Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline
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Annals of Internal Medicine CLINICAL GUIDELINE
Management of Blood Pressure in Patients With Chronic Kidney
Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical
Practice Guideline
Charles R.V. Tomson, MA, BM, BCh, DM; Alfred K. Cheung, MD; Johannes F.E. Mann, MD; Tara I. Chang, MD, MS;
William C. Cushman, MD; Susan L. Furth, MD, PhD; Fan Fan Hou, MD, PhD; Gregory A. Knoll, MD, MSc;
Paul Muntner, PhD, MHS; Roberto Pecoits-Filho, MD, PhD; Sheldon W. Tobe, MD, MScCH (HPTE); Lyubov Lytvyn, BSc, MSc;
Jonathan C. Craig, MBChB, DipCH, M Med (Clin Epi), PhD; David J. Tunnicliffe, PhD; Martin Howell, PhD;
Marcello Tonelli, MD, SM, MSc; Michael Cheung, MA; Amy Earley, BS; Joachim H. Ix, MD, MAS*; and Mark J. Sarnak, MD, MS*
Description: The Kidney Disease: Improving Global Outcomes the recommendations and rate the strength and quality of the
(KDIGO) 2021 clinical practice guideline for the management of evidence. Practice points were included to provide guidance
blood pressure (BP) in patients with chronic kidney disease when evidence was insufficient to make a graded recommen-
(CKD) not receiving dialysis is an update of the KDIGO 2012 dation. The guideline was revised after public consultation
guideline on the same topic and reflects new evidence on the between January and March 2020.
risks and benefits of BP-lowering therapy among patients with
CKD. It is intended to support shared decision making by health Recommendations: The updated guideline comprises 11
care professionals working with patients with CKD worldwide. recommendations and 20 practice points. This synopsis sum-
This article is a synopsis of the full guideline. marizes key recommendations pertinent to the diagnosis
and management of high BP in adults with CKD, excluding
Methods: The KDIGO leadership commissioned 2 co-chairs those receiving kidney replacement therapy. In particular,
to convene an international Work Group of researchers and the synopsis focuses on recommendations for standardized
clinicians. After a Controversies Conference in September BP measurement and a target systolic BP of less than 120
2017, the Work Group defined the scope of the evidence mm Hg, because these recommendations differ from some
review, which was undertaken by an evidence review team other guidelines.
between October 2017 and April 2020. Evidence reviews were
done according to the Cochrane Handbook. The GRADE Ann Intern Med. doi:10.7326/M21-0834 Annals.org
(Grading of Recommendations Assessment, Development and For author, article, and disclosure information, see end of text.
Evaluation) approach was used to guide the development of This article was published at Annals.org on 22 June 2021.
L arge-scale, prospective, observational studies have
demonstrated a log-linear relationship between usual
blood pressure (BP) (down to 115/75 mm Hg) and subse-
cause hypertension. The evidence that BP lowering (for
example, SBPCLINICAL GUIDELINE Summary of KDIGO Guideline on Blood Pressure Management in CKD with less risk for progression to kidney failure than in updated; otherwise, new systematic reviews were done, in previous studies done exclusively in CKD populations accordance with the Cochrane Handbook (24). From a total (15–18). In particular, SPRINT, which randomly assigned of 6863 citations screened, 290 RCTs, 35 systematic reviews, 9361 participants to intensive (SBP
Summary of KDIGO Guideline on Blood Pressure Management in CKD CLINICAL GUIDELINE
Table 1. Recommendations and Practice Points From the KDIGO 2021 Clinical Practice Guideline for the Management of BP in
CKD
Chapter 1: BP measurement Recommendation 3.2.3: We recommend starting RASI therapy (ACEI or
Recommendation 1.1: We recommend standardized office BP mea- ARB) for people with high BP, CKD, and moderately-to-severely
surement in preference to routine office BP measurement for the increased albuminuria (CKD G1–G4; albuminuria categories A2 and A3)
management of high BP in adults (1B). with diabetes (1B).
Practice Point 1.1: An oscillometric BP device may be preferable to a Practice Point 3.2.1: It may be reasonable to treat people with high BP,
manual BP device for standardized office BP measurement; how- CKD, and no albuminuria, with or without diabetes, with RASI (ACEI
ever, standardization emphasizes adequate preparations for BP or ARB).
measurement, not the type of equipment. Practice Point 3.2.2: RASI (ACEI or ARB) should be administered using
Practice Point 1.2: Automated office BP, either attended or unat- the highest approved dose that is tolerated to achieve the benefits
tended, may be the preferred method of standardized office BP described because the proven benefits were achieved in trials using
measurement. these doses.
