ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORT, ADENOSINE-TRIPHOSPHATASE ACTIVITY AND SODIUM-POTASSIUM FLUXES IN INSULIN-DEPENDENT DIABETES

Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/potassium flux (at 1 degrees C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268+/-99 and 299(277-465), respectively, vs. 166+/-65 mu mol/(l cellsxh)] and was positively correlated (r=0.36, P< 0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP-content was found to be significantly higher (P< 0.001) in erythrocytes from diabetic patients compared with control subjects (1,196+/-276 vs. 833+/-253 mu mol/l cells and 353+/-97 vs. 255+/-64 mu mol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A(1c) (r=0.39, P< 0.05). These results demonstrate that changes in the activity of membrane cation transport, occurring in early nephropathy, are not confined to sodium-lithium countertransport, but involve various pathways, thus reflecting underlying membrane alterations which are at least partially influenced by the diabetic milieu.