Uloric®), in the hyperuricosuric kidney-stone-forming population has not been established. Animal studies have shown the reversibility of renal fat and restoration of urinary acidification parameters with an insulin-sensitizing drug, thiazolidinedione (TZD).78


The effect of this novel treatment in patients with UA nephrolithiasis is being investigated in an on-going, double-blind, placebo- controlled study.


Conclusion


With the worldwide epidemic of obesity it is expected that UA stone prevalence will progressively increase. UA stones have emerged as a major health concern given its links to the MS, obesity, and T2DM.3,5–7 Significant advances have been made in our understanding of the pathophysiological mechanism(s) of UA urolithiasis. Several metabolic studies have demonstrated that abnormal urine acidity in this population can be attributed to dual mechanisms: defective urinary NH4+ excretion and increased acid production.10,21–25,60,92–94


Experimental


studies using ZDF rats and cell culture models have suggested that renal steatosis is responsible for decreased NH4+ secretion.77,78


n TZD, a drug


that is known to reduce tissue steatosis, has been shown to reduce renal triglyceride accumulation and reverse urinary acidification profiles in a ZDF rat model.78


the impact of medical therapy on the management of nephrolithiasis in obese patients, J Urol, 2004;172(1):159–63.


5. Daudon M, Lacour B, Jungers P, High prevalence of uric acid calculi in diabetic stone formers, Nephrol Dial Transplant, 2005;20(2):468–9.


6. Daudon M, Traxer O, Conort P, Lacour B, Jungers P, Type 2 diabetes increases the risk for uric acid stones, J Am Soc Nephrol, 2006;17(7):2026–33.


7. Daudon M, Lacour B, Jungers P, Influence of body size on urinary stone composition in men and women, Urol Res,


2006;34(3):193–9.


8. Henneman PH, Wallach S, Dempsey EF, The metabolism defect responsible for uric acid stone formation, J Clin Invest, 1962;41:537–42.


9. Asplin JR, Uric acid stones, Semin Nephrol, 1996;16(5):412–24. 10. Maalouf NM, Cameron MA, Moe OW, et al., Low urine pH: a novel feature of the metabolic syndrome, Clin J Am Soc Nephrol, 2007;2(5):883–8.


11. Kral JG, Morbidity of severe obesity, Surg Clin North Am, 2001;81(5):1039–61.


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US NEPHROLOGY


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