PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
 
J Clin Invest. 1986 June; 77(6): 1888–1896.
PMCID: PMC370548

Evidence that serum calcium oxalate supersaturation is a consequence of oxalate retention in patients with chronic renal failure.

Abstract

Serum oxalate rises in uremia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uremic patients. Crystal formation suggests that either uremic serum is supersaturated with calcium oxalate, or local oxalate production or accumulation causes regional supersaturation. To test the first alternative, we ultrafiltered uremic serum and measured supersaturation with two different methods previously used to study supersaturation in urine. First, the relative saturation ratio (RSR), the ratio of the dissolved calcium oxalate complex to the thermodynamic calcium oxalate solubility product, was estimated for 11 uremic (before and after dialysis) and 4 normal serum samples using a computer program. Mean ultrafiltrate oxalate predialysis was 89 +/- 8 microM/liter (+/- SEM), 31 +/- 4 postdialysis, and 10 +/- 3 in normals. Mean RSR was 1.7 +/- 0.1 (predialysis), 0.7 +/- 0.1 (postdialysis), and 0.2 +/- 0.1 (normal), where values greater than 1 denote supersaturation, less than 1, undersaturation. Second, the concentration product ratio (CPR), the ratio of the measured calcium oxalate concentration product before to that after incubation of the sample with calcium oxalate monohydrate crystal, was measured in seven uremic and seven normal serum ultrafiltrates. Mean oxalate was 91 +/- 11 (uremic) and 8 +/- 3 (normal). Mean CPR was 1.4 +/- 0.2 (uremic) and 0.2 +/- 0.1 (normal). Predialysis, 17 of 18 uremic ultrafiltrates were supersaturated with respect to calcium oxalate. The degree of supersaturation was correlated with ultrafiltrate oxalate (RSR, r = 0.99, r = 29, P less than 0.001; CPR, r = 0.75, n = 11, P less than 0.001). A value of ultrafiltrate oxalate of 50 microM/liter separated undersaturated from supersaturated samples and occurred at a creatinine of approximately 9.0 mg/dl.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Constable AR, Joekes AM, Kasidas GP, O'Regan P, Rose GA. Plasma level and renal clearance of oxalate in normal subjects and in patients with primary hyperoxaluria or chronic renal failure or both. Clin Sci (Lond) 1979 Apr;56(4):299–304. [PubMed]
  • Zarembski PM, Hodgkinson A, Parsons FM. Elevation of the concentration of plasma oxalic acid in renal failure. Nature. 1966 Oct 29;212(5061):511–512. [PubMed]
  • Boer P, van Leersum L, Hené RJ, Mees EJ. Plasma oxalate concentration in chronic renal disease. Am J Kidney Dis. 1984 Sep;4(2):118–122. [PubMed]
  • Balcke P, Schmidt P, Zazgornik J, Kopsa H, Deutsch E. Secondary oxalosis in chronic renal insufficiency. N Engl J Med. 1980 Oct 16;303(16):944–944. [PubMed]
  • ELDER TD, WYNGAARDEN JB. The biosynthesis and turnover of oxalate in normal and hyperoxaluric subjects. J Clin Invest. 1960 Aug;39:1337–1344. [PMC free article] [PubMed]
  • Hodgkinson A, Wilkinson R. Plasma oxalate concentration and renal excretion of oxalate in man. Clin Sci Mol Med. 1974 Jan;46(1):61–73. [PubMed]
  • Prenen JA, Boer P, Dorhout Mees EJ, Endeman HJ, Yoe OH. Determination of oxalic acid clearance and plasma concentration by radioisotope infusion. Results in a family with hyperoxaluria. Acta Med Scand. 1981;209(1-2):87–91. [PubMed]
  • Weinman EJ, Frankfurt SJ, Ince A, Sansom S. Renal tubular transport of organic acids. Studies with oxalate and para-aminohippurate in the rat. J Clin Invest. 1978 Mar;61(3):801–806. [PMC free article] [PubMed]
  • Knight TF, Sansom SC, Senekjian HO, Weinman EJ. Oxalate secretion in the rat proximal tubule. Am J Physiol. 1981 Apr;240(4):F295–F298. [PubMed]
  • Senekjian HO, Weinman EJ. Oxalate transport by proximal tubule of the rabbit kidney. Am J Physiol. 1982 Sep;243(3):F271–F275. [PubMed]
