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 (Vmax 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; Vmax 55.6 +/- 10.3 mmol.l-1.min-1; p less than 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; Vmax 61.0 +/- 13.6 mmol.l-1.min-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.
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LL
Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Simmons
D
D
Frighi
V
V
Garrido
M C
MC
Bomford
J
J
Hockaday
T D
TD
D000419:Albuminuria; D001794:Blood Pressure; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D012016:Reference Values; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers