• K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004 May;43(5 Suppl 1):S1-290. [625 references] PubMed

Definitions for the Recommendations Ratings (A-C) are provided at the end of the "Major Recommendations" field.

Guideline 1: Goals of Antihypertensive Therapy in Chronic Kidney Disease (CKD)

Hypertension is common in CKD and is a risk factor for faster progression of kidney disease and development and worsening of cardiovascular disease (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).

Guideline 2: Evaluation of Patients With Chronic Kidney Disease or Hypertension

Careful initial evaluation and frequent re-evaluation are essential for effective treatment of hypertension and use of antihypertensive agents in CKD. Because CKD and hypertension are often present together and both are generally asymptomatic, Guideline 2 considers evaluations of patients 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 glomerular filtration rate (GFR), and level of proteinuria (see table below titled "Laboratory Measurements for Ascertainment of CKD") (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 (see table below titled "Measurements for Ascertainment of CVD and CVD Risk Factors in CKD) (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, and 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 (see table below titled "Stages of CKD: A Clinical Action Plan") (B).

2.4. Recommended intervals for follow-up evaluation should be guided by clinical conditions (see table below titled "Recommended Interval for Follow-up Evaluation in CKD") (C).

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

2.6. Patients should be referred to specialists, when possible, for certain indications (see table below titled "Recommendations for Referral to Specialists for Consultation and Co-Management of CKD").

Table. Laboratory Measurements for Ascertainment of CKD

Table. Measurements for Ascertainment of CVD and CVD Risk Factors in CKD

Table. Stages of CKG: A Clinical Action Plan

Notes: CKD is defined as either kidney damage or GFR <60 mL/min/1.73 m² for >3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies.
*Includes actions from preceding stages.

Table. Recommended Interval for Follow-up Evaluation in CKD

Notes: Clinicians are advised to evaluate each parameter and select the follow-up interval for the parameter that requires the earliest follow-up ^afor thiazide or loop diuretic therapy, ^bfor angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) therapy.
* 120-129 mm Hg, to monitor for hypertension; 130-139 mm Hg to reach blood pressure goal.

Table. Recommendations for Referral to Specialists for Consultation and Co-Management of CKD*.

* Availability of specialists may vary, depending on location.
** Defined as "fast" GFR decline (>4 mL/min/1.73 m² per year) or risk factors for fast GFR decline. Short-term decline in GFR up to 30% may be seen after initiation of ACE inhibitor or ARB and does not require referral to specialists in the absence of other indications.
Note: Letters in parentheses indicate strength of recommendations.

Guideline 3: Measurement of Blood Pressure in Adults

Blood pressure can be determined by resting blood pressure measurement in the health-care provider's office (casual blood pressure [CBP]), self-measured blood pressure (SMBP), or ambulatory blood pressure monitoring (ABPM).

3.1. Blood pressure should be measured according to the recommendations for indirect measurement of arterial blood pressure of the American Heart Association and Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) (A).

3.2. Patients should be taught to measure and record their blood pressure, whenever possible (C).

3.3. Ambulatory blood pressure monitoring should be considered for patients with CKD for the following indications (C):

• 3.3.a. Suspected white coat hypertension
• 3.3.b. Resistant hypertension
• 3.3.c. Hypotensive symptoms while taking antihypertensive medications
• 3.3.d. Episodic hypertension
• 3.3.e. Autonomic dysfunction

Guideline 4: Evaluation for Renal Artery Disease

Renal artery disease (RAD) is a cause of CKD and hypertension and can be present in patients with other causes of CKD, such as diabetes or hypertensive nephrosclerosis, and CKD in the kidney transplant.

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

• 4.1.a. Estimate the probability of RAD using a predictive index derived from clinical characteristics (B)
• 4.1.b. Obtain a noninvasive screening test for RAD (A)
• 4.1.c. Refer to a kidney disease or hypertension specialist for evaluation (C).

