Crystallization and stone formation inside the nephron.

A model is presented visualizing the events leading to calcium-salt, crystal- and stone-formation inside the nephron. For each nephron segment, handling of urine components relevant to stone formation is considered and urine composition determined. This information was applied to nucleation experiments simulating passage of urine through a nephron. The model and in vitro experiments suggest that within normal transit times for the respective nephron segments, particles of a hydroxyapatite-like material first form near the bend in the Loop of Henle of juxtamedullary nephrons. From there on, calcium oxalate particles start to appear: first dihydrate, then monohydrate. In the collecting duct system, particle size increases primarily due to crystal agglomeration. Several conclusions with clinical and experimental relevance can be drawn. An increase in urinary volume does not decrease the chance of crystal formation in the Loop of Henle, but does decrease passage time through the collecting ducts, and thus, the time allowed for large particle formation. A calcium load does not increase the risk for nucleation up to the distal tubule, but does increase the risk of large particle formation in the collecting ducts. An oxalate load increases the chance for nucleation throughout the nephron. For experiments simulating crystallization processes occurring inside the nephron, diluted urines should be used. They should be diluted 16 to 50 times for testing nucleation, 2 to 30 times for testing crystal growth, and 2 to 20 times for testing crystal agglomeration. Undiluted urines may be used to mimic conditions in the pelvis and the bladder.