Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 43, Issue 6 (Jun 2005)

Issues

Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study

Paul Otto Schwille
  • Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen-Nürnberg, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mahimaidos Manoharan
  • Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen-Nürnberg, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Angelika Schmiedl
  • Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen-Nürnberg, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2005-07-05 | DOI: https://doi.org/10.1515/CCLM.2005.103

Abstract

Background: The site of origin of idiopathic recurrent calcium urolithiasis (IRCU) – a disorder characterized by stones composed of calcium oxalate (CaOx) and/or calcium phosphate (CaPi) – is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed. Aims: To evaluate whether imbalance of antioxidants and oxidants might be present in IRCU patients that is then followed by abnormal urine, plasma and intracellular mineral homeostasis, and stones. Methods: Males were investigated in the laboratory under standardized conditions, and three trials were organized. Trial 1 was cross-sectional, comparing IRCU patients with (n=111) and without stones in situ (n=126), focussing on abnormalities of oxypurines and minerals in urine and plasma, and metabolic activity (MA) of the disease. Trial 2 was partly controlled (n=14 healthy subjects; n=53 IRCU patients), comparing the plasma levels of total antioxidant status (TAS) and uric acid, the major antioxidant in humans, using the subsets Low (n=26) and High (n=27) TAS among IRCU patients in terms of plasma levels of uric acid, ascorbic acid, albumin, α-tocopherol and minerals, urinary minerals, CaOx and CaPi (hydroxyapatite) supersaturation. Trial 3, comprising stone-free IRCU patients (n=8) and healthy controls (n=8), compared minerals and mineral ratios in plasma and red blood cells (RBCs). Established analytical methodologies were used throughout. Results: In trial 1, uricemia, hypoxanthinuria and proteinuria were elevated, fractional urinary clearance (FE) of uric acid was decreased in stone-bearing patients, and MA correlated positively with uricemia and urinary total protein excretion. In trial 2, TAS was significantly decreased in IRCU patients vs. healthy controls; low TAS coincided with low plasma uric acid and albumin, unchanged ascorbic acid, α-tocopherol and parathyroid hormone, but increased FE-uric acid and Pi excretion; the latter correlated negatively with TAS. In trial 3, plasma minerals were significantly decreased in IRCU patients vs. controls, and Ca/Pi, (Ca/Pi)/Mg and (Ca/Pi)/Na molar ratios increased; the latter ratio was also increased in RBCs, and correlated highly positively with the same ratio in plasma. Conclusions: In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and protein-uria, and high MA suggest that a systemic metabolic anomaly underlies stone formation; 2) antioxidant deficit is frequent, unrelated to the presence or absence of stones but apparently related to poor renal uric acid recycling, low uricemia and albuminemia, exaggerated urinary Pi excretion, and low MA; 3) the combination of low plasma TAS, disordered Ca/Pi and other mineral ratios in urine, plasma and RBCs, but unchanged urinary Ca salt supersaturation is compatible with the view that CaPi solid and Ca microlith formation start inside oxidatively damaged cells.

Keywords: antioxidant deficit; erythrocytes; idiopathic calcium urolithiasis; mineral metabolism; molar calcium/phosphate; plasma; stone absence or presence; urine.

References

  • 1

    Herrmann U, Schwille PO, Kuch P. Crystalluria determined by polarization microscopy. Technique and results in healthy control subjects and patients with idiopathic calcium urolithiasis classified in accordance with calciuria. Urol Res 1991; 19: 151–8. CrossrefGoogle Scholar

  • 2

    Fan J, Chandhoke PS. Examination of crystalluria in freshly voided urines of recurrent calcium stone formers and normal individuals using a new filter technique. J Urol 1999; 161: 1685–8. Google Scholar

  • 3

    Finlayson B, Reid F. The expectation of free and fixed particles in urinary stone disease. Invest Urol 1978; 15: 442–8. Google Scholar

  • 4

    Kok DJ, Khan SR. Calcium oxalate nephrolithiasis, a free or fixed particle disease. Kidney Int 1994; 46: 847–54. CrossrefGoogle Scholar

  • 5

    Manoharan M, Schwille PO. Oxypurines, protein, glucose and the functional state of blood vasculature are markers of renal calcium stone-forming processes? Observations in men with idiopathic recurrent calcium urolithiasis. Clin Chem Lab Med 2002; 40: 266–77. CrossrefGoogle Scholar

