Urinary factors affecting renal stone disease

Abstract

This study investigates the physicochemical aspects of calcium oxalate (CaOx) crystallization. Two major classes of crystallization modifiers were studied urinary glycoproteins (GPs) and urinary glycosaminoglycans (GAGs) by the mixed suspension mixed product removal (MSMPR) system - a continuous crystallization system. Total urinary GPs were shown to promote CaOx crystallization. Although whole urinary GAGs showed no significant differences on CaOx crystallization, individual GAGs showed that chondroitin sulphate and heparan sulphate promoted the CaOx crystallization while hyaluronan (HA) promoted the formation of smaller CaOx crystals but showed no significance in the crystal density of CaOx formed in the urine. Since HA is reported as a promoter of CaOx crystallization which is a distant form of other GAGs species, we studied both total urinary GAGs and HA excretion in stone-formers (SF), post-treated SF and compared with normal individuals. Active-SF and post-treated SF groups had lower total GAGs excretion but increased proportion of HA than that of the normal controls indicating that urinary GAGs and HA are probably protective/risk factors for the occurrence and recurrence of renal stone disease. CD44 is known as a HA receptor and CD44 is found on various cell surfaces including epithelial cells and shown to bind with HA when released by cells in several studies due to cell injury induced by inflammatory response. Therefore, HA excretion and CD44 expression in renal cells as an inflammatory response and HA expression on CaOx induced cell injury were also studied. This study suggested the possible events during subclinical CaOx renal stone disease. HA was secreted during CaOx induced cell injury and the injured cells will also secrete IL-1β as the inflammatory cytokine. This can eventually lead to further HA secretion as well as CD44 expression that can interact with the HA being secreted for CaOx crystal attachment and retention for stone formation during the healing of the injured renal cells. Melamine renal stone disease incident in Chinese infants in late 2007 lead to the concern on how melamine affected renal stone disease. Unlike CaOx crystallization, the physicochemical nature of melamine in urine and its handling were largely unknown at that time. Therefore, the well-established MSMPR system on CaOx crystallization was applied for melamine crystallization studies. The physiochemical properties of melamine crystallization including pH and ionic strength were studied. Melamine was found to crystallize in normal acidic urinary pH (pH 6.0) so that normal urine can provide an optimal condition for melamine crystallization. Besides, it was also found that melamine can interact with other lithogenic salts including calcium, oxalate and uric acid. Presence of melamine significantly enhanced the precipitation of calcium oxalate while the presence of uric acid significantly reduced melamine crystallization. Urinary tract infection (UTI) is common in children. As melamine stones occurred in infants and children, the main pathogen of UTI E. coli on melamine crystallization was studied. E. coli promotes melamine crystallization and thus appropriate measure such as treating UTI prior to stone removal can reduce the severity of melamine stone disease and the complications of UTI. Currently used therapeutic agents on CaOx stone disease were also prescribed on melamine stone subjects. However, the effectiveness of these drugs on melamine crystallization was largely unknown. Therefore, the effects of currently prescribed therapeutic agents including potassium citrate and sodium bicarbonate on melamine crystallization were investigated. Both citrate and bicarbonate did significantly reduce melamine crystallization so that they were effective against melamine crystallization and melamine stone formation. Traditional Chinese medicines (TCM) have been used for treating renal stones due to their anti-lithogenic activities. Previous study found that a Chinese herb Shi Wei (Folium Pyrrosiae) has a potential to inhibit urinary crystallization by reducing the urinary specific gravity and enhancing the urinary magnesium. This study showed that the human urine after Shi Wei supplementation had significant acute inhibitory effect on melamine crystallization but the effect was diminished or even levelled off after 1 week supplementation. Thus, Shi Wei may also be a suitable therapeutic agent for the quick control of melamine stones in infants by inhibition of further melamine crystals formation.