oxalates and Necrosis

Formation of calcium oxalate (CaOx) kidney stones was investigated using three approaches.. Pathogenesis of crystalluria and crystal deposition in the kidneys was examined in vivo by inducing hyperoxaluria in rats. Cultures of LLC-PK1 and MDCK cells were exposed to oxalate (Ox) and CaOx crystals to examine the effect on cells in various sections of the renal tubules. The nucleation potential of various substrates was examined by incubating them in metastable solutions of CaOx.. Calcium oxalate crystals and nonphysiologic levels of Ox were injurious to renal epithelial cells. To combat these nephrotoxins, renal epithelial cells produce a variety of macromolecules such as bikunin and osteopontin, which are modulators of crystallization and may also be involved in crystal attachment to the cells. Sustained hyperoxaluria in association with CaOx crystals induced apoptosis as well as necrosis. Cellular degradation products induced heterogeneous nucleation of crystals at lower and physiologic levels of oxalate. They also promoted aggregation.. Crystals begin to form in earlier segments of the nephron with a chance to grow and be retained in the collecting ducts after aggregation with other large crystals. Crystal deposits in the collecting ducts near the papillary surface, when exposed to the renal pelvic urine, become nidi for the development of kidney stones.

Topics: Animals; Calcium Oxalate; Cell Aggregation; Cell Line; Crystallization; Dogs; Ethylene Glycol; Humans; Hyperoxaluria; Kidney; Kidney Calculi; Kidney Tubules; Lipid Peroxidation; Membrane Glycoproteins; Necrosis; Osteopontin; Oxalates; Rats; Sialoglycoproteins; Time Factors; Trypsin Inhibitor, Kunitz Soybean

Topics: Aged; Beverages; Female; Fingers; Humans; Ischemia; Necrosis; Oxalates; Plant Extracts; Plant Preparations; Taraxacum

Renal protection and antiurolithiasic effects of two extracts of Paronychia argentea (PA), a traditional Algerian plant commonly known as Algerian tea, were evaluated. This study was carried out to determine whether the aqueous extract (APA) or the butanolic extract (BPA) of aerial parts could prevent or reduce calculi aggregation in experimental calcium oxalate (Ox) nephrolithiasis in Wistar rats.. The two extracts (APA and BPA) were administrated orally and daily, during 28 days to nephrolithiasic treated rats at the dose of 250, 500 mg/kg b.w. and 10, 20mg/kg b.w. respectively. Body weight, renal index, liver index, serum level of creatinine, uric acid, urea, K(+), Ca(2+), Mg(2+), Na(+) and transaminase (alanine aminotransferase, ALT; aspartate aminotransferase, AST), phosphatase alkaline activity (PAL) were evaluated following the 28 days treatment in rats. In addition histopathological changes in kidney and liver were stained in hematoxylin eosin (HE).. The effect of the extracts could be advantageous in preventing urinary stone retention by reducing renal necrosis and thus inhibit crystal retention. In contradiction with APA, the two doses of BPA attenuated elevation in the serum creatinine (p<0.01) and blood urea levels (p<0.01) (nephroprotective effect). However, the increase in ALT (27%) and PAL (31-51%) serum levels and in the relative liver weights (p<0.01) in the groups treated with doses of APA may indicate that this extract has not a hepatoprotective effect against oxalate toxicity.. The presented data indicate that administration of the butanolic extract of aerial parts to rats with NaOx induced lithiasis, and reduced and prevented the growth of urinary stones in experimental calcium oxalate nephrolithiasis in Wistar rats.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Calcium Oxalate; Caryophyllaceae; Creatinine; Disease Models, Animal; Kidney; Kidney Calculi; Liver; Male; Necrosis; Nephrolithiasis; Organ Size; Oxalates; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats; Rats, Wistar; Urea

The interaction between tubular epithelial cells and calcium oxalate crystals or oxalate ions is a very precarious event in the lithogenesis. Urine contains ions, glycoproteins and glycosaminoglycans that inhibit the crystallization process and may protect the kidney against lithogenesis. We examined the effect of oxalate ions and calcium oxalate crystals upon the synthesis of glycosaminoglycans in distal [Madin-Darby canine kidney (MDCK)] and proximal (LLC-PK1) tubular cell lines.. Glycosaminoglycan synthesis was analyzed by metabolic labeling with (35)S-sulfate and enzymatic digestion with specific mucopolysaccharidases. Cell death was assessed by fluorescent dyes and crystal endocytosis was analised by flow cytometry.. The main glycosaminoglycans synthesized by both cells were chondroitin sulfate and heparan sulfate most of them secreted to the culture medium or present at cellular surface. Exposition of MDCK cells to oxalate ions increased apoptosis rate and the incorporation of (35)S-sulfate in chondroitin sulfate and heparan sulfate, while calcium oxalate crystals were endocyted by LLC-PK1, induced necrotic cell death, and increased (35)S-sulfate incorporation in glycosaminoglycans. These effects seem to be specific and due to increased biosynthesis, since hydroxyapatite and other carboxylic acid did not induced cellular death or glycosaminoglycan synthesis and no changes in sulfation degree or molecular weight of glycosaminoglycans could be detected. Thapsigargin inhibited the glycosaminoglycan synthesis induced by calcium oxalate in LLC-PK1, suggesting that this effect was sensitive to the increase in cytosolic calcium.. Tubular cells may increase the synthesis of glycosaminoglycans to protect from the toxic insult of calcium oxalate crystals and oxalate ions, what could partially limit the lithogenesis.

