Uric Acid Renal Lithiasis: New Concepts

Uric acid (UA) stones are responsible for 5-10% of the formation of all kidney stones. Recently, an association between UA stones and insulin resistance, diabetes mellitus, and obesity has been demonstrated and so the incidence has increased. The development of UA stones is dependent on several risk factors, including genetic predisposition, geographical location, dietary indiscretion, and various metabolic characteristics.

UA nephrolithiasis can arise from diverse etiologies, all with distinct underlying defects converging to one or more of 3 defects of hyperuricosuria, acidic urine pH, and low urinary volume. Low urinary pH is the commonest and by far the most important factor in UA nephrolithiasis, but the reason for this defect is unknown. Patients with UA nephrolithiasis have normal acid-base parameters assessed according to conventional clinical tests. Studies have revealed that there could be an insufficient production of urinary ammonium buffer. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Because low urine pH is the most important pathogenic factor of UA stone formation, urine alkalinization is an effective intervention to reduce UA crystallization and dissolve UA stones. Key Messages: Epidemiological and metabolic studies have indicated an association between UA nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule or due to substrate competition by free fatty acids. The identification of novel complementary DNA has provided an interesting insight into the renal handling of UA, including one genetic cause of renal UA wasting.