**2.1 The road to kidney stone formation**

Kidney stones affect 10% of the world's population. Although the structure of kidney stones varies, calcium oxalate stones are the most common. Oversaturation of the urine with calcium oxalate creates a driving force in the kidney, resulting in crystal precipitation. The accumulated crystals form calcium oxalate stones [15].

*Effect of Ascorbic Acid on the Kidneys DOI: http://dx.doi.org/10.5772/intechopen.111913*

**Figure 1.** *Ascorbate metabolism [13].*

The main determinants of urinary oxalate excretion and the formation of calcium oxalate crystals appear to be dietary oxalate and its precursors. It is known that the ratio of dietary oxalate intake to oxalate in urine is 50% in healthy individuals. Endogenous biosynthesis, dietary intake, renal and fecal excretion are all balanced to maintain oxalate homeostasis. Endogenous oxalate biosynthesis and transport may be disrupted by genetic mutations such as hyperoxaluria, increased dietary oxalate precursors, and gastrointestinal pathologies caused by microbial factors [15, 16].

Oxalate is a potentially toxic substance eliminated from the kidneys through glomerular filtration and tubular secretion. Increased oxalate concentrations in the blood and urine have been linked to kidney stone formation. The increase in oxalate concentration is explained by an increase in ascorbic acid synthesis as a metabolic end product or by dietary intake of oxalate and its precursors [16, 17].

The first studies on endogenous oxalate synthesis stemmed from research on kidney stone formation in people with primary hyperoxaluria, a rare genetic disease. As a result of the research, it was discovered that endogenous oxalate biosynthesis was higher in these patients than in healthy people. The liver is the primary site of endogenous oxalate production [15, 18].

Glyoxalate has been identified as an oxalate precursor in the liver. Lactate dehydrogenase is the enzyme responsible for the conversion of glyoxalate to oxalate. Hydroxyproline, glycine, phenylalanine, glyoxal, and glycolate are all precursors to glyoxalate synthesis [15, 19]. The most important factor to increase oxalate formation is dietary ascorbic acid. Ascorbic acid is thought to be an important component of the structure of calcium oxalate crystals since it is converted to oxalate non-enzymatically as a result of its metabolization. Calcium oxalate crystals are formed when oxalate combines with cations such as calcium. Calcium oxalate crystals that form build up in the kidney and cause stone formation. Crystal deposition and stone formation may result in renal tubular damage [20–22].
