Effect of Angiotensin-Converting Enzyme and Calcium Channel Inhibition on Progression of IgA Nephropathy

Abstract

Recent attention has been focused on the role of glomerular haemodynamic alterations in the progression of IgA nephropathy (IgAN) and other forms of chronic glomerulonephritis. In particular, glomerular capillary hypertension has been suggested to play an important role in this process [I]. Angiotensin-converting enzyme inhibitors (ACEI) preferentially dilate the efferent glomerular arteriole thereby lowering glomerular capillary pressure and studies in experimental animals [2] and man [3] have now documented improvement in the rate of decline of renal function after treatment with ACE!. However, it is not clear whether such benefits of ACEI on renal failure in man is disease specific. Recent evidence has demonstrated that the correlation between improved renal function and lowering of glomerular capillary pressure is not consistent and indeed the protective effects of ACEI do not necessarily correlate with either control of systemic blood pressure [4] or with glomerular capillary pressure [5]. Moreover, ACEI appear to stop hypertrophy of nonrenal blood vessels independent of their vasodilatory effects [6]. Glomerular capillary hypertension may therefore be a consequence of glomerular damage rather than the reverse.Most trials of ACEI therapy aimed at assessing the effect on progressive renal disease have used conventional 'triple' therapy (~-blocker, diuretic, vasodilator) as a control group. However, relatively few prospective, randomized, control studies have compared ACEI with calcium antagonists (CA) which have many properties of an 'ideal' antihypertensive, particularly in view of their lack of adverse metabolic effects. These drugs lower blood pressure by reducing calcium

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

“…It has been suggested that AngII-induced mesangial cell contraction with efferent arteriolar vasoconstriction initiates intraglomerular hypertension and may eventually lead to enhanced matrix formation and renal fibrosis after increased synthesis of TGF-␤ (12). The beneficial effects of either angiotensin-converting enzyme (ACE) inhibitors (ACEI) or AngII subtype 1 (AT 1 ) receptor antagonists on proteinuria and creatinine clearance (independent of BP reduction) highlight the importance of this system in IgAN (13,14). In this study, we explore whether pIgA1 isolated from patients with IgAN exerts any stimulatory effect on the RAS of mesangial cells, resulting in increased synthesis of TGF-␤.…”

Circadian Blood Pressure Changes and Cardiac Abnormalities in IgA Nephropathy

“…inhibition of cell proliferation, reduction of intraglomerular pressure) [24][25][26][27]. Therefore, in the treatment of hypertension developing in chronic GN, an ACEI should be the drug of choice, which may have to be supplemented with a calcium channel blocker, provided our choice is not influenced by other factors.…”

Treatment of Hypertension in Chronic Renal Insufficiency.

“…In addition to the prognostic values in histopathological alterations, high blood pressure is an important negative prognostic marker in IgA nephropathy and should be treated early in the course (21). Conversly, antihypertensive treatment ameliorates the progression of renal dysfunction in patients with IgA nephropathy (22). Cattran et al showeda retrospective analysis comparingangiotensin-converting enzymeinhibitors in 27 patients to other treatment in 55 and no treatment in 33 patients (23).…”