TY - JOUR
T1 - Effect of 6 weeks of vitamin E administration on renal haemodynamic alterations following a single dose of neoral in healthy volunteers
AU - Bárány, Peter
AU - Stenvinkel, Peter
AU - Ottosson-Seeberger, Astrid
AU - Alvestrand, Anders
AU - Morrow, Jason
AU - Roberts, J. Jackson
AU - Salahudeen, Abdulla K.
N1 - Funding Information:
Acknowledgements. The authors thank Mrs Inger Sjödin and Mrs Ann Dreiman-Lif for technical assistance. The study was financially supported by Novartis Sverige AB (Stockholm, Sweden).
PY - 2001
Y1 - 2001
N2 - Background. A single oral dose of cyclosporin-A (CsA) transiently reduces renal plasma flow (RPF) and glomerular filtration rate (GFR) in transplant patients and, in some patients, chronic administration of CsA leads to renal impairment and fibrosis. Based on experimental studies, several mediators including free radicals have been proposed to account for CsA-nephrotoxicity. We have previously reported that administration of the antioxidant vitamin E in a rat model of chronic CsA-nephrotoxicity reduces renal fibrosis and maintains renal function. Methods. In the present study, the effect on renal haemodynamics of a single dose of the new oral formulation of CsA (neoral) was assessed before and after 6 weeks of vitamin E (800 IU/day, 2-fold increase in serum vitamin E). GFR (inulin clearance) and RPF (para-amino hippuric acid clearance) were measured before and after a single dose of 5 mg/kg of neoral in 12 healthy subjects under standardised conditions. Results. Although the mean area under the curve of the CsA levels was 21% lower after the vitamin E period, the peak CsA level at 120 min after neoral was similar both before and after vitamin E administration. At 120 min after neoral, a transient reduction in RPF and GFR was noted both before and after vitamin E administration. The nadir of the reductions in RPF (-81±27 ml/min) and GFR (-14±6 ml/min) at 120 min compared with baseline tended to be lower before than after the treatment with vitamin E (-51±33 ml/min of RPF and -12±8, ml/min of GFR, respectively). Plasma and urine levels of F2-isoprostanes (free radical-catalysed vasoconstrictive prostanoids (F2-iso) at 120 min after the administration of neoral were not different from the pre-neoral levels. Conclusion. The findings demonstrate that a single oral dose of neoral causes transient, yet significant, reductions in RPF and GFR, and suggest that F2-iso might not be involved in the CsA-induced acute renal vasoconstriction. The tendency for a lower reduction in RPF and GFR following CsA during the vitamin E period in healthy humans warrants additional studies in transplant patients.
AB - Background. A single oral dose of cyclosporin-A (CsA) transiently reduces renal plasma flow (RPF) and glomerular filtration rate (GFR) in transplant patients and, in some patients, chronic administration of CsA leads to renal impairment and fibrosis. Based on experimental studies, several mediators including free radicals have been proposed to account for CsA-nephrotoxicity. We have previously reported that administration of the antioxidant vitamin E in a rat model of chronic CsA-nephrotoxicity reduces renal fibrosis and maintains renal function. Methods. In the present study, the effect on renal haemodynamics of a single dose of the new oral formulation of CsA (neoral) was assessed before and after 6 weeks of vitamin E (800 IU/day, 2-fold increase in serum vitamin E). GFR (inulin clearance) and RPF (para-amino hippuric acid clearance) were measured before and after a single dose of 5 mg/kg of neoral in 12 healthy subjects under standardised conditions. Results. Although the mean area under the curve of the CsA levels was 21% lower after the vitamin E period, the peak CsA level at 120 min after neoral was similar both before and after vitamin E administration. At 120 min after neoral, a transient reduction in RPF and GFR was noted both before and after vitamin E administration. The nadir of the reductions in RPF (-81±27 ml/min) and GFR (-14±6 ml/min) at 120 min compared with baseline tended to be lower before than after the treatment with vitamin E (-51±33 ml/min of RPF and -12±8, ml/min of GFR, respectively). Plasma and urine levels of F2-isoprostanes (free radical-catalysed vasoconstrictive prostanoids (F2-iso) at 120 min after the administration of neoral were not different from the pre-neoral levels. Conclusion. The findings demonstrate that a single oral dose of neoral causes transient, yet significant, reductions in RPF and GFR, and suggest that F2-iso might not be involved in the CsA-induced acute renal vasoconstriction. The tendency for a lower reduction in RPF and GFR following CsA during the vitamin E period in healthy humans warrants additional studies in transplant patients.
KW - Cyclosporin A
KW - Glomerular filtration rate
KW - Renal plasma flow
KW - Tocopherol
KW - Vitamin E
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U2 - 10.1093/ndt/16.3.580
DO - 10.1093/ndt/16.3.580
M3 - Article
C2 - 11239035
AN - SCOPUS:0035095274
SN - 0931-0509
VL - 16
SP - 580
EP - 584
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 3
ER -