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Acute effects of calcium sodium citrate supplementation of a test meal on mineral homeostasis, oxalate, and calcium oxalate crystallization in the urine of healthy humans--preliminary results in patients with idiopathic calcium urolithiasis.

Calcium, in the form of regular food supplementation, can improve bone metabolism, but it can also increase the risk for renal calcium stones, and may aggravate pre-existing calcium urolithiasis. To study the first of these two aspects, ten healthy volunteers were given a conventional test meal (breakfast; calcium content 28 mg) with or without two dosages of calcium (as calcium-sodium citrate, CSC 1, 680 mg; CSC 2 1,360 mg), taken after an overnight 12 h fast. To study the latter aspect, patients with idiopathic recurrent calcium urolithiasis (ICU) received a balanced test meal of fixed composition, containing 1,000 mg calcium either as CSC (Meal + CSC3; n = 6) or as calcium gluconate (Mcal; n = 8). In normals, CSC induced a dose-dependent increasing intestinal absorption of calcium, and a decrease in oxalate absorption; in serum, CSC increased calcitonin and suppressed parathyroid hormone, but left unchanged the markers of bone turnover, serum osteocalcin and bone alkaline phosphatase. In urine, CSC decreased bone resorption markers (collagen crosslinks) and phosphaturia increased citrate, created signs of metabolic alkalosis, and inhibited several parameters of CaOx crystallization. In ICU, the CSC3 load failed to promote the crystallization of CaOx and calcium phosphate. It was concluded that CSC supplementation of a meal: (1) is well tolerated by healthy subjects and ICU patients, renders calcium highly available to bone, and prevents post-prandial oxaluria from rising; and, (2) is followed by the inhibition of crystallization of renal stone forming calcium-containing substances. Long-term studies aimed at evaluating the usefulness of CSC in preserving healthy bone, and in the metaphylaxis of renal stones would appear justified.

Adult↗

Oxalate ions and calcium oxalate crystal-induced up-regulation of osteopontin and monocyte chemoattractant protein-1 in renal fibroblasts.

OBJECTIVE: To examine the responses of renal fibroblasts to high oxalate (Ox) and calcium Ox (CaOx) crystals, as the latter are found in the renal interstitium of patients with primary or enteric hyperoxaluria, and in animals with experimental CaOx nephrolithiasis, and are associated with tubulointerstitial inflammation (TI). TI might begin with the production of chemoattractants by the renal epithelial cells exposed to high Ox and/or CaOx crystals; as Ox levels are also high in the renal interstitium and crystal deposition in nephrolithiasis might start in the interstitium, we hypothesized that renal fibroblasts might also be involved in the development of TI. MATERIALS AND METHODS: We exposed renal fibroblast cells of line NRK 49F in vitro to Ox ions (500 micromol/L) or CaOx monohydrate crystals (67 microg/cm(2)). We assessed the production of osteopontin and monocyte chemoattractant protein-1 (MCP-1), and expression of their mRNA, in the cells. We also determined the cellular malondialdehyde content as a marker of reactive oxygen species (ROS)-induced lipid peroxidation, and Trypan blue staining and the release of lactate dehydrogenase as markers of injury. RESULTS: Similar to renal epithelial cells, renal fibroblasts were stimulated by exposure to Ox and CaOx crystals. They showed signs of injury and ROS-induced lipid peroxidation. The mRNA expression and production of osteopontin and MCP-1 increased significantly. CONCLUSIONS: These results indicate that fibroblasts respond to high Ox and CaOx crystals by up-regulating specific pathways producing pro-inflammatory conditions. Migration of monocytes/macrophages to sites of interstitial crystal deposits can lead to localized interstitial inflammation and fibrosis.

Animals↗

Specific modulatory effect of arachidonic acid on human red blood cell oxalate transport: clinical implications in calcium oxalate nephrolithiasis.

