Allen L. Rodgers

Effect of Mineral Water Containing Calcium and Magnesium on Calcium Oxalate Urolithiasis Risk Factors

Calcium oxalate kidney stone formers are invariably advised to increase their fluid intake. In addition, magnesium therapy is often administered. Recently, a prospective study showed that a high dietary intake of calcium reduces the risk of symptomatic kidney stones. The present study was performed to test whether simultaneous delivery of these factors--high fluid intake, magnesium ingestion and increased dietary calcium--could reduce the risk of calcium oxalate kidney stone formation. A French mineral water, containing calcium and magnesium (202 and 36 ppm, respectively) was selected as the dietary vehicle. Twenty calcium oxalate stone-forming patients of each sex as well as 20 healthy volunteers of each sex participated in the study. Each subject provided a 24-hour urine collection after ingestion of mineral water over a period of 3 days; after a suitable rest period the protocol was repeated using local tap water (Ca: 13 ppm, Mg: 1 ppm). In addition, 24-hour urines were collected by each subject on their free diets. The entire cycle was repeated at least twice by each subject. Several risk factors (excretion of oxalate; relative supersaturations of calcium oxalate, brushite and uric acid; calcium oxalate metastable limit; oxalate:magnesium ratio and oxalate:metastable limit ratio) were favourably altered by the mineral water and tap water regimens but the former was more effective. In addition, the mineral water protocol produced favourable but unique changes in the excretion of citrate and magnesium as well as in the relative supersaturation of brushite which were not achieved by the tap water regimen. To the contrary, tap water produced an unfavourable change in the magnesium excretion. The group which benefitted most were male stone formers in whom 9 risk factors were favourably altered by the mineral water protocol. It is concluded that mineral water containing calcium and magnesium, such as that used in this study, deserves to be considered as a possible therapeutic or prophylactic agent in calcium oxalate kidney stone disease.

Effect of cola consumption on urinary biochemical and physicochemical risk factors associated with calcium oxalate urolithiasis

Abstract Since stone formers are advised to increase their intake of fluid, the present study was undertaken to determine the effect of cola beverage consumption on calcium oxalate kidney stone risk factors. Fourteen males and 31 females provided 24-h urines before and after an acute load of cola. Relative supersaturations, activity products and empirical risk indices, ratios and quotients were calculated from urinary biochemical data to assess calcium oxalate crystal and stone formation risk. Several risk factors changed unfavourably following consumption of cola. In males, oxalate excretion, the Tiselius risk index and modified activity product increased significantly (P < 0.05). In females, oxalate excretion increased significantly while magnesium excretion and pH decreased significantly (P < 0.05). Scanning electron microscopy showed that urines obtained from both sexes after cola consumption supported calcium oxalate crystallization to a greater extent than the control urines. It is concluded that consumption of cola causes unfavourable changes in the risk factors associated with calcium oxalate stone formation and that therefore patients should possibly avoid this soft drink in their efforts to increase their fluid intake.

Apatite in Kidney Stones is a Molecular Composite With Glycosaminoglycans and Proteins: Evidence From Nuclear Magnetic Resonance Spectroscopy, and Relevance to Randall's Plaque, Pathogenesis and Prophylaxis

PURPOSE We characterized the biomacromolecular composition of phosphatic urinary stones using solid state nuclear magnetic resonance spectroscopy. We identified possible parallels between the nature of the organic matrix-mineral interface in stones and that in other mineralized tissue using nuclear magnetic resonance spectroscopy rotational echo double resonance. MATERIALS AND METHODS We analyzed 28 phosphatic (apatite and mixed apatite-struvite) surgically removed stones by nuclear magnetic resonance spectroscopy using (31)P, (13)C and a 9.4 Tesla magnetic field. Ten samples had sufficient signal from biomacromolecular organic material to characterize the mineral/organic interface by (13)C{(31)P} rotational echo double resonance. RESULTS Biomacromolecular organic material was most abundant in phosphatic stones in which apatite predominated. Nuclear magnetic resonance spectroscopy detected variable proportions of protein, glycosaminoglycan, lipid and carbonate. Rotational echo double resonance revealed strong interaction between mineral and glycosaminoglycan molecules, and to a lesser extent protein molecules, on the sub-nm length scale, implying that glycosaminoglycan and protein are composited into or onto the mineral lattice by strong physicochemical interactions. Carbonate ions substituted into apatite crystal lattices also showed the expected strong (13)C{(31)P} rotational echo double resonance effects. Conversely when present, lipid, calcium oxalate hydrates and uric acid showed no rotational echo double resonance effects, proving that they exist as deposits or crystals distinct from phosphatic mineral/biomacromolecular composites. CONCLUSIONS The intimate coexistence of biomacromolecules, especially glycosaminoglycan, with apatite in phosphatic stones supports the notion that they may have a key role in stone pathogenesis. The underlying intermolecular relationships may reflect those governing the formation of Randalls plaque in nascent stones.

