S 14 Indian Journal of Nephrology Indian J Nephrol 2005;15, Supplement 1: S14-S22

Clinical practice guidelines on hypertension

and antihypertensive agents
in chronic kidney disease (CKD)

ypertension is a cause and complications of CKD. target blood pressure.

H Hypertension in CKD increases the risk of important
adverse outcomes, including loss of kidney function and
CKD is defined as kidney damage, as confirmed by kidney
biopsy or markers of damage, or glomerular filtration rate
kidney failure, early development and accelerated
(GFR) <60 mL/min/1.73 m2 for > 3 months Markers of
progression of cardiovascular disease (CVD), and
kidney damage include proteinuria, abnormalities on the
premature death. In the ongoing effort to improve
urine dipstick or sediment examination, or abnormalities
outcomes of CKD, the National Kidney Foundation (NKF)
on imaging studies of the kidneys. GFR can be estimated
Kidney Disease Outcomes Quality Initiative (K/DOQI)
from prediction equations based on serum Creatinine and
appointed a Work Group and an Evidence Review Team
other variables, including age, sex, race, and body size.
in 2001 to develop clinical practice guidelines on
(Table 1 and 2)
hypertension and use of antihypertensive agents in CKD.
During this same time, clinical practice guidelines on this Among individuals with CKD, the stage of disease is
topic relevant to CKD were also under development by based on the level of GFR, irrespective of the cause of
other organizations, including the Seventh Report of the kidney disease. The high prevalence of earlier stages of
Joint National Committee on the Prevention, Detection, CKD emphasizes the importance for all health-care
Evaluation, and Treatment of High Blood Pressure (JNC providers, not just kidney disease specialists, to detect,
7) and the 2003 report of the American Diabetes evaluate, and treat CKD.
Association (ADA) on the Treatment of Hypertension in
Adults with Diabetes.
Hypertension in CKD

But several of the drugs like clonidine and prazosin which
are commonly used in Indian scenario are not mentioned
in these guidelines. Clonidine is very cost effective and
useful drug these patients being economical for initial
treatment and in those whose blood pressure is refractory
to control and require more than 3-4 drugs to achieve the
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 4
illustrates the classification of individuals based on
presence or absence of kidney damage and hypertension

Table 1 - Definition of CKD

Copyright © 2005 by The Indian Society of Nephrology

Indian J Nephrol 2005;15, Supplement 1: S14-S22
Table 2 - Stages and Prevalence of CKD
and level of GFR. Approximately 50% to 75% of
individuals with GFR <60mL/min/1.73 m2, (CKD stages
3-5) have hypertension Among individuals with GFR
<60mL/min/1.73 m2 distinguishing CKD Stages 1 and 2
from “hypertension” and hypertension with decreased
GFR” requires assessment for markers of kidney damage.
This is especially important in the elderly, in whom both
hypertension and decreased GFR are common (Table 3)
Cardiovascular Disease in CKD
CKD is a risk factor for cardiovascular disease (CVD).
Dialysis patient have a 50 to 500 times increased risk of
CVD mortality compared to age-marched individuals from
the general population. Earlier stages of CKD are also
associated with an increased risk of CVD. CKD is
associated with an increased prevalence and severity of
Table 3 - Classification of blood pressure for adult age>18 years (JNC 7)
Clinical practice guidelines for HT in CKD S 15
both “traditional” and “nontraditional” risk factors for CVD.
Traditional risk factors include those initially described in
the Framingham Study. Among traditional risk factors,
hypertension is closely linked to CKD and has often been
implicated as the main cause of CVD in CKD. Other
traditional risk factors for CVD that are common in CKD
include 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 an
increased risk of CVD, even after controlling for many of
these risk factors. Early detection and treatment of CKD,
including detection and treatment of hypertension and o
these risk actors. Early detection and treatment of CKD,
including detection and treatment of hypertension and
Copyright © 2005 by The Indian Society of Nephrology
S 16 Indian Journal of Nephrology Indian J Nephrol 2005;15, Supplement 1: S14-S22

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

Copyright © 2005 by The Indian Society of Nephrology

Indian J Nephrol 2005;15, Supplement 1: S14-S22 Clinical practice guidelines for HT in CKD S 17

