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).
CKD is a world-wide public health problem, with increasing incidence and prevalence, high cost, and poor outcomes. 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. 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. Pharmacological therapy includes selection of antihypertensive agents and blood pressure goals.
Level of proteinuria and changes in the level of proteinuria may be a guide to modifications of antihypertensive therapy (Weak). Most patients with CKD will require multiple interventions to slow progression of CKD and prevent development or worsening of CVD (Strong). Individual decision-making is necessary to resolve discrepancies between recommendations for slowing CKD progression and reducing CVD risk (Strong). In addition to the JNC, several organizations have issued recommendations for blood pressure management in CKD.
Diet, exercise, and education remain the foundation of all type 2 diabetes treatment programmes. After metformin, it is reasonable to consider combination therapy with an additional 1-2 oral or injectable agents with the objective of minimising side-effects where possible. For many patients insulin therapy alone or in combination with other agents will ultimately be required to maintain glucose control. All treatment decisions, where possible, should take into account the patient’s preferences, needs and values.
Diabetes may be diagnosed based on HbA1c criteria or plasma glucose criteria, either the fasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral glucose tolerance test (OGTT).
For all patients, particularly those who are overweight or obese, testing should begin at age 45 years. Two primary techniques are available to assess the effectiveness of glycaemic control: Patient self-monitoring of blood glucose (SMBG) or interstitial glucose and A1C. Patients on multiple-dose insulin or insulin pump therapy should perform SMBG prior to meals and snacks, occasionally postprandially, at bedtime, prior to exercise, when they suspect low blood glucose, after treating low blood glucose until they are normoglycaemic, and prior to critical tasks such as driving. Initial therapy: Most patients should begin with lifestyle changes – healthy eating, weight control, increased physical activity, and diabetes education. Advancing to dual combination therapy: If the HbA1c target is not achieved after ~3 months with metformin, there are six drug choices including a second oral agent (sulfonylurea, TZD, DPP-4 inhibitor, or SGLT2 inhibitor), a GLP-1 receptor agonist, or basal insulin.
Advancing to triple combination therapy: Evidence suggests that there is some advantage in adding a third noninsulin agent to a two-drug combination not achieving the glycaemic target.
Do you agree that private hospitals should be paid via the NTPF to cut public hospital waiting lists? Some antihypertensive agents also slow the progression of kidney disease by mechanisms in addition to their antihypertensive effect.
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. Antihypertensive agents are defined as agents that lower blood pressure and are usually prescribed to hypertensive individuals for this purpose.
Figure 28 and Table 45 describe a the general approach recommended by the Work Group to integrate goals of lowering blood pressure, reducing CVD risk, slowing progression of kidney disease, and considerations regarding proteinuria. The Work Group accepted the principle that recommendations should maximize net health benefits for the target population (see Appendix 1). However, it should be noted that most clinical studies (observational studies and controlled trials) do not provide an adequate framework for examining the possibility of conflicts. For example, should a patient with Stage 3 CKD due to Type 1 diabetes, a recent myocardial infarction, and Stage 1 hypertension be treated with an ACE inhibitor, beta-blocker, or diuretic? Previous recommendations by the NKF and other groups are listed in Table 46.1,15,108-121 Guidelines for CVD risk reduction in individuals without CKD are reviewed in Guideline 7. 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.
Diabetes may be identified in seemingly low risk individuals who happen to have glucose testing, in symptomatic patients, and in higher-risk individuals who are tested because of a suspicion of diabetes. When lifestyle efforts alone have not achieved or maintained glycemic goals, metformin monotherapy should be added at, or soon after, diagnosis (in patients intolerant, or with contraindications for, metformin, select initial drug from other treatment options).
Increasing evidence indicates that the adverse outcomes of CKD can often be prevented or delayed through early detection and treatment. The goals of antihypertensive therapy in CKD are to lower blood pressure, reduce the risk of CVD, and slow progression of CKD. 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.
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).