Crystallization of calcium oxalate in minimally diluted urine

Crystallization of calcium oxalate was studied in minimally diluted (92%) urine using a mixed suspension mixed product crystallizer in series with a Malvern particle sizer. The crystallization was initiated by constant flow of aqueous sodium oxalate and urine into the reaction vessel via two independent feed lines. Because the Malvern cell was in series with the reaction vessel, noninvasive measurement of particle sizes could be effected. In addition, aliquots of the mixed suspension were withdrawn and transferred to a Coulter counter for crystal counting and sizing. Steady-state particle size distributions were used to determine nucleation and growth kinetics while scanning electron microscopy was used to examine deposited crystals. Two sets of experiments were performed. In the first, the effect of the concentration of the exogenous sodium oxalate was investigated while in the second, the effect of temperature was studied. Calcium oxalate nucleation and growth rates were found to be dependent on supersaturation levels inside the crystallizer. However, while growth rate increased with increasing temperature, nucleation rates decreased. The favored phases were the trihydrate at 18°C, the dihydrate at 38° and the monohydrate at 58°C. The results of both experiments are in agreement with those obtained in other studies that have been conducted in synthetic and in maximally diluted urine and which have employed invasive crystal counting and sizing techniques. As such, the present study lends confidence to the models of urinary calcium oxalate crystallization processes which currently prevail in the literature.

Effects of 5 Different Diets On Urinary Risk Factors For Calcium Oxalate Kidney Stone Formation: Evidence of Different Renal Handling Mechanisms in Different Race Groups

PURPOSE Since the incidence of renal calculi in the South African black population is extremely rare while in white subjects it occurs at the same rate as elsewhere in the western world, we investigated the possibility that different renal handling mechanisms in response to different dietary challenges might occur in the 2 race groups. MATERIALS AND METHODS We administered 5 different dietary protocols, including low calcium, high oxalate, vitamin C, high salt and lacto-vegetarian, to 10 healthy male subjects from each race group. We collected 24-hour urine at baseline and after 4 days on the prescribed diet which were analyzed for biochemical and physicochemical risk factors. Dietary intake was controlled throughout the experimental period. A 24-hour dietary recall questionnaire was recorded at baseline and analyzed using food composition tables. Statistical analysis of variance was performed on all the data. RESULTS The low calcium diet caused statistically significant changes only in black subjects, which consisted of urinary oxalate increase (0.17 to 0.23 mmol./24 hours, p = 0.01), relative supersaturation of calcium oxalate decrease (1.88 to 0.97, p = 0.03) and relative supersaturation of brushite increase (0.85 to 1.69, p = 0.03). The high oxalate diet caused statistically significant changes in both race groups but these changes were different in the 2 groups. In white subjects urinary pH increased (6.24 to 6.62, p = 0.01), potassium excretion increased (40.01 to 73.49, p = 0.01) and relative supersaturation of brushite increased (1.34 to 2.12, p = 0.05). In black subjects urinary citrate increased (1.94 to 2.99 mmol./24 hours, p = 0.01). Clinically unimportant changes occurred in both race groups after the other 3 diets. CONCLUSIONS Renal handling of dietary calcium and oxalate in South African black and white subjects is different and may explain the different stone incidence in the 2 race groups.

Epidemiology of stone disease across the world

Nephrolithiasis is a highly prevalent disease worldwide with rates ranging from 7 to 13% in North America, 5–9% in Europe, and 1–5% in Asia. Due to high rates of new and recurrent stones, management of stones is expensive and the disease has a high level of acute and chronic morbidity. The goal of this study is to review the epidemiology of stone disease in order to improve patient care. A review of the literature was conducted through a search on Pubmed®, Medline®, and Google Scholar®. This review was presented and peer-reviewed at the 3rd International Consultation on Stone Disease during the 2014 Société Internationale d’Urologie Congress in Glasgow. It represents an update of the 2008 consensus document based on expert opinion of the most relevant studies. There has been a rising incidence in stone disease throughout the world with a narrowing of the gender gap. Increased stone prevalence has been attributed to population growth and increases in obesity and diabetes. General dietary recommendations of increased fluid, decreased salt, and moderate intake of protein have not changed. However, specific recommended values have either changed or are more frequently reported. Geography and environment influenced the likelihood of stone disease and more information is needed regarding stone disease in a large portion of the world including Asia and Africa. Randomized controlled studies are lacking but are necessary to improve recommendations regarding diet and fluid intake. Understanding the impact of associated conditions that are rapidly increasing will improve the prevention of stone disease.

