Effects of Angiotensin-Converting Enzyme Inhibition versus Conventional Antihypertensive Therapy on the Glomerular Filtration Rate

Abstract

Antihypertensive treatment has been shown to slow down the decline in glomerular filtration rate (GFR) with time. This has been most extensively studied in patients with diabetic nephropathy and, to some extent, with other forms of renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. This important aspect of antihypertensive treatment has not been studied previously in patients with essential hypertension. Preliminary results regarding the effects of two different antihypertensive therapies on the loss of GFR with time, determined with ⁵¹Cr-EDTA clearance after 6, 12, and 24 months of treatment, are presented here. The GFR was assessed in a prospective, randomized, double-blind trial in 257 patients with essential hypertension. All had a normal renal function, and none had diabetes mellitus or glucosuria. The two therapeutic modalities were the ACE inhibitor cilazapril and the β-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering the systolic blood pressure. However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure after 6, 12, and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months, the reduction in GFR was 1.0 (cilazapril) vs. 4.0 (atenolol) ml/min × 1.73 m² (p < 0.01). After 12 months the corresponding changes were 2.0 vs. 4.5 ml/min × 1.73 m² (p < 0.05) and after 24 months 3.0 vs. 4.0 ml/min × 1.73 m² (n.s.). These results indicate that an ACE-inhibitor-based antihypertensive therapy with cilazapril in patients with essential hypertension prevents the decline in GFR with time better than a β-blocker-based regimen after 6 and 12 months of treatment. Thus, the advantage of ACE inhibition in this regard, which has previously been shown in patients with diabetic nephropathy, holds true also in essential hypertension.

Improving Antihypertensive Agent Selection to Promote Nephroprotection

“…Elevated intraglomerular pressure is a direct result of the tonic constriction of the efferent arteriole caused by Ang II, an effect which is increased by diuretics and ameliorated by ACE inhibitors and ARBs. For an equal reduction of systemic blood pressure, there is less reduction in GFR with ACE inhibitors and ARBs than with other antihypertensive medications [10][11][12][13]. The favorable effects of ACE inhibitors and ARBs are due also to antiproliferative properties (e.g., blockade of the growth-stimulating factor Ang II).…”