Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.
OBJECTIVE
Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients.


METHODS
Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs.


RESULTS
Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2.


CONCLUSIONS
We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.
Hetzel
G R
GR
Klinik für Nephrologie und Rheumatologie, Heinrich-Heine-Universität, Düsseldorf, Germany. hetzel@med.uni-duesseldorf.de
Hermsen
D
D
Hohlfeld
T
T
Rettich
A
A
Ozcan
F
F
Fusshöller
A
A
Grabensee
B
B
Plum
J
J
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000139:chemically induced; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D016030:Kidney Transplantation; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage*; D011453:Prostaglandins / Q000378:metabolism*; D013777:Tetrazoles / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000187:drug effects*; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011453:Prostaglandins; C508960:TGFB1 protein, human; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003404:Creatinine; C081643:candesartan; D020913:Perindopril