Telmisartan Versus Losartan in Kidney Transplantation
Status:
Completed
Trial end date:
2014-01-01
Target enrollment:
Participant gender:
Summary
In renal transplant recipients, residual renal insufficiency combined to the effects of
immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity
and may contribute to several of the abnormalities associated with the metabolic syndrome,
such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance,
hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess
cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes
subjects with over diabetic nephropathy)and may also accelerate progressive renal function
deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the
related metabolic syndrome is a key component of treatments aimed to improve patient and
graft survival in renal transplant recipients. Recently, drugs such as peroxisome
proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and
metabolic syndrome, have become available.These agents, however, can provoke fluid retention,
weight gain, edema and, in some cases, heart failure.
Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in
addition to block the angiotensin II type 1 - a key surface receptor involved in the
regulation of blood pressure - may also activate peroxisome proliferators-activated
receptor-gamma activators, thus improving some of the features of the metabolic syndrome.
Thus telmisartan may substantially reduce the overall cardiovascular and renal risk of renal
transplant recipients by ameliorating some of the modifiable components of the metabolic
syndrome. On the other hand, telmisartan is devoid of the adverse effects of peroxisome
proliferators-activated receptor-gamma activators such as fluid retention, and has therefore
a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the
beneficial effects of a reference angiotensin II type 1 receptor antagonist (such as
losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal
transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth
investigating.
Phase:
Phase 2
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research