Clinical Practice Guidelines on Hypertension

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This is the html version of the file Google automatically generates html versions of documents as we crawl the web. Page 1 K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease GUIDELINE 1: GOALS OF ANTIHYPERTENSIVE THERAPY IN CKD 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 a
  This is the html version of the file    Google automatically generates html versions of documents as we crawl the web. Page 1   K/DOQI Clinical Practice Guidelines on Hypertension and   Antihypertensive Agents in Chronic Kidney Disease GUIDELINE 1: GOALS OF ANTIHYPERTENSIVE THERAPY IN CKD   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) (seeGuideline   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) (seeGuidelines 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).   INTRODUCTION  CKD is a world-wide public health problem, with increasing incidence and prevalence, high cost,and poor outcomes. The major outcomes of CKD are loss of kidney function and development of CVD. Increasing evidence indicates that the adverse outcomes of CKD can often be prevented or delayed through early detection and treatment.Hypertension is both a cause and a complication of CKD; more than 50% to 75% of patientswith CKD have blood pressure >140/90 mm Hg. In addition, hypertension is a risk factor for  progression of kidney disease and for CVD. The goals of antihypertensive therapy in CKD are tolower blood pressure, reduce the risk of CVD, and slow progression of CKD. 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 Page 2   clinicians. The seventh report (JNC 7), issued in 2003, suggests stratification of risk for CVD inindividuals with high blood pressure to determine the intensity of treatment. Individuals athighest risk should receive most intensive treatment, including prompt pharmacological therapy,a lower blood pressure goal, and use of specific antihypertensive agents for compellingindications, including CKD. 5,5a Hypertension is common in CKD, affecting 50% to 75% of individuals. The Work Group for thisK/DOQI Guideline on Hypertension and Antihypertensive Agents in CKD proposesrecommendations for all patients with CKD, whether or not they have hypertension. Guideline 1reviews the goals of antihypertensive therapy; multi-intervention strategies for CKD; and   possible discrepancies between goals of slowing progression of CKD and reducing CVD risk. Itconcludes with a review of key recommendations of the guidelines and compares therecommendations to those made by the JNC 7, as well as with previous reports by the NKF andADA. Limitations, implementation issues, and research recommendations are covered insubsequent guidelines. RATIONALE    Definitions   Antihypertensive therapy includes lifestyle modifications and pharmacological therapy thatreduce 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 lifestylemodifications that lower blood pressure. Lifestyle modifications are discussed in more detail inGuideline 6.  Pharmacological therapy includes selection of antihypertensive agents and blood pressuregoals. 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 salutaryeffects on CKD and CVD in addition to lowering systemic blood pressure, such as reducing proteinuria, slowing GFR decline, and inhibiting other pathogenetic mechanisms of kidneydisease progression and CVD. General principles of pharmacological therapy and target blood pressure for reducing CVD risk are discussed inGuideline 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, aredefined as preferred agents for those conditions. Preferred agents for specific types of CVD arediscussed inGuideline 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. Theseagents also reduce proteinuria and may be considered for this purpose as well. Preferred agents Page 3   for CKD are discussed inGuidelines 8through10. ACE inhibitors and angiotensin receptor   blockers are discussed inGuideline 11, and diuretics are discussed inGuideline 12.  Strength of Evidence    Patients with CKD are in the highest-risk group for CVD (Strong). Patients with CKD are atincreased risk of CVD. Hypertension is a risk factor for CVD events in CKD. However, therehave been few controlled trials to demonstrate the efficacy of blood pressure lowering to reducethe risk of CVD in CKD; therefore, the Work Group made recommendations for CKD based onextrapolation 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 thatindividuals with CKD should be included in the highest-risk group for implementation of antihypertensive therapy to reduce CVD risk.Table 42shows recommendations from JNC 7 for the highest-risk group.Guideline 7discusses 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 sometypes of CKD, the blood pressure goal recommended for CVD risk reduction in high-risk groupshas been shown to slow the progression of CKD. Thus, the Work Group recommended thatantihypertensive therapy in CKD also be guided by the type of kidney disease.Table 43showsgeneral recommendations to slow the progression of CKD.Guidelines 8through10discuss 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 isa 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 benefitmore from preferred agents and a lower target blood pressure (Table 29). In addition, it has beenhypothesized that changes in the level of proteinuria during treatment may be a surrogate Page 4   outcome for kidney disease progression. The Work Group concluded that there is not yetsufficient evidence to confirm this hypothesis. However, it was the opinion of the Work Groupthat proteinuria should be monitored during the course of CKD, and that under somecircumstances it would be appropriate to consider modifications to antihypertensive therapy,such as a lower blood pressure goal or measures to reduce proteinuria, such as increasing thedosage of preferred agents and selection of additional antihypertensive agents (Table 44). Thesemeasures are discussed in more detail inGuidelines 8through11. In general, these measures should be undertaken in consultation with a kidney disease specialist. The Work Group stronglyrecommended further research on this topic.  