Kidney International (1997) 51, 640–645; doi:10.1038/ki.1997.93
Relationship between supersaturation and crystal inhibition in hypercalciuric rats
John R Asplin, David A Bushinsky, Wijeyasekaran Singharetnam, Daniel Riordon, Joan H Parks and Fredric L Coe
Nephrology Program, University of Chicago, Chicago, Illinois and Nephrology Unit, University of Rochester, Rochester, New York, USA
Correspondence: John R Asplin MD, University of Chicago, Section of Nephrology, MC 5100, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
Received 26 June 1996; Revised 27 September 1996; Accepted 30 September 1996.
Top of pageAbstract
Relationship between supersaturation and crystal inhibition in hypercalciuric rats. Calcium oxalate (CaOx) and calcium phosphate (CaP) crystals do not precipitate in large amounts in normal urine despite considerable supersaturation (SS), partly because urine inhibits crystal nucleation, aggregation, and growth. In normal rats and rats bred for hypercalciuria (GHS), we varied SS by varying calcium intake to test the hypothesis that increased SS might deplete inhibitors and reduce inhibition of crystal formation. In normal rats when compared to a low calcium diet (0.02% Ca), a high calcium diet (1.2% Ca) raised the SS of CaOx from 0.8 to 8.2. The high calcium diet also raised the upper limit of metastability (ULM) of CaOx (the SS at which crystals form in urine) from 11.8 to 36. In GHS rats, diet change altered CaOx SS from 1.5 to 12, and ULM from 17 to 50 (all differences, P < 0.001). Because ULM rose with SS, the increased SS had little potential to increase CaOx stone risk. For CaP, however, SS rose from 0.6 to 2.4 and 1.1 to 8 in normal and GHS rats (P < 0.001 for both), respectively, whereas ULM for CaP did not increase significantly (8 vs. 7 and 7 vs. 11; P = NS, both changes). Therefore, CaP SS rose close to the ULM, posing a high stone risk. The stones formed by these rats are composed of CaP. Increasing CaOx SS by diet raises ULM for CaOx thereby offsetting the risk of CaOx stones in rats.
Top of pageReferences
- Finlayson B: Physicochemical aspects of urolithiasis. Kidney Int 13:344–360, 1978 | PubMed | ISI | ChemPort |
- Bushinsky DA, Favus MJ: Mechanism of hypercalciuria in genetic hypercalciuric rats. Inherited defect in intestinal calcium transport. J Clin Invest 82:1585–1591, 1988 | PubMed | ISI | ChemPort |
- Krieger NS, Stathopoulos VM, Bushinsky DA: Increased sensitivity to 1,25(OH)2D3 in bone from genetic hypercalciuric rats. Am J Physiol (in press)
- Li X, Tembe V, Horwitz GM, Bushinsky DA, Favus MJ: Increased intestinal vitamin D receptor in genetic hypercalciuric rats. J Clin Invest 91:661–667, 1993 | PubMed | ISI | ChemPort |
- Bushinsky DA, Kim M, Sessler N, Nakagawa Y, Coe FL: Increased urinary saturation and kidney calcium content in genetic hypercalciuria rats. Kidney Int 45:58–65, 1994 | Article | PubMed | ISI | ChemPort |
- Bushinsky DA, Grynpas MD, Nilsson EL, Nakagawa Y, Coe FL: Stone formation in genetic hypercalciuric rats. Kidney Int 48:1705–1713, 1995 | Article | PubMed | ISI | ChemPort |
- Pak CYC, Holt K: Nucleation and growth of brushite and calcium oxalate in urine of stone formers. Metabolism 25:665–673, 1976 | Article | PubMed | ISI | ChemPort |
- Lieske JC, Coe FL: Urinary inhibitors and renal stone formation, in Kidney Stones: Medical and Surgical Management, edited by Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger GM, Philadelphia, Lippincott-Raven, 1996, p 65
- Asplin J, Deganello S, Nakagawa YN, Coe FL: Evidence that nephrocalcin and urine inhibit nucleation of calcium oxalate monohydrate crystals. Am J Physiol 261:F824–F830, 1991 | PubMed | ISI | ChemPort |
- Shiraga H, Min W, Vandusen WJ, Claymen MD, Miner D, Terrel CH, Sherbotie JR, Foreman JW, Przysiecki C, Neilson EG, Hoyer JR: Inhibition of calcium oxalate crystal growth in vitro by uropontin: Another member of the aspartic acid-rich protein super-family. Proc NatAcad Sei USA 89:426–430, 1992 | Article |
- Nakagawa Y, Abram V, Parks JH, Lau HS, Kawooya JK, Coe FL: Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis. J Clin Invest 76:1455–1462, 1985
- Hess B, Nakagawa Y, Coe FL: Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins. Am J Physiol 257:F99–F106, 1989 | PubMed | ISI | ChemPort |
- Hess B, Nakagawa Y, Parks JH, Coe FL: Molecular abnormality of Tamm-Horsfall glycoprotein in calcium oxalate nephrolithiasis. Am J Physiol 260:F569–F578, 1991 | PubMed | ISI | ChemPort |
- Nicar MJ, Hill K, Pak CY: A simple technique for assessing the propensity for crystallization of calcium oxalate and brushite in urine from the increment in oxalate or calcium necessary to elicit precipitation. Metabolism 32:906–910, 1983 | Article | PubMed | ISI | ChemPort |
- Francis MD, Webb NC: Hydroxyapatite formation from a hydrated calcium monohydrogen phosphate precursor. Calc Tiss Res 6:335–342, 1971 | Article |
- Nakagawa Y, Ahmed M, Hall SL, Deganello S, Coe FL: Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid. J Clin Invest 79:1782–1787, 1987 | PubMed | ISI | ChemPort |
- Kim M, Sessler NE, Tembe V, Favus MJ, Bushinsky DA: Response of genetic hypercalciuric rats to a low calcium diet. Kidney Int 43:189–196, 1993 | Article | PubMed | ISI | ChemPort |
- Brown CM, Purich DL: Physical-chemical processes in kidney stone formation, in Disorders of Bone and Mineral Metabolism, edited by Coe FL, Favus MJ, New York, Raven Press, 1992, p 613
- Hess B, Nakagawa Y, Coe FL: A new spectrophotometric method for measuring calcium oxalate monohydrate crystal aggregation in the absence of supersaturation: Inhibitory effects of urinary glycoproteins. Urol Res 17:149–150, 1989 | PubMed | ChemPort |
- Silverman BW: Density Estimation for Statisitics and Data Analysis. London, Chapman and Hall, 1986
- Ito H, Coe FL: Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine. Am J Physiol 233:F455–F463, 1977
- Yamaguchi S, Yoshioka T, Utsunomiya M, Koide T, Osafune M, Okuyama A, Sonoda T: Heparan sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization. Urol Res 21:187–192, 1993 | Article |
- Atmani F, Khan SR: Characterization of uronic-acid-rich inhibitor of calcium oxalate crystallization isolated from rat urine. Urol Res 23:95–101, 1995 | Article | PubMed | ChemPort |
- Wilson JWL, Werness PG, Smith LH: Inhibitors of crystal growth of hydroyapatite: A constant composition approach. J Urol 134:1255–1258, 1985
- Crawford MA, Milne MD, Scribner BH: The effects of changes in acid-base balance of urinary citrate in the rat. J Physiol 149:413–432, 1959 | PubMed |
- Brennan S, Hering-Smith K, Hamm LL: Effect of pH on citrate reabsorption in the proximal convoluted tubule. Am J Physiol 255:F301–F306, 1988 | PubMed | ChemPort |