Effects of oral magnesium supplementation on acute experimental cyclosporin nephrotoxicity.
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 15 mg/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, P < 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 < 0.01). Magnesium supplementation increased PMg (2.11 versus 1.57 mg/dl P < 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 (36 IU/gCr, P < 0.05) values only in the CsAMg(-) rats. No differences were observed in intraerythrocyte Mg, blood pressure, and urinary excretion of N-acetyl-beta-D-glucosaminidase among groups. Renal histology was similar in CsA rats independent of magnesium supplementation: mild vacuolization and tubular collapse in proximal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Burdmann
E A
EA
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Andoh
T F
TF
Lindsley
J
J
Houghton
D C
DC
Bennett
W M
WM
D000284:Administration, Oral; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008274:Magnesium / Q000008:administration & dosage* / Q000378:metabolism; D008275:Magnesium Deficiency / Q000139:chemically induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016572:Cyclosporine; D008274:Magnesium