Pathomechanisms of nephrolithiasis.

Lithiasis continues to be an important factor in chronic renal disease, since it leads to chronic tubulo-interstitial nephritis, which is estimated to be involved in 15- 30% of cases of end stage chronic renal insufficiency. It is believed that in order for a stone to be formed, a solid phase needs to be first produced from microcrystals (the nucleus), which are formed from salts (and other substances) that are found dissolved in the urine (nucleosis of crystals). Afterwards, the crystals that constitute the core increase in size and link up with each other (incorporation). The main physiochemical factors that participate in the creation of the nucleus are the hypersaturation of urine, the lack of inhibitors of nucleosis and probably the organic substrate. In order for the increase in size and the incorporation of crystals to take place, hypersaturation, the lack of inhibitors, the organic substrate and the epitaxis, during which crystals of a substance are attached to the surface of other crystals of a different chemical structure (e.g. crystals of oxalic calcium onto crystals of uric acid) are needed. Various molecules have been found in urine, which modify to an important degree the adherence of crystals to the surface of epithelial cells. It also seems very likely that certain reactions of renal epithelial cells that follow the uptake of calcium oxalate monohydrate (COM) crystals are due to oxalate ions, which are released during the process of deconstruction of the intracellular crystals. From here, the crystals migrate in the median tissue, where an inflammatory reaction takes place and finally the crystals are destroyed. Macrophages gather in the crystals of the median tissue. The osteopontin which is related to the crystals acts as a chemotactic factor for the macrophages and therefore is perhaps involved in this process too. The uptake of crystals appears to be subjected to regulating mechanisms, as molecules which regulate the endocytosis of COM crystals, a process that is related to changes in the special components of the cytoskeleton, have been observed. In conclusion, the processes of adherence and of endocytosis promote the detention of crystals in the nephron, whilst intracellular deconstruction is an important factor of defence against the deposition of calcium in the kidney.