Risk factors for crystallization in the nephron: the role of renal development

Several studies indicate that crystallization, the essential first step for stone formation, starts in the nephron. First a calcium phosphate mineral precipitates in the loop of Henle and this may induce formation of calcium oxalate in the late nephron segments. This study investigated the factors that determine the risk of the first calcium phosphate crystallization step in the loop of Henle. Data from a theoretical model that describes the fluid composition in the different nephron segments are combined with data from nucleation experiments. From this, an assessment was made regarding how changes in plasma and urine composition, tubular functions, and renal anatomy effect the chance of initial crystallization of calcium phosphate in the loop of Henle. The results show that parameters like hypercalciuria and hyperoxaluria do not completely reflect the risk for the initial nucleation step. A combination with data on plasma composition and on tubular function is needed to assess this risk. Renal growth from birth to adulthood and the concomitant increase in renal concentrating capacity are shown to increase the risk for crystallization in the loop of Henle. This coincides with the increasing incidence of calcium oxalate urolithiasis. Treating crystallization and stone formation as a nephron event opens new ways for investigating and understanding the process of urinary stone formation.