Practice Point 1.3: Oscillometric devices can be used to measure BP Practice Point 3.2.3: Changes in BP, serum creatinine, and serum potas-
among patients with atrial fibrillation. sium should be checked within 2–4 weeks of initiation or increase in
Recommendation 1.2: We suggest that out-of-office BP measurements the dose of a RASI, depending on the current GFR and serum
with ABPM or HBPM be used to complement standardized office BP potassium.
readings for the management of high BP (2B). Practice Point 3.2.4: Hyperkalemia associated with use of RASI can often
be managed by measures to reduce the serum potassium levels
Chapter 2: Lifestyle interventions for lowering BP in patients with rather than decreasing the dose or stopping RASI.
CKD not receiving dialysis Practice Point 3.2.5: Continue ACEI or ARB therapy unless serum creati-
Recommendation 2.1.1: We suggest targeting a sodium intakeCLINICAL GUIDELINE Summary of KDIGO Guideline on Blood Pressure Management in CKD
Figure 1. Checklist for standardized office BP measurement.
1. Properly prepare the 1. Have the patient relax, sitting in a chair (feet on floor, back supported) for >5 min
patient 2. The patient should avoid caffeine, exercise, and smoking for at least 30 min
before measurement
3. Ensure patient has emptied his/her bladder
4. Neither the patient nor the observer should talk during the rest period or during
the measurement
5. Remove all clothing covering the location of cuff placement
6. Measurements made while the patient is sitting or lying on an examining table
do not fulfill these criteria
2. Use proper technique 1. Use a BP measurement device that has been validated, and ensure that the
for BP measurements device is calibrated periodically
2. Support the patient's arm (e.g., resting on a desk)
3. Position the middle of the cuff on the patient's upper arm at the level of the right
atrium (the midpoint of the sternum)
4. Use the correct cuff size, such that the bladder encircles 80% of the arm, and note
if a larger- or smaller-than-normal cuff size is used
5. Either the stethoscope diaphragm or bell may be used for auscultatory readings
3. Take the proper 1. At the first visit, record BP in both arms. Use the arm that gives the higher reading
measurements needed for subsequent readings
for diagnosis and 2. Separate repeated measurements by 1–2 min
treatment of elevated 3. For auscultatory determinations, use a palpated estimate of radial pulse
BP obliteration pressure to estimate SBP. Inflate the cuff 20–30 mm Hg above this
level for an auscultatory determination of the BP level
4. For auscultatory readings, deflate the cuff pressure 2 mm Hg per second, and
listen for Korotkoff sounds
4. Properly document 1. Record SBP and DBP. If using the auscultatory technique, record SBP and DBP as
accurate BP readings onset of the first Korotkoff sound and disappearance of all Korotkoff sounds,
respectively, using the nearest even number
2. Note the time of most recent BP medication taken before measurements
5. Average the readings Use an average of ≥2 readings obtained on ≥2 occasions to estimate the
individual's level of BP
6. Provide BP readings Provide patients with the SBP/DBP readings verbally and in writing
to patient
Modification for pediatrics: BP in infants should be measured while supine, and the use of the bell is recommended. BP = blood pressure; DBP = dia-
stolic BP; SBP = systolic BP. (Reproduced from Whelton and colleagues [26], with permission.).
BP (Figure 2) (27). Similarly, a study of 3074 SPRINT par- of concerns that the targets will be applied to routine BP
ticipants compared 3 or more outpatient readings from measurements, this KDIGO BP guideline makes a critical dis-
the electronic health record versus standardized BP tinction, recommending widespread adoption of standar-
measurements taken during the trial and found that out- dized BP measurements and thereby applying SBP targets
patient BPs were generally higher than standardized BP with proven efficacy in clinical trials, among participants with
measurements. More important, heterogeneity in differ- CKD.
