Hypertension Management in Chronic Kidney Disease: ACEIs/ARBs and Practical Issues (original) (raw)
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RAAS Blockade as First-Line Antihypertensive Therapy among People with CKD
Renin-Angiotensin System - Past, Present and Future, 2017
Hypertension among people with chronic kidney disease is highly prevalent and remains often poorly controlled. To adequately control blood pressure (BP), a combination antihypertensive drug therapy is often required. The choice of the appropriate antihypertensive regimen should be individualized according to the patient clinical characteristics, the severity of chronic kidney disease (CKD), the levels at which BP should be targeted and the presence or absence of proteinuria. In proteinuric CKD, solid evidence from large-scaled randomized trials suggest that agents blocking the reninangiotensin-aldosterone system (RAAS) should be the antihypertensive therapy of first choice, given their superiority over the other antihypertensive drug classes in reducing proteinuria and delaying nephropathy progression to end-stage-renal-disease (ESRD). In contrast, inhibition of the RAAS is shown to have no additional benefits towards renoprotection in people with non-proteinuric CKD. Combined RAAS blockade as an alternative approach to gain additive reduction in proteinuria and greater retardation of renal function decline is shown to be associated with increased risk of hypotension, serious hyperkalemia and acute kidney injury. In this chapter, we discuss the role of RAAS blockade as first-line antihypertensive therapy among people with proteinuric and non-proteinuric nephropathy, providing an overview of the evidence derived from large-scaled renal outcome trials.
Management of Hypertension in Patients with Chronic Kidney Disease and Diabetes Mellitus
The American Journal of Medicine, 2008
Treatment of patients at high risk for developing cardiovascular disease aims at controlling blood pressure, optimizing blood glucose levels, and providing renoprotection. Chronic kidney disease (CKD) and diabetes mellitus are prevalent causes of cardiovascular disease owing to associations with major cardiovascular risk factors, such as hypertension, and they are substantial health burdens. Even mild-to-moderate CKD and prehypertension increase cardiovascular risk. First-line agents for reducing cardiovascular risk are inhibitors of the renin-angiotensin system: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). In clinical trials, treatment of high-risk patients with ACE inhibitors and ARBs delays or prevents the onset of diabetes and prevents progression of renal disease and cardiovascular events, including cardiovascular mortality. Current evidence indicates that the clinical efficacy of these end points includes effects that may be beyond blood pressure reduction.
American Journal of Kidney Diseases, 2004
Hypertension is common in CKD, and is a risk factor for faster progression of kidney disease and development and worsening of CVD. Some antihypertensive agents also slow the progression of kidney disease by mechanisms in addition to their antihypertensive effect. 1.1 Antihypertensive therapy should be used in CKD to: 1.1.a Lower blood pressure (A); 1.1.b Reduce the risk of CVD, in patients with or without hypertension (B) (see Guideline 7); 1.1.c Slow progression of kidney disease, in patients with or without hypertension (A) (see Guidelines 8, 9,10). 1.2 Modifications to antihypertensive therapy should be considered based on the level of proteinuria during treatment (C) (see Guidelines 8, 9, 10,11). 1.3 Antihypertensive therapy should be coordinated with other therapies for CKD as part of a multi-intervention strategy (A). 1.4 If there is a discrepancy between the treatment recommended to slow progression of CKD and to reduce the risk of CVD, individual decision-making should be based on risk stratification (C). BACKGROUND The Joint National Committee (JNC) for Prevention, Detection, Evaluation and Treatment of High Blood Pressure issues regular reports that are meant to provide guidance for primary-care clinicians. The seventh report (JNC 7), issued in 2003, suggests stratification of risk for CVD in individuals with high blood pressure to determine the intensity of treatment. Individuals at highest risk should receive most intensive treatment, including prompt pharmacological therapy, a lower blood pressure goal, and use of specific antihypertensive agents for "compelling indications," including CKD. 5,5a Hypertension is common in CKD, affecting 50% to 75% of individuals. The Work Group for this K/DOQI Guideline on Hypertension and Antihypertensive Agents in CKD proposes recommendations for all patients with CKD, whether or not they have hypertension. Guideline 1 reviews the goals of antihypertensive therapy; multi-intervention strategies for CKD; and possible discrepancies between goals of slowing progression of CKD and reducing CVD risk. It concludes with a review of key recommendations of the guidelines and compares the recommendations to those made by the JNC 7, as well as with previous reports by the NKF and ADA. Limitations, implementation issues, and research recommendations are covered in subsequent guidelines. RATIONALE Definitions Antihypertensive therapy includes lifestyle modifications and pharmacological therapy that reduce blood pressure, in patients with or without hypertension. Lifestyle modifications include changes in diet, exercise, and habits that may slow the progression of CKD or lower the risk of CVD. These guidelines focus specifically on lifestyle modifications that lower blood pressure. Lifestyle modifications are discussed in more detail in Guideline 6. Pharmacological therapy includes selection of antihypertensive agents and blood pressure goals. Antihypertensive agents are defined as agents that lower blood pressure and are usually prescribed to hypertensive individuals for this purpose. Other agents may also lower blood pressure as a side-effect. It is important to note that antihypertensive agents may have salutary effects on CKD and CVD in addition to lowering systemic blood pressure, such as reducing proteinuria, slowing GFR decline, and inhibiting other pathogenetic mechanisms of kidney disease progression and CVD. General principles of pharmacological therapy and target blood pressure for reducing CVD risk are discussed in Guideline 7. "Preferred