The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis

1990 ◽  
Vol 36 (10) ◽  
pp. 1717-1730 ◽  
Author(s):  
R A Conyers ◽  
R Bais ◽  
A M Rofe

Abstract A dose-related toxicity syndrome of renal, cerebral, and liver dysfunction; metabolic acidosis; and deposition of calcium oxalate crystals in tissues is reported in association with various apparently unrelated treatments for a wide range of diseases. The parenteral nutrient xylitol, the hyperosmolar agent glycerol, the polysorbate emulsifiers (e.g., in vitamin E preparations), the anesthetic methoxyflurane, and possibly the experimental hypoglycemic agent dichloroacetate all produce a toxicity syndrome very similar to that of ethylene glycol poisoning. In long-term, high-dose oral toxicity studies with rodents, these or similar agents also produce calcium oxalate bladder stones and bladder tumors. Studies with both unlabeled and labeled agents in humans and animals and in vitro experiments with purified enzymes, tissue homogenates, and isolated hepatocytes have provided both strong circumstantial and direct evidence for the existence of minor pathways of carbohydrate metabolism and of oxidative dealkylation and dehalogenation reactions in drug biotransformations that link these agents to endogenous oxalate production. Because urinary oxalate is now considered to be a critical factor in stone formation and because it is increasingly accepted that 80-90% of urinary oxalate is produced endogenously, it is now possible to formulate pathways that link oxalate production with dietary macronutrients. Therapeutic modifications of diet, in vivo hormonal milieu, and intracellular metabolic controls in relation to endogenous oxalate production may provide new forms of treatment for urolithiasis.

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0006942020
Author(s):  
Jessica J. Saw ◽  
Mayandi Sivaguru ◽  
Elena M. Wilson ◽  
Yiran Dong ◽  
Robert A. Sanford ◽  
...  

Background: Human kidney stones form via repeated events of mineral precipitation, partial dissolution and reprecipitation, which are directly analogous to similar processes in other natural and man-made environments where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fidelity metagenomic (microscopy-to-omics) analyses, applicable to all forms of biomineralization, have been applied to assemble definitive evidence of in vivo microbiome entombment during urolithiasis. Methods: Stone fragments were collected from a randomly chosen cohort of 20 patients using standard percutaneous nephrolithotomy (PCNL). Fourier transform infrared (FTIR) spectroscopy indicated that 18 of these patients were calcium oxalate (CaOx) stone formers, while one patient each formed brushite and struvite stones. This apportionment is consistent with global stone mineralogy distributions. Stone fragments from 7 of these 20 patients (5 CaOx, 1 brushite and 1 struvite) were thin sectioned and analyzed using brightfield (BF), polarization (POL), confocal, superresolution autofluorescence (SRAF) and Raman techniques. DNA from remaining fragments, grouped according to each of the 20 patients, were analyzed with amplicon sequencing of 16S rRNA gene sequences (V1-V3, V3-V5) and internal transcribed spacer (ITS1, ITS2) regions. Results: Bulk entombed DNA was sequenced from stone fragments in 11 of the 18 CaOx patients, as well as the brushite and struvite patients. These analyses confirmed the presence of an entombed low-diversity community of bacteria and fungi, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Aspergillus niger. Bacterial cells ~1  µm in diameter were also optically observed to be entombed and well-preserved in amorphous hydroxyapatite spherules and fans of needle-like crystals of brushite and struvite. Conclusions: These results indicate a microbiome is entombed during in vivo CaOx stone formation. Similar processes are implied for brushite and struvite stones. This evidence lays the groundwork for future in vitro and in vivo experimentation to determine how the microbiome may actively and/or passively influence kidney stone biomineralization.


1994 ◽  
Vol 87 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Phulwinder K. Grover ◽  
Villis R. Marshall ◽  
Rosemary L. Ryall