Greater arachidonic acid (AA) contents, which were correlated with erythrocyte transmembrane oxalate (Ox) transport, were observed in plasma and erythrocyte membrane phospholipids of patients with idiopathic calcium renal stones, suggesting a link between membrane phospholipid fatty acid composition and cellular Ox transport. To confirm this hypothesis, the effects of exogenous red blood cell incorporation of three different fatty acids (i.e., oleic acid, AA, and eicosapentaenoic acid) on Ox transport and the phosphorylation status of band 3 protein, which has been shown to mediate red blood cell Ox flux, were investigated. Preincubation of erythrocytes with AA induced a dose-dependent increase in the phosphorylation level of band 3 protein and an increase in transmembrane Ox self-exchange. In contrast, inhibitory effects on both parameters were observed after the incorporation of oleic and eicosapentaenoic acids. These data, together with previous observations of dietary effects on erythrocyte Ox transport and urinary Ox excretion, indicate that genetic and/or nutritional changes in membrane phospholipid fatty acid composition play a crucial role in modulating cellular Ox transport in idiopathic calcium Ox nephrolithiasis.

Adult↗

[Effect of nifedipine on kidney output of calcium, oxalic acid, and saturation of urinary calcium oxalate].

The study involved 30 patients treated with nifedipine in daily dose of 30 mg for 7 days. Calcium, magnesium, phosphate, oxalate, and uric acid levels in the urine were measured. It was found that nifedipine significantly decreased oxaluria urinary excretion of calcium, magnesium, phosphate, and uric acid remained unchanged following nifedipine therapy. Results may suggest that nifedipine may exert an influence on renal stone formation.

Adult↗

[Comparative study of urinary calcium, oxalate and uric acid in calcium oxalate lithiasis].

The purpose of this study was to determine and to compare the frequency of hypercalciuria, hyperoxaluria and hyperuricosuria in 49 patients with a pure or mixed calcium oxalate urolithiasis. During this study, all patients were on a normal diet and had no special disease or medication. We noted that hypercalciuria (35%) and hyperoxaluria (24%) were more often associated (18%) than isolated (8 and 2%). They were more frequent in mixed stones (44% et 39%) than in pure one (29% and 16%). Hyperuricuria (39%) had a same frequency wathever the renal stone type may be. A same frequency was noted when hyperuricuria was associated with hypercalciuria and hyperoxaluria (12%) or isolated (14%). None of these three biologic disturbances was observed in 45% of our patients.

Adult↗

A contribution to the formation mechanism of calcium oxalate urinary calculi. IV. Experimental investigations of the intrarenal crystallisation of calcium oxalate in rabbit.

Rabbits were given glyoxylic acid to induce intrarenal calcium oxalate crystal formation. The point of crystallisation in the renal tubule, the structure and the composition of the intrarenal crystals were studied. The initial crystallisation takes place in the proximal tubule. Calcium phosphate formation was excluded by microprobe examination. The comparison of the structures of the intrarenally formed crystals with those of Whewellite stones by scanning electron microscopy and the examination of isolated crystals by x-ray diffraction showed the intratubular crystals to consist of Whewellite.

Animals↗

Dissolved urate salts out calcium oxalate in undiluted human urine in vitro: implications for calcium oxalate stone genesis.

Hyperuricosuria has long been documented as a predisposing factor to calcium oxalate (CaOx) stone pathogenesis. However, its mechanism is still without sound scientific foundation. Previously, we showed that hyperuricosuria, simulated by the addition of dissolved sodium urate, promotes the crystallization of CaOx. In the present study, we demonstrate that the urate's effect on the crystallization is attributable to its salting out CaOx from solution. Furthermore, analysis of urines revealed that their metastable limit decreased with increases in the product of the prevailing concentrations of calcium and urate: this has implications for CaOx stone genesis. We also outline anti-salting out strategies for future research for the prevention and/or treatment of CaOx calculi.

Calcium Oxalate↗

The role of Tamm-Horsfall mucoprotein in calcium oxalate crystallization. N-acetylcysteine--a new therapy for calcium oxalate urolithiasis.

