Abnormal kinetics of erythrocyte sodium lithium countertransport in renal transplant recipients.
Cardiovascular disease is now the most common cause of death in renal transplantation. Cyclosporine (CsA)-associated hypertension might be a major cause of cardiovascular risk factors. There is evidence suggesting that one mechanism of CsA toxicity might be mediated through alteration of membrane lipid peroxidation, which can activate cellular pathways. Erythrocyte sodium lithium countertransport (Na/Li CT) is a sensitive membrane protein that is abnormal in several hypertensive-related diseases. We have studied the kinetics of erythrocyte Na/Li CT in 38 renal transplant recipients. Group 1 (15 patients) received CsA, azathioprine, and prednisolone (C+A+P), Group 2 (15 patients) CsA and prednisolone (C+P), and Group 3 (8 patients) azathioprine and prednisolone (A+P). Compared with the normal subjects, the Michaelis constant for extracellular sodium (Km) of erythrocyte Na/Li CT was lower among the CsA-based regimen groups (C+A+P and C+P), but not the A+P group. The maximum velocity (Vmax)/Km ratio was also higher among the C+A+P and C+P groups than the A+P group. These abnormalities of Na/Li CT kinetics might be due to abnormalities of cell membrane functions, caused by immunosuppressive drugs, particularly CsA. Further studies involving the effect of CsA on the physiological function of membrane thiol proteins are required.
Vareesangthip
K
K
Renal Division, Department of Medicine, Siriraj Hospital, Bangkok, Thailand.
Hanlakorn
P
P
Suwannaton
L
L
Pidetcha
P
P
Ong-Aj-Yooth
L
L
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017920:Antiporters / Q000097:blood*; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D000959:Antihypertensive Agents; D017920:Antiporters; D007166:Immunosuppressive Agents; C045885:sodium-lithium countertransporter