Renal protection in hypertensive patients: selection of antihypertensive therapy.Drugs. 2005; 65 Suppl 2:29-39.D
Hypertension is common in chronic renal disease and is a risk factor for the faster progression of renal damage, and reduction of blood pressure (BP) is an efficient way of preventing or slowing the progression of this damage. International guidelines recommend lowering BP to 140/90 mm Hg or less in patients with uncomplicated hypertension, and to 130/80 mm Hg or less for patients with diabetic or chronic renal disease. The attainment of these goals needs to be aggressively pursued with multidrug antihypertensive regimens, if needed. The pathogenesis of hypertensive renal damage involves mediators from various extracellular systems, including the renin-angiotensin system (RAS). Proteinuria, which occurs as a consequence of elevated intraglomerular pressure, is also directly nephrotoxic. As well as protecting the kidneys by reducing BP, antihypertensive drugs can also have direct effects on intrarenal mechanisms of damage, such as increased glomerular pressure and proteinuria. Antihypertensive drugs that have direct effects on intrarenal mechanisms may, therefore, have nephroprotective effects additional to those resulting from reductions in arterial BP. Whereas BP-lowering effects are common to all antihypertensive drugs, intrarenal effects differ between classes and between individual drugs within certain classes. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have beneficial effects on proteinuria and declining renal function that appear to be mediated by factors additional to their effects on BP. These RAS inhibitors are recommended as a first-line antihypertensive approach in patients with chronic kidney disease. The addition of diuretics and calcium channel antagonists to RAS inhibitor therapy is also considered to be a rational strategy to reduce BP and preserve renal function. Calcium channel antagonists are a highly heterogeneous class of compounds, and it appears that some agents are more suitable for use in patients with chronic renal disease than others. Manidipine is a third-generation dihydropyridine (DHP) calcium channel antagonist that blocks both L and T-type calcium channels. Unlike older-generation DHPs, which preferentially act on L-type channels, manidipine has been shown to have beneficial effects on intrarenal haemodynamics, proteinuria and other measures of renal functional decline in the first clinical trials involving hypertensive patients with chronic renal failure. Preliminary results from a trial in diabetic patients who had uncontrolled hypertension and microalbuminuria despite optimal therapy with an ACE inhibitor or an ARB suggest that manidipine may be an excellent antihypertensive drug in combination with RAS inhibitor treatment in order to normalise BP and albumin excretion in patients with diabetes.