Differences in Renal Outcomes with ACE Inhibitors in Type 1 and Type 2 Diabetic Patients: Possible Explanations

Abstract

In type 1 diabetic patients, ACE inhibitors exert a renoprotective effect which appears to be additional to, but not entirely independent of, changes in systemic blood pressure. This effect includes attenuation of albumin excretion rate (AER) as well as prevention or slowing of the rate of decline of the glomerular filtration rate (GFR). In type 2 diabetic patients, the results of ACE inhibition are more varied with some studies showing similar renoprotection to that observed in type 1 diabetes and others showing no additional effect to lowering of systemic blood pressure. This may be due to the diverse manifestations of the disease itself or to renal factors which may modify the response to ACE inhibitors. The major sytemic causes of diversity are variations in age, race and blood pressure. The major renal causes of diversity include changes in the relationship or ‘coupling’ of AER to onset of decline in GFR and a heterogeneity of renal ultrastructural changes in the glomeruli, tubules, interstitium and the renal vasculature. Factors that may be responsible for different renal responses to ACE inhibitors in type 2 diabetes include coexistence of coronary heart disease which may introduce survival bias in long-term studies, a lower specificity of microalbuminuria for diabetic nephropathy, early onset of a decline in GFR in hypertensive or normotensive patients at or prior to the onset of microalbuminuria, a greater contribution of arteriosclerotic changes in renal arteries to decline in renal function, a higher prevalence of nondiabetic renal disease, a higher prevalence of hypertension in the elderly and yet to be characterized genetic factors. These variants of type 2 diabetes may be expected to influence the response to ACE inhibitors either by altering the initial proteinuric response or by altering the hypotensive response. Future studies taking into account the above variables may help to determine the relative importance of the above factors in modifying the renal responses to ACE inhibitors and thereby leading to different renal outcomes in type 1 and type 2 diabetic patients. Such studies may also help to assess the relative importance of changes in systemic blood pressure and intrarenal effects as well as the role of hemodynamic versus structural factors in contributing to differences in renal outcome with ACE inhibitors in type 1 and type 2 diabetes.