is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex cause. Randall's plaque While supersaturation of urine may lead to crystalluria, it does not necessarily promote the formation of a kidney stone because the particle may not reach the sufficient size needed for renal attachment. On the other hand, Randall's plaques, which were first identified by Alexander Randall in 1937, are calcium phosphate deposits that form in the papillary interstitium and are thought to be the nidus required for stone development. In addition to Randall's plugs, which form in the Duct of Bellini, these structures can generate reactive oxygen species that further enhance stone formation. Pathogenic bacteria Some bacteria have roles in promoting stone formation. Specifically, urease-positive bacteria, such as Proteus mirabilis can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. This increases the urinary pH and promotes struvite stone formation. Additionally, non-urease producing bacteria can provide bacteria components that can promote calcium oxalate crystallization, though this mechanism is poorly understood. Inhibitors of stone formation Normal urine contains chelating agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin (an S-100 calcium-binding protein), Tamm–Horsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide, and bikunin (uronic acid-rich protein). The biochemical mechanisms of action of these substances have not yet been thoroughly elucidated. However, when these substances fall below their normal proportions, stones can form from an aggregation of crystals. Sufficient dietary intake of magnesium and citrate inhibits the formation of calcium oxalate and calcium phosphate stones; in addition, magnesium and citrate operate synergistically to inhibit kidney stones. The efficacy of magnesium in subduing stone formation and growth is dose-dependent. Hypocitraturia Hypocitraturia or low urinary-citrate excretion (variably defined as less than 320 mg/day) can be a contributing cause of kidney stones in up to 2/3 of cases. The protective role of citrate is linked to several mechanisms; citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Therapy with potassium citrate is commonly prescribed in clinical practice to increase urinary citrate and to reduce stone formation rates. Alkali citrate is also used to increase urine citrate levels. It can be prescribed or found over-the-counter in pill, liquid or powder