  • Fayemi AO, Ali M, Braun EV. Oxalosis in hemodialysis patients: a pathologic study of 80 cases. Arch Pathol Lab Med. 1979 Feb;103(2):58–62. [PubMed]
  • Salyer WR, Keren D. Oxalosis as a complication of chronic renal failure. Kidney Int. 1973 Jul;4(1):61–66. [PubMed]
  • Hoffman GS, Schumacher HR, Paul H, Cherian V, Reed R, Ramsay AG, Franck WA. Calcium oxalate microcrystalline-associated arthritis in end-stage renal disease. Ann Intern Med. 1982 Jul;97(1):36–42. [PubMed]
  • op de Hoek CT, Diderich PP, Gratama S, Weijs- von Hofwegen EJ. Oxalosis in chronic renal failure. Proc Eur Dial Transplant Assoc. 1980;17:730–735. [PubMed]
  • Salyer WR, Hutchins GM. Cardiac lesions in secondary oxalosis. Arch Intern Med. 1974 Aug;134(2):250–252. [PubMed]
  • Fantasia JE, Miller AS, Chen SY, Foster WB. Calcium oxalate deposition in the periodontium secondary to chronic renal failure. Oral Surg Oral Med Oral Pathol. 1982 Mar;53(3):273–279. [PubMed]
  • Smith LH, Jr, Bauer RL, Williams HE. Oxalate and glycolate synthesis by hemic cells. J Lab Clin Med. 1971 Aug;78(2):245–254. [PubMed]
  • Hautmann R, Lehmann A, Komor S. Intrarenal distribution of oxalic acid, calcium, sodium, and potassium in man. Eur J Clin Invest. 1980 Apr;10(2 Pt 1):173–176. [PubMed]
  • Ramsay AG, Reed RG. Oxalate removal by hemodialysis in end-stage renal disease. Am J Kidney Dis. 1984 Sep;4(2):123–127. [PubMed]
  • Wolthers BG, Hayer M. The determination of oxalic acid in plasma and urine by means of capillary gas chromatography. Clin Chim Acta. 1982 Mar 26;120(1):87–102. [PubMed]
  • Balcke P, Schmidt P, Zazgornik J, Haubenstock A, Kopsa H. In vitro synthesis of oxalic acid has no relevant influence on plasma oxalic acid levels in haemodialysis patients. J Clin Chem Clin Biochem. 1984 Mar;22(3):261–263. [PubMed]
  • Coburn JW, Popovtzer MM, Massry SG, Kleeman CR. The physicochemical state and renal handling of divalent ions in chronic renal failure. Arch Intern Med. 1969 Sep;124(3):302–311. [PubMed]
  • Pak CY, Holt K. Nucleation and growth of brushite and calcium oxalate in urine of stone-formers. Metabolism. 1976 Jun;25(6):665–673. [PubMed]
  • Weber DV, Coe FL, Parks JH, Dunn MS, Tembe V. Urinary saturation measurements in calcium nephrolithiasis. Ann Intern Med. 1979 Feb;90(2):180–184. [PubMed]
  • Contiguglia SR, Alfrey AC, Miller NL, Runnells DE, Le Geros RZ. Nature of soft tissue calcification in uremia. Kidney Int. 1973 Sep;4(3):229–235. [PubMed]
  • Forster HV, Dempsey JA, Thomson J, Vidruk E, DoPico GA. Estimation of arterial PO2, PCO2, pH, and lactate from arterialized venous blood. J Appl Physiol. 1972 Jan;32(1):134–137. [PubMed]
  • Robertson WG, Peacock M, Nordin BE. Inhibitors of the growth and aggregation of calcium oxalate crystals in vitro. Clin Chim Acta. 1973 Jan 10;43(1):31–37. [PubMed]
  • Robertson WG, Peacock M, Nordin BE. Activity products in stone-forming and non-stone-forming urine. Clin Sci. 1968 Jun;34(3):579–594. [PubMed]
  • Pak CY, Hayashi Y, Finlayson B, Chu S. Estimation of the state of saturation of brushite and calcium oxalate in urine: a comparison of three methods. J Lab Clin Med. 1977 Apr;89(4):891–901. [PubMed]
  • Zarembski PM, Hodgkinson A. The fluorimetric determination of oxalic acid in blood and other biological materials. Biochem J. 1965 Sep;96(3):717–721. [PubMed]
  • Cole FE, Gladden KM, Bennett DJ, Erwin DT. Human plasma oxalate concentration re-examined. Clin Chim Acta. 1984 May 30;139(2):137–143. [PubMed]
  • Akcay T, Rose GA. The real and apparent plasma oxalate. Clin Chim Acta. 1980 Feb 28;101(2-3):305–311. [PubMed]
  • Hayashi T, Tsuchiya H, Todoriki H, Naruse H. High-performance liquid chromatographic determination of alpha-keto acids in human urine and plasma. Anal Biochem. 1982 May 1;122(1):173–179. [PubMed]
  • Hodgkinson A, Williams A. An improved colorimetric procedure for urine oxalate. Clin Chim Acta. 1972 Jan;36(1):127–132. [PubMed]
