Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in a rat model.
OBJECTIVE
To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation.


METHODS
The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation.


RESULTS
As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity.


CONCLUSIONS
In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile.
Laboratory of Pharmacology and Experimental Therapeutics, IBILI, Medicine Faculty, Coimbra University, Coimbra, Portugal.
José
J
Sereno
Ana M
AM
Romão
Belmiro
B
Parada
Patrícia
P
Lopes
Eugénia
E
Carvalho
Frederico
F
Teixeira
Flávio
F
Reis