ences was high between BP recorded in the electronic The Work Group recognized that standardized BP
health record and standardized trial measurements (28). measurements increase the burden to patients, health care
It may seem feasible to simply subtract the mean differ- providers, and health care facilities. However, this recom-
ence from the routine BP to obtain an estimate of stand- mendation was rated as strong because obtaining standar-
ardized BP; however, these data consistently show wide dized BPs is essential for the implementation of the BP
limits of agreement (for example, 46.1 to +20.7 mm targets developed in trials. The recommendation also places
Hg) (27), making such adjustments highly unreliable for a high value on avoidance of misclassification so as to pre-
the individual patient, such that both over- and undertreat- vent over- or undertreatment of high BP—an issue that
ment are likely if routine BPs are used to manage BP. These becomes increasingly important when targeting lower BPs.
results highlight the importance of the standardized BP mea- Oscillometric BP devices may be preferred over
surement technique and an inability to apply 1 common cor- manual BP devices (Table 1, Practice Point 1.1) because
rection factor to approximate research-quality BP estimates they minimize potential sources of inaccuracy in BP
when BP is not measured appropriately in routine clinical measurements that can occur with human errors associ-
practice. The recommendation to measure standardized BP ated with manual BP measurement, such as those result-
is consistent with other recent guidelines (for example, from ing from improper deflation rate, terminal digit bias, or
the American College of Cardiology and American Heart hearing impairment. However, RCTs have used standar-
Association [26, 29] and European Society of Cardiology dized office BP measured with either oscillometric or
and European Society of Hypertension [30]). However, manual devices, and studies that directly compared the
whereas other guidelines have relaxed BP targets because 2 techniques do not suggest overt differences in
4 Annals of Internal Medicine Annals.orgSummary of KDIGO Guideline on Blood Pressure Management in CKD CLINICAL GUIDELINE
Figure 2. Bland–Altman plot showing the mean differences between various BP recordings and their limits of agreement.
100 100 100
Systolic
50 50 50
0 0 0
Daytime Ambulatory, mm Hg
Daytime Ambulatory, mm Hg
Research-Grade Clinc Minus
Research-Grade Clinc Minus
–50 –50 –50
Routine Clinlc, mm Hg
Routine Clinc Minus
–100 –100 –100
100 150 200 50 100 150 200 100120140 160180 200
100 Diastolic 100 100
50 50 50
0 0 0
–50 –50 –50
n = 275
–100 –100 –100
20 40 60 80 100 120 40 60 80 100 120 40 60 80 100 120
Average of Research- Average of Research-Grade Average of Routine
Grade Clinc and Clinc and Daytime Clinc and Daytime
Routine Clinlc, mm Hg Ambulatory, mm Hg Ambulatory, mm Hg
The top panel shows systolic BP, and the bottom panel shows diastolic BP. Research-grade BP was, on average, 12.7/12.0 mm Hg lower (bias) than rou-
tine clinic BP and had wide limits of agreement. BP = blood pressure. (Reproduced from Agarwal [27].).
readings (31–33); therefore, manual BP devices are also (Figure 3): normotension, white coat hypertension, sustained
acceptable when oscillometric devices are unavailable. hypertension, and masked hypertension. In those receiving
The Work Group recognized that oscillometric BP devi- BP-lowering medications, 4 similar groups can be catego-
ces may cost more and may be unavailable in some rized: white coat effect, sustained controlled hypertension,
settings. sustained uncontrolled hypertension, and masked uncon-
Automated office BP devices may be the preferred trolled hypertension. Observational studies indicate a
method for standardized office BP measurement (Table 1, stronger association with cardiovascular and kidney out-
Practice Point 1.2). They may increase the likelihood
comes for out-of-office than in-office BP measurements in
of adherence to proper preparation because they can be
the general population and persons with CKD (42–44). For
programmed to include a rest period. They can also auto-
matically take multiple BP measurements and provide an example, masked hypertension and masked uncontrolled
average. Automated devices can measure BP either with hypertension are associated with higher risk for cardio-
or without a health care provider in the room. Although a vascular disease and kidney outcomes than are sustained
recent meta-analysis suggested that unattended measure- normotension and sustained controlled hypertension,
ments result in lower average BPs than attended measure- respectively; these subgroups cannot be defined without
ments (34), the differences were small when restricted to ABPM measurements and have potential treatment impli-
studies that randomized the order in which measurements cations (42).
were made (35–40). Of note, several large trials, including The KDIGO BP guideline regarded out-of-office BP
SPRINT, used automated office BP as their measurement measurements as a complement to standardized office
method. The SPRINT protocol did not specify whether BP readings for the management of high BP. We recom-
automated office BP should be attended or unattended, mend using initial ABPM, where available, to supplement
and reductions in BP and cardiovascular risk were similar
standardized office BP and HBPM for ongoing manage-
regardless of whether the measurement was attended or
ment of BP. Providers working in areas where ABPM is
unattended (41).
