Leucocyte Na⁺/H⁺ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy

The development of proteinuria in Type 1 (insulin-dependent) diabetic patients may depend on predisposition to essential hypertension in addition to poor glycaemic control. Previous work has shown increased leucocyte Na^-/H⁺ antiport activity in essential hypertension and increased erythrocyte Li⁺/Na⁺ exchange in Type 1 diabetic patients with proteinuria. To test whether susceptibility to nephropathy in Type 1 diabetes was linked to abnormalities of leucocyte Na⁺/H⁺ antiport activity, we measured the intracellular pH and kinetics of the Na⁺/H⁺ antiport in 19 Type 1 diabetic subjects with, and 15 diabetic subjects without albuminuria and compared them to 25 matched normal control subjects. Intracellular pH (mean ±SD 7.59 ± 0.14) and maximal transport capacity of the antiport (V_max 87.7 ±24.9 mmol· 1^-1·min^-1) were higher in diabetic subjects with albuminuria compared to normotensive control subjects (pH 7.44±0.09; V_max 55.6±10.3 mmol·1^-1min^-1; p <0.001 for both), similar to the defect described in essential hypertension. These differences were not seen in diabetic subjects with normal urinary albumin/creatinine ratios (pH 7.46 ±0.09; V_max 61.0 ±13.6mmol·1^-1min^-1). Buffering characteristics of the leucocytes at different pH in the Type 1 diabetic subjects with albuminuria differed from normal control subjects and diabetic subjects with normal urinary albumin/creatinine ratios. We conclude that increased leucocyte Na⁺/H⁺ antiport activity, a known marker of essential hypertension, is usually associated with nephropathy in Type 1 diabetes.