Topics: Animals; Calcium; Calcium Oxalate; Cell Death; Cell Survival; Crystallization; Dogs; Durapatite; Endocytosis; Formates; Glycosaminoglycans; Ionophores; Ions; Kidney Tubules, Distal; Kidney Tubules, Proximal; LLC-PK1 Cells; Necrosis; Oxalates; Sulfates; Sulfur Radioisotopes; Swine; Thapsigargin; Urinary Calculi

Many aspects of calcium oxalate (CaOx) deposition in renal transplant biopsies are not known. Review of all renal transplant biopsies performed in a 7-year period showed that CaOx deposition could be classified into three groups. Group I: Seven biopsies within a month post-transplant displayed rare CaOx foci against a background of acute tubular necrosis or acute cell-mediated rejection. At follow-up, five grafts functioned well and two failed due to chronic allograft nephropathy. CaOx in this context was an incidental finding secondary to a sudden excretion of an end-stage renal disease-induced increased body burden of CaOx. Group II: Two biopsies performed 2 and 10 months post-transplant showed rare CaOx foci against a background of chronic allograft nephropathy, leading to graft loss. CaOx in this context reflected nonspecific parenchymal deposition due to chronic renal failure regardless of causes. Group III: One biopsy with recurrent PH1 characterized by marked CaOx deposition associated with severe tubulointerstitial injury and graft loss 6 months post-transplant. There were two previously reported cases in which CaOx deposition in the renal allografts was due the antihypertensive drug naftidrofuryl oxalate or increased intestinal absorption of CaOx. CaOx deposition in renal allografts can be classified in different categories with distinctive morphologic features and clinical implications.

Topics: Absorption; Adolescent; Adult; Aged; Biopsy; Cadaver; Calcium Oxalate; Creatinine; Female; Graft Rejection; Humans; Kidney Transplantation; Kidney Tubules; Living Donors; Male; Middle Aged; Nafronyl; Necrosis; Oxalates; Renal Insufficiency; Time Factors; Transplantation, Homologous; Vasodilator Agents

Studies in various tissues, including the kidney, have demonstrated that toxins elicit apoptosis under certain conditions and necrosis under others. The nature of the response has important consequences for the injured tissue in that necrotic cells elicit inflammatory responses, whereas apoptotic cells do not. Thus, there has been considerable interest in defining the mode of cell death elicited by known cytotoxins. The present studies examined the response of renal epithelial cells to oxalate, a metabolite excreted by the kidney that produces oxidant stress and death of renal cells at pathophysiological concentrations. These studies employed LLC-PK1 cells, a renal epithelial cell line from pig kidney and NRK-52E (NRK) cells, a line from normal rat kidney, and compared the effects of oxalate with those of known apoptotic agents. Changes in cellular and nuclear morphology, in nuclear size, in ceramide production, and in DNA integrity were assessed. The ability of bcl-2, an anti-apoptotic gene product, to attenuate oxalate toxicity was also assessed. These studies indicated that oxalate-induced death of renal epithelial cells exhibits several features characteristic of apoptotic cell death, including increased production of ceramide, increased abundance of apoptotic bodies, and marked sensitivity to the level of expression of the anti-apoptotic gene bcl-2. Oxalate-induced cell death also exhibits several characteristics of necrotic cell death in that the majority of the cells exhibited cellular and nuclear swelling after oxalate treatment and showed little evidence of DNA cleavage by TUNEL assay. These results suggest that toxic concentrations of oxalate trigger both forms of cell death in renal epithelial cells.

Topics: Animals; Apoptosis; Cell Count; Epithelial Cells; Kidney; Kinetics; LLC-PK1 Cells; Necrosis; Oxalates; Proto-Oncogene Proteins c-bcl-2; Rats; Swine

Topics: Aged; Bronchi; Foreign Bodies; Humans; Inhalation; Male; Necrosis; Oxalates; Plants, Medicinal; Rheum; Trachea

Topics: Angiography; Arteriovenous Shunt, Surgical; Autopsy; Female; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Metabolism, Inborn Errors; Microradiography; Necrosis; Nephritis; Oxalates; Postoperative Complications; Thrombosis; Transplantation, Homologous; Vascular Diseases

Topics: Acute Kidney Injury; Aged; Chemical and Drug Induced Liver Injury; Female; Hepatic Encephalopathy; Humans; Kidney; Metabolic Diseases; Methoxyflurane; Necrosis; Oxalates

Topics: Animals; Blood Chemical Analysis; Calcium; Female; Glycols; Haplorhini; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Necrosis; Oxalates

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Autopsy; Coronary Vessels; Female; Heart Diseases; Humans; Kidney; Male; Metabolic Diseases; Middle Aged; Myocarditis; Necrosis; Oxalates; Raynaud Disease

Topics: Coloring Agents; Drug Therapy; Humans; Necrosis; Oxalates; Povidone; Rectal Neoplasms; Rectum

Topics: Humans; Kidney; Kidney Diseases; Necrosis; Oxalates; Uremia; Urologic Diseases