URIC ACID–RELATED NEPHROLITHIASIS
Section snippets
SOLUBILITY CHARACTERISTICS
Uric acid (2,6,8-trioxypurine) is a weak acid with solubility characteristics dependent on concentration and environmental pH (Fig. 1). Urinary volume and uric acid excretion influence concentration; however, urinary pH is the principal determinant of uric acid solubility. A pKa of 5.5 governs the loss of the first dissociable proton from uric acid to form anionic urate.18 A second pKa of 10.3 controls the loss of a second proton from urate but is physiologically unimportant in humans. The
SOURCES OF URIC ACID
Uric acid is an end product of purine metabolism with no known physiologic activity in humans. Purines come from three sources: (1) dietary, (2) de novo synthesis, and (3) cellular RNA from tissue catabolism (Fig. 3). The average daily turnover of uric acid is 600 to 800 mg. Endogenous purine production from de novo purine synthesis and tissue catabolism under most normal conditions is constant at 300 to 400 mg/d. Clinical conditions associated with endogenous overproduction include gout,
ELIMINATION
Once formed, uric acid is eliminated principally through renal excretion or intestinal uricolysis. Renal excretion accounts for approximately two thirds of uric acid disposal, whereas extrarenal routes excrete the remaining one third. Renal compromise results in a compensatory increase in extrarenal disposal.61
CLASSIFICATION
Uric acid solubility is determined by three main factors: (1) urinary volume, (2) uric acid excretion, and (3) urinary pH. Patients with excessive uric acid excretion or who are dehydrated chronically have high urinary concentrations of uric acid and are prone to uric acid stone formation. Most importantly, any clinical condition resulting in a persistently acidic urinary environment predisposes to uric acid nephrolithiasis. A classification scheme based on these three factors for uric acid
HYPERURICOSURIA AND CALCIUM UROLITHIASIS
Although uric acid stone formation is associated with hyperuricosuria, dehydration, and acidic urinary pH less than 5.5, hyperuricosuric calcium oxalate nephrolithiasis (HUCN) is characterized by calcium oxalate or calcium phosphate stone formation in the setting of hyperuricosuria, urinary pH greater than 5.5, and normocalciuria.42 The pKa of uric acid promotes the formation of monosodium urate in uric acid solutions containing sodium at pH greater than 5.5.50 Monosodium urate promotes calcium
DIAGNOSIS
The diagnosis and treatment of uric acid urolithiasis is based on an understanding of the pathophysiology of stone formation. Any patient presenting with renal colic found to have acidic urine (pH < 5.5) or a clinical history that predisposes them to hyperuricosuria or chronic dehydration, or patients with a past history of uric acid lithiasis, should be suspected as having a uric acid stone. Uric acid stones are most common in middle-aged white men. In addition to comorbidities, a thorough
STONE FEATURES
Uric acid stones can range from small rounded calculi that spontaneously pass to fully branched staghorn calculi that fill the entire renal collecting system. Unlike calcium oxalate stones, which often are jagged, uric acid stones are typically smooth and round and more readily passed spontaneously. They have an affinity for urochromes and typically appear yellow to deep brown in color but also can be black.
Pure uric acid stones are classically radiolucent on standard radiographs. Other
TREATMENT
Treatment of uric acid stones can be classified as active for an existing stone versus prophylactic against stone recurrences. Uric acid stones are unique in that they are the only common renal stone readily amenable to dissolutional therapy. Active and prophylactic therapy focus on altering the urinary environment to optimize the solubility characteristics of uric acid. Consequently, treatment of uric acid stones is directed at increasing urinary volume, alkalinizing urinary pH, and decreasing
TREATMENT OF HYPERURICOSURIC CALCIUM OXALATE STONES DISEASE
HUCN accounts for 10% to 15% of patients with calcium urolithiasis.12, 45 Treatment for HUCN involves reducing the propensity for monosodium urate–induced calcium oxalate crystallization. This is accomplished by decreasing urinary uric acid excretion and limiting dietary sodium intake (<150 mEq/d). The hyperuricosuria of HUCN most often is attributed to overindulgence of dietary proteins and successful prophylactic therapy often results from dietary protein reduction.12 Hyperuricosuria in
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Evaluation of anti-urolithiatic and diuretic activities of watermelon (Citrullus lanatus) using in vivo and in vitro experiments
2018, Biomedicine and PharmacotherapyCitation Excerpt :Increase in phosphate secretion leads to the generation of calcium phosphate crystals which along with oxalate stress favours the environment suitable for stone formation. These calcium phosphate crystals, in turn, epitaxially induce CaOX deposition [29,30]. Our study showed that pulp extract reduced the risk of stone formation by significantly reducing the urinary phosphate levels.
Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats
2017, International Journal of Biological MacromoleculesDetermination of thermodynamic parameters for complexation of calcium and magnesium with chondroitin sulfate isomers using isothermal titration calorimetry: Implications for calcium kidney-stone research
2017, Journal of Crystal GrowthCitation Excerpt :Also of relevance in motivating the present study is that changes in urinary pH have been shown to exacerbate CaOx crystallization [22,23]. At pH less than 5.5, the solubility of uric acid in urine decreases, leading to crystallization of this substance [24–26]. On the other hand, urinary pH greater than 6.0 has a tendency to form calcium phosphate crystals which may develop into apatite and brushite stones [27,28].
Chenopodium album Linn. leaves prevent ethylene glycol-induced urolithiasis in rats
2017, Journal of EthnopharmacologyProtective Effect of Propolis in Proteinuria, Crystaluria, Nephrotoxicity and Hepatotoxicity Induced by Ethylene Glycol Ingestion
2016, Archives of Medical ResearchCitation Excerpt :In our experiment, EG decreased magnesium that was alleviated by the use of HAPE or cystone. Regarding uric acid, another factor in stone formation (31), EG increased urinary excretion of uric acid and protein, plasma uric acid, and significantly decreased creatinine excretion in urine. Uric acid crystal adsorbs organic compounds and participates in calcium oxalate stone formation.
Serum uric acid as a predictor of future hypertension: Stratified analysis based on body mass index and age
2016, Preventive MedicineCitation Excerpt :Oxidative stress, inflammation, nitric oxide (NO) production impairment, vascular endothelial dysfunction, vascular smooth muscle proliferation, and renin angiotensin system enhancement have been reported as mechanisms for developing hypertension by hyperuricemia (Corry et al., 2008; Glantzounis et al., 2005; Kang et al., 2005a, 2005b; Khosla et al., 2005; Kono et al., 2010). Crystallization of UA itself has also been reported to cause inflammation, gouty kidney, and urinary tract calculi, and progression to renal failure (Chonchol et al., 2007; Iseki et al., 2004; Low and Stoller, 1997; Weiner et al., 2008). Vascular disorders are important as a mechanism of incident hypertension by hyperuricemia, and there have been two reported pathways in previous studies (Battelli et al., 2014; Kang et al., 2005a, 2005b; Neogi et al., 2012; Price et al., 2006).
Address reprint requests to Marshall L. Stoller, MD, Department of Urology, U-575, University of California, 553 Parnassus Avenue, US75, San Francisco, CA 94143–0738
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Department of Urology, University of California, Davis, School of Medicine, Sacramento (RKL), and the Department of Urology, University of California, San Francisco, School of Medicine, San Francisco (MLS), California