A multidisciplinary team could include one or more of the following in addition to the physician: nurse practitioner, registered nurse, registered dietitian, masters prepared social worker, pharmacist, and physician assistant. 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. All classes of agents may be indicated, but if the blood pressure is too low, which agents should be used preferentially?
There is a spectrum of risk from very high to low, and patients were classified into three general risk categories.
Shared decision making with the patient is important to help in the selection of therapeutic option. Since diabetes is associated with progressive beta-cell loss, many patients, especially those with long-standing disease, will ultimately need to be transitioned to insulin. 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. 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. Thus, the guidelines recommend the use of specific classes of antihypertensive agents in certain types of CKD, even if hypertension is not present.
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.
In addition, some other modifiable risk factors (proteinuria and activity of the RAS) are also affected by antihypertensive therapy. In addition, it has been hypothesized that changes in the level of proteinuria during treatment may be a surrogate outcome for kidney disease progression. In general, there were few studies that adequately assessed both outcomes; thus, the Work Group made recommendations on the basis of separate studies on each outcome.
In part, differences among studies may be related to differences in study populations and definition and ascertainment of endpoints.
Where recommendations are discrepant, health-care providers must make decisions to maximize the net health benefits for the individual patient. In this discussion, the focus is on recommendations by JNC and ADA because these are the most widely used guidelines for treatment of individuals with hypertension and diabetesthe two most common causes of CKD. These definitions and goals do not differ according to age (among adults), gender, or race. The choice is based on patient and drug characteristics, with the over-riding goal of improving glycaemic control while minimising side-effects.
Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Position statement of the American Diabetes Association and the European Association for the Study of Diabetes.
Limitations, implementation issues, and research recommendations are covered in subsequent guidelines.
General principles of pharmacological therapy and target blood pressure for reducing CVD risk are discussed in Guideline 7. The Work Group concluded that there is not yet sufficient evidence to confirm this hypothesis. This is a reasonable approach, 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. 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 kidney disease) and have carefully measured kidney function. The Work Group recommends that such individual decision-making be based on risk stratification. Lifestyle modification is recommended for 6 to 12 months, followed by antihypertensive therapy if blood pressure remains above goal. 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.
However, it was the opinion of the Work Group that proteinuria should be monitored during the course of CKD, and that under some circumstances 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 the dosage of preferred agents and selection of additional antihypertensive agents (Table 44).
A more detailed approach to decision-making and protocols for action are given in later sections. Other approaches, such as decision analysis, with or without regard to cost, could be useful to determine net health benefits in this situation. On the other hand, studies of CVD risk reduction have generally excluded patients with elevated serum creatinine, did not routinely measure urine protein, and concentrated on ascertainment of CVD events. In general, the selection of antihypertensive therapy should be directed to the clinical condition that is most likely to occur and that has the most serious consequences on overall survival and quality of life of the individual patient. The recommended initial antihypertensive agent is generally a diuretic, in combination with an ACE inhibitor, ARB, ß-adrenergic blocker, or a calcium-channel blocker if more than one agent is necessary to reach the target blood pressure. In using triple combinations the essential consideration is obviously to use agents with complementary mechanisms of action. ACE inhibitors and angiotensin receptor blockers are discussed in Guideline 11, and diuretics are discussed in Guideline 12. Thus, the Work Group recommended that antihypertensive therapy in CKD also be guided by the type of kidney disease. Thus, it is likely that studies on CKD enrolled patients at greater risk for progression of CKD than for CVD events and had greater statistical power to detect effects on CKD progression than on CVD events. Clinical practice guidelines cannot substitute for individual decision-making in patients with complex medical problems. 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). In general, these measures should be undertaken in consultation with a kidney disease specialist. Similarly, studies on CVD enrolled patients at greater risk for CVD events than for progression of 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 are discussed in an attempt to resolve discrepancies in findings and, in some studies, secondary outcomes are discussed.
Overall recommendations are based on the sum of evidence, after taking into consideration all these factors.
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