title: Oxalate is toxic to renal tubular cells only at supraphysiologic concentrations.
abstract: BACKGROUND
  Oxalate-induced tissue damage may play an initiating role in the pathophysiology of calcium oxalate nephrolithiasis. The concentration of oxalate is higher in the renal collecting ducts ( approximately 0.1 to 0.5 mmol/L) than in the proximal tubule ( approximately 0.002 to 0.1 mmol/L). In the present investigation, we studied the damaging effect of oxalate to renal proximal and collecting tubule cells in culture.
  
  
  METHODS
  Studies were performed with the renal proximal tubular cell lines, LLC-PK1 and Madin Darby canine kidney II (MDCK-II), and the renal collecting duct cell lines, rat renal cortical collecting duct (RCCD1) and MDCK-I. Confluent monolayers cultured on permeable growth substrates in a two-compartment culture system were apically exposed for 24 hours to relatively low (0.2, 0.5, and 1.0 mmol/L) and high (5 and 10 mmol/L) oxalate concentrations, after which several cellular responses were studied, including monolayer morphology (confocal microscopy), transepithelial electrical resistances (TER), prostaglandin E(2) (PGE(2)) secretion, lactate dehydrogenase (LDH) release, DNA synthesis ([(3)H]-thymidine incorporation), total cell numbers, reactive oxygen species (H(2)O(2)) generation, apoptotic (annexin V and DNA fragmentation), and necrotic (propidium iodide influx) cell death.
  
  
  RESULTS
  Visible morphologic alterations were observed only at high oxalate concentrations. TER was concentration-dependently decreased by high, but not by low, oxalate. Elevated levels of PGE(2), LDH, and H(2)O(2) were measured in both cell types after exposure to high, but not to low oxalate. Exposure to high oxalate resulted in elevated levels of DNA synthesis with decreasing total cell numbers. High, but not low, oxalate induced necrotic cell death without signs of programmed cell death.
  
  
  CONCLUSIONS
  This study shows that oxalate is toxic to renal tubular cells, but only at supraphysiologic concentrations.
authors.affiliation: Department of Urology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Marieke S J
authors.initials: MS
authors.lastname: Schepers
authors.forename: Eddy S
authors.initials: ES
authors.lastname: van Ballegooijen
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Carl F
authors.initials: CF
authors.lastname: Verkoelen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002129:Calcium Oxalate / Q000737:chemistry / Q000633:toxicity*; D002452:Cell Count; D002460:Cell Line; D003460:Crystallization; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D007669:Kidney Calculi / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D007686:Kidney Tubules, Distal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009336:Necrosis; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D014316:Tritium; D002129:Calcium Oxalate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; D013936:Thymidine