Table 8 - Topics and guidelines

Table 9

Copyright © 2005 by The Indian Society of Nephrology

S 18 Indian Journal of Nephrology
other CVD risk factors may reduce the risk of CVD in
CKD. Achieving these goals in CKD will require co-
ordinating antihypertensive therapy with therapy for other
CVD risk factors (Table 4,5 and 6).
Recommendations for antihypertensive therapy in the
general population are based on observational studies
and controlled trials relating blood pressure level and
antihypertensive therapy to CVD risk. Few patients with
CKD were included in these studies. Thus,
recommendations to reduce CVD risk in CKD are based
largely on extrapolation from the general population.
Progression of CKD
Most kidney diseases worsen progressively over time.
Antihypertensive therapy affects several modifiable key
factors related to the progression of kidney disease,
including hypertension, proteinuria, and other
mechanisms, such as increased acitivity of the
reninangiotensin system (RAS). Several large, controlled
trials have examined the effect of antihypertensive
therapy on the progression of kidney disease in patients
with and without hypertension. While these trials have
provided important answers about therapy, the
relationships among these “progression factors” are
complex, and many questions remain unanswered,
especially regarding the mechanisms underlying the
therapeutic benefit of the interventions (Table 7, 8 and
9).
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 use din CKD
to:
a. Lower blood pressure
b. Reduce the risk of CVD, in patients with or
without hypertension
c. Slow progression of kidney disease, in patients
with or without hypertension
1.2 Modifications to antihypertensive therapy should
be considered based on the level of proteinuria
during treatment ©.
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
Copyright © 2005 by The Indian Society of Nephrology
Indian J Nephrol 2005;15, Supplement 1: S14-S22
should be based on risk stratification ©.
GUIDELINE 2:
Evaluation of patients with CKD or
hypertension
1 Blood pressure should be measured at each health
encounter (A).
2 Initial evaluation should include the following
elements:
a. Description of CKD;
1 Type (diagnosis), level of GKR, and level
of 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 diet
and other lifestyle modifications, adherence to
pharmacological 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 evaluation
should be guided by clinical conditions ©
2.3 Patients with resistant hypertension should undergo
additional evaluation to ascertain the cause (B)
2.4 Patient should be referred to specialists, when
possible
GUIDELINE 3:
Measurement of blood pressure in adults
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 ©.
3.3 Ambulatory blood pressure monitoring should be
considered for patients with CKD for the following
indications ©:
a Suspected white coat hypertension
b Resistant hypertension
c Hypotensive symptoms while taking
Indian J Nephrol 2005;15, Supplement 1: S14-S22
antihypertensive medications
d Episodic hyeptension
e Autonomic dysfunction
GUIDELINE 4:
Evaluation for renal arteyr disease
Renal artery disease (RAD) is a cause of CKD and
hypertenion, and can be present in patients with other
causes of CKD, sucha s 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:
a. Estimate the probability of RAD using a
predictive index derived from clinical
characteristics (B)
b
. Obtain a noninavasive screening test for RAD
(A)
c. Refer to a kidney disease or hypertension
specialist for evaluation ©
4.2 Patients found to have hemodynamically significant
RAD should be referred to a kidney disease or
hypertenion specialist for management ©
GUIDELINE 5:
Education on self-management behavior
Antihypertensive therapy must take into consideration
the patient’s perception of the health-care provicer’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
toeconomic 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.
Clinical practice guidelines for HT in CKD S 19
6.1 Dietary sodium intake of less than 2.4g/d (less than
100mmgl/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 (B)
6.3 Lifestyle modifications recommended for CVD risk
reduction including Exercise, Yoga should be
recommended as part of the treatment regimen (B)
6.4 Referral to a registered dietitian should be considered
to help patients achieve dietary recommendations
©
GUIDELINE 7:
Pharmacological therapy: use of
antihypertensive agents in CKD
All antihypertensive agents can be used to lower blood
pressure in CKD. Multidrug 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 Paitents 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 <130/80mmHg (B)
7.3 Antihypertensive agents should be prescribed as
follows, when possible:
a. Preferred agents for CKD should be used first
(A);
b. Diuretics should be included in the
antihypertensive regimen in most patients (A)
c. Choose additional agents based on
cardiovascular disease-specific indications to
achieve therapeutic and preventive targets and
to avoid side-effects and interactions (B)
7.4 The antihypertensive regimen should be simplified
as much as possible (B)
i
. Long-active (once-daily agents) should be used
when possible (B)
i. Two agents, either as separate prescriptions or
as a fixed-dose combination containing
preferred agents, may be considered as initial
therapy for SBP 20mmHg above goal according
to the stage of CKD and CVD risk ©
