clinical practice guidelines on hypertension and - medind

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Copyright © 2005 by The Indian Society of Nephrology

Indian Journal of Nephrology Indian J Nephrol 2005;15, Supplement 1: S14-S22

Clinical practice guidelines on hypertensionand antihypertensive agents

in chronic kidney disease (CKD)

Hypertension is a cause and complications of CKD.Hypertension in CKD increases the risk of important

adverse outcomes, including loss of kidney function andkidney failure, early development and acceleratedprogression of cardiovascular disease (CVD), andpremature death. In the ongoing effort to improveoutcomes of CKD, the National Kidney Foundation (NKF)Kidney Disease Outcomes Quality Initiative (K/DOQI)appointed a Work Group and an Evidence Review Teamin 2001 to develop clinical practice guidelines onhypertension and use of antihypertensive agents in CKD.During this same time, clinical practice guidelines on thistopic relevant to CKD were also under development byother organizations, including the Seventh Report of theJoint National Committee on the Prevention, Detection,Evaluation, and Treatment of High Blood Pressure (JNC7) and the 2003 report of the American DiabetesAssociation (ADA) on the Treatment of Hypertension inAdults with Diabetes.

But several of the drugs like clonidine and prazosin whichare commonly used in Indian scenario are not mentionedin these guidelines. Clonidine is very cost effective anduseful drug these patients being economical for initialtreatment and in those whose blood pressure is refractoryto control and require more than 3-4 drugs to achieve the

target blood pressure.

CKD is defined as kidney damage, as confirmed by kidneybiopsy or markers of damage, or glomerular filtration rate(GFR) <60 mL/min/1.73 m2 for > 3 months Markers ofkidney damage include proteinuria, abnormalities on theurine dipstick or sediment examination, or abnormalitieson imaging studies of the kidneys. GFR can be estimatedfrom prediction equations based on serum Creatinine andother variables, including age, sex, race, and body size.(Table 1 and 2)

Among individuals with CKD, the stage of disease isbased on the level of GFR, irrespective of the cause ofkidney disease. The high prevalence of earlier stages ofCKD emphasizes the importance for all health-careproviders, not just kidney disease specialists, to detect,evaluate, and treat CKD.

Hypertension in CKD

JNC 7 defines hypertension as systolic blood pressure(SBP > 140mm Hg or diastolic blood pressure (DBP) >90mmHg, respectively, Although common in CKD,hypertension is not part of the definition of CKD. Table 4illustrates the classification of individuals based onpresence or absence of kidney damage and hypertension

Table 1 - Definition of CKD

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Indian J Nephrol 2005;15, Supplement 1: S14-S22

and level of GFR. Approximately 50% to 75% ofindividuals with GFR <60mL/min/1.73 m2, (CKD stages3-5) have hypertension Among individuals with GFR<60mL/min/1.73 m2 distinguishing CKD Stages 1 and 2from “hypertension” and hypertension with decreasedGFR” requires assessment for markers of kidney damage.This is especially important in the elderly, in whom bothhypertension and decreased GFR are common (Table 3)

Cardiovascular Disease in CKDCKD is a risk factor for cardiovascular disease (CVD).Dialysis patient have a 50 to 500 times increased risk ofCVD mortality compared to age-marched individuals fromthe general population. Earlier stages of CKD are alsoassociated with an increased risk of CVD. CKD isassociated with an increased prevalence and severity of

both “traditional” and “nontraditional” risk factors for CVD.Traditional risk factors include those initially described inthe Framingham Study. Among traditional risk factors,hypertension is closely linked to CKD and has often beenimplicated as the main cause of CVD in CKD. Othertraditional risk factors for CVD that are common in CKDinclude older age, diabetes and hyperlipidemia.Nontraditional risk factors for CVD such as inflammation,malnutrition, mineral disorders (calcium and phosphorus),and anemia are also common in CKD. In addition,albuminuria and decreased GFR are associated with anincreased risk of CVD, even after controlling for many ofthese risk factors. Early detection and treatment of CKD,including detection and treatment of hypertension and othese risk actors. Early detection and treatment of CKD,including detection and treatment of hypertension and

