Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects.
BACKGROUND
The side effects of cyclosporine, nephrotoxicity and hypertension, contribute to long-term renal graft failure and cardiovascular morbidity in graft recipients. It is not clear whether tacrolimus is as nephrotoxic and hypertensive as cyclosporine. Data on this subject are not consistent because of differences in dosage and duration of treatment and the presence of comorbidity in the studied patients. A comparison of both drugs with respect to renal hemodynamics and blood pressure has not been performed yet in healthy subjects.


METHODS
We studied blood pressure, glomerular filtration rate, and effective renal plasma flow in eight healthy subjects at baseline and after 2 weeks administration of cyclosporine and tacrolimus, in randomized order. Trough levels of either drug were within the currently recommended therapeutical range of 100-200 ng/ml for cyclosporine and 5-15 ng/ml for tacrolimus.


RESULTS
Tacrolimus did not influence renal hemodynamic parameters, in contrast to cyclosporine. During cyclosporine, glomerular filtration rate decreased from 98+/-9 ml/min/1.732 to 85+/-10 ml/min/1.732 (P<0.05), and ERPF decreased from 597+/-108 ml/min/1.732 to 438+/-84 ml/min/1.732 (P<0.01). Mean arterial blood pressure increased from 93+/-8 mmHg to 108+/-10 mmHg (P<0.05) during cyclosporine and remained unchanged during tacrolimus.


CONCLUSIONS
We conclude that tacrolimus given during 2 weeks in the currently advised dosage has no unfavorable effects on renal hemodynamics and blood pressure in healthy individuals. The use of tacrolimus in organ transplant recipients may in the long-term lead to better renal function and less cardiovascular morbidity than the use of cyclosporine.
Klein
Inge H H T
IH
Department of Nephrology and Hypertension, University Medical Center Utrecht, The Netherlands.
Abrahams
Alferso
A
van Ede
Thomas
T
Hené
Ronald J
RJ
Koomans
Hein A
HA
Ligtenberg
Gerry
G
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D016572:Cyclosporine / Q000009:adverse effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017595:Renal Plasma Flow / Q000187:drug effects; D016559:Tacrolimus / Q000009:adverse effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus