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

Increased erythrocyte sodium-lithium countertransport activity has bee n 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 in cipient diabetic nephropathy. We measured erythrocyte sodium-lithium c ountertransport, passive sodium/potassium flux (at 1 degrees C), adeni ne nucleotide content in intact erythrocytes and sodium/potassium-, ma gnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without micr oalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-mat ched healthy control subjects. Sodium-lithium countertransport was ele vated in diabetic patients with normo- and microalbuminuria compared w ith 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 erythroc yte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP-content was found to be significantly highe r (P< 0.001) in erythrocytes from diabetic patients compared with cont rol 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 po tassium leakage correlated with hemoglobin A(1c) (r=0.39, P< 0.05). Th ese results demonstrate that changes in the activity of membrane catio n transport, occurring in early nephropathy, are not confined to sodiu m-lithium countertransport, but involve various pathways, thus reflect ing underlying membrane alterations which are at least partially influ enced by the diabetic milieu.