Table 2 - Stages and Prevalence of CKD

Table 3 - Classification of blood pressure for adult age>18 years (JNC 7)

Clinical practice guidelines for HT in CKD

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Table 4 - Stages of CKD and relationship hypertension

Table 5 - Goals for antihypertensive therapy in CKD

Table 6 - Startegies and therapeutic targets for antihypertensive therapy in CKD

Table 7 - Importance of proteinuria in CKD

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Table 8 - Topics and guidelines

Table 9


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other CVD risk factors may reduce the risk of CVD inCKD. Achieving these goals in CKD will require co-ordinating antihypertensive therapy with therapy for otherCVD risk factors (Table 4,5 and 6).

Recommendations for antihypertensive therapy in thegeneral population are based on observational studiesand controlled trials relating blood pressure level andantihypertensive therapy to CVD risk. Few patients withCKD were included in these studies. Thus,recommendations to reduce CVD risk in CKD are basedlargely on extrapolation from the general population.

Progression of CKD

Most kidney diseases worsen progressively over time.Antihypertensive therapy affects several modifiable keyfactors related to the progression of kidney disease,including hypertension, proteinuria, and othermechanisms, such as increased acitivity of thereninangiotensin system (RAS). Several large, controlledtrials have examined the effect of antihypertensivetherapy on the progression of kidney disease in patientswith and without hypertension. While these trials haveprovided important answers about therapy, therelationships among these “progression factors” arecomplex, and many questions remain unanswered,especially regarding the mechanisms underlying thetherapeutic benefit of the interventions (Table 7, 8 and9).

GUIDELINE 1:Goals of antihypertensive therapy in CKD

Hypertension is common in CKD, and is a risk factor forfaster progression of kidney disease and developmentand worsening of CVD. Some antihypertensive agentsalso slow the progression of kidney disease bymechanisms in addition to their antihypertensive effect.

1.1 Antihypertensive therapy should be use din CKDto:

a. Lower blood pressure

b. Reduce the risk of CVD, in patients with orwithout hypertension

c. Slow progression of kidney disease, in patientswith or without hypertension

1.2 Modifications to antihypertensive therapy shouldbe considered based on the level of proteinuriaduring treatment ©.

1.3 Antihypertensive therapy should be coordinated withother therapies for CKD as part of a multi-intervention strategy (A).

1.4 If there is a discrepancy between the treatmentrecommended to slow progression of CKD and toreduce the risk of CVD, individual decision-making

should be based on risk stratification ©.

GUIDELINE 2:Evaluation of patients with CKD orhypertension

1 Blood pressure should be measured at each healthencounter (A).

2 Initial evaluation should include the followingelements:

a. Description of CKD;

1 Type (diagnosis), level of GKR, and levelof proteinuria

2 Complications of decreased GFR (A)

3 Risk for progression of kidney disease (A)

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

c. Comorbid conditions (A)

d. Barriers to self-management, adherence to dietand other lifestyle modifications, adherence topharmacological therapy (B)

e. Complications of pharmacological therapy (A)

2.1 A clinical plan should be developed for each patient,based on the stage of CKD (B).

2.2 Recommended intervals for follow-up evaluationshould be guided by clinical conditions ©

2.3 Patients with resistant hypertension should undergoadditional evaluation to ascertain the cause (B)

2.4 Patient should be referred to specialists, whenpossible

GUIDELINE 3:Measurement of blood pressure in adults

3.1 Blood pressure should be measured according tothe recommendations for indirect measurement ofarterial blood pressure of the American HeartAssociation and Seventh Report of the JointNational Committee on the Prevention, Detection,Evaluation and Treatment of High Blood Pressure(JNC 7) (A)

3.2 Patients should be taught to measure and recordtheir blood pressure, whenever possible ©.

3.3 Ambulatory blood pressure monitoring should beconsidered for patients with CKD for the followingindications ©:

a Suspected white coat hypertension

b Resistant hypertension

c Hypotensive symptoms while taking

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antihypertensive medications

d Episodic hyeptension

e Autonomic dysfunction

GUIDELINE 4:Evaluation for renal arteyr diseaseRenal artery disease (RAD) is a cause of CKD andhypertenion, and can be present in patients with othercauses of CKD, sucha s diabetes or hypertensivenephrosclerosis, and CKD in the kidney transplant.

