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 t
hat determine the risk of the first calcium phosphate crystallization step
in the loop of Henle. Data from a theoretical model that describes the flui
d composition in the different nephron segments are combined with data from
nucleation experiments. From this, an assessment was made regarding how ch
anges in plasma and urine composition tubular functions, and renal anatomy
effect the chance of initial crystallization of calcium phosphate in the lo
op of Henle. The results show that parameters like hypercalciuria and hyper
oxaluria 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 co
ncomitant increase in renal concentrating capacity are shown to increase th
e risk for crystallization in the loop of Henle. This coincides with the in
creasing incidence of calcium oxalate urolithiasis. Treating crystallizatio
n and stone formation as a nephron event opens new ways for investigating a
nd understanding the process of urinary stone formation.