Kidney stones occur when the salt that causes stone formation is found in excess in the urine of the individual (when the urine is supersaturated with stone-forming salt). However, it is stated that these salts (calcium oxalate, calcium phosphate and uric acid) are found in a supersaturated form in the urine of healthy individuals, and accordingly, about 15-20% of healthy individuals have crystallurin. On the other hand, the fact that crystalluria is more prominent in the first morning urine of patients with recurrent kidney stone disease than in patients without recurrent stone disease may suggest that the recurrence of the stone is related to the severity and degree of crystalluria.
The crystallization processes of salts that play a role in stone formation have not been fully elucidated. Calcium oxalate in the urine crystallizes as either calcium oxalate monohydrate (COM) or calcium oxalate dihydrate (COD). Calcium oxalate stones contain mostly thermodynamically more stable COM. Macromolecular inhibitors that block COM formation facilitate COD formation. In vitro, it has been shown that COD crystals do not fuse with organic compounds and do not adhere to renal epithelial cell surfaces. The low ability of COD crystals in urine to form stable aggregates and adhere to epithelial cells suggests that these crystals are protective against kidney stone formation.
Especially after meals, urine becomes supersaturated (supersaturated) with an acidic calcium phosphate salt “brushite (CaHPO4.2H2O)”. This salt may act as a core focus for the formation of calcium oxalate crystals (especially COM).
Data on the presence of crystallization inhibitors in urine suggest that they also play a role during stone formation. Citrate, magnesium and pyrophosphate are indicated as clinically important major crystallization inhibitors.
The first step in kidney stone formation is considered to be the formation of crystals in the ultrafiltrate. In the later stage, it is assumed that the crystal either grows directly to the extent that it blocks the tubular lumen, or adheres to the urinary epithelium and begins to grow there. However, the typical transit time of a crystal across the nephron is about 3 minutes. This period, on the other hand, seems to be very short in terms of creating a focus for stone formation, growth and lumen obstruction.
Evan and Coe, in their studies to explain how stones form in the kidney in patients with idiopathic hypercalciuria, it was shown that crystallization occurs in the basement membrane of the epithelial cells lining the thin leg of the loop of Henle. The core of the stone is calcium phosphate. This calcium phosphate crystal comes from there to the renal pelvis and settles as the core of the stone to be formed here, and grows by interacting with the urine saturated with calcium oxalate. It cannot be explained how the calcium phosphate salt precipitates on the basolateral membrane of the epithelial cells lining the thin leg of the loop of Henle. It is known that postprandial proximal tubular calcium reabsorption decreases in patients with idiopathic hypercalciuria. This finding explains how the urine becomes saturated with calcium salts in these cases.
In the formation of calcium phosphate stones, “brushite” crystals accumulate on the luminal membrane of epithelial cells in the inner dilated medullary collecting duct (dilated inner medullary collecting duct) and grow from there to the renal pelvis, and are surrounded by interstitial fibrosis areas. It has been shown that the inner medullary collecting ducts cause dilatation.
There is a relationship between urine pH and kidney stone formation. For example, increased uric acid level in the blood and acidic urine pH play an important role in the formation of radiolucent uric acid stones (which cannot be visualized in direct film and computerized tomography examination without drugs, but can be visualized by ultrasonography examination). On the other hand, alkalinity of urine pH plays an important role for the formation of “struvite” stones, known as infection stones, which are formed by bacteria that decompose urea.
