[The effect of angiotensin-converting enzyme inhibitors on the progression of chronic renal failure].
SEVERAL MECHANISMS: The progression in renal failure first implies hemodynamic mechanisms and among which angiotensin II has a central role, but also an increase in proteinuria and the induction of many inflammatory and mitogenic mediators that enhance fibrosis (TGF-beta), an effect stimulating the thrombotic mechanism. Among these factors of progression in renal failure, hypertension and proteinuria are the two major factors. Proteinuria is "nephrotoxic" and leads to glomerular and tubulo-interstitial lesions. THE ROLE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS: Angiotensin-converting enzyme inhibitors (ACE) affect the different mechanisms that lead to glomerulosclerosis: antihypertensive effect, with the normalisation of blood pressure having demonstrated its determining role in the production of nephrosis in various epidemiological studies; hemodynamic effect with a decrease in glomerular capillary pressure, in the filtration fraction, and inhibition of the bradykinin deterioration; antiproteinuric effect superior to that of other anti-hypertensive drugs (excepting angiotensin II-receptor antagonists). Two indications ACE inhibitors have demonstrated their efficacy in slowing the progression of renal failure in two large pathological fields: diabetic nephropathy in which this effect is demonstrated in type I diabetes, although the results are not as obvious in type II diabetes in which the nephropathy is multi-factor. The recent French and American recommendations are that ACE inhibitors should be used in first intention in diabetic nephropathies and aimed at tight blood pressure control; non-diabetic nephropathies Two pivotal studies have demonstrated the efficacy of ACE inhibitors in nephropathies whatever their type. These data have led to propose ACE inhibitors in first intention in patients exhibiting chronic nephropathies, whether hypertensive or not THE COMBINATION WITH OTHER HYPERTENSIVE DRUGS: Calcium channel blockers have a beneficial trophic effect in renoprotection and can be combined with ACE inhibitors, particularly in the case of diabetic nephropathies. ACE inhibitors and angiotensin II-receptor antagonists have comparable effect on hemodynamics and glomerulosclerosis factors. Clinically, the decrease in proteinuria is identical. Endothelin antagonists have also been studied in renoprotection and appear to have a beneficial effect when combined with ACE inhibitors. GLOBALLY: ACE inhibitors remain the only treatment with demonstrated long-term efficacy in the progression of chronic renal failure. However, the concept of renoprotection needs to be widened to all the factors implied in the progression of chronic renal failure, and ACE inhibitors only represent one aspect of treatment. The role of angiotensin II-receptor antagonists, alone or combined, is clearly promising.
Bernadet-Monrozies
Pauline
P
Service de néphrologie, hypertension artérielle, dialyse et transplantation, Hôpital Rangueil, 31403 Toulouse.
Rostaing
Lionel
L
Kamar
Nassim
N
Durand
Dominique
D
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology; D004359:Drug Therapy, Combination; D016232:Endothelins / Q000037:antagonists & inhibitors; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D011507:Proteinuria / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D011945:Receptors, Angiotensin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D016232:Endothelins; D007211:Indoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D017311:Amlodipine; C052035:trandolapril; D014700:Verapamil; D000077405:Irbesartan