iii. Fixed-dose combinations may be used for
maintenance therapy after the antihypertensive
regimen has been established (B)
GUIDELINE 8:
Copyright © 2005 by The Indian Society of Nephrology
S 20 Indian Journal of Nephrology
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 <130/80mmHg
8.2 Patients with diabetic kidney disease, with or without
hypertension, should be treated with an ACE inhibitor
or an ARB
GUIDELINE 9:
Pharmacological therapy: nondiabetic kidney
disease
Nondiabetic kidney diseases include glomerular diseases
other than diabetes, vascular disease 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
if urine protein <1g/day should be <130/80mmHg.
9.2 Patients with nondiabetic kidney disease and spot
urine total protein to Creatinine ratio >200mg/g, with
or without hypertension, should be treated with an
ACE inhibitor or ARB, target BP <125/75mmHg
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 <130/80mmHg
10.2 Patients with CKD in the kidney transplant should
be treated with any of the following to reach the
target blood pressure: CCB, diuretics, ACE inhibitor,
ARB, or beta-blocker
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
Copyright © 2005 by The Indian Society of Nephrology
Indian J Nephrol 2005;15, Supplement 1: S14-S22
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 incombination
to lower blood pressure or reduce proteinuria ©
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
(B)
11.6 In most patients, the ACE inhibitor or ARB can be
continued if:
a. GFR decline 4 months is <30% from baseline
value (B)
b. Serum potassium is 5.5mEq/l (B)
11.7 ACE inhibitors and ARBs should not be used or
used with caution in certain circumstances
GUIDELINE 12:
Use of diuretics in CKD
Diuretics are useful in the management of most patients
with CKD. They reduce ECF volume; lower blood pressure;
protentiate 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)
i
. Thiazide diuretics given once daily are
recommended in patients with GFR >30ml/
min1.73 m2 (CKD stages 1-3) (A)
i. Loop diuretics given once or twice daily are
recommended in patients with GFR <30ml/
min1.73 m2 (CKD stages 4-5) (A)
iii. Loop diuretics given once or twice daily, in
combinatin with thiazide diuretics, can be used
for patients with ECF volume expansion and
edema (A)
iv. Potassium – sparing diuretics should be used
with caution:
1. In patients with GFR<30ml/min1.73 m2
(CKD stages 4-5) (A)
2. In patients receiving cocomitant therapy
with ACE inhibitors or ARBs (A)
3. In patients with additional risk factors for
Indian J Nephrol 2005;15, Supplement 1: S14-S22
hyperkalemia (A)
12.2 Patients treated with diuretics should be monitored
for:
a. Volume depletion, manifest by hypotension or
decreased GFR (A)
b. Hypokalemia and other electrolyte abnormalities
(A)
c. The interval for monitoring depends on baseline
values for blood pressure, GFR and serum
potassium concentration (B)
12.3 Long-acting diuretics and combinations of diuretics
with other antihypertensive agents should be
considered to increase patient adherence (B)
GUIDELINE 13:
use of alpha blockers
13.1 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 insulin
sensitivity and control of dyslipidemia
13.4 However, it needs to be evaluated for autonomoc
neuropathy before starting these drugs and long
term data on mortality and morbidity is controversial
13.5 It is useful in patients with concomitant benign
hyperplasia fo prostate and CKD for symptomatic
relief.
GUIDELINE 14:
Use of centrally acting drugs eg clonidine,
methyl dopa
a. Clonidine is very effective and cost effective
antihypertensive
b. It is very useful to use the drug particularly to
achieve 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 children
Hypertesion 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, childredn with CKD are at high risk of
complications from hypertension.
15 .1 Measurement of blood pressure in children should
be performed with age and size appropriate
Clinical practice guidelines for HT in CKD S 21
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)
15.2 The cause of CKD and age of the child should be
considered in selecting the class of antihypertensive
agent (A)
15.3 Target blood pressure in children should be lower
than the 90th percentile for normal values adjusted
for age, gender and height or 120/80 mmHg,
whichever is lower (B)
15.4 Because of the specialized nature of CKD and blood
pressure 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 particularly
renovascular disease and reglux nephropathy
GUIDELINE 16:
Special considerations in adult
16.1 Frequency of BP measurement should be
individualized
16.2 Daily home monitoring particularly with uncontrolled
BP
16.3 More frequent measurement with uncontrolled BP
16.4 Postural hypotension should be periodically checked
in patients with autonomic neuropathy
16.5 Electronic BP instrument should be standardized
with mercury shygometer
16.6 Patient should be seated quietly for at least 5
minutes in a chair rather than on a examination
table, with feet on the floor and arm supported at
heart level. An appropriate size cuff, cuff bladder
encircling at least 80% of the arm, should be used
to ensure accuracy. At least 2 measurements should
be made. Phase l, appearance of sound, should be
considered 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.
Copyright © 2005 by The Indian Society of Nephrology
S 22 Indian Journal of Nephrology
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