The kidney in diabetes mellitus : urinary transfer in excretion, hypertension, the Renin-Angiotensin-Aldosterone system, and the role of angiotensin converting enzyme inhibitors in therapy

Abstract

Patients with diabetic renal disease develop elevated urinary albumin excretion rates [AER] and hypertension. Preliminary data from several groups suggest that diabetic patients handle transferrin, a protein similar in size and weight, in a different fashion from albumin. In the first part of this thesis I report the results of clinical studies of urinary transferrin excretion [TER] in diabetes mellitus. More than 80% type 1 [insulin dependent] diabetic patients have increased TER but less than 40% have increased AER. TER may be provoked by exercise in uncomplicated type 1 diabetes and the rise is proportionally far greater than that for AER. Newly diagnosed type 2 [non-insulin dependent] diabetic subjects have increased TER which falls with improved glycaemic control. Interventional studies with lisinopril, an angiotensin converting enzyme [ACE] inhibitor, in microalbuminuric and macroalbuminuric diabetic subjects show a reduction in TER independent of reduction in blood pressure. Data are presented suggesting a role for altered renal tubular function in TER in diabetes. The second part of the thesis examines the role of the system in the hypertension of diabetic renal disease. Patients with elevated AER have increased resting plasma renin activity. Those with uncomplicated diabetes show an exaggerated blood pressure reponse to exercise. ACE inhibition reduces blood pressure in hypertensive patients and AER in both hypertensive and normotensive patients