  • Bushinsky DA, Krieger NS, Geisser DI, Grossman EB, Coe FL. Effects of pH on bone calcium and proton fluxes in vitro. Am J Physiol. 1983 Aug;245(2):F204–F209. [PubMed]
  • Coe FL, Firpo JJ, Jr, Hollandsworth DL, Segil L, Canterbury JM, Reiss E. Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man. Kidney Int. 1975 Oct;8(4):263–273. [PubMed]
  • Coe FL, Strauss AL, Tembe V, Le Dun S. Uric acid saturation in calcium nephrolithiasis. Kidney Int. 1980 May;17(5):662–668. [PubMed]
  • Millman S, Strauss AL, Parks JH, Coe FL. Pathogenesis and clinical course of mixed calcium oxalate and uric acid nephrolithiasis. Kidney Int. 1982 Oct;22(4):366–370. [PubMed]
  • Heinegård D, Tiderström G. Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta. 1973 Feb 12;43(3):305–310. [PubMed]
  • Ma RS, Chan JC. Endogenous sulphuric acid production: a method of measurement by extrapolation. Clin Biochem. 1973 Jun;6(2):82–87. [PubMed]
  • LIDDLE L, SEEGMILLER JE, LASTER L. The enzymatic spectrophotometric method for determination of uric acid. J Lab Clin Med. 1959 Dec;54:903–913. [PubMed]
  • Bennett DJ, Cole FE, Frohlich ED, Erwin DT. A radioenzymatic isotope-dilution assay for oxalate in serum or plasma. Clin Chem. 1979 Oct;25(10):1810–1813. [PubMed]
  • Robertson WG, Peacock M, Marshall RW, Marshall DH, Nordin BE. Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract. N Engl J Med. 1976 Jan 29;294(5):249–252. [PubMed]
  • Nakagawa Y, Abram V, Kézdy FJ, Kaiser ET, Coe FL. Purification and characterization of the principal inhibitor of calcium oxalate monohydrate crystal growth in human urine. J Biol Chem. 1983 Oct 25;258(20):12594–12600. [PubMed]
  • FLEISCH H, BISAZ S. Isolation from urine of pyrophosphate, a calcification inhibitor. Am J Physiol. 1962 Oct;203:671–675. [PubMed]
  • Crawhall JC, Watts RW. The metabolism of glyoxylate by human- and rat-liver mitochondria. Biochem J. 1962 Oct;85(1):163–171. [PubMed]
  • Milgram JW, Salyer WR. Secondary oxalosis of bone in chronic renal failure. A histopathological study of three cases. J Bone Joint Surg Am. 1974 Mar;56(2):387–395. [PubMed]
  • Hautmann R, Osswald H. Concentration profiles of calcium and oxalate in urine, tubular fluid and renal tissue--some theoretical considerations. J Urol. 1983 Feb;129(2):433–436. [PubMed]
  • Barsotti G, Cristofano C, Morelli E, Meola M, Lupetti S, Giovannetti S. Serum oxalic acid in uremia: effect of a low-protein diet supplemented with essential amino acids and ketoanalogues. Nephron. 1984;38(1):54–56. [PubMed]
  • O'Callaghan JW, Arbuckle SM, Craswell PW, Boyle PP, Searle JW, Smythe WR. Rapid progression of oxalosis-induced cardiomyopathy despite adequate haemodialysis. Miner Electrolyte Metab. 1984;10(1):48–51. [PubMed]
  • Fayemi AO, Ali M. Sarcoid-like granulomas in secondary oxalosis: a case report. Mt Sinai J Med. 1980 May-Jun;47(3):255–257. [PubMed]
  • Boogaerts MA, Hammerschmidt DE, Roelant C, Verwilghen RL, Jacob HS. Mechanisms of vascular damage in gout and oxalosis: crystal induced, granulocyte mediated, endothelial injury. Thromb Haemost. 1983 Aug 30;50(2):576–580. [PubMed]
  • HOCKADAY TD, CLAYTON JE, FREDERICK EW, SMITH LH., Jr PRIMARY HYPEROXALURIA. Medicine (Baltimore) 1964 May;43:315–345. [PubMed]
  • Moorhead PJ, Cooper DJ, Timperley WR. Progressive peripheral neuropathy in patient with primary hyperoxaluria. Br Med J. 1975 May 10;2(5966):312–313. [PMC free article] [PubMed]
  • Frascino JA, Vanamee P, Rosen PP. Renal oxalosis and azotemia after methoxyflurane anesthesia. N Engl J Med. 1970 Sep 24;283(13):676–679. [PubMed]
  • Parry MF, Wallach R. Ethylene glycol poisoning. Am J Med. 1974 Jul;57(1):143–150. [PubMed]
  • Balcke P, Schmidt P, Zazgornik J, Kopsa H, Deutsch E. Effect of vitamin B6 administration on elevated plasma oxalic acid levels in haemodialysed patients. Eur J Clin Invest. 1982 Dec;12(6):481–483. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation