Guideline 2_ Evaluation of Patients With Ckd or Hypertension 1

8/10/2019 Guideline 2_ Evaluation of Patients With Ckd or Hypertension 1

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12/15/2014 GU ID ELIN E 2: EVALU AT ION OF PAT IEN TS W ITH C KD OR H YPER TEN SION

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NKF K/DOQI GUIDELINES

Executive Summaries| Anemia| Hemodialysis| Peritoneal Dialysis|Vascular Access| Nutrition| CKD 2002 | Dyslipidemias| Bone Metabolism

| Hypertension and Antihypertensive Agents | History of K/DOQI

K/DOQI Clinical Practice Guidelines on Hypertension and AntihypertensiveAgents in Chronic Kidney Disease

GUIDELINE 2: EVALUATION OF PATIENTS WITH CKD OR HYPERTENSION

Careful initial evaluation and frequent re-evaluation are essential for effective treatment ofhypertension and use of antihypertensive agents in CKD. Because CKD and hypertension are often

present together and both are generally asymptomatic, Guideline2 considers evaluations ofpatients with either condition.

2.1 Blood pressure should be measured at each health encounter (A).

2.2 Initial evaluation should include the following elements:

2.2.a Description of CKD

2.2.a.i Type (diagnosis), level of GFR, and level of proteinuria (Table 49)(A)

2.2.a.ii Complications of decreased GFR (A)

2.2.a.iii Risk for progression of kidney disease (A).

2.2.b Presence of clinical CVD and CVD risk factors (Table 50) (A)

2.2.c Comorbid conditions (A)

2.2.d Barriers to self-management, adherence to diet and other lifestyle modifications,adherence to pharmacological therapy (see Guidelines 5, 6,7) (B)

2.2.e Complications of pharmacological therapy (see Guidelines 7, 11-12) (A).

2.3 A clinical action plan should be developed for each patient, based on the stage of CKD ( Table

51) (B).

2.4 Recommended intervals for follow-up evaluation should be guided by clinical conditions (Table52) (C).

2.5 Patients with resistant hypertension should undergo additional evaluation to ascertain thecause (B).

2.6 Patients should be referred to specialists, when possible (Table 53).

BACKGROUND
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Appropriate evaluation is the first step to achieving treatment goals. Since hypertension iscommon inCKDand, conversely, CKD is common in hypertensionGuideline 2 includes evaluation for bothCKD and hypertension. Several comprehensive guidelines to hypertension evaluation are readily

available, and the principles described in JNC 7 are appropriate. 5,5aWith particular respect to CKD,general principles of the approach to the evaluation have been described in the K/DOQI Clinical Practice

Guidelines for CKD(Guidelines 7,13, and 15, and Part 9).1Key elements of both evaluations will bereiterated here.

The question of whether particular demographic factors require modification of blood pressuremanagement was addressed during the process of data abstraction of all studies of treatment that met theinclusion criteria. The literature searches were not restricted to studies in particular demographic groups,nor were searches focused on any demographic factors. Data abstractors were requested to comment onany results from analysis of subgroups or interaction terms suggestive of effect modification throughdemographic factors. In addition, the studies included in summary tables were reviewed in view of the

prominent demographics of the populations studied, for example elderly or African-Americans. Separatesummary tables were not developed.
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RATIONALE

Framework

The general principles of evaluation of the patient with hypertension as outlined in the JNC

guidelines5,5aare appropriate for patients at all stages of CKD. Initial evaluation and re-evaluation inpatients with CKD is extensive and may be performed over many visits with a variety of health-careproviders working either alone or as part of a team. Health-care providers are encouraged to set up aroutine system for efficiently conducting these evaluations. Some groups have found it helpful to utilizea multidisciplinary approach (physicians, nurse practitioners, registered nurses, registered dietitians,masters prepared social workers, pharmacists, physician assistants, and other professionals) for this

purpose.

Strength of Evidence

Initial Evaluation

The objectives of the evaluation are (1) detection of identifiable causes of hypertension, including CKD(2) assessment of target organ damage, including CKD and (3) identification of other CVD risk factorsor concomitant disorders that may define prognosis and guide treatment (Table 54). With respect to

patients with CKD, the high prevalence of CVD should be noted and should guide particular attention toCVD risk factors. In addition, nontraditional risk factors for CVD include the level of GFR and the

presence of albuminuria or proteinuria.7
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Initial evaluation of the patient with hypertension should include assessment for the presence of CKD(Table 55) (Strong).

