Research Article: New Pathophysiological Aspects of Growth and Prevention of Kidney Stones

Date Published: May 20, 2012

Publisher: Hindawi Publishing Corporation

Author(s): J. M. Baumann, B. Affolter.


Kidney stones probably grow during crystalluria by crystal sedimentation and aggregation (AGN) on stone surfaces. This process has to occur within urinary transit time (UT) through the kidney before crystals are washed out by diuresis. To get more information, we studied by spectrophotometry the formation and AGN of Ca oxalate (Ca Ox) crystals which were directly produced in urine of 30 stone patients and 30 controls by an oxalate (Ox) titration. Some tests were also performed after removing urinary macromolecules (UMs) by ultrafiltration. To induce rapid crystallization, high Ox additions (0.5–0.8 mM) were necessary. The most important finding was retardation of crystal AGN by UM. In urine of 63% of controls but only 33% of patients, no AGN was observed during an observation of 60 minutes (P < 0.05). Also growth and sedimentation rate of crystals were significantly reduced by UM. For stone metaphylaxis, especially for posttreatment residuals, avoiding dietary Ox excesses to prevent crystal formation in the kidney and increasing diuresis to wash out crystals before they aggregate are recommended.

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After minimal invasive treatment, stone residuals are found in 20–25% of patients [1, 2]. These stone fragments are an interesting model to study stone growth in vivo. Depending on observation time, 20–37% of stone residuals show further growth which can lead to complications and secondary interventions [2, 3]. On the other hand, in a retrospective study, the size of isolated and not infected stone residuals after extracorporeal shock wave lithotripsy (ESWL) remained stable in 24 of 83 patients even during an average observation time of 3.5 years [3]. These observations suggest that stone formation occurs only periodically. Therefore, questions arise about factors inducing stone growth and about rational measures of prevention.

Figure 1 shows a typical spectrophotometric crystallization curve which can be separated into a titration and a sedimentation phase. After 6 min of Ox titration corresponding to an addition of 0.6 mM sodium oxalate, optical density (OD) started to increase (Pt. 1). From this critical Ox addition called metastable limit (ML) and the initial urinary Ox concentration in the test system, the critical supersaturation being necessary to induce crystal nucleation can be calculated. Pt. 2 marks the maximal OD or crystal concentration, respectively, reached by the Ox titration. After the end of the titration where stirring was stopped, a phase of slow OD decrease started almost immediately (Figure 1, Pt. 2-3). In previous studies, this slow OD decrease could be attributed by scanning electron microscopy (SEM) of the corresponding sediments to the sedimentation of single crystals of Ca Ox monohydrate [17, 18]. After a certain time (Pt. 3) called suspension stability (SS), a rapid decrease of OD was observed, which indicates AGN since sediments obtained after such rapid OD decreases showed large crystal aggregates in high concentration [17, 18].

Retardation of crystal aggregation (AGN) by urinary macromolecules (UMs) was the most important finding when studying Ca Ox crystallization directly in urine. Although crystallization was induced by high Ox concentrations, urine of 63% controls but only of 33% stone patients showed no signs of AGN during an observation time of 60 minutes. In the remaining urines, AGN occurred with an average delay of 20 minutes. For stone growth, AGN between crystals being suspended in urine and kidney stones has to occur within urinary transit time (UT) through the renal pelvis, before crystals are washed out by diuresis. Therefore, retardation of AGN seems to be a natural mechanism to prevent stone growth. Average UT in renal pelvis being reciprocal to diuresis was calculated dividing average volume of renal pelvis of 7 mL by an average diuresis of 0.6 mL/min and found to be in the range of 12 minutes [16]. Retardation of AGN by UM together with other factors discussed below may explain why stone formation is limited to about 10% of the population and has a recurrence rate of only 0.10–0.15 stones/patient and year [20], although urinary supersaturation especially with respect to Ca oxalate and crystalluria is common.

There is evidence that kidney stones grow by crystal AGN on stone surfaces during crystalluria. To aggregate, crystals have to settle to the stone surfaces by sedimentation. Sedimentation rate increases with increasing particle size. Therefore, urinary macromolecules (UMs) inhibiting crystal growth and decreasing sedimentation rates are an important factor preventing stone growth. Another even more important factor is the ability of UM to retard AGN until crystals, being suspended in urine, are washed out of the kidney by diuresis. Rational prevention of stone growth therefore tends to increase diuresis and to avoid excessive oxalate intake which can provoke crystal formation already in the kidney.




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