OBJECTIVE: To assess the role of Tamm-Horsfall mucoprotein (THM), obtained from normal subjects (nTHM) and stone-formers (sfTHM), on crystallization of calcium oxalate (CaOx) in whole urine, and to assess the effects of N-acetylcysteine (AC) in preventing renal stone formation. MATERIALS AND METHODS: A modified rapid evaporation method was used to test the effects of THM and AC on crystallization of CaOx in vitro. Animal experiments involving 30 rats and a clinical study involving 17 patients with idiopathic CaOx urolithiasis were also performed to identify further the role of AC in preventing CaOx stone formation in vivo. RESULTS: The results showed that the volume of CaOx crystals was greatly reduced, by ultrafiltration, to 39.1% of untreated urine, but increased to 81.4% by adding nTHM (35 mg/l). sfTHM was a more potent promoter. AC was found to inhibit the transformation of THM and lower the crystallization of CaOx both in vitro and in vivo. CONCLUSION: We believe that the transformation of THM is an important step in the formation of urolithiasis. AC might be a new way to prevent renal stone formation and recurrence.

Acetylcysteine↗

Effect of diuresis on the oxalate excretion and the calcium-oxalate product in non-stone formers.

We studied the effect of variations of fluid intake on the oxalate (Ox) excretion in healthy subjects. The relation of Ox excretion to urine volume was examined. The Ca excretion was measured as well and the ionized Ca and the Ca X Ox product were calculated. With a fluid intake between 800 and 4,200 ml a urine volume between 550 and 4,200 ml was found. We saw a strong correlation between urine volume and Ox excretion and a strong negative correlation between urine volume and urinary Ox concentration. The upper limit of urinary Ox excretion to define hyperoxaluria should therefore be modified by taking the urine volume into consideration or should be replaced by the Ox concentration.

Adult↗

Influence of different factors on the formation of calcium oxalate stones. I. Discriminant analytical computations of morphological parameters of the pelvic-calyceal systems of calcium oxalate stone formers and controls.

Until now almost exclusively clinicochemical urine parameters have been used to determine the risk of urinary stone formation. In part I of this study, pelvic-calyceal systems of healthy persons and calcium oxalate stone formers are compared with regard to their morphology, whereas urine parameters will be briefly included in part II. Discriminant functions are given by means of which it is possible to calculate the risk and, e.g. to quantify a follow-up.

Calcium Oxalate↗

Influence of different factors on the formation of calcium oxalate stones. II. Discriminant analytical computations of morphological parameters of pelvic-calyceal systems and clinicochemical urine parameters of controls and calcium-oxalate stone formers.

Until now almost exclusively clinicochemical urine parameters have been used to determine the risk of urinary stone formation. In part I of this study pelvic-calyceal systems of healthy persons and calcium oxalate stone formers are compared with regard to their morphology, whereas urine parameters will be briefly included in part II. Discriminant functions are given by means of which it is possible to calculate the risk and, e.g. to quantify a follow-up.

Calcium Oxalate↗

Crystaloptical and spectroscopical findings with calcium oxalate crystals in the urine sediment: a contribution to the genesis of oxalate stones.

Transmitted light microscope and scanning electron microscope investigations reveal various shapes of urine calcium oxalate crystals. In addition to tetragonal bipyramids, weddellite forms further crystal shapes that have been heretofore interpreted exclusively as whewellite crystals. Weddellite is stabilized by urine foreign ions. In vivo formation of whewellite crystals occurs with massive crystallization only.

Animals↗

Oxalate and spin-labeled oxalate as probes of the anion binding site of human transferrin. Metal to anion distance.

The spin-labeled anion N-[4-(2,2,6,6-tetramethylpiperidin-1-oxyl)] oxamate has been synthesized and characterized. In the presence of this compound, a specific iron-transferrin-anion complex is formed, as evidenced by the development of a characteristic red color. No EPR signal was observed for the nitroxyl radical in the protein complex, presumably due to broadening of the signal by the paramagnetic metal ion. Failure to observe a signal implies that the metal to nitroxyl distance is less than or equal to 6 A. This suggests that the anion is directly attached to the metal ion in the protein. The pH dependence of iron dissociation from iron-transferrin-oxalate is also reported. This complex is more stable at low pH than iron-transferrin-carbonate.

Binding Sites↗