Approach to hypertension and use of antihypertensive agents in CKD (Strong). Figure 28andTable 45describe a the general approach recommended by the Work Group to integrate goals of  lowering blood pressure, reducing CVD risk, slowing progression of kidney disease, andconsiderations regarding proteinuria. Fig 28. General approach to hypertension and use of antihypertensive agents in CKD.   Diamonds indicate decisions. Rectangles indicate actions. Superscripts refer to items listed   inTable 45. A more detailed approach to decision-making and protocols for action are   given in later sections.    Most patients with CKD will require multiple interventions to slow progression of CKD and     prevent development or worsening of CVD (Strong). Most patients with CKD have multiple risk  Page 5   factors for progression of kidney disease and for development or deterioration of CVD. 3,4 Optimal management of CKD requires coordination of antihypertensive therapy with other therapies, such as smoking cessation, lipid-lowering therapy, and management of diabetes, andother dietary and life-style modifications, which is best accomplished by a coordinated effortamong practitioners, either in an individual or a team setting 101,102 For example, the ADArecommends a multidisciplinary team approach for management of diabetes, 6 and some studiesshow improved outcomes for diabetic kidney disease, using a multidisciplinary approach todeliver multiple interventions.  103,104 The Work Group recommended coordination of antihypertensive therapy with other therapies for CKD and CVD as part of a multi-interventionstrategy, using the resources of a multidisciplinary team, if available. A multidisciplinary teamcould include one or more of the following in addition to the physician: nurse practitioner,registered nurse, registered dietitian, masters prepared social worker, pharmacist, and physicianassistant.  Individual decision-making is necessary to resolve discrepancies between recommendations    for slowing CKD progression and reducing CVD risk (Strong). The Work Group accepted the principle that recommendations should maximize net health benefits for the target population(seeAppendix 1). Having defined the goals for antihypertensive therapy to include slowing progression of CKD and reducing CVD risk in addition to lowering blood pressure, the Work Group searched for evidence in the target population for each clinical outcome. In general, therewere few studies that adequately assessed both outcomes; thus, the Work Group maderecommendations on the basis of separate studies on each outcome. This is a reasonableapproach, if the recommendations to slow progression of CKD and reduce risk of CVD agree;however, if there is a discrepancy between recommendations, this approach may not be adequate.Other approaches, such as decision analysis, with or without regard to cost, could be useful todetermine net health benefits in this situation. Page 6   In general, the Work Group found few examples of such discrepancies. However, it should benoted that most clinical studies (observational studies and controlled trials) do not provide anadequate framework for examining the possibility of conflicts. Nonetheless, there areinconsistent results among some recent controlled trials with regard to the beneficial effect of ACE inhibitors aside from their antihypertensive effect on slowing progression of CKD andreducing risk of CVD. 105-107 Pertinent results will be discussed in later guidelines, but somegeneral comments are appropriate here. In part, differences among studies may be related todifferences in study populations and definition and ascertainment of endpoints. For example,studies on the progression of CKD have included patients with either markers of kidney damage(eg, diabetic patients with proteinuria) or decreased GFR (eg, most studies of nondiabetic kidneydisease) and have carefully measured kidney function. On the other hand, studies of CVD risk reduction have generally excluded patients with elevated serum creatinine, did not routinelymeasure urine protein, and concentrated on ascertainment of CVD events. Thus, it is likely thatstudies on CKD enrolled patients at greater risk for progression of CKD than for CVD eventsand had greater statistical power to detect effects on CKD progression than on CVD events.Similarly, studies on CVD enrolled patients at greater risk for CVD events than for progressionof CKD and had greater statistical power to detect effects on CVD events than progression of CKD. Hence, the Work Group generally restricted the interpretation of these studies to the primary outcome, as specified in advance by the authors. Differences in study design arediscussed in an attempt to resolve discrepancies in findings and, in some studies, secondaryoutcomes are discussed. Overall recommendations are based on the sum of evidence, after takinginto consideration all these factors.In clinical practice, health-care providers must be concerned with all outcomes of care, not just a primary outcome. Health-care providers caring for patients with CKD routinely encounter  patients at high risk of both progression of CKD and CVD events and must make decisions aboutthe implementation of recommendations about lifestyle modifications, blood pressure targets,
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