Abnormal kinetics of erythrocyte sodium lithium countertransport in patients with diabetic nephropathy in Thailand.
BACKGROUND
In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned.


OBJECTIVE
The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients.


METHODS
Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects.


RESULTS
The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand.


CONCLUSIONS
Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.
Vareesangthip
Kriengsak
K
Renal Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand. sikwn@mahidol.ac.th
Panthongdee
Weerawat
W
Shayakul
Chairat
C
Nitiyanant
Wannee
W
Ong-Aj-Yooth
Leena
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D017920:Antiporters / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D013785:Thailand
D017920:Antiporters; C045885:sodium-lithium countertransporter