4.1 For patients in whom there is a clinical suspicion ofRAD, the clinician should do one or more of thefollowing:

a. Estimate the probability of RAD using apredictive index derived from clinicalcharacteristics (B)

b. Obtain a noninavasive screening test for RAD(A)

c. Refer to a kidney disease or hypertensionspecialist for evaluation ©

4.2 Patients found to have hemodynamically significantRAD should be referred to a kidney disease orhypertenion specialist for management ©

GUIDELINE 5:Education on self-management behaviorAntihypertensive therapy must take into considerationthe patient’s perception of the health-care provicer’s adviceand prescriptions, factors that may influence self-management behaviors, and the likelihood that the patientwill adhere to recommendations.

5.1 Self management principles should be incorporatedinto the treatment plan (B)

5.2 Patient and family education about antihypertensivetherapy should be culturally sensitive, sensitivetoeconomic considerations, and based on thepatient’s level of understanding (B)

5.3 All patients should be assessed for barriers toadherence and self-management (B), and referredfor further counseling as needed (to a nursepractitioner, registered nurse, registered dietitian,masters prepared social worker, pharmacist,physician assistant, or other professional (C)

GUIDELINE 6:Dietary and other therapeutic lifestylechanges in adultsDietary and other therapeutic lifestyle modifications arerecommended as part of a comprehensive strategy tolower blood pressure and reduce CVD risk in CKD.

6.1 Dietary sodium intake of less than 2.4g/d (less than100mmgl/d) should be recommended in most adultswith CKD and hypertension (A)

6.2 Other dietary recommendations for adults shouldbe modified according to the stage of CKD (B)

6.3 Lifestyle modifications recommended for CVD riskreduction including Exercise, Yoga should berecommended as part of the treatment regimen (B)

6.4 Referral to a registered dietitian should be consideredto help patients achieve dietary recommendations©

GUIDELINE 7:Pharmacological therapy: use ofantihypertensive agents in CKD

All antihypertensive agents can be used to lower bloodpressure in CKD. Multidrug regimens will be necessaryin most patients with CKD to achieve therapeutic goals.Patients with specific causes of kidney disease and CVDwill benefit from specific classes of agents.

7.1 Paitents with CKD should be considered in the“highest-risk” group for CVD for implementingrecommendations for pharmacological therapy,irrespective of cause of CKD (A)

7.2 Target blood pressure for CVD risk reduction in CKDshould be <130/80mmHg (B)

7.3 Antihypertensive agents should be prescribed asfollows, when possible:

a. Preferred agents for CKD should be used first(A);

b. Diuretics should be included in theantihypertensive regimen in most patients (A)

c. Choose additional agents based oncardiovascular disease-specific indications toachieve therapeutic and preventive targets andto avoid side-effects and interactions (B)

7.4 The antihypertensive regimen should be simplifiedas much as possible (B)

i. Long-active (once-daily agents) should be usedwhen possible (B)

ii. Two agents, either as separate prescriptions oras a fixed-dose combination containingpreferred agents, may be considered as initialtherapy for SBP 20mmHg above goal accordingto the stage of CKD and CVD risk ©

iii. Fixed-dose combinations may be used formaintenance therapy after the antihypertensiveregimen has been established (B)

GUIDELINE 8:


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Pharmacological therapy: diabetic kidneydiseaseDiabetes mellitus is the most common cause of kidneyfailure in the United States. Diabetic kidney disease ischaracterized by the early onset of albuminuria,hypertension, and a high risk of coexistent or subsequentCVD.

8.1 Target blood pressure in diabetic kidney diseaseshould be <130/80mmHg

8.2 Patients with diabetic kidney disease, with or withouthypertension, should be treated with an ACE inhibitoror an ARB

GUIDELINE 9:Pharmacological therapy: nondiabetic kidneydisease

Nondiabetic kidney diseases include glomerular diseasesother than diabetes, vascular disease other than renalartery disease, tubulointerstitial diseases, and cysticdisease. Among these diseases, the level of proteinuriais useful for diagnosis and prognosis. Glomerular diseasesare characterized by higher levels of proteinuria than otherdiseases. Higher levels of proteinuria are associated withfaster progression of kidney disease and increased riskof CVD.