  • 6

    Rice-Evans C. Free radicals and antioxidants in normal and pathological processes. In: Rice-Evans C, Bruckdorfer KR, editors. Oxidative stress, lipoproteins and cardiovascular dysfunction. London: Portland Press, 1995:1–32. Google Scholar

  • 7

    Rosell M, Regnström J, Kallner A, Hellenius ML. Serum urate determines antioxidant capacity in middle-aged men – a controlled, randomized diet and exercise intervention studies. J Int Med 1999; 246: 219–26. CrossrefGoogle Scholar

  • 8

    Cutler RG. Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species. Arch Gerontol Geriatr 1984; 3: 321–48. CrossrefGoogle Scholar

  • 9

    Manoharan M, Schwille PO, Schmiedl A. Are plasma and red blood cell (RBC) levels of antioxidative vitamins and uric acid disordered in idiopathic calcium urolithiasis (ICU)? A preliminary report. In: Rodgers AL, Hibbert BE, Hess B, Khan SR, Preminger GM, editors. Urolithiasis 2000. Cape Town: University of Cape Town, 2000:547–9. Google Scholar

  • 10

    Rasmussen H. Possible cellular aspect of renal stone formation. In: Finlayson B, Hench LL, Smith LH, editors. Urolithiasis. Physical aspects. Washington, DC: National Academy of Sciences, 1972;161–7. Google Scholar

  • 11

    Schmiedl A, Schwille PO, Bergé B, Markovic M, Dvorak O. Reappraisal of the quantity and nature of renal calcifications and mineral metabolism in the magnesium-deficient rat. Urol Int 1998; 61: 76–85. CrossrefGoogle Scholar

  • 12

    Sakakura T, Fujita K, Yasui T, Sasaki S, Mabuchi Y, Iguchi M, et al. Calcium phosphate stones produced by Madin-Darby canine kidney (MDCK) cells inoculated in nude mice. Urol Res 1999; 27: 200–5. CrossrefGoogle Scholar

  • 13

    Schwille PO, Herrmann U, Schmiedl A, Kissler H, Wipplinger J, Manoharan M. Urinary phosphate excretion in the pathophysiology of idiopathic calcium urolithiasis: hormonal interactions and lipid metabolism. Urol Res 1997; 25: 417–26. CrossrefGoogle Scholar

  • 14

    Prié D, Ravery V, Boccon-Gibol L, Friedlander G. Frequency of renal phosphate leak among patients with calcium nephrolithiasis. Kidney Int 2001; 60: 272–6. CrossrefGoogle Scholar

  • 15

    Carbonneau MA, Peuchant E, Sess D, Canioni P, Clerc M. Free and bound malonedialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma. Clin Chem 1991; 37: 1423–9. Google Scholar

  • 16

    Schwille PO, Rümenapf G. Idiopathic calcium urolithiasis – clinical problems and suggested approaches in an ambulatory stone clinic. In: Wickham JEA, Buck A, editors. Renal tract stone: metabolic basis and clinical practice. Edinburgh, London, Melbourne, New York: Churchill Livingstone, 1990:217–38. Google Scholar

  • 17

    Schmiedl A, Schwille PO. Is magnesium a marker of disordered mineral metabolism in males with idiopathic recurrent calcium urolithiasis? Observations focusing on fasting magnesiuria and magnesiemia, protein and other substances in urine and plasma. Magnes Res 2003; 16: 192–205. Google Scholar

  • 18

    Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993; 84: 407–12. CrossrefGoogle Scholar

  • 19

    Smart D, McCusker C, Lamont JV, Fitzgerald SP, Lapin A, Temml C. Reference values for various antioxidant parameters in a normal working population. In: Proceedings of the XVIth International Congress on Clinical Chemistry, London, 1996: Poster B 548. Google Scholar

  • 20

    Habdous M, Herbeth B, Vincent-Viry M, Lamont JV, Peters SF, Visvikis S, et al. Serum total antioxidant status, erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities in the Stanislas cohort: influencing factors and reference intervals. Clin Chem Lab Med 2003; 41: 209–15. CrossrefGoogle Scholar

