Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function

Abstract

A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system.

Influence of Genetic Polymorphisms of the Renin-Angiotensin System on IgA Nephropathy

“…Treatment with ACE inhibitors has been shown to reduce proteinuria [50]and slow the rate of progression of IgAN [51]but there is considerable variation in the response of individual patients [52]. In consistency to our findings a greater reduction of proteinuria in the ACE-D allele was demonstrated in patients with IgAN [28], diabetic nephropathy [53]and chronic renal disease resulting from a variety of causes [54, 55].…”

Effect of Angiotensin Converting Enzyme Inhibition by Perindopril on Proteinuria of Primary Renal Diseases

“…Indeed, in 1 placebo-treated patient, who had urinary protein excre tion of 15.1 g/24 h at the end of the placebo period, responded to perindopril with a fall in urinary protein excretion to 0.60 g/24 h after 4 months of therapy. Sup port for an effect of the initial level of urinary protein excretion on the antiproteinuric effect of ACE inhibitors is found in the published reports [8,10,11,13,17,18], In all these studies, a variety of ACE inhibitors, such as captopril, enalapril, fosinopril, lisinopril, were effective in reducing proteinuria when the urinary protein excre tion was modest ranging from a mean of 1.79 ± 1.2 to 7.5 + 1.9 g/24 h. It is of interest that in the study of Hceg ct al. [8], 12 of their 13 patients had modest proteinuria and responded to treatment with lisinopril, while the 13th patient who had urinary protein excretion of 12.4 g/ 24 h did not respond to therapy.…”

“…It is of interest that all the responders to perindopril were fe males while 4 of the 5 nonresponders were males, raising the theoretical possibility that the gender of the patient may modify the response to the drug. However, this seems unlikely since the antiproteinuric effect of other ACE inhibitors was not related to gender of the patient [10,11,13]. Finally, the responder patients had signifi cantly (p < 0.01) lower urinary protein excretion (6.1 ± 1.0 g/24 h) at the start of the study than the nonresponder (13 ± 2.2 g/24 h), suggesting that the initial degree of proteinuria may influence the response to perindopril but not necessarily predict the efficacy of the drug.…”

Nitrendipine and amlodipine mimic the acute effects of enalapril on renal haemodynamics and reduce glomerular hyperfiltration in patients with chronic kidney disease

“…Any substance that not only reduces systemic vascular resistances, but also induces preferential dilatation of the efferent arteriole, could thus cause a reduction in glomerular capillary pressure and in the incidence of glomerular sclerosis. 4,5 The theory that glomerular hypertension has a fundamental role in the progression of renal injury justifies the continuing search for treatment regimens that may succeed in reducing this hypertension. Assuming that in humans with chronic kidney disease, the onset of glomerular hypertension in the nephrons of the residual renal parenchyma might predispose toward progression of renal damage, antihypertensive drugs could exert an important effect on the glomerular haemodynamics of nephrons spared by the initial pathogenic noxae.…”