Fetuin, matrix-Gla protein and osteopontin in calcification of renal allografts

PLoS One. 2012;7(12):e52039. doi: 10.1371/journal.pone.0052039. Epub 2012 Dec 17.

Abstract

Background: Calcification of renal allografts is common in the first year after transplantation and is related to hyperparathyroidism. It is associated with an impaired long-term function of the graft (Am J Transplant 5∶1934-41, 2005). Aim of this study is to examine the role of the anti-calcifying/calcifying factors in the pathophysiology of renal allograft calcification.

Methods: We analyzed protocol allograft biopsies, blood and urine samples of 31 patients with and 27 patients without allograft calcification taken at 6 weeks, 3 and 6 months after transplantation. Patient demographical data, cold ischemia time, initial graft function and donor characteristics were comparable between the two groups. Biopsies were stained for osteopontin, fetuin, and matrix-gla-protein. Serum and urine electrolytes, matrix-gla-protein, fetuin, Vitamin D and intact parathyroid hormone in serum and osteopontin (OPN) in urine were examined.

Results: Serum levels of fetuin and matrix-Gla protein as well as urinary levels of OPN showed specific time dependent changes (6 weeks vs. 3 months vs. 6 months; all p<0.0001). In patients with calcifications, urinary levels of OPN were decreased by 55% at 6 weeks and increased thereafter, showing 54% higher levels at 6 months compared to patients without calcification (6 weeks: p<0.01, 6 months: p<0.05). Local protein expression of fetuin-A, matrix-Gla protein and OPN in the graft was specifically increased around calcified plaques, without differences in the mRNA tissue expression.

Conclusion: Anticalcifying factors show significant changes in the early phase after renal transplantation, which may be important for the prevention of allograft calcification. The differences in OPN indicate an involvement of this factor in the regulation of calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcinosis / blood
  • Calcinosis / metabolism*
  • Calcinosis / urine
  • Calcium / blood
  • Calcium-Binding Proteins / blood
  • Calcium-Binding Proteins / metabolism*
  • Electrolytes / blood
  • Electrolytes / urine
  • Extracellular Matrix Proteins / blood
  • Extracellular Matrix Proteins / metabolism*
  • Fetuins / metabolism*
  • Humans
  • Kidney Diseases / blood
  • Kidney Diseases / metabolism*
  • Kidney Diseases / urine
  • Kidney Transplantation*
  • Matrix Gla Protein
  • Osteopontin / blood
  • Osteopontin / metabolism*
  • Osteopontin / urine
  • Parathyroid Hormone / blood
  • Transplantation, Homologous
  • Vitamin D / blood

Substances

  • Calcium-Binding Proteins
  • Electrolytes
  • Extracellular Matrix Proteins
  • Fetuins
  • Parathyroid Hormone
  • Osteopontin
  • Vitamin D
  • Calcium

Grants and funding

This work was supported by a grant of the German Ministry for Education and Research (IFB-Tx to W.G. and J.L.) as well as the German Research Foundation (DFG LO 1736/1-1 to JL). The German Research Foundation funded the cost of Open Access publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.