The renin-angiotensin system and endothelial nitric oxide synthase gene polymorphisms and cyclosporine toxicity in renal transplant patients.
Although cyclosporine has improved graft survival, the toxicity of the drug frequently causes problem for renal transplant patients. Cyclosporine displays deleterious effects due to direct toxicity to the nephrons and vasoconstriction of afferent arterioles, effects that may be due to increased angiotensin II and decreased nitric oxide activity. We sought to examine the relation between cyclosporine toxicity and the RAS (angiotensin-converting enzyme, angiotesinogen, angiotensin 1 and 2 receptors, and ecNOS) gene polymorphisms in 111 renal transplant patients. Retrospectively, we correlated the results of graft biopsies from these 111 patients, with the cumulative drug doses (mg), mean blood levels (mg/mL), mean daily doses (mg), and mean doses (mg/kg/d) of cyclosporine. Overall 125 patients (38 women, 87 men) were enrolled in the study. Their mean age was 34.47 +/- 11.04 years. Twenty patients displayed cyclosporine toxicity on graft biopsy; 91 showed no evidence of the disorder. We could not find any relation between cyclosporine toxicity and gene polymorphisms (P >.05), although the mean mg/kg/d dose was significantly high among cyclosporine toxicity group (P =.028, RR = 1.42). In recent studies angiotensin II and nitric oxide have been suggested to be related to cyclosporine toxicity; however, our results failed to reveal an association between cyclosporine toxicity and angiotensin II or nitric oxide-related gene polymorphisms.
Ozdemir
F N
FN
Department of Nephrology, Başkent University School of Medicine, Ankara, Turkey. foz310@hotmail.com
Miçozkadioğlu
H
H
Ataç
F B
FB
Verdi
H
H
Colak
T
T
Ozdemir
B H
BH
Arat
Z
Z
Sezer
S
S
Haberal
M
M
D000808:Angiotensinogen / Q000235:genetics; D016572:Cyclosporine / Q000633:toxicity*; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D016030:Kidney Transplantation / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D007166:Immunosuppressive Agents; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D016572:Cyclosporine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A