9.1 Target blood pressure in nondiabetic kidney diseaseif urine protein <1g/day should be <130/80mmHg.

9.2 Patients with nondiabetic kidney disease and spoturine total protein to Creatinine ratio >200mg/g, withor without hypertension, should be treated with anACE inhibitor or ARB, target BP <125/75mmHg

GUIDELINE 10:Pharmacological therapy: kidney disease inthe kidney transplant recipient

Most kidney transplant recipients have CKD andhypertension. High blood pressure in kidney transplantrecipients is a risk factor for faster progression of CKDand development of CVD.

10.1 The target blood pressure in kidney transplantrecipients should be <130/80mmHg

10.2 Patients with CKD in the kidney transplant shouldbe treated with any of the following to reach thetarget blood pressure: CCB, diuretics, ACE inhibitor,ARB, or beta-blocker

GUIDELINE 11:Use of angiotensin – converting enzymeinhibitors and angiotensin receptor blockersin CKDACE inhibitors and ARBs can be used safely in mostpatients with CKD

11.1 ACE inhibitors and ARBs should be used at moderateto high doses, as used in clinical trials (A)

11.2 ACE inhibitors and ARBs should be used asalternatives to each other, if the preferred classcannot be used (B)

11.3 ACE inhibitors and ARBs can be used incombinationto lower blood pressure or reduce proteinuria ©

11.4 Patients treated with ACE inhibitors or ARBs shouldbe monitored for hypotension, decreased GFR, andhyperkalemia (A)

11.5 The interval for monitoring blood pressure, GFR,and serum potassium depends on baseline levels(B)

11.6 In most patients, the ACE inhibitor or ARB can becontinued if:

a. GFR decline 4 months is <30% from baselinevalue (B)

b. Serum potassium is 5.5mEq/l (B)

11.7 ACE inhibitors and ARBs should not be used orused with caution in certain circumstances

GUIDELINE 12:Use of diuretics in CKDDiuretics are useful in the management of most patientswith CKD. They reduce ECF volume; lower blood pressure;protentiate the effects of ACE inhibitors, ARBs, and otherantihypertensive agents; and reduce the risk of CVD inCKD. Choice of diuretic agents depends on the level ofGFR and need for reduction in ECF volume.

12.1 Most patients with CKD should be treated with adiuretic (A)

i. Thiazide diuretics given once daily arerecommended in patients with GFR >30ml/min1.73 m2 (CKD stages 1-3) (A)

ii. Loop diuretics given once or twice daily arerecommended in patients with GFR <30ml/min1.73 m2 (CKD stages 4-5) (A)

iii. Loop diuretics given once or twice daily, incombinatin with thiazide diuretics, can be usedfor patients with ECF volume expansion andedema (A)

iv. Potassium – sparing diuretics should be usedwith caution:

1. In patients with GFR<30ml/min1.73 m2(CKD stages 4-5) (A)

2. In patients receiving cocomitant therapywith ACE inhibitors or ARBs (A)

3. In patients with additional risk factors for

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hyperkalemia (A)

12.2 Patients treated with diuretics should be monitoredfor:

a. Volume depletion, manifest by hypotension ordecreased GFR (A)

b. Hypokalemia and other electrolyte abnormalities(A)

c. The interval for monitoring depends on baselinevalues for blood pressure, GFR and serumpotassium concentration (B)

12.3 Long-acting diuretics and combinations of diureticswith other antihypertensive agents should beconsidered to increase patient adherence (B)

GUIDELINE 13:use of alpha blockers13.1 Hypertension is difficult to control in patients with

CKD and frequently requires more than 3-4 drugs

13.2 Prazosin is used complementary to ACE inhibitors,Angiotensin II blockers, Calcium channel blockers,beta-blockers and diuretics

