State of the art lecture: pharmacological intervention for the reduction of progression of diabetic nephropathy - abstract

Reduction of bloodpressure has been known, from the work of Parving et al (1987), to reduce the rate of decline of renal function in the nephropathy associated with Type-1 diabetes mellitus (IDDM), using conventional anti-hypertensive agents. More recently, interest in angiotensin-converting enzyme inhibitors (ACE-Is), and calcium channel blockers (CCBs) in the treatment of diabetic nephropathy, has been forthcoming. In diabetic nephropathy, induced in rats by streptozotocin, ACE-Is clearly alter renal haemodynamics and reduce proteinuria. Reduction of proteinuria is also seen in humans with diabetic nephropathy, and there is a suggestion of preservation of renal function, although no long-term studies have been published. Two studies are underway in non-hypertensive microalbuminuric subjects, but these have also not been published. The group of ACE-Is appears to have similar action in reducing proteinuria in diabetic nephropathy, but the same cannot be said for the CCBs. They differ in their action in reducing proteinuria, and dilitiazem may stand alone in reducing proteinuria in human diabetic nephropathy. Debate continues on the mechanism for reduction in proteinuria. Amelioration in systemic hypertension plays a role for all classes of antihypertensive drugs used, but the ACE-Is may alter glomerular permselectivity and thereby bring about reduction in proteinuria. Dietary reduction or protein intake may also play a protein preserving renal function as may reduction of lipids (AU)

The effects of blood pressure treatment on the kidney in patients with diabetes mellitus - abstract

Diabetes mellitus is the commonest cause of end-stage renal disese today, and both metabolic and haemodynamic factors, including systemic hypertension and intraglomerular hypertension, are important in the pathogenesis of Diabetic Nephropathy. It is now generally accepted that hypertension can contribute to a progressive deterioration in renal function, and that treatment of hypertension can retard this rate of decline. There are, however, conflicting results with regard to the effects of specific antihypertensive agents on the kidney in humans. We recently did a meta-analysis of 100 investigations of measurements of changes in blood pressure levels, glomerular filtration rate (GFR), renal blood flow and/or protein excretion in patients with diabetes mellitus. ACE inhibitors, calcium antagonists and beta blockers were each shown to have a beneficial effect on blood pressure levels which was associated with a proportional improvement in GFR. However, only ACE inhibitors were associated with an improvement in GFR and proteinuria that was additive to, and statistically independent from, improvement due to bloodpressure. Most of the studies were less than one year in duration and did not examine the impact on renal histology. It is therefore possible that the effects of ACE inhibitors were acute and functional rather than long-term and structural. Since this meta-analysis, there have been five long-term (greater than one year) looking at the rate of decline of GFR with blood pressure treatment in diabetes mellitus. Although some investigators found some improvement in the rate of decline of GFR when using Enalapril, others found no difference when using ACE inhibitors compared to other antihypertensive agents. There may actually have been an early acute decline of GFR when using ACE inhibitors that was followed by a reduced long-term rate of decline. Again, renal histology was not examined but the rate of end-stage renal disease was significantly less with Captopril compared to controls in the study where this was looked at, even though the numbers were small. The potential renoprotective effects of an antihypertensive agent should not be the only criteria used to determine its suitability for use in patients with diabetes mellitus. Indeed, some agents may increase or decrease the risk for atherosclerotic cardiovascular disease as well as cause alterations in serum electrolytes, leading to adverse outcome (AU)