4.2. Patients found to have hemodynamically significant RAD should be referred to a kidney disease or hypertension specialist for management (C).

Guideline 5: Education on Self-Management Behavior

Antihypertensive therapy must take into consideration the patient's perception of the health-care provider's advice and prescriptions, factors that may influence self-management behaviors, and the likelihood that the patient will adhere to recommendations.

5.1. Self-management principles should be incorporated into the treatment plan (B).

5.2. Patient and family education about antihypertensive therapy should be culturally sensitive, sensitive to economic considerations, and based on the patient's level of understanding (B).

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

Guideline 6: Dietary and Other Therapeutic Lifestyle Changes in Adults

Dietary and other therapeutic lifestyle modifications are recommended as part of a comprehensive strategy to lower blood pressure and reduce CVD risk in CKD.

6.1. Dietary sodium intake of less than 2.4 g/d (less than 100 mmol/d) should be recommended in most adults with CKD and hypertension (A).

6.2. Other dietary recommendations for adults should be modified according to the stage of CKD (see table below titled "Macronutrient Composition and Mineral Content of the Dietary Approaches to Stop Hypertension [DASH] Recommended by JNC 7, with Modifications for Stages 3-4 of CKD") (B).

6.3. Lifestyle modifications recommended for CVD risk reduction should be recommended as part of the treatment regimen (see table below titled "Other Lifestyle Modifications Recommended by JNC 7") (B).

6.4. Referral to a registered dietitian should be considered to help patients achieve dietary recommendations (C).

Table. Macronutrient Composition and Mineral Content of the Dietary Approaches to Stop Hypertension (DASH) Recommended by JNC 7, with Modifications for Stages 3-4 of CKD

*Not recommended for patients with "salt-wasting."
**Adjust so total calories from protein, fat, and carbohydrate is 100%.

Table. Other Lifestyle Modifications Recommended by JNC 7

Guideline 7: Pharmacological Therapy: Use of Antihypertensive Agents in CKD

All antihypertensive agents can be used to lower blood pressure in CKD. Multi-drug regimens will be necessary in most patients with CKD to achieve therapeutic goals. Patients with specific causes of kidney disease and CVD will benefit from specific classes of agents.

7.1. Patients with CKD should be considered in the "highest-risk" group for CVD for implementing recommendations for pharmacological therapy, irrespective of cause of CKD (A).

7.2. Target blood pressure for CVD risk reduction in CKD should be <130/80 mm Hg (B).

7.3. Antihypertensive agents should be prescribed as follows, when possible:

• 7.3.a. Preferred agents for CKD should be used first (see Guidelines 8, 9, 10, 11) (A).
• 7.3.b. Diuretics should be included in the antihypertensive regimen in most patients (A).
• 7.3.c. Choose additional agents based on cardiovascular disease-specific indications to achieve therapeutic and preventive targets (see table below titled "Preferred Antihypertensive Agents for CVD") and to avoid side-effects and interactions (B).

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

• 7.4.a. Long-acting (once-daily agents) should be used when possible (B).
• 7.4.b. Two agents, either as separate prescriptions or as a fixed-dose combination containing preferred agents, may be considered as initial therapy for systolic blood pressure (SBP) >20 mm Hg above goal according to the stage of CKD and CVD risk (C).
• 7.4.c. Fixed-dose combinations may be used for maintenance therapy after the antihypertensive regimen has been established (B).

Table. Preferred Antihypertensive Agents for CVD

^a Only some beta-blockers (carvedilol, bisoprolol, metoprolol succinate)
^b Nondihydropyridine calcium-channel blockers

Guideline 8: Pharmacological Therapy: Diabetic Kidney Disease

Diabetes mellitus is the most common cause of kidney failure in the United States. Diabetic kidney disease is characterized by the early onset of albuminuria, hypertension, and a high risk of coexistent or subsequent CVD.