13.3 The beneficial side effects are increase in insulinsensitivity and control of dyslipidemia

13.4 However, it needs to be evaluated for autonomocneuropathy before starting these drugs and longterm data on mortality and morbidity is controversial

13.5 It is useful in patients with concomitant benignhyperplasia fo prostate and CKD for symptomaticrelief.

GUIDELINE 14:Use of centrally acting drugs eg clonidine,methyl dopa

a. Clonidine is very effective and cost effectiveantihypertensive

b. It is very useful to use the drug particularly toachieve the target level

c. It can be used complementary to ACE inhibitors,Angiotensin II blockers, Calcium channel blockers,beta-blockers and diuretics

GUIDELINE 15:Special considerations in childrenHypertesion is common in children with CKD. Becauseof their young age at onset of CKD and hypertension,children have a high lifetime exposure to risk factors forCVD. Thus, childredn with CKD are at high risk ofcomplications from hypertension.

15 .1 Measurement of blood pressure in children shouldbe performed with age and size appropriate

equipment, and blood pressure values should beinterpreted according to normal values adjusted forage, gender, and height percentile, as recommendedby the 1996 Update on the Task Force Report onHigh Blood Pressure in Children and Adolescents:A Working Group Report from the National HighBlood Pressure Education Program (A)

15.2 The cause of CKD and age of the child should beconsidered in selecting the class of antihypertensiveagent (A)

15.3 Target blood pressure in children should be lowerthan the 90th percentile for normal values adjustedfor age, gender and height or 120/80 mmHg,whichever is lower (B)

15.4 Because of the specialized nature of CKD and bloodpressure management in children ©

a. BP should be measured in all children with CKD

b. Use correct size of cuff

c. Target BP 90th percentile

d. Rule out secondary cause particularlyrenovascular disease and reglux nephropathy

GUIDELINE 16:Special considerations in adult16.1 Frequency of BP measurement should be

individualized

16.2 Daily home monitoring particularly with uncontrolledBP

16.3 More frequent measurement with uncontrolled BP

16.4 Postural hypotension should be periodically checkedin patients with autonomic neuropathy

16.5 Electronic BP instrument should be standardizedwith mercury shygometer

16.6 Patient should be seated quietly for at least 5minutes in a chair rather than on a examinationtable, with feet on the floor and arm supported atheart level. An appropriate size cuff, cuff bladderencircling at least 80% of the arm, should be usedto ensure accuracy. At least 2 measurements shouldbe made. Phase l, appearance of sound, should beconsidered as systolic BP and phase 5,disappearance of sound as diastolic BP

16.7 Physicians should provide verbally and in writing,their specific BP numbers and BP goals.


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1. K/DOQI clinical practice guidelines for chronic kidneydisease: Evaluation, classification, and stratification.Kidney Disease Outcome Quality Initiative. Am J KidneyDis 2002; 39:S1-S266, (suppl 2)

2. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN,Kasiske BL, Klag MJ, Mailloux LU, Manske CL, MeyerKB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW,Wright JT Jr: Controlling the epidemic of cardiovasculardisease in chronic renal disease: what do we know?What do we need to learn? Where do we go from here?National Kidney Foundation Task Force onCardiovascular Disease. Am J Kidney Dis 1998; 32:853-906

3. Levey AS: Controlling the epidemic of cardiovasculardisease in chronic renal disease: Where do we start?Am J Kidney Dis 1998; 32:S5-S13 (suppl 3)

References

4. Chobanian AV, Bakris GL, Black HR, Cushman WC,Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S,Wright JT Jr, Roccella EJ: The Seventh Report of theJoint National Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure: TheJNC 7 report. JAMA 2003; 289:2560-2572

5. Chobanian AV, Barkris GL, Black HR, Cushman WC,Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S,Wright JT Jr, Roccella EJ: Seventh Report of the JointNational Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure.Hypertension 2003; 42:1206-1252

6. Coresh J, We L Mc Quillan G et al. Prevalence of highblood pressure and elevated serum cratinine level inthe United States. Arch Intern Med 2001; 161: 1207-1216.

7. Henry T. Yu. Progression of Chronic renal failure. ArchIntern Med 2003; 23:1419-1429

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