Diabetic Renal Disease: The Quest for Normotension—and Beyond

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Abstract
Over the past two decades there has been an increasing interest in hypertension as a risk factor for diabetic renal disease and in particular for the possibility of early antihypertensive intervention. Therefore, it would seem timely to review the history of hypertension in diabetes, with special reference to renal disease and the need for normotension, in a manner resembling glycaemic control. Elevated blood pressure (BP) associated with diabetes mellitus has been recognized since the beginning of the century and was initially particularly documented in association with the demonstration of the striking histological lesion in glomeruli, starting with the observation of Kimmelstiel and Wilson in 1936. These patients in many cases also showed hypertension, as confirmed in several subsequent reports, very similar to the studies of Kimmelstiel and Wilson. However, the development was hampered by the lack of effective antihypertensive agents and also by some who believed that elevated BP could be of importance to preserve renal function in these individuals. Indeed, it was suggested that reduction of BP could mean permanent deterioration in renal function. BP remained very high in the standard care of diabetic patients up to the middle 1970s. At this time it was documented that elevated BP was very closely related to development of diabetic renal disease in Type 1 (insulin-dependent) diabetic (IDDM) patients, and studies also showed a correlation between blood pressure and rate of progression. This correlation stimulated research in intervention, and indeed in the 1980s and 1990s several long-term studies reported that antihypertensive treatment can reduce the rate of decline in glomerular filtration rate (GFR) from about 12 ml min-1 yr-1 down to about 2 ml min-1 yr-1 in the most optimistic reports; usually a mean level of 2-5 ml min-1 yr-1 is achievable by antihypertensive treatment, in clinical situations where glycaemic control often is far from perfect. Many studies have also documented that BP starts to rise in the early phase of incipient diabetic nephropathy characterized by microalbuminuria. This is a stage with well-preserved GFR and therefore probably an ideal stage for intervention in these at risk patients. Many studies, in particular those employing angiotensin converting enzyme (ACE) inhibitors based on important pathophysiological concepts proposed by Brenner, have shown that microalbuminuria can be reduced or stabilized by early antihypertensive treatment, just as we see with optimized glycaemic control. ACE inhibitors have also been widely used in patients with overt nephropathy and the rate of decline in GFR has been reduced considerably.(ABSTRACT TRUNCATED AT 400 WORDS)