We suggest that out-of-office BP measurements with not available may choose to use HBPM instead of an ini-
ambulatory BP monitoring (ABPM) or home BP monitor- tial ABPM procedure.
ing (HBPM) be used to complement standardized office The Work Group, however, acknowledged the lack
BP readings for the management of high BP (2B). of RCTs that specifically address whether and how best
Techniques for out-of-office BP measurement include to treat BP profiles identified by out-of-office BP meas-
HBPM and 24-hour ABPM. In patients not receiving BP- urements (Appendix Table 4, available at Annals.org).
lowering medications, the following 4 groups can be catego- The recommendation to obtain such measurements is
rized on the basis of in- and out-of-office BP measurements therefore weak because no large RCTs have targeted
out-of-office BP values in adults.
Annals.org Annals of Internal Medicine 5CLINICAL GUIDELINE Summary of KDIGO Guideline on Blood Pressure Management in CKD
Figure 3. BP patterns informed by out-of-office BP measurements in addition to standardized office BP measurement.
Not receiving antihypertensive medication Receiving antihypertensive medication
Hypertension based on
Hypertension based on
standardized office BP
standardized office BP
White coat Sustained White coat Sustained uncontrolled
Yes Yes
hypertension hypertension effect hypertension
Masked Sustained controlled Masked uncontrolled
No Normotension No
hypertension hypertension hypertension
No Yes No Yes
Hypertension based on Hypertension based on
out-of-office BP out-of-office BP
BP = blood pressure.
RECOMMENDATIONS FOR BP TARGETS outcomes in the trials was similar, and the difference in sta-
We suggest that adults with high BP and CKD be tistical significance with the primary end point may have
treated with a target SBP ofSummary of KDIGO Guideline on Blood Pressure Management in CKD CLINICAL GUIDELINE
for benefit from strong in the CKD subpopulation with low
Table 2. Certainty of the Evidence Supporting an SBP eGFR and severely increased albuminuria to weak or absent
Target of 50 y apy to achieve the SBP target of less than 120 mm Hg; no
High risk for cardiovascular disease
RCTs have compared different combination therapies in
Less certain CKD. Evidence-based recommendations are therefore lim-
Age 80 y ited to the choice of initial therapy.
Diabetes with CKD
CKD G4 or G5* We recommend starting RASI therapy (ACEI or ARB)
Proteinuria >1 g/d*
White coat hypertension
for people with high BP, CKD, and severely increased al-
Pretreatment SBP of 120–129 mm Hg buminuria (CKD G1 to G4; albuminuria category A3) with-
Prior stroke out diabetes (1B).
Very low DBP Evidence supporting use of RASI in CKD without dia-
Polycystic kidney disease
betes with severely increased albuminuria comes from 4
Severe hypertension—e.g., SBP ≥180 mm Hg while receiving no
treatment or ≥150 mm Hg despite >4 antihypertensive agents placebo-controlled RCTs (63–67) showing clear evidence
CKD = chronic kidney disease; DBP = diastolic blood pressure; SBP =
of reduction in the risks for both kidney failure and cardi-
systolic blood pressure. ovascular events (based on a meta-analysis by the guide-
* CKD G4–G5 indicates an estimated glomerular filtration rateCLINICAL GUIDELINE Summary of KDIGO Guideline on Blood Pressure Management in CKD
We recommend avoiding any combination of ACEI, consistent with the recently published KDIGO 2020
ARB, and direct renin inhibitor therapy in patients with Guideline for Diabetes Management in CKD, providing con-
CKD with or without diabetes (1B). sistency across guidelines (84).