Sialylation of urinary prothrombin fragment 1 is implicated as a contributory factor in the risk of calcium oxalate kidney stone formation

Urinary glycoproteins are important inhibitors of calcium oxalate crystallization and adhesion of crystals to renal cells, both of which are key mechanisms in kidney stone formation. This has been attributed to glycosylation of the proteins. In South Africa, the black population rarely form stones (incidence < 1%) compared with the white population (incidence 12–15%). A previous study involving urinary prothrombin fragment 1 from both populations demonstrated superior inhibitory activity associated with the protein from the black group. In the present study, we compared N‐linked and O‐linked oligosaccharides released from urinary prothrombin fragment 1 isolated from the urine of healthy and stone‐forming subjects in both populations to elucidate the relationship between glycosylation and calcium oxalate stone pathogenesis. The O‐glycans of both control groups and the N‐glycans of the black control samples were significantly more sialylated than those of the white stone‐formers. This demonstrates a possible association between low‐percentage sialylation and kidney stone disease and provides a potential diagnostic method for a predisposition to kidney stones that could lead to the implementation of a preventative regimen. These results indicate that sialylated glycoforms of urinary prothrombin fragment 1 afford protection against calcium oxalate stone formation, possibly by coating the surface of calcium oxalate crystals. This provides a rationale for the established roles of urinary prothrombin fragment 1, namely reducing the potential for crystal aggregation and inhibiting crystal–cell adhesion by masking the interaction of the calcium ions on the crystal surface with the renal cell surface along the nephron.

A multiple technique approach to the analysis of urinary calculi

Summary10 urinary calculi have been qualitatively and quantitatively analysed using X-ray diffraction, infra-red, scanning electron microscopy, X-ray fluorescence, atomic absorption and density gradient procedures. Constituents and compositional features which often go undetected due to limitations in the particular analytical procedure being used, have been identified and a detailed picture of each stones composition and structure has been obtained. In all cases at least two components were detected suggesting that the multiple technique approach might cast some doubt as to the existence of “pure” stones. Evidence for a continuous, non-sequential deposition mechanism has been detected. In addition, the usefulness of each technique in the analysis of urinary stones has been assessed and the multiple technique approach has been evaluated as a whole.

Glycosylation of prothrombin fragment 1 governs calcium oxalate crystal nucleation and aggregation, but not crystal growth

Urinary glycoproteins play an important role in the modulation of calcium oxalate crystallisation. In several cases, this has been attributed to glycosylation of the proteins as evidenced by urinary prothrombin fragment 1 where there is a correlation between sialylation and calcium oxalate kidney stone disease. In the present study, plasma-derived prothrombin fragment 1 (PTF1) was enzymatically modified in order to generate its asialo and aglyco forms. The parent glycoprotein and its two glycoforms were used in calcium oxalate crystallisation studies to assess the role of the carbohydrate moeity in PTF1’s potent inhibitory activity. The glycans inhibited crystal aggregation and promoted crystal nucleation, but had no effect on crystal growth. The terminal sialic acid residues had a small effect on inhibition of crystal aggregation whereas they contributed significantly to promotion of nucleation. These results indicate that glycosylation of PTF1 governs calcium oxalate crystal nucleation and aggregation but it does not affect the protein’s role in inhibiting crystal growth. Since promotion of nucleation and inhibition of aggregation are both regarded as protective mechanisms against calcium oxalate urinary stone formation, the kringle domain on which the glycans are located is implicated in PTF1’s inhibitory activity. It is speculated that modifications in the glycosylation of urinary PTF1 in stone-formers may regulate its capacity to protect against calcium urolithiasis.

Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure aqueous solution and urine

Calcium oxalate (CaOx) is the most common component of human kidney stones. Heterogeneous nucleation is regarded as the key mechanism in this process. In this study, we have used an imprinted 6-methacrylamidohexanoic acid/divinylbenzene co-polymer as a biomimetic surface to nucleate CaOx crystal formation. The polymer was imprinted with either calcium oxalate monohydrate (COM) or dihydrate (COD) template crystals. These were washed out of the polymer, which was then immersed in various test solutions. The test solutions were an aqueous solution of calcium chloride and sodium oxalate, artificial urine and a sample of real urine. Crystals that formed on the polymer surface were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, atomic absorption spectroscopy and scanning electron microscopy. Results showed that in the aqueous solution the COM-imprinted polymer induced the nucleation of COM. The COD-imprinted polymer induced only trace amounts of COD crystallization, together with larger quantities of COM. In artificial and real urines, COM also specifically precipitated on the COM-imprinted surface. The results show that, at least to some extent, the imprinted polymers direct formation of their morphologically matched crystals. In the case of COD, however, it appears that either rapid hydrate transformation of COD to COM occurs, or the more stable COM polymorph is directly co-precipitated by the polymer. Our results support the hypothesis that heterogeneous nucleation plays a key role in CaOx stone formation and that the imprinted polymer model could provide an additional and superior diagnostic tool for stone researchers to assess stone-risk in urine.