[Which optimal antihypertensive bitherapy for kidney patients?]. 2007

Jean-François Bonne, and Irina Shahapuni, and Sébastien Mailliez, and Roxana Oprisiu, and Mohamed Temmar, and Gabriel Choukroun, and Ziad A Massy, and Albert Fournier
Service de néphrologie, CHU d'Amiens, hôpital Sud, avenue René-Laennec, 80054 Amiens cedex 01, France.

In this editorial review on the optimal antihypertensive treatment for chronic kidney disease (CKD) patients, we start with the controversy triggered by Casas et al., for proposing a bitherapy optimal not only for nephroprotection, but also for global cardiovascular protection. The incidence of cardiovascular complications are indeed much greater than the occurrence of end stage renal disease (ESRD) in these patients, so that their prevention has at least the same priority. We explain the huge amount of discordant papers, on the basis of methodology deficiencies in the studies aiming at evidencing the truth of 2 antinomic concepts underlying this controversy: 1) "The correction by antihypertensive drugs of the cardiovascular risk excess in hypertensive patients is exclusively related to their blood pressure lowering effect, the optimal blood pressure (BP) level being defined by epidemiologists at 115/75 mmHg"; 2) "Independently of BP lowering effect, antihypertensive drugs may have intrinsic, protective or deleterious, renal and cardiovascular effects which may be variable according to the target organ". We think that truth is conciliating and that both mechanisms should not be exclusive. However more rigorous studies are still needed to evidence it. Meanwhile we propose the optimal therapy by hypokaliemic diuretics (thiazides+/-loop diuretics according to glomerular filtration decline)+inhibitors of the angiotensin AT1-receptor (ACE inhibitors or AT1RB), in preference to the association of dihydropyridines with diuretics. This recommendation is strong however, only for CKD patients with macroproteinuria. The priority that we give to diuretic therapy is based on the evidence that this class confers good prevention against both heart failure and strokes, which is not the case for all AT1-inhibitors and dihydropyridines. Furthermore the diuretics are the drugs with the longest antihypertensive effect (many weeks) and their efficiency in CKD patients is proportional to the sodium depletion they initially induce and therefore to the dose (specially of the loop diuretics). Indeed volemia control is an incontrovertible factor for optimal BP control in renal insufficiency. As regards the use of betablockers, they should no more be considered as first drug for hypertension because they have the strongest diabetogenic effect. They should be used selectively for their specific cardiologic indications such as angina, heart failure, arythmia and as substitute for ACEI or AT1RB when general anesthesia is considered. Regarding the choice between ACEI and AT(1)RB, on the basis of indirect comparisons, we think that the latter may grant a comparable cardiac protection while giving a better cerebral protection. We shall have to wait the results of ONTARGET study to have or not the evidence for this preference. Finally, we want to stress the necessity to individualize the treatment by taking into account coexistence of cardiovascular complications and of other diseases, as well as the tolerance of the treatment (which may be influenced by seasons, in particular the canicula one), and the cost of the drugs.

UI MeSH Term Description Entries
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D002318 Cardiovascular Diseases Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM. Adverse Cardiac Event,Cardiac Events,Major Adverse Cardiac Events,Adverse Cardiac Events,Cardiac Event,Cardiac Event, Adverse,Cardiac Events, Adverse,Cardiovascular Disease,Disease, Cardiovascular,Event, Cardiac
D004232 Diuretics Agents that promote the excretion of urine through their effects on kidney function. Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000806 Angiotensin-Converting Enzyme Inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. ACE Inhibitor,ACE Inhibitors,Angiotensin Converting Enzyme Inhibitor,Angiotensin I-Converting Enzyme Inhibitor,Angiotensin-Converting Enzyme Inhibitor,Kininase II Inhibitor,Kininase II Inhibitors,Angiotensin I-Converting Enzyme Inhibitors,Angiotensin-Converting Enzyme Antagonists,Antagonists, Angiotensin-Converting Enzyme,Antagonists, Kininase II,Inhibitors, ACE,Inhibitors, Angiotensin-Converting Enzyme,Inhibitors, Kininase II,Kininase II Antagonists,Angiotensin Converting Enzyme Antagonists,Angiotensin Converting Enzyme Inhibitors,Angiotensin I Converting Enzyme Inhibitor,Angiotensin I Converting Enzyme Inhibitors,Antagonists, Angiotensin Converting Enzyme,Enzyme Antagonists, Angiotensin-Converting,Enzyme Inhibitor, Angiotensin-Converting,Enzyme Inhibitors, Angiotensin-Converting,II Inhibitor, Kininase,Inhibitor, ACE,Inhibitor, Angiotensin-Converting Enzyme,Inhibitor, Kininase II,Inhibitors, Angiotensin Converting Enzyme
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive

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