Several large trials have tested the hypothesis that Intervention studies and systematic reviews have
dual RAS blockade (a combination of 2 of ACEI, ARB, and firmly established the effects of regular physical activity
direct renin inhibitor) would confer additional benefit, on BP lowering, in addition to other health benefits in the
compared with monotherapy, in high-risk populations. general population. As with dietary sodium intake, data
Meta-analysis of these studies shows no evidence of ben- on effects of exercise in populations with CKD are more
efit on cardiovascular outcomes or progression of CKD, limited. The ERT found low-quality evidence from a sin-
apart from a reduction in albuminuria; adverse effects gle, small, randomized study in a CKD population show-
include increased risks for acute kidney injury and hyper- ing that physical activity lowered SBP and diastolic BP
kalemia (76). and may limit the rate of eGFR decline over 12 months
Since the full guideline was finalized, the FIDELIO- (85). Observational studies also show a dose–response
DKD (Finerenone in Reducing Kidney Failure and relationship between greater amounts of physical activity
Disease Progression in Diabetic Kidney Disease) trial and lower risk for death in CKD populations (86). The
results were published, showing that the addition of available data did not allow differentiation of the type,
finerenone to background ACEI or ARB therapy reduced quantity, or critical elements of exercise that were most
the composite primary outcome of GFR decline, kidney beneficial to persons with CKD. Nevertheless, the Work
failure, or renal death, and also reduced risk for cardio- Group agreed that physical exercise is likely to be benefi-
vascular events (77) but increased risk for hyperkalemia. cial in CKD populations, as in the general population,
The implications of these findings will be assessed in and that the available data are consistent with this.
future updates of this guideline. However, patients with CKD have a high degree of
Recommendations for further research on choice of comorbidity and frailty and will not all be able to achieve
BP-lowering drug therapy are given in Appendix Table 6 the levels of physical activity recommended for the gen-
(available at Annals.org). eral population. In the absence of specific information on
type and intensity of exercise in CKD, the Work Group
chose targets set by the World Health Organization (83)
RECOMMENDATIONS FOR DIET AND LIFESTYLE and a lifestyle guideline from the American College of
We suggest targeting a sodium intake ofSummary of KDIGO Guideline on Blood Pressure Management in CKD CLINICAL GUIDELINE
fact that prior trials consistently used standardized office the importance of CKD as a risk factor for both high BP
BP measurements, the Work Group was concerned that and cardiovascular disease, recent RCTs have systematically
targeting a systolic BP of less than 120 mm Hg may lead recruited larger subgroups with CKD to address the efficacy
to overtreatment and associated adverse events if routine and safety of intensive BP lowering. With the emergence of
office BP was used instead of standardized BP. Thus, the new evidence on mortality and cardiovascular benefits of inten-
KDIGO 2021 BP guideline makes detailed and strong rec- sive BP lowering in patients with high BP and CKD, the KDIGO
ommendations regarding standardized BP measurement, 2021 Clinical Practice Guideline for the Management of Blood
and the target SBP of less than 120 mm Hg is specific to Pressure in Chronic Kidney Disease in patients not receiving di-
use of standardized BP measurements only. alysis recommends systematically using standardized office BP
The KDIGO 2021 BP guideline adopts a target SBP of measurement and targeting an SBP of less than 120 mm Hg.
less than 120 mm Hg for persons with CKD because of the
benefits of intensive BP control on cardiovascular and all-
From Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust,
cause mortality. The effects of intensive BP control on the
Newcastle upon Tyne, United Kingdom (C.R.T.); University of Utah,
risk for progressive CKD are much less certain.
Salt Lake City, Utah (A.K.C.); KfH Kidney Center, University Hospital,
The KDIGO 2021 BP guideline also recognizes that there
Friedrich-Alexander University, Erlangen-Nuremberg, Germany (J.F.
are certain subpopulations in CKD where the evidence to
M.); Stanford University, Palo Alto, California (T.I.C.); University of
support the SBP target of less than 120 mm Hg is less well
Tennessee Health Science Center, Memphis, Tennessee (W.C.C.);
developed, and hence the risk–benefit tradeoffs are less cer-
Perelman School of Medicine at the University of Pennsylvania and
tain. These include persons with diabetes, advanced CKD
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
(G4 or G5), proteinuria greater than 1 g/d, extremes of age,
(S.L.F.); Nanfang Hospital, Southern Medical University, Guangzhou,
white coat hypertension, or very low diastolic BP. Additional
China (F.F.H.); The Ottawa Hospital, Ottawa Hospital Research
RCTs are needed in these subpopulations.