Definition of CKD.CKD is defined as kidney damage, as confirmed by kidney biopsy or markers of

damage, or GFR


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either treatment or prognosis. In most patients, diagnosis is assigned based on recognition of markers ofkidney damage, in association with well-defined clinical presentations and causal factors based onclinical evaluation.

Decreased GFR.The level of GFR is accepted as the best measure of overall kidney function in healthand disease. The normal level of GFR varies according to age, gender, and body size. Normal GFR in

young adults is approximately 120 to 130 mL/min/1.73 m2and declines with age. A GFR level


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Fig 29. Age-associated decline in estimated GFR in NHANES III. GFR estimated from serumcreatinine using MDRD Study equation. Age 20, N = 15, 600.

Traditionally, the age-related decline in GFR has been considered "normal." However, decreased GFR in

the elderly requires adjustment in drug-dosing and appears to be an independent predictor of adverseoutcomes, such as mortality and CVD. Thus, the definition of CKD is not modified based on age. This isanalogous to blood pressure levels in the population and the definition and prevalence of hypertension.Blood pressure rises with age, but hypertension in the elderly is associated with adverse outcomes thus,the definition of hypertension is not age-dependent, and the majority of elderly individuals are classifiedas having hypertension. Similarly, because of the age-related decline in GFR, the prevalence of CKDincreases with age approximately 17% of individuals greater than 60 years of age have an estimated

GFR


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Cause of CKD.Cause of CKD is important, since some antihypertensive agents are "preferred agents"for some types of CKD, even in patients without hypertension. Table 62shows a simple classification of

types of CKD and the proportion of patients with new onset of kidney failure from these diseases.17

History of CKD.Initial assessment should include a complete medical history, including history of andseverity of CKD (Table 63) known duration and levels of HBP evidence of CVD presence of othercomorbid conditions such as diabetes and dyslipidemia symptoms suggesting identifiable causes ofhypertension in addition to CKD extracellular fluid volume status lifestyle issues which may impact onCKD and blood pressure management prescribed and other medications (including NSAIDs, herbal

remedies, and illicit drugs) results of current and prior antihypertensive therapy and psychosocial andenvironmental factors.1For additional diagnostic clues in children, see Guideline 13.
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Physical examination.A complete physical examination should be performed, to assess severity of

hypertension, presence of end-organ damage, and extracellular fluid (ECF) volume (Table 64).5,15Mostkidney diseases do not cause alterations in the physical examination. Infrequently, secondary causes of

hypertension other than CKD can be detected. Renal artery disease (see Guideline 4) can coexist withother types of CKD.

Laboratory tests.Routine laboratory tests are also recommended. These should include those tests thatare recommended for the evaluation of CKD (Table 65). In particular, prediction equations should be

used to estimate GFR from serum creatinine in adults123-125and children126,127, and a spot urine sample

should be obtained to estimate albuminuria or proteinuria.1Of note, JNC 7 concurs with measuring

serum creatinine to estimate GFR, but considers testing for albuminuria or proteinuria as "optional."5,5a

The Work Group recommends that all patients with hypertension be tested for albuminuria orproteinuria, since CKD is both a cause and a consequence of hypertension, and since CKD is a risk factorfor CVD.
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In addition, basic blood chemistries should be obtained, as well as a glucose and fasting lipid panel. Allpatients should also have a 12-lead EKG, to screen for LVH. Optional additional tests may include

thyroid-stimulating hormone, calcium, and uric acid levels.5,5a

Proteinuria.K/DOQI Guidelines for CKD recommend testing for albuminuria in allpatients at

increased risk for CKD.1Current guidelines define albuminuria as spot urine albumin to creatinine ratio

>30 mg/g in both men and women,1,6,128,129although some studies have suggested different cut-off

values for men and women.18,19

The Work Group has modified this recommendation for the purpose oftreatment of hypertension and use of antihypertensive agents since, as described in Guidelines 8and 9,decision-making is based on quantification of albuminuria (spot urine albumin to creatinine ratio >30mg/g) in diabetic patients, and on quantification of proteinuria (spot urine total protein to creatinine ratio>200 mg/g) in nondiabetic patients.

