A REVIEW ON THERAPEUTIC POTENTIAL OF CITRIC ACID IN NEPHROLITHIASIS: MECHANISM OF STONE FORMATION AND PREVENTION

Nephrolithiasis is a frequently occurring urological problem worldwide. The worldwide prevalence of nephrolithiasis is at least 11% of the U.S. population and significantly greater than 11% of the world's population, with men being more frequently diagnosed than women. Its development is also affected by multiple mechanisms, including urinary supersaturation, crystal nucleation; crystal growth, and crystal aggregation; interaction of crystals with renal tubular epithelial cells; and retention of the stone in the renal tubular system. Several metabolic disorders also play a large role in nephrolithiasis development, such as hypercalciuria, hyperoxaluria, hyperuricaemia, and hypocitraturia; environmental factors such as obesity, diabetes mellitus, hypertension; and dehydration, as well as dietary habits, can all result in increased nephrolithiasis. Citrate is an important dietary precursor of citric acid and may help to protect against nephrolithiasis; increased consumption of citric acid results in increased urinary citrate excretion, and citric acid is a strong anti-lithogenic agent for calcium oxalate monohydrate crystals. In addition, citrate, an important endogenous inhibitor of urine crystallization, is able to reduce urine supersaturation by binding free calcium. The binding of free calcium to citrate also has the effect of directly inhibiting calcium salt crystal nucleation, growth, and aggregation, in addition to inhibiting the adhesion of renal tubular epithelial cells to calcium salt crystals. This review discusses the major risk factors, the potential therapeutic benefit of citric acid and citrate, and also outlines the current limitations of these treatments and future directions for research in this area.