The Way from Renal Calcifications and Urinary Crystals to Kidney Stones: An Important Aspect in the Pathogenesis of Calcium Nephrolithiasis

Abstract

The formation of calcium (Ca) stones occurs in an initial phase by fixed growth on kidney calcifications consisting either of intratubular crystal accumulations protruding in renal calices (Randall's plugs) or of interstitial hydroxyapatite deposits (Randall's plaques) broken through the covering epithelial layers. Crystal aggregation (AGN) seems to be responsible for stone growth during crystalluria. This chapter reports on new aspects of the AGN of calcium oxalate being the most frequent stone compound and tries to explain why despite the widespread occurrence of kidney calcifications and crystalluria not everybody forms stones. Urinary crystals normally are protected from AGN by coats of urinary macromolecules (UMs) which by their identical electronegative charge create zones of electrostatic repulsion. At high urinary concentration or ionic strength respectively, these zones are compressed and can be bridged by self-aggregated UMs. Self-AGN occurs in concentrated urine by the adsorption of UMs on free surfaces like Randall's plugs or plaques. High oxalate excretion and high urine concentration favoring intratubular crystal accumulation, breaking of epithelial layers on Randall's plaques and self-AGN of UMs are most deleterious factors in Ca stone formation and have to be avoided by stone metaphylaxis.

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

“…In recurrent stone formers CaOx and CaP nucleation can take place at the end of the descending limb of the loop of Henle [15, 29]. However, in most patients CaOx crystallization seems to start at the end of the collecting ducts where urinary passage is only in the order of few seconds [10]. Urinary transit time (UT) through the renal pelvic system on the other hand endures several minutes and is essentially influenced by diuresis.…”

“…Eleven proteins are thought to be relevant for stone formation [9]. Measurement of crystal growth showed that the growth of CaOx is too slow to allow particles within the short urinary transit time through the kidney to be able to reach dimensions being big enough to be retained in the narrow renal tubular system [10]. However freshly formed crystals by aggregation (AGN) tend to form big conglomerates.…”

“…Even in stone patients RPL was found to persist during decades without stone formation [20]. CaOx crystallization experiments performed in the presence of UM and HAP suggest that under special conditions UM coated RPL can give rise to stone formation by crystal AGN during crystalluria [10].…”