Prevention of Calcium Nephrolithiasis: The Influence of Diuresis on Calcium Oxalate Crystallization in Urine

Abstract

A high fluid intake is still the most evidence-based measure for the prevention of idiopathic stone disease. The recommendation of current guidelines on urolithiasis to increase diuresis to 2-2.5 L/day is mainly based on a single clinical study. The present paper shows the influence of diuresis on calcium oxalate (CaOx) crystallization and especially aggregation (AGN) which can explain the initial development of Ca stones on papillary calcifications as well as stone growth in the renal pelvic system. Diuresis determines the urinary transit time (UT) through the kidney and together with the afflux of Ca and Ox the state of urinary saturation with respect to CaOx being the most frequent stone mineral. High supersaturation inducing crystallization during UT and a high urinary ion concentration interfering with the inhibition of crystal AGN by urinary macromolecules seem to be critical parameters for stone formation. Using data from the literature the influence of diuresis on these parameters is evaluated for short-term recurrent stone formers (RSF), idiopathic stone patients, and healthy controls, the latter two collectives with and without excessive oxalate ingestion. This investigation suggests that a diuresis of 2 L/day may protect from stone formation even after dietary Ox excesses and in RSF. However, in RSF with a continuously high Ca and Ox afflux into urine a permanent high diuresis is required which is difficult to sustain over 24 hours.

Figure 1

Crystallization curves in urine obtained by Ox titration. (a) Urine with inhibition of AGN demonstrated by slow decrease of optical density (-dOD/d). (b) Urine with massive AGN indicated by a phase of rapid -dOD/dt.

Figure 2

Maximal decrease of optical density (mOD/dt) in crystallization tests performed in urine and albumin solution (AS, 20 mg/ml) without (native) and after the addition of UM coated hydroxyapatite (+cHAP, 0.05 mg/ml) and in dissolved Ca phosphate precipitates (DP) from urine and AS.

Figure 3

Particle size distribution in albumin solution (AS, 20 mg/ml) and in dissolved Ca phosphate precipitate of AS (DP from AS).

Figure 4

Molar urinary concentration products of Ca times Ox (CP_m, mM²) in stone formers (SF) and healthy controls (HC), with dietary Ox load (+OL) and in recurrent SF (RSF) compared to molar solubility products of CaOx (SP_m) at different states of diuresis (L/day): CP_m at the average diuresis in the group (o).

Figure 5

Induction time of crystallization (IT, minutes) in SF and HC, with dietary Ox load (+OL) and in RSF compared to urinary transit time (UT) through the renal pelvic system (volume 7 mL) at different states of diuresis (L/day): IT at the average diuresis in the group (o), crystallization occurring within the kidney (shaded area).

Figure 6

Urinary sodium concentration (Na, mM) in SF and HC, with dietary Ox load (+OL) and in RSF at different states of diuresis (L/day) and critical Na concentration for AGN (100 mM): Na concentration at the average diuresis in the group (o), risk of AGN (shaded area).