Epidemiology and clinical pathophysiology of uric acid kidney stones.
There is global diversity in the prevalence of uric acid (UA) nephrolithiasis. UA nephrolithiasis comprises 8-10 % of all kidney stones in the United States. However, its prevalence is higher in patients with type 2 diabetes mellitus and those with obesity. Three significant urinary abnormalities have been described as the main etiologic factors for the development of UA nephrolithiasis; low urinary pH, hyperuricosuria and low urinary volume. However, an unduly acidic urine below the ionization constant of uric acid (pKa < 5.5) increases the urinary content of undissociated uric acid and thereby uric acid precipitation. Previous studies have shown the two major pathogenic mechanisms for unduly urinary pH are increased net acid excretion (NAE) and reduced renal ammonium (NH4 (+)), with a combination resulting in overly acidic urine. The impaired ammonium excretion has been demonstrated in a steady state in 24-hour urine and also following an oral ammonium chloride (NH4Cl) challenge to amplify ammoniogenic defects in this population. Similar abnormalities have been disclosed in normal populations and also in T2DM populations without kidney stones. To date, the underlying mechanism of increased acid production, source and nature of putative organic acid anions have not been fully elucidated. One plausible mechanism is the production of organic acid by intestinal and aerobic metabolism. This may occur in obese, diabetic and uric acid stone formers due to the differences in gut microflora.
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8885, USA, khashayar.sakhaee@utsouthwestern.edu.
Khashayar
K
Sakhaee
D064751:Ammonium Compounds / Q000378:metabolism; D000818:Animals; D015897:Comorbidity; D003460:Crystallization; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D014527:Uric Acid / Q000378:metabolism*
D064751:Ammonium Compounds; D014527:Uric Acid