8.1. Target blood pressure in diabetic kidney disease should be <130/80 mm Hg (Guideline 7) (see table below titled "Hypertension and Antihypertensive Agents in Diabetic Kidney Disease").

8.2. Patients with diabetic kidney disease, with or without hypertension, should be treated with an ACE inhibitor or an ARB (see table below titled "Hypertension and Antihypertensive Agents in Diabetic Kidney Disease ").

Table. Hypertension and Antihypertensive Agents in Diabetic Kidney Disease

Note: Letters in parentheses denote strength of recommendations.

Guideline 9: Pharmacological Therapy: Nondiabetic Kidney Disease

Nondiabetic kidney diseases include glomerular diseases other than diabetes, vascular diseases other than renal artery disease, tubulointerstitial diseases, and cystic disease. Among these diseases, the level of proteinuria is useful for diagnosis and prognosis. Glomerular diseases are characterized by higher levels of proteinuria than other diseases. Higher levels of proteinuria are associated with faster progression of kidney disease and increased risk of CVD.

9.1. Target blood pressure in nondiabetic kidney disease should be <130/80 mm Hg (Guideline 1) (see table below titled "Hypertension and Antihypertensive Agents in Nondiabetic Kidney Disease").

9.2. Patients with nondiabetic kidney disease and spot urine total protein to creatinine ratio >200 mg/g, with or without hypertension, should be treated with an ACE inhibitor or ARB (see table below titled "Hypertension and Antihypertensive Agents in Nondiabetic Kidney Disease").

Table. Hypertension and Antihypertensive Agents in Nondiabetic Kidney Disease

Note: Letters in parentheses denote strength of recommendations.

Guideline 10: Pharmacological Therapy: Kidney Disease in the Kidney Transplant Recipient

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

10.1. The target blood pressure in kidney transplant recipients should be <130/80 mm Hg (see Guideline 7) (see table below titled "Hypertension and Antihypertensive Agents in Kidney Disease in the Kidney Transplant Recipient").

10.2. Patients with CKD in the kidney transplant should be treated with any of the following to reach the target blood pressure: calcium channel blocker (CCB), diuretics, ACE inhibitor, ARB, or beta-blocker (see table below titled "Hypertension and Antihypertensive Agents in Kidney Disease in the Kidney Transplant Recipient").

Table. Hypertension and Antihypertensive Agents in Kidney Disease in the Kidney Transplant Recipient

Note: Letters in parentheses denote strength of recommendations.

Guideline 11: Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in CKD

ACE inhibitors and ARBs can be used safely in most patients with CKD.

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

11.2. ACE inhibitors and ARBs should be used as alternatives to each other, if the preferred class cannot be used (B).

11.3. ACE inhibitors and ARBs can be used in combination to lower blood pressure or reduce proteinuria (C).

11.4. Patients treated with ACE inhibitors or ARBs should be monitored for hypotension, decreased GFR, and hyperkalemia (A).

11.5. The interval for monitoring blood pressure, GFR, and serum potassium depends on baseline levels (see table below titled "Recommended Intervals for Monitoring Blood Pressure, GFR, and Serum Potassium for Side Effects of ACE Inhibitors or ARBs in CKD") (B).

11.6. In most patients, the ACE inhibitor or ARB can be continued if:

• 11.6.a. GFR decline over four months is <30% from baseline value (B).
• 11.6.b. Serum potassium is <5.5 mEq/L (B).

11.7 ACE inhibitors and ARBs should not be used or used with caution in certain circumstances (see table below titled "Circumstances in which ACE Inhibitors and ARBs Should Not Be Used").

Table. Recommended Intervals for Monitoring Blood Pressure, GFR, and Serum Potassium for Side Effects of ACE Inhibitors or ARBs in CKD

*See Guideline 7 for recommended intervals to reach blood pressure goal.