agents." Classes of antihypertensive agents that have beneficial effects on progression of CKD or reducing CVD risk, in addition to their antihypertensive effects, are defined as "preferred agents" for those conditions. Preferred agents for specific types of CVD are discussed in Guideline 7. In certain types of CKD, specific classes of antihypertensive agents, notably those that inhibit the renin-angiotensin system (RAS), are preferred agents for slowing progression of kidney disease. Thus, the guidelines recommend the use of specific classes of antihypertensive agents in certain types of CKD, even if hypertension is not present. These agents also reduce proteinuria and may be considered for this purpose as well. Preferred agents for CKD are discussed in Guidelines 8 through 10. ACE inhibitors and angiotensin receptor blockers are discussed in Guideline 11, and diuretics are discussed in Guideline 12. Strength of Evidence Patients with CKD are in the "highest-risk" group for CVD (Strong). Patients with CKD are at increased risk of CVD. Hypertension is a risk factor for CVD events in CKD. However, there have been few controlled trials to demonstrate the efficacy of blood pressure lowering to reduce the risk of CVD in CKD; therefore, the Work Group made recommendations for CKD based on extrapolation from evidence on the efficacy of antihypertensive therapy in the general population. Because of the high risk of CVD in CKD, the Work Group concluded that individuals with CKD should be included in the "highest-risk group" for implementation of antihypertensive therapy to reduce CVD risk. Table 42 shows recommendations from JNC 7 for the highest-risk group. Guideline 7 discusses the appropriate blood pressure target to reduce risk of CVD in the highest-risk group. Some classes of antihypertensive agents are preferred in certain types of CKD (Strong). Most patients with CKD experience progressive GFR decline over time. Hypertension is a risk factor for faster progression of kidney disease. In addition, some other modifiable risk factors (proteinuria and activity of the RAS) are also affected by antihypertensive therapy. RCTs demonstrate that some classes of antihypertensive agents (notably, those that inhibit the RAS) are "preferred agents" for slowing progression of specific types of CKD. In addition, for some types of CKD, the blood pressure goal recommended for CVD risk reduction in high-risk groups has been shown to slow the progression of CKD. Thus, the Work Group recommended that antihypertensive therapy in CKD also be guided by the type of kidney disease. Table 43 shows general recommendations to slow the progression of CKD. Guidelines 8 through 10 discuss specific types of CKD. Level of proteinuria and changes in the level of proteinuria may be a guide to modifications of antihypertensive therapy (Weak). Proteinuria is important in CKD for a number of reasons. It is a marker for kidney damage, a clue to the type (diagnosis of CKD), and a risk factor for faster progression of kidney disease and development of CVD, and it identifies patients who benefit more from preferred agents and a lower target blood pressure (Table 29). In addition, it has been hypothesized that changes in the level of proteinuria during treatment may be a surrogate widely used guidelines for treatment of individuals with hypertension and diabetes the two most common causes of CKD. During the Work Group s meetings, JNC 6 15 and ADA 2002 115,116 were available. Risk stratification (Table 47). JNC 6 suggested risk stratification of individuals with hypertension for therapeutic decisions. 15 Although JNC 7 simplified this classification, the Work Group found the concepts useful in its deliberations. There is a spectrum of risk from very high to low, and patients were classified into three general risk categories. Patients at "low risk" (Group A) were defined as those without pre-existing CVD or target organ damage, without diabetes, and with no other risk factors for CVD other than hypertension. Patients at "high risk" (Group B) were defined as those without CVD or target organ damage, without diabetes, but with one or more with other risk factors for CVD. Patients at "very high risk" (Group C) were defined as those with CVD, target organ damage, or compelling indications, such as diabetes and CKD. Because there are few studies of antihypertensive therapy on CVD in CKD and because patients with CKD are in the highest-risk category for CVD, the Work Group recommends extrapolating the results from studies in the general population and other highest-risk populations to CKD (see Guideline 7).
Treatment of Hypertension in Patients with Renal Disease
Cardiovascular Therapeutics, 2007
Management of hypertension in people with kidney disease is challenging and generally requires at least three different and complementary acting antihypertensive agents to achieve the recommended blood pressure goal by the JNC VI and WHO guidelines of <130/85 mmHg. This is also true for the recent blood pressure goal for diabetes of <130/80 mmHg recommended by both the National Kidney Foundation and American Diabetes Association for reduction of cardiovascular risk and preservation of kidney function. Commonly used combinations include an ACE inhibitor, which has compelling indications for use in people with kidney disease with a diuretic, generally a thiazide type agent. Angiotensin receptor blockers have clearly shown effectiveness for slowing nephropathy progression in Type 2 diabetes and clearly have a role as first-line agents in that disease. If additional therapy is required, either a beta blocker or calcium antagonist may be added to this antihypertensive 'cocktail'. Beta blockers are particularly effective in people with a high sympathetic drive, i.e. high pulse rates, to lower pressure and reduce cardiovascular risk. Moreover, in recent studies their benefits on kidney function both by reducing proteinuria and slowing decline of kidney function make them good agents to add in the appropriate clinical setting. Given recent data from an analysis of the NHANES III database showing only 11% of people being treated for hypertension with diabetic kidney disease have achieved the blood pressure goal of <130/85 mmHg, it's no wonder the incidence of people starting dialysis continues to climb. Physicians need to work harder and educate patients on the importance of achieving these lower blood pressure guidelines.