Institute, Ottawa, Ontario, Canada (G.A.K.); University of Alabama
The KDIGO guideline differs from other recent guidelines
at Birmingham, Birmingham, Alabama (P.M.); Arbor Research
based on the same evidence, including those that have spe-
Collaborative for Health, Ann Arbor, Michigan, and Pontifical
cific recommendations for patients with CKD (26, 30, 87, 88),
Catholic University of Paraná, Curitiba, Brazil (R.P.); University of
in that the “default” SBP target is less than 120 mm Hg and
Toronto, Toronto, and Northern Ontario School of Medicine,
that this target applies only to measurements taken under
Sudbury, Ontario, Canada (S.W.T.); MAGIC Evidence Ecosystem
standardized conditions. Of note, the Hypertension Canada
Foundation, McMaster University, Hamilton, Ontario, Canada (L.L.);
guidelines (89) also adopt SBP less than 120 mm Hg for
College of Medicine and Public Health, Flinders University,
adults with CKD. The SBP recommendation is conditional,
Adelaide, South Australia, and Cochrane Kidney and Transplant,
implying a shared decision-making process in which clinicians
Sydney, New South Wales, Australia (J.C.C.); Sydney School of
and patients discuss the risks and benefits of more versus less
Public Health, The University of Sydney, Sydney, New South Wales,
intensive BP control. Targets should be individualized on the
Australia (D.J.T., M.H.); University of Calgary, Calgary, Alberta,
basis of patient preference and individual risks and benefits,
Canada (M.T.); KDIGO, Brussels, Belgium (M.C., A.E.); University of
particularly in groups in whom the evidence favoring more in-
California San Diego and Veterans Affairs San Diego Healthcare
tensive control is less certain. The recommendation for stand-
System, San Diego, California (J.H.I.); and Tufts University, Boston,
ardized BP measurement is strong because overwhelming
Massachusetts (M.J.S.).
evidence indicates that “routine” office BP measurement is
unreliable. Clinicians would not accept such unreliability in
laboratory tests or other physiologic measurements. One of Acknowledgment: The Work Group thanks the KDIGO Co-
the major reasons that most other guidelines are more con- Chairs, Michel Jadoul and Wolfgang C. Winkelmayer, for their
servative is the concern that clinicians would apply a more in- invaluable guidance. The Work Group also acknowledges all
tensive target to “routine” office BP measurements and thus who provided feedback during the public review of the draft
risk overtreatment. This is understandable, but the KDIGO guideline.
Work Group formed the strong view that clinical practice
must change. Adoption of a more conservative SBP target Financial Support: The development of this guideline is strictly
and acceptance of substandard BP measurement techniques funded by KDIGO, and neither KDIGO nor its guideline Work
would likely result in many patients with CKD around the Group members sought or received monies or fees from corpo-
world being denied the clear benefits of more intensive BP rate or commercial entities in connection with this work.
control (19). These and other controversies are explored in
more detail in Appendix Table 8 (available at Annals.org). Disclosures: Disclosures can be viewed at www.acponline.org
Like all evidence-based guidelines, the KDIGO BP in /authors/icmje/ConflictOfInterestForms.do?msNum=M21-0834.
CKD guideline is limited by the available evidence. In
particular, evidence is lacking on how best to use ABPM Corresponding Author: Joachim H. Ix, MD, MAS, Division of
or HBPM measurements in the treatment of high BP and Nephrology and Hypertension, Department of Medicine,
on how patients with CKD and high BP would weigh the University of California San Diego, San Diego VA Healthcare
benefits and risks of such options as intensive versus less System, 3350 La Jolla Village Drive, Mail Code 111-H, San
intensive treatment. Diego, CA 92161; e-mail, joeix@health.ucsd.edu.
In summary, the Work Group recognizes that the risks for
cardiovascular disease and death are greater than the risk for Current author addresses and author contributions are avail-
kidney failure in most individuals living with CKD. Recognizing able at Annals.org.