An algorithm for further ascertainment of proteinuria is shown in Fig 30. A spot urine sample should betested using either a standard dipstick in patients without diabetes (left side) or an albumin-specificdipstick in patients with diabetes (right side). Proteinuria should be quantitated in patients with a positivetest a spot urine sample should be tested for total protein to creatinine ratio in patients without diabetesor albumin to creatinine ratio in patients with diabetes. The level of proteinuria is important to ascertain

as it will help determine if there is a preferred agent for the management of hypertension. Follow-up ofelevated urine protein levels is discussed in Guidelines 8through 10.

Fig 30. Evaluation for proteinuria for evaluation of hypertension and use of antihypertensiveagents in CKD. Figure is modified from CKD Guideline 5, Fig 57, because criteria for selection ofpreferred agents in nondiabetic kidney disease are based on measurements of urine total protein

rather than urine albumin.1

Other laboratory tests.The rationale for other laboratory tests is to identify the cause of CKD, inparticular causes of nondiabetic kidney disease (Guideline 9). The interpretation of urinalysis, serumelectrolyte concentrations, and imaging studies in the diagnosis of type of CKD are discussed in CKD
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Guidelines (Guideline 6and Part 9).1Imaging studies should be performed to detect obstruction of theurinary tract, polycystic kidney disease, stones, or congenital disorders.

Coexistence of renal artery disease and other identifiable causes of hypertension.Once the initialdata are available for evaluation, consideration should also be given to the presence of renal arterydisease (RAD) or other identifiable causes of hypertension, in addition to CKD. These include primaryhyperaldosteronism, pheochromocytoma, thyroid disease, aortic coarctation, Cushing syndrome, andhyperparathyroidism.

Evaluation for RAD is challenging, particularly in patients with CKD. The approach is based onidentification of clinical factors associated with a higher risk of RAD and estimation of the probability ofRAD using prediction equations (Guideline 4). In all cases, however, the risk of toxicity fromangiographic contrast and revascularization procedures must be considered when assessing therisk/benefit ratio of detection and intervention. If available, gadolinium should be substituted for standardcontrast agents in patients with CKD.

Complications of decreased GFR.Table 66lists clinical problems and additional evaluation for

patients with GFR


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contribute to kidney disease progression through mechanisms in addition to hypertension and proteinuria.

Risk factors for acute GFR decline.GFR decline may be variable. Acute decline in GFR may be

superimposed on CKD (Table 68). CKD Guideline 13discusses risk factors for acute decline in GFR.1

The initial evaluation should include ascertainment of clinical CVD and CVD risk factors (Strong).As reviewed in Guideline 1, patients with CKD are considered in the highest-risk group for CVD. High

priority must be given to identification and treatment of CVD, as well as to identification and treatmentof CVD risk factors other than HBP and CKD (Table 69).

The initial evaluation should include ascertainment of comorbid conditions (Strong). Attention mustbe paid to the presence of comorbid conditions, particularly those conditions that affect kidney functionor blood pressure require treatment with antihypertensive agents require treatment with medicationsthat raise blood pressure constitute an absolute or relative contraindication to specific classes ofantihypertensivetherapy require additional diet or lifestyle modification or require diet modifications ormedications that interact with antihypertensive medications (Table 70). For example, many commonly

used drugs may increase blood pressure or interfere with the efficacy of antihypertensive agents.5,15
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Initial evaluation should include assessment of barriers to self-management (see Guideline 5),adherence to diet and other lifestyle modification (Guideline 6), and adherence to pharmacologicaltherapy (Guideline 7) (Moderately Strong).

Initial evaluation should include development of a clinical action plan, based on the stage of CKD(Moderately Strong).

Among individuals with CKD, the stage of disease and the clinical action plan is based on the level ofGFR (Table 51), irrespective of the cause of kidney disease. The action plan for stages of CKD is

discussed in more detail in NKF- K/DOQI Guidelines for Chronic Kidney Disease.1Evaluation ofhypertension and treatment with antihypertensive agents is part of the action plan for all stages of CKD.

