Abnormal Kinetics of Erythrocyte Sodium Lithium Countertransport in Patients with Diabetic Nephropathy in Thailand
Kriengsak Vareesangthip MD, PhD*, Weerawat Panthongdee MD*, Chairat Shayakul MD*, Wannee Nitiyanant MD**, Leena Ong-Aj-Yooth MD*
Affiliation : *Renal Division, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University ** Endocrine Division, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
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.
Materials and 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.
Conclusion : 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.
Keywords : Cardiovascular disease, Diabetic nephropathy, Sodium lithium countertransport, Type II, Type 2 diabetes mellitus