  • 21

    Manoharan M, Schwille PO. Measurement of oxalate in human plasma ultrafiltrate by ion chromatography. J Chromatogr B Biomed Sci Appl 1997; 700: 261–8. Google Scholar

  • 22

    Manoharan M, Schwille PO. Measurement of ascorbic acid in human plasma and urine by high performance liquid chromatography. Results in healthy subjects and patients with idiopathic calcium urolithiais. J Chromatogr B Biomed Sci Appl 1994; 654: 134–9. Google Scholar

  • 23

    Postaire E, Kouyate D, Rousser G, Regnault C, Lati E, Bejot M, et al. Plasma concentrations of β-carotene, vitamin A and vitamin E after β-carotene and vitamin E intake. Biomed Chromatogr 1993; 7: 136–8. CrossrefGoogle Scholar

  • 24

    Kontush A, Finckh B, Karten B, Kohlschütter A, Beisiegel U. Antioxidant and prooxidant activity of α-tocopherol in human plasma and low density lipoprotein. J Lipid Res 1996; 37: 1436–48. Google Scholar

  • 25

    Lowry OH, Roseburgh, NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–75. Google Scholar

  • 26

    Jacob HS, Karnovsky ML. Concomitant alterations of sodium fluxes and membrane phospholipid metabolism in red blood cells: studies in hereditary spherocytosis. J Clin Invest 1967; 46: 173–7. CrossrefGoogle Scholar

  • 27

    Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet 1975; 16: 309–10. CrossrefGoogle Scholar

  • 28

    Werness PG, Brown CM, Smith LH. EQUIL-2: a BASIC computer program for calculation of urinary saturation. J Urol 1985; 134: 1242–4. Google Scholar

  • 29

    Cheng PT, Pritzker KPH. Solution Ca/Pi ratio affects calcium phosphate crystal phases. Calcif Tiss Int 1983; 35: 596–601. CrossrefGoogle Scholar

  • 30

    Zajicek H, Wang H, Kumar V, Wilson P, Levi M. Role of glycosphingo-lipids in the regulation of renal phosphate transport. Kidney Int 1997; 52(Suppl 61): 3–8. Google Scholar

  • 31

    Saugstad OD. Hypoxanthine as an indicator of hypoxia: its role in health and disease through free radical production. Pediatr Res 1988; 23: 143–50. CrossrefGoogle Scholar

  • 32

    Opara EC, Abdel-Rhaman E, Soliman S, Kamel WA, Souka S, Lowe JE, et al. Depletion of antioxidant capacity in type II diabetes. Metab Clin Exp 1999; 48: 1414–7. CrossrefGoogle Scholar

  • 33

    Kemp GJ, Berington A, Russell RG. Erythrocyte phosphate metabolism and pH in vitro: a model for clinical phosphate disorders in acidosis and alkalosis. Min Electrol Metab 1988; 14: 266–70. Google Scholar

  • 34

    Finlayson B, Khan SR, Hackett R. Theoretical chemical models of urinary stones. In: Wickham JEA, Buck AC, editors. Renal tract stone. Metabolic basis and clinical practice. Edinburgh, London, Melbourne, New York: Churchill Livingstone, 1990:133–47. Google Scholar

  • 35

    Schmiedl A, Schwille PO, Bonucci E, Erben RG, Grayczyk A, Sharma V. Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction. Urol Res 2000; 28: 404–15. CrossrefGoogle Scholar

  • 36

    Cao G, Prior RL. Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 1998; 44: 1309–15. Google Scholar

  • 37

    Knight JA. Free radicals: their history and current status in aging and disease. Ann Clin Lab Sci 1998; 28: 331–46. Google Scholar

  • 38

    Tagesson C, Källberg M, Wingren G. Urinary malonedialdehyde and 8-hydroxydeoxy-guanosine as potential markers of oxidative stress in industrial art glass workers. Int Arch Occup Environ Health 1996; 69: 5–13. CrossrefGoogle Scholar

  • 39

    Anuradha CV, Selvam R. Increased lipid peroxidation in the erythrocytes of kidney stone formers. Ind J Biochem Biophys 1989; 26: 39–42. Google Scholar

  • 40

    Bracci R. Calcium involvement in free radical effects. Calcif Tiss Int 1992; 51: 401–5. CrossrefGoogle Scholar

