Effects of oral magnesium supplementation on acute experimental cyclosporin nephrotoxicity

E. A. Burdmann, T. F. Andoh, J. Lindsley, D. C. Houghton, W. M. Bennett

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Hypomagnesaemia with magnesuria are common findings in cyclosporin-(CsA)-treated patients and have been proposed as both a cause and a consequence of nephrotoxicity. To investigate the role of Mg depletion in the pathogenesis of acute CsA nephrotoxicity, rats kept on a low-salt diet were maintained on plain water (Mg(–)group) or water supplemented with 2% MgCl2 (Mg(+) group) and randomly assigned to treatment with CsA 15mg/kg (CsA) or vehicle (VH) s.c. for 7 days. Water and food ingestion in VH animals was adjusted to the intake of CsA animals. CsAMg(–)group showed a significant plasma magnesium (PMg) reduction as compared to baseline (1.13 versus 1.53 mg/dl, /)<0.001) or VH values (versus 1.60 mg/dl, P< 0.001) and a significantly greater posttreatment fractional excretion of magnesium (FeMg) as compared to VH (9.4 versus 5.4%, P<0.0l). Magnesium supplementation increased PMg (2.11 versus 1.57 mg/dl /><0.001) and FeMg (13.6 versus 6.2%, P< 0.001) but did not prevent a reduction in GFR with CsA treatment. Alanine aminopeptidase (AAP) excretion at 7 days was significantly greater than baseline (130 versus 44 IU/gCr, P<0.05) or VH (36IU/gCr, /<0.05) values only in the CsAMg(-) rats. No differences were observed in intraerythrocyte Mg, blood pressure, and urinary excretion of N-acetyl- /?-D-glucosaminidase among groups. Renal histology was similar in CsA rats independent of magnesium supplementation: mild vacuolization and tubular collapse in proximal tubules. In conclusion, Mg depletion could not be implicated in the pathogenesis of acute CsA-induced glomerular dysfunction, but Mg replacement may protect from some of the tubular toxicity of CsA.

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalNephrology Dialysis Transplantation
Volume9
Issue number1
DOIs
StatePublished - Jan 1 1994

Keywords

  • Cyclosporin
  • Enzymuria
  • Magnesium
  • Nephrotoxicity
  • Rats
  • Renal function

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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