Table. Circumstances in which ACE Inhibitors and ARBs Should Not Be Used

*Including renal artery stenosis in the kidney transplant or in a solitary kidney.
Note: Letters in parentheses denote strength of recommendations.

Guideline 12: Use of Diuretics in CKD

Diuretics are useful in the management of most patients with CKD. They reduce extracellular fluid (ECF) volume; lower blood pressure; potentiate the effects of ACE inhibitors, ARBs, and other antihypertensive agents; and reduce the risk of CVD in CKD. Choice of diuretic agents depends on the level of GFR and need for reduction in ECF volume.

12.1. Most patients with CKD should be treated with a diuretic (A).

• 12.1.a. Thiazide diuretics given once daily are recommended in patients with GFR >30 mL/min/1.73 m² (CKD Stages 1-3) (A).
• 12.1.b. Loop diuretics given once or twice daily are recommended in patients with GFR <30 mL/min/1.73 m² (CKD Stages 4-5) (A).
• 12.1.c. Loop diuretics given once or twice daily, in combination with thiazide diuretics, can be used for patients with ECF volume expansion and edema (A).
• 12.1.d. Potassium-sparing diuretics should be used with caution:
  • 12.1.d.i. In patients with GFR <30 mL/min/1.73 m² (CKD Stages 4-5) (A)
  • 12.1.d.ii. In patients receiving concomitant therapy with ACE inhibitors or ARBs (A)
  • 12.1.d.iii. In patients with additional risk factors for hyperkalemia (A)

12.2. Patients treated with diuretics should be monitored for:

• 12.2.a. Volume depletion, manifest by hypotension or decreased GFR (A)
• 12.2.b. Hypokalemia and other electrolyte abnormalities (A)
• 12.2.c. The interval for monitoring depends on baseline values for blood pressure, GFR, and serum potassium concentration (see table below titled "Recommended Intervals for Monitoring Blood Pressure, GFR, and Serum Potassium for Side Effects of Diuretics in CKD") (B).

12.3. Long-acting diuretics and combinations of diuretics with other antihypertensive agents should be considered to increase patient adherence (B).

Table. Recommended Intervals for Monitoring Blood Pressure, GFR, and Serum Potassium for Side Effects of ACE Diuretics in CKD

*See Guideline 7 for recommended intervals to reach blood pressure goal.

Guideline 13: Special Considerations in Children

Hypertension is common in children with CKD. Because of their young age at onset of CKD and hypertension, children have a high lifetime exposure to risk factors for CVD. Thus, children with CKD are at high risk of complications from hypertension.

13.1. Measurement of blood pressure in children should be performed with age- and size-appropriate equipment, and blood pressure values should be interpreted according to normal values adjusted for age, gender, and height percentile, as recommended by the 1996 Update on the Task Force Report on High Blood Pressure in Children and Adolescents: A Working Group Report from the National High Blood Pressure Education Program (A).

13.2. The cause of CKD and age of the child should be considered in selecting the class of antihypertensive agent (A).

13.3. Target blood pressure in children should be lower than the 90th percentile for normal values adjusted for age, gender, and height or 130/80 mm Hg, whichever is lower (B).

13.4. Because of the specialized nature of CKD and blood pressure management in children, a pediatric kidney disease specialist should be involved in their care, when possible (C).

Definitions:

Recommendations Rating Scheme

Grade A

It is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong evidence that the practice improves health outcomes.

Grade B

It is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately strong evidence that the practice improves health outcomes.

Grade C

It is recommended that clinicians consider following the guideline for eligible patients. This recommendation is based on either weak evidence or on the opinions of the Work Group and reviewers, that the practice might improve health outcomes.

Health outcomes are health-related events, conditions, or symptoms that can be perceived by individuals to have an important effect on their lives. Improving health outcomes implies that benefits outweigh any adverse effect.

• K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004 May;43(5 Suppl 1):S1-290. [625 references] PubMed

Electronic copies: Available from the National Kidney Foundation (NKF) Web site.

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