The impact of antihypertensives on kidney disease
F1000Research, 2017
Arterial hypertension and chronic kidney disease (CKD) are intimately related. The control of blood pressure (BP) levels is strongly recommended in patients with CKD in order to protect the kidney against the accompanying elevation in global cardiovascular (CV) risk. Actually, the goal BP in patients with CKD involves attaining values <140/90 mmHg except if albuminuria is present. In this case, it is often recommended to attain values <130/80 mmHg, although some guidelines still recommend <140/90 mmHg. Strict BP control to values of systolic BP around 120 mmHg was recently shown to be safe in CKD according to data from the SPRINT trial, albeit more data confirming this benefit are required. Usually, combination therapy initiated with an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEi) and commonly followed by the addition of a calcium channel blocker and a diuretic is needed. Further studies are required as well as new drugs in particular...
Blood Pressure, Hypertension, RAAS Blockade, and Drug Therapy in Diabetic Kidney Disease
Advances in Chronic Kidney Disease, 2014
Type 2 diabetes is the most common cause of CKD and ESRD in the United States and the Western world. Hypertension is prevalent in this cohort, and control of blood pressure is perhaps the most important risk factor to reduce CKD progression. The most recent evidence of blood pressure targets recommended by the Kidney Disease: Improving Global Outcomes and Kidney Disease Outcomes Quality Initiative guideline committees is less than 140/90 mmHg for all patients with CKD Q3 . There is some evidence, for those with 1 g or more of albuminuria, albeit weak, to support a blood pressure target of less than 130/80 mmHg. Multiple studies demonstrate that renin-angiotensin-aldosterone system (RAAS) blockers are important in reducing cardiovascular risk and progression of CKD in those with advanced proteinuric nephropathy. However, there is no evidence that they prevent nephropathy or that reduction in microalbuminuria alone is associated with a slowed nephropathy progression. The purpose of this article is to review the major studies that have evaluated cardiovascular and kidney endpoints in patients with diabetes and the role of RAAS blockers in the treatment of this disease.
Management of Hypertension in Chronic Kidney Disease
Chronic kidney disease (CKD) is an increasingly prevalent condition globally and is strongly associated with incident cardiovascular disease (CVD). Hypertension is both a cause and effect of CKD and affects the vast majority of CKD patients. Control of hypertension is important in those with CKD as it leads to slowing of disease progression as well as reduced CVD risk. Existing guidelines do not offer a consensus on optimal blood pressure (BP) targets. Therefore, an understanding of the evidence used to create these guidelines is vital when considering how best to manage individual patients. Nonpharmacological interventions are useful in reducing BP in CKD but are rarely sufficient to control BP adequately. Patients with CKD and hypertension will often require a combination of antihypertensive medications to achieve target BP. Certain pharmacological therapies provide additional BP-independent renoprotective and/or cardioprotective action and this must be considered when instituting therapy. Managing hypertension in the context of haemodialysis and following kidney transplantation presents further challenges. Novel therapies may enhance treatment in the near future. Importantly, a personalised and evidence-based management plan remains key to achieving BP targets, reducing CVD risk and slowing progression of CKD.
High Blood Pressure & Cardiovascular Prevention, 2021
With chronic kidney disease (CKD) being a global arising health problem, strategies for delaying kidney disease progression and reducing the high cardiovascular risk inherent to CKD, are the main objectives of the actual management of patients with kidney diseases. In these patients, the control of arterial hypertension is essential, as high blood pressure (BP) is a strong determinant of worst cardiovascular and renal outcomes. Achieving target blood pressures recommended by international guidelines is mandatory and often demands a multiple levels management, including several pharmacological and lifestyle measures. Even in the presence of adequate BP control, the residual cardiovascular risk remains high. In this respect, the recent demonstration that novel agents such as sodium glucose transporter 2 (SGLT2) inhibitors or the new non-steroidal mineralocorticoid antagonist finerenone can retard the progression of kidney diseases and reduce cardiovascular mortality on top of standard of care treatment with renin-angiotensin system inhibitors represent enormous progresses. These studies also demonstrate that cardiovascular and renal protection can be obtained beyond blood pressure control. Other promising novelties are still to come such as renal denervation and endothelin receptor antagonists in the setting of diabetic and non-diabetic kidney diseases. In the present review, we shall discuss the classic and the new aspects for the management of hypertension in CKD, integrating the new data from recent clinical studies.