Chronic kidney disease (CKD) is a major public health issue worldwide. Hypertension is the first risk factor in patients with CKD for mortality, cardiovascular disease and end-stage renal disease. It's now well established that lowering blood pressure (BP) reduces renal and cardiovascular complications in this high-risk population. In the general population, in addition to lifestyle interventions, the strategy to initiate and escalate a BP-lowering drug treatment is well described. The drug therapies recommended to achieve optimal BP control in the general population are the following: blockers of the renin-angiotensin system (angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)), diuretics (thiazides and thiazide-like diuretics), and calcium channel blockers. For patients with CKD, the guidelines advise to start the BP-lowering agent with ACEi or ARB, but then, there is no strong evidence to support the preferential use of any particular agent in controlling BP and the results of clinical trials are discordant. In the NephroTest cohort, a French cohort of patients with CKD stage 1 to 5, among 2015 patients, 1782 had hypertension, only 54% had a diuretic and 44% had uncontrolled hypertension. In this cohort, extracellular fluid (ECF) overload was an independent determinant of hypertension, uncontrolled hypertension and apparent treatment resistant hypertension. In the same cohort, ECF overload was independently associated with end-stage kidney disease and death. Our hypothesis is that patients with CKD and uncontrolled hypertension are fluid overloaded and that the second line of treatment after an ACEi or an ARB should be a diuretic. We hypothesize that a specific algorithm to lower BP in patients with moderate to severe CKD based on diuretics will be more effective in term of cardiovascular event, mortality and evolution to end-stage kidney disease as compared to standard of care.
Male or female >=18 years with a clinical frailty score ≤5 for patient aged over 80
Advanced or moderate chronic kidney disease (eGFR 15 to 44.9 mL/min/1.73m² using CKD-EPI formula)
Arterial hypertension treated with at least one blood pressure lowering drug therapy among blockers of the renin-angiotensin system (ACEi or ARB), at the maximal posology tolerated by the patients stable since at least one month. Other blood pressure lowering drug therapies are tolerated in combination with or in the event of intolerance to ACE inhibitors or ARBs.
Uncontrolled office BP
Patient following any measures of legal presentation
Pregnant or breastfeeding woman
woman of childbearing without a highly effective contraceptive measure (combined or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device or intrauterine hormone-releasing system)
Clinical signs of hypovolemia
Parallel
Antihypertensive algorithm
DrugAntihypertensive algorithm based on diuretics agents
Standard of care
Drugstandard of care management for antihypertensive therapy intensification
End stage kidney disease
The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality
eGFR decline of at least 40%
The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality
Cardiovascular events
The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality
All cause mortality
The primary endpoint is a time to event outcome, considering the following composite endpoint: * End stage kidney disease * eGFR decline of at least 40% * Cardiovascular events among myocardial infarction, heart failure, hospitalization and stroke * All cause mortality
Time to end-stage kidney disease
All components of the composite endpoint will be assessed separately
Time to eGFR decrease of at leat 40%
All components of the composite endpoint will be assessed separately
Time to the first cardiovascular event among myocardial infarction, heart failure, hospitalization and stroke
All components of the composite endpoint will be assessed separately
All-cause mortality
All components of the composite endpoint will be assessed separately
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