1. Increasing the concentration of dissolved urate promotes calcium oxalate crystallization in urine from which Tamm-Horsfall mucoprotein, an inhibitor of calcium oxalate crystal aggregation, has almost completely been removed. This study aimed to determine whether the effect of urate could be reduced or abolished by a physiological concentration of Tamm-Horsfall mucoprotein. This was approached in two ways. 2. The effect of Tamm-Horsfall mucoprotein on calcium oxalate crystallization induced by urate was tested in ultrafiltered (10 kDa) urine samples from 10 healthy men. Tamm-Horsfall mucoprotein (35 mg/l) was added to half of each specimen, the urate concentration was increased by the addition of sodium urate solution and crystallization was induced by a standard load of oxalate. The remainder of each urine specimen was used as a control; these specimens were treated with an identical amount of urate solution, but contained no Tamm-Horsfall mucoprotein. Tamm-Horsfall mucoprotein had no effect on the urinary metastable limit or on the deposition of calcium oxalate, but significantly reduced the size of the particles precipitated. 3. The effect of increasing the urate concentration in the presence of Tamm-Horsfall mucoprotein was tested. Tamm-Horsfall mucoprotein (35 mg/l) was added to 10 ultrafiltered urine samples as before, the samples were divided, and the concentration of urate was increased in half of each specimen. Compared with the control to which no urate was added, urate significantly reduced the amount of oxalate required to induce spontaneous calcium oxalate nucleation and increased the median volume and the particle size of the material deposited. 4. It was concluded that, in vivo, (a) hyperuricosuria would encourage the formation of calcium oxalate stones by promoting calcium oxalate crystallization, (b) Tamm-Horsfall mucoprotein would not lessen the effect of urate on calcium oxalate nucleation or bulk deposition but would reduce its effect on crystal aggregation; it could therefore reduce the likelihood of stone formation in patients with hyperuricosuria.


1995 ◽  
Vol 2 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Takuo Koide ◽  
Seiji Yamaguchi ◽  
Masato Utsunomiya ◽  
Toshiaki YoshiokaY ◽  
Kiyoshi Sugiyawia

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Atsushi Okada ◽  
Takahiro Yasui ◽  
Kazumi Taguchi ◽  
Yasuhiko Hirose ◽  
Kazuhiro Niimi ◽  
...  

2019 ◽  
Vol 9 (4-s) ◽  
pp. 702-704
Author(s):  
Bhavisha Bhupendrabhai Patel

Kidney stone disease is an increasing disorder of humans. It affects about 12% of the world population. Epidemiological data have shown that calcium oxalate is the predominant mineral in a majority of kidney stones. [1] It has been associated with an increased risk of end-stage renal failure. Kidney stones   result from a succession of several physicochemical events including super saturation, nucleation, growth, aggregation, and retention within the kidneys. Kidney stones may cause extreme pain and blockage of urine flow .The average life time risk of stone formation has been reported in the range of 5-10 %.Recurrent stone formation is a common part of the medical care of patients with stone disease.[2] Kidney stone disease is usually treated with medications that may cause a number of side-effects. Even improved and besides the high cost that imposes, compelling data now suggest that exposure to shock waves in therapeutic doses may cause acute renal injury, decrease in renal function and an increase in stone recurrence. Data from in vitro, in vivo and clinical trials reveal that phytotherapeutic agents could be useful as either an alternative therapy in the management of urolithiasis. The present review therefore critically explains the potential usefulness of herbal medicines in the management of urolithiasis. Keywords:  Kidney stones, Calcium oxalate, Herbal plant extracts, Alternative medicine


2019 ◽  
Vol 9 (5) ◽  
pp. 4305-4310 ◽  

Increased urinary oxalate is considered a major risk factor in the formation of calcium oxalate kidney stones. Gut microbiota may reduce the risk of stone formation. Anyway, the first step for any research about monitoring of oxalate content (both in vitro and in vivo) is a determination of its concentration, while there are different methods reported in the literature for oxalate content determination. In this research, the main reported methods including titration with two titrators (potassium permanganate, and NaOH) as well as enzymatic method (oxalate assay kit) are presented and compared for the measurement of oxalate in both inoculated and non-inoculated media.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Alastimmanahalli Narasimhiah Ravikumar ◽  
Joby Jacob ◽  
Sreeraj Gopi ◽  
Tumkur Subbarao Jagannath

A series of toxicological investigations were conducted in order to evaluate the genotoxic potential and repeated-dose oral toxicity of CuroWhite, a proprietary extract of curcumin that has been hydrogenated and standardized to not less than 25% hydrogenated curcuminoid content. All tests were conducted in general accordance with internationally accepted standards. The test item was not mutagenic in the bacterial reverse mutation test or in vitro mammalian chromosomal aberration test, and no in vivo genotoxic activity was observed in rat bone marrow in the micronucleus test. A 90-day repeated-dose study was conducted in male and female Sprague-Dawley rats. Two mortalities occurred in the main and satellite high-dose groups and were determined due to gavage error. No organ specific or other toxic effects of the test item were observed up to the maximum dose of 800 mg/kg bw/day, administered by gavage. NOAEL was, therefore, estimated as 800 mg/kg bw/day.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.


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