Follow-Up Evaluation

Follow-up evaluation includes many of the same elements as the initial evaluation. Particular attention isgiven to adherence to lifestyle modifications and pharmacological therapy, the level of blood pressure,volume status, GFR, proteinuria, serum electrolytes, adverse effects of and interactions withantihypertensive medications, complications of CKD, CVD risk factors in addition to hypertension,CVD, and comorbid conditions.

Frequency of follow-up evaluation after initiation of antihypertensive agents depends on level of bloodpressure, GFR, and serum potassium (Weak). In general, follow-up should be in approximately 412

weeks if SBP is 120139 mm Hg, GFR 60 mL/min/1.73 m2, and serum potassium 4.5 mEq/L for

patients prescribed an ACE inhibitor or ARB or >4.5 meq/L in patients prescribed a thiazide or loopdiuretic. Follow-up should be considered sooner if SBP, GFR, or serum potassium is not within theseranges (Table 52).

After a stable blood pressure management regimen is achieved, follow-up should be every 612 months,

and more frequently if GFR


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modified from JNC 7.5,5aIn patients with CKD, deterioration in blood pressure control may be a clue toprogression of kidney disease. These patients are also at high risk for volume-dependent hypertensionfailure to increase diuretic therapy as CKD worsens can often aggravate blood pressure control. Some

patients with resistant hypertension can develop hypertensive crisis (defined as severe elevations in bloodpressure [>180/120 mm Hg] with or without impending or progressive organ dysfunction). Treatment of

these conditions is beyond the scope of these guidelines and is discussed in JNC 7. 5,5a

Referral to Specialists

Patients should be referred to a kidney disease specialist for GFR


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with various forms of kidney disease including HIV-associated nephropathy136and sickle cell

nephropathy.137Gender does not significantly affect the beneficial effects of antihypertensive

therapy.138-140

Fig 31. Evaluation of Patients With CKD for Treatment of Hypertension and Use ofAntihypertensive Agents

SUMMARY

Figure 31and Table 72summarize the initial and follow-up evaluation.
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LIMITATIONS

The risks of hypertension and the need for prompt recognition and evaluation in the general populationare well documented. Far less evidence specific to the CKD population is available, and it must beacknowledged that many of the major hypertension trials upon which JNC guidelines are basedspecifically excluded patients with kidney disease. Nevertheless, the CVD and CKD progression risksare well documented, and so it seems only prudent to follow accepted recommendations in this patient

population.

IMPLEMENTATION ISSUES

Effective evaluation and treatment of hypertension is a challenge, and particularly so in the CKDpopulation. Insurance coverage and financial resources will frequently dictate the degree of laboratoryevaluation that may be performed. Fortunately, the most important basic lab tests (urinalysis, chemistry

panel) are relatively inexpensive, as are a number of effective generic antihypertensive medications.Lifestyle issues that complicate treatment of hypertension are often occult and difficult to elicit. Asmentioned above, the toxicity to the kidney of angiographic dye may make the decision whether to lookfor renal artery stenosis particularly difficult.

In general, there are no specific implementation issues for any particular population subgroup. However,in choosing initial and subsequent pharmacological agents, known differences in drug efficacy should be

noted. For example, diuretics are particularly effective in the elderly and in African-Americans.15ACEinhibitors are recognized to be slightly less effective at reducing HBP in African-Americans than inCaucasians, and yet have been shown to be effective in slowing the progression of kidney disease in this

group.141In all groups, it should be recognized that effective blood pressure control will require multipleagents, and therefore minor differences in efficacy of one class or the other can be easily circumvented

by addition of other drugs.

RESEARCH RECOMMENDATIONS

The current clinical questions related to essential hypertension are all areas that require further researchin CKD. These questions cannot be answered unless patients with CKD are included in large randomizedtrials. Areas for investigation include:

Studies on the effect of various clinical and genetic factors on the response to antihypertensivetherapy, to determine what factors should be included in the evaluation.Studies on the relationship between levels of proteinuria and albuminuria, to simplify thedetection, evaluation and management of CKD.Studies on the cost-effectiveness of various components of the evaluation and the frequency offollow-up.
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Guideline 2_ Evaluation of Patients With Ckd or Hypertension 1

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