  • 41

    Snyder LM, Fortier NL, Trainer J, Jacobs J, Leb L, Lubin B, et al. Effect of hydrogen peroxide exposure on normal human erythrocyte deformability, morphology, surface characteristics, and spectrin-hemoglobin cross-linking. J Clin Invest 1985; 76: 1971–7. CrossrefGoogle Scholar

  • 42

    Xiao Y, Desrosiers RR, Beliveau R. Effect of ischemia reperfusion in the renal brush-border membrane sodium-dependent phosphate cotransporter NaPi-2. Can J Physiol Pharmacol 2001; 79: 206–12. CrossrefGoogle Scholar

  • 43

    Maesaka JK, Fishbane S. Regulation of renal urate excretion: a critical review. Am J Kidney Dis 1998; 917–33. CrossrefGoogle Scholar

  • 44

    Kuller H, Eichner JE, Orchard TJ, Grandits JA, McCallum L, Tracy RP. The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial. Am J Epidem 1991; 134: 1266–77. CrossrefGoogle Scholar

  • 45

    Naito Y, Ohtawara Y, Kageyama S, Nakano M, Ichiyama A, Fujita M, et al. Morphological analysis of renal cell culture models of calcium phosphate stone formation. Urol Res 1997; 25: 59–65. CrossrefGoogle Scholar

  • 46

    Kohri K, Nomura S, Kitamura Y, Nagata T, Yoshioka K, Iguchi M, et al. Structure and expression of the mRNA encoding urinary stone protein (osteopontin). J Biol Chem 1993; 268: 15810–5. Google Scholar

  • 47

    Travis SF, Sugerman HJ, Ruberg RL, Dudrick SJ, Delivoria-Papadopoulos M, Miller LD, et al. Alterations of red-cell glycolytic intermediates and oxygen transport as a consequence of hypophosphatemia in patients receiving intravenous hyperalimentation. N Engl J Med 1971; 285: 763–8. Google Scholar

  • 48

    Vanhoutte PM. Endothelium-derived free radicals: for worse and for better. J Clin Invest 2001; 107: 23–5. Google Scholar

About the article

Corresponding author: Paul O. Schwille, MD, Finkenweg 5, 91080 Uttenreuth/Erlangen, Germany Phone: +49-9131-59790, Fax: +49-9131-533331,


Received: 2005-01-17

Accepted: 2005-03-14

Published Online: 2005-07-05

Published in Print: 2005-06-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.103.

Export Citation

© Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
C. A. Wright, S. Howles, D. C. Trudgian, B. M. Kessler, J. M. Reynard, J. G. Noble, F. C. Hamdy, and B. W. Turney
Molecular & Cellular Proteomics, 2011, Volume 10, Number 8, Page M110.005686
[2]
Seolhye Kim, Yoosoo Chang, Kyung Eun Yun, Hyun-Suk Jung, Soo-Jin Lee, Hocheol Shin, and Seungho Ryu
American Journal of Kidney Diseases, 2017, Volume 70, Number 2, Page 173
[3]
Yang Wang, Chun Sun, Chengyang Li, Yaoliang Deng, Guohua Zeng, Zhiwei Tao, Xiang Wang, Xiaofeng Guan, and Yutong Zhao
Urolithiasis, 2017, Volume 45, Number 2, Page 159
[4]
Yongwang Liu, Haibin Xu, Wenting Zhong, Qingpeng Shen, Tenghan Zhuang, and Kehe Huang
Biological Trace Element Research, 2015, Volume 168, Number 2, Page 392
[5]
Saeed R. Khan and Benjamin K. Canales
Urolithiasis, 2015, Volume 43, Number S1, Page 109
[8]
Saeed R. Khan and Patricia A. Glenton
The Journal of Urology, 2010, Volume 184, Number 3, Page 1189
[9]
Yuebin Ke, Xiaobei Duan, Feiqiu Wen, Xinyun Xu, Gonghua Tao, Li Zhou, Renli Zhang, and Baoming Qiu
Archives of Toxicology, 2010, Volume 84, Number 4, Page 301
[10]
Cheng Yang Li, Yao Liang Deng, and Bing Hua Sun
Urological Research, 2009, Volume 37, Number 4, Page 211

Comments (0)

Please log in or register to comment.
Log in