PRESSURE AND KIDNEY

Several randomized studies have investigated the effects of antihypertensive treatment by examining various indicators of renal function, such as microalbuminuria, albuminuria, glomerular filtration and the end stages of renal disease in diabetic patients without diabetes or simply hypertension. Due to the heterogeneity of clinical conditions, endpoints, the size and statistical power of studies, the results have not been the subject of meta-analysis, as evidenced by the criticism that accompanied the publication of a recent meta-analysis on the subject probably the best approach is to analyze the results available individually and critically.

An important objective of antihypertensive therapy in renal patients is to reduce blood pressure below the threshold for patients with uncomplicated hypertension, ie below 130/80 mmHg. But do not seem to evidence in this regard. Much of the information derived from a trial, the MDRD, which had the peculiarity of the long follow-up. The results of this trial showed, the group of patients with diabetic nephropathy is not where you are in therapy achieved average blood pressure <92 mmHg (ie values <120/80 mmHg), decreased progression of renal disease compared with that the average pressure was <107 mmHg (ie <140/90 mmHg). Results of other trials in which they were achieved the same goal pressure in diabetic and nondiabetic patients have not confirmed this trend. In a further trial, which evaluated normotensive diabetic subjects, where blood pressure were reduced by valsartan below 120/80 mmHg, it could not show any effect on creatinine clearance in the group receiving a more aggressive treatment (target pressure <120/80 mm.Hg).
In contrast, the urinary excretion of protein is positively influenced by more aggressive antihypertensive treatment. In another study, conducted in nondiabetic kidney disease, it was noted that the greater blood pressure reduction, obtained by the calcium channel blocker / ACE inhibitor, did not reduce the progression of renal dysfunction or proteinuria. Dell'MDRD Positive results were also confirmed by a retrospective analysis dell'IDNT and 11 trials conducted in non-diabetic nephropathy. The analysis of these studies has been inferred the benefit related to systolic blood pressure reduction to <120 mm Hg. One may conclude that the controversy on the pressure to achieve goals in diabetic patients is unnecessary, whereas the information available has confirmed the benefit (particularly in terms of cardiovascular events) associated with greater blood pressure reduction, even reaching values <130 / 90 mmHg.

Several randomized trials have evaluated the properties nephroprotective of different antihypertensive agents, particularly ACE inhibitors and ARBs. In addition, numerous studies have compared the effects of active therapy (receptor blockers, ACE inhibitors and diuretics ACEinibitore or low dose) versus placebo on progression of renal disease, the deterioration in creatinine and microalbuminuria / proteinuria in patients with diabetic nephropathy and non-diabetic. Effect nephroprotective (less development of proteinuria) compared to placebo was also described for spironolactone. In all placebo-controlled studies, except one, has been shown that the properties nephroprotective of antihypertensive therapy are more pronounced in the presence of a greater blood pressure control. In fact, even in the Syst-Eur study, the nitrendipina has been able to provide better renal protection compared to placebo.

Less conclusive results emerge from the trials that compared active drugs with each other. Two studies, one conducted in diabetic nephropathy patients with proteinuria and the other in non-diabetic kidney disease, have shown the superiority of the ACE inhibitor and receptor blockers compared with calcium in slowing the progression of kidney disease or increase in values plasma creatinine. However, a subanalysis of the ALLHAT study that included only the subgroup of hypertensive patients with impaired renal function (data on proteinuria are not known) have failed to show significant differences between drugs (diuretics, calcium channel blockers, ACE inhibitors).

Although studies aimed at assessing the effects of treatment on glomerular filtration rate did not provide unequivocal results. Only one study has shown beneficial effects of the ACE inhibitor compared with beta-blocker or calcium. All other studies have not observed significant differences between ACE inhibitors and calcium channel blockers or beta blockers or angiotensin receptor blockers or calcium binding / diuretics In another study, calcium channel blocker and diuretic produced results very similar. Studies that have compared the effects of different classes of antihypertensive agents on microalbuminuria or proteinuria have provided more convincing results. And 'demonstrated a greater efficacy of such an ARB on proteinuria compared with a beta blocker, a calcium channel blocker, or a thiazide diuretic. Other studies have also shown the superiority of an aldosterone antagonist and an ACE inhibitor compared with a calcium channel. These results, however, were not confirmed by three other studies in which comparable efficacy was observed between ACE inhibitors, calcium channel blockers and diuretics.

Some more recent studies that have compared the combination ARB / ACE inhibitor than individual monotherapy, results have provided some interest. The co-operative study showed a greater reduction in the progression of nondiabetic renal disease in patients in combination therapy compared with monotherapy, but does not find significant differences in pressure between groups. Other studies have shown a greater antiproteinuric effect when it was set to a combination therapy can exert antihypertensive effects most marked This is confirmed by evidence that if ACE inhibitors are titrated to achieve the same blood pressure reduction induced by combination therapy The antiproteinuric effect was similar in both groups. A recent meta-analysis that included data from all published studies, confirms the greater antiproteinuric effect of combination therapy, and its antihypertensive effect more pronounced. Two small studies have shown that high-dose angiotensin receptor blockers may have additive antiproteinuric effects than standard dose without causing further blood pressure reduction. These results, however, must be confirmed by larger clinical studies.

 

>>>see first page

>>>see also RICERCA