The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted.
In idiopathic recurrent calcium urolithiasis (RCU) the state of insulin and carbohydrate metabolism, and relationships to minerals such as phosphate, are insufficiently understood. Therefore, in two groups of males with RCU (n = 30) and healthy controls (n = 8) the response to an oral carbohydrate- and calcium-rich test meal was studied with respect to glucose, insulin, and C-peptide in peripheral venous blood (taken before and up to 180 min post-load), and phosphate and glucose in fasting and post-load urine. In one RCU group (n = 16) the meal was supplemented with ascorbic acid (ASC; 5 mg/kg body weight). The mean age (RCU 29, RCU + ASC 30, controls 27 years) and mean body mass index [RCU 24.4, RCU + ASC 25.0, controls 24.0 kg/m2] were similar. Insulin resistance (synonymous sensitivity of peripheral organs to insulin) was calculated from insulin serum concentration, as was also integrated insulin, C-peptide, and glucose. Untreated stone patients (RCU) developed hyperinsulinaemia between 60 and 120 min post-load, increased integrated insulin, and insulin resistance (P < or = 0.05 vs controls), whereas the rise of C-peptide and glycaemia (absolute and integrated values) was only of borderline significance. Fasting phosphaturia was low in both RCU subgroups vs controls; however, phosphaturia in untreated RCU rose in response to the meal, contrasting sharply with a decrease in controls. ASC supplementation of the meal (in the RCU + ASC subgroup) normalized insulin, failed to normalize post-load phosphaturia, but reduced post-load glucosuria and urinary pH significantly (mean pH values 5.55 vs 5.93 in untreated RCU, controls 5.50). Postprandial urinary oxalate, calcium, protein, and supersaturation products were not changed. The postprandial changes in phosphaturia and insulin sensitivity were inversely correlated (n = 38, r = -0.44, P = 0.007). It was concluded that in younger RCU males: (1) postprandial hyperinsulinaemia, the failure to reduce phosphaturia and - within limits - glucosuria, appropriately, as well as poor urine acidification are important features of the metabolism; (2) these phenomena are probably caused by insulin resistance of organs, the kidney included; and (3) the addition of a supraphysiological dose of ASC to a meal, the subsequent abolition of hyperinsulinaemia, and the restoration of normal urine acidification suggest that this antioxidant is capable of counteracting some pre-existing basic abnormality of cell metabolism in RCU.
A retrospective study was done on the nature and degree of crystalluria in fasting and postprandial urine in patients with recurrent idiopathic calcium urolithiasis (RCU) for whom stone analysis was available. RCU was stratified into subgroups in accordance with stone analysis. The crystals were obtained and identified using a filter technique and polarization microscopy, respectively. Crystalluria score, relative saturation products (RSPs), and low-molecular-weight inhibitors were assessed. Calcium oxalate crystals were never observed in either male or female patients with stones composed exclusively of calcium oxalate, and only sporadically in patients with mixed stones (the additional component was calcium phosphate in most cases). Other crystalluria phases, such as amorphous calcium phosphate, a urate-containing phase, and a phase presenting as spherolytic particles, were slightly more frequent in patients with mixed stones. In contrast to crystalluria, RSPs and inhibitors differed in male and female patients, suggesting that crystalluria may not be under the exclusive control of these factors. The following conclusions were reached. (1) Calcium oxalate crystalluria is absent from RCU with pure calcium oxalate stones; hence, calcium oxalate crystalluria does not qualify as a diagnostic aid. (2) The co-existence of the isotropic phase and mixed stones may indicate that the formation of these concretions is characteristic for a major RCU subgroup. (3) On the basis of clinical chemistry and physicochemical data in urine and of crystalluria, it appears that the pathogenesis of RCU differs in male and female subjects.
A number of environmental factors are under discussion as possibly implicated in the etiology of RCU. On the basis of data in the literature and our own results, we attempted a critical weighting up of the possible contributions of climate, pollution, stress, nutrition in general and especially oxalate and minerals in the nutrition. It was concluded that there is a need for more in-depth research into the response of the body to challenges from the environment, in particular nutrition.
A retrospective study was done on the nature and degree of crystalluria in spontaneously voided fasting and postprandial urine of patients with recurrent idiopathic calcium urolithiasis (RCU) divided into normocalciuria (20 males, 20 females) and hypercalciuria patients (20 males, 20 females), and controls (20 males, 20 females). The crystals were obtained using a filter technique and identified by microscopy. In addition, individual data, clinical chemistry variables and indices reflecting the risk of calcium phosphate and calcium oxalate crystallization were evaluated. In contrast to findings of other investigators of crystalluria we observed only a few crystals on the filters. The most frequently occurring phases were (in this order) a urate-containing phase (tentatively termed uric), an amorphous calcium phosphate phase (tentatively termed isotropic) and a phase of spheroid-like particles, not yet definitely characterized (tentatively termed spheroid). Calcium oxalate crystals were found only exceptionally. There was no relationship between the degree of calciuria (normo- versus hypercalciuric RCU) and crystalluria. Among RCU, males generally had a predominance of the isotropic, females of the spheroid phase, as compared with controls. Also, RCU females were generally obese, and their spheroid score and lean body mass correlated negatively and significantly. The calcium phosphate and calcium oxalate risk indices were always low in normal individuals, higher in RCU. Patients of both sexes with urinary stones had normal parathyroid gland function, but higher total calcium in fasting serum and higher urinary pH as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous work in younger males with recurrent idiopathic calcium urolithiasis (RCU) demonstrated inappropriately high postprandial phosphaturia, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU patients with a mean age corresponding to the life period with peak formation of calcium-containing stones, two trials were carried out in 155 males of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and calcium but low in phosphorus. In trial 1, comprising control subjects (n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years), phosphate (Pi) excretion and fractional Pi excretion in postprandial urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were hyperinsulinemic but still normoglycemic versus controls. In trial 2, carried out in unclassified (in terms of calciuria) RCU patients (n = 119, mean age 40 years) only, the post-load Pi-uria was similar in magnitude to Pi-uria of RCU patients in trial 1; increased postprandial Pi-uria was a phenomenon also of normocalciuria but was slightly more pronounced in hypercalciuria, while changes in calcium phosphate (brushite) and calcium oxalate supersaturation of urine were unrelated to calciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. When urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appeared unrelated to age, but positively associated with postprandial glycemia as the best predictor, followed by insulinemia, insulin resistance, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Pi-uria during fasting but impaired renal Pi conservation in response to a mixed meal, a situation carrying the risk of Pi deficiency over the long term; (2) represent a population developing hyperPi-uria despite suppressed PTH; (3) exhibit insulin resistance but are still able to maintain normoglycemia at the expense of hyperinsulinemia. It is suggested that calcium-containing renal stones are related to impaired Pi and glucose translocation across cell membranes, and that the role of lipids in this setting deserves further investigation.
The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known.
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