Potential role of fluctuations in the composition of renal tubular fluid through the nephron in the initiation of Randall’s plugs and calcium oxalate crystalluria in a computer model of renal function

This article describes an updated computer model which attempts to simulate known renal reabsorption and secretion activity through the nephron (NEPHROSIM) and its possible relevance to the initiation of calcium-containing renal stones. The model shows that, under certain conditions of plasma composition, de novo nucleation of both calcium oxalate (CaOx) and calcium phosphate (CaP) can take place at the end of the descending limb of the Loop of Henle (DLH), particularly in untreated, recurrent idiopathic CaOx stone-formers (RSF). The model incorporates a number of hydrodynamic factors that may influence the subsequent growth of crystals nucleated at the end of the DLH as they progress down the renal tubules. These include the fact that (a) crystals of either CaOx or CaP nucleated at the end of the DLH and travelling close to the walls of the tubule travel at slower velocities than the fluid flowing at the central axis of the tubule, (b) the transit of CaOx crystals travelling close to the tubule walls may be delayed for up to at least 25 min, during which time the crystals may continue to grow if the relative supersaturation with respect to CaOx (RSS CaOx) is high enough and (c) such CaOx crystals may stop moving or even fall back in upward-draining collecting ducts (CD) owing to the Stokes gravitational effect. The model predicts, firstly, that for small, transient increases in plasma oxalate concentration, crystallisation only takes place in the CD and leads to the formation of small crystals which are comfortably passed in the urine and, secondly, that for slightly greater increases in the filtered load of oxalate, spontaneous and/or heterogeneous nucleation of CaOx may occur both at the end of the DLH and in the CD. This latter situation leads to the passage in the final urine of a mixture of large crystals of CaOx (arising from nucleation at the end of the DLH) and small crystals of CaOx (as a result of nucleation originating in the CD). As a result of the higher calcium and oxalate concentrations in the urine of RSF, these patients have an increased probability of initiating CaOx crystallisation in the DLH and so of going on to form the large crystals and aggregates found in their fresh urines, but not in the fresh urines from normal subjects (N). These predictions are supported by evidence from clinical studies on six RSF and six normal controls (NC) who were maintained for 4 days on a fixed basal diet. Their patterns of CaOx crystalluria were measu