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12 Annals of Internal Medicine Annals.orgCurrent Author Addresses: Dr. Tomson: Newcastle upon Tyne Author Contributions: Conception and design: C.R.V. Tomson, Hospitals NHS Foundation Trust, Freeman Road, High Heaton, J.F.E. Mann, G.A. Knoll, J.C. Craig, A. Earley, J.H. Ix, M.J. Sarnak. Newcastle upon Tyne NE7 7DN, United Kingdom. Analysis and interpretation of the data: C.R.V. Tomson, J.F.E. Dr. Cheung: Division of Nephrology & Hypertension, 295 Mann, T.I. Chang, S.L. Furth, F.F. Hou, G.A. Knoll, S.W. Tobe, L. Chipeta Way, Room 4000, Salt Lake City, UT 84108. Lytvyn, J.C. Craig, D.J. Tunnicliffe, M. Howell, M. Tonelli, A. Dr. Mann: University of Erlangen-Nürnberg, Schloßplatz 4, Earley, J.H. Ix, M.J. Sarnak. 91054 Erlangen, Germany. Drafting of the article: C.R.V. Tomson, S.L. Furth, F.F. Hou, G.A. Dr. Chang: MC 5851, 777 Welch Road Suite DE, Room D100, Knoll, S.W. Tobe, J.C. Craig, M. Howell, A. Earley, J.H. Ix, M.J. Stanford, CA 94305-5851. Sarnak. Dr. Cushman: Department of Preventive Medicine, The Critical revision of the article for important intellectual content: University of Tennessee Health Science Center, Suite 651, 66 C.R.V. Tomson, A.K. Cheung, J.F.E. Mann, T.I. Chang, W.C. North Pauline Street, Memphis, TN 38163. Cushman, S.L. Furth, F.F. Hou, G.A. Knoll, P. Muntner, R. Dr. Furth: Children's Hospital of Philadelphia, 3401 Civic Center Pecoits-Filho, S.W. Tobe, J.C. Craig, D.J. Tunnicliffe, M. Howell, Boulevard, Philadelphia, PA 19104. M. Tonelli, A. Earley, J.H. Ix, M.J. Sarnak. Dr. Hou: Nanfang Hospital, Southern Medical University, 1838 Final approval of the article: C.R.V. Tomson, A.K. Cheung, J.F.E. North Guangzhou Avenue, Guangzhou 510515, China. Mann, T.I. Chang, W.C. Cushman, S.L. Furth, F.F. Hou, G.A. Dr. Knoll: 1967 Riverside Drive, Ottawa, ON K1H 7W9, Canada. Knoll, P. Muntner, R. Pecoits-Filho, S.W. Tobe, L. Lytvyn, J.C. Dr. Muntner: School of Public Health, University of Alabama at Craig, D.J. Tunnicliffe, M. Howell, M. Tonelli, M. Cheung, A. Birmingham, Ryals Public Health Building (RPHB), 1665 Earley, J.H. Ix, M.J. Sarnak. University Boulevard, Suite 140J, Birmingham, AL 35294. Provision of study materials or patients: D.J. Tunnicliffe. Dr. Pecoits-Filho: Arbor Research, 3700 Earhart Road, Ann Statistical expertise: J.F.E. Mann, P. Muntner, J.C. Craig, D.J. Arbor, MI 48105. Tunnicliffe, M. Howell. Dr. Tobe: Sunnybrook Health Sciences Centre, Kidney Care Administrative, technical, or logistic support: J.F.E. Mann, L. Centre at the CNIB Centre, 1929 Bayview Avenue, Third Floor, Lytvyn, J.C. Craig, M. Tonelli, M. Cheung, A. Earley. Room 380, Toronto, ON M4G 3E8, Canada. Collection and assembly of data: C.R.V. Tomson, F.F. Hou, D.J. Ms. Lytvyn: Department of Health Research Methods, Evidence, Tunnicliffe, M. Howell, A. Earley. and Impact, McMaster University, McMaster University Medical Centre, 1280 Main Street West, 2C Area, Hamilton, ON L8S 4K1, Canada. Dr. Craig: College of Medicine and Public Health, Flinders University, Level 3, Health Sciences Building, Room 3.34, Bedford Park, SA 5042, Australia. Drs. Tunnicliffe and Howell: The University of Sydney, Cochrane Kidney and Transplant, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia. Dr. Tonelli: University of Calgary, 7th Floor, TRW Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada. Mr. Cheung and Ms. Earley: KDIGO (Kidney Disease: Improving Global Outcomes), Avenue Louise 65, Suite 11, 1050 Brussels, Belgium. Dr. Ix: Division of Nephrology, 3350 La Jolla Village Drive, Mail Code 9111-H, San Diego, CA 92161. Dr. Sarnak: Box 391, Division of Nephrology, Tufts Medical Center, 800 Washington Street, Boston MA 02111. Annals.org Annals of Internal Medicine
Appendix Table 1. Factors That Influence the Strength of a Recommendation
Factor Comment
Balance of benefits and harms The larger the difference between desirable and undesirable effects, the more
likely a strong recommendation is warranted. The narrower the gradient, the
more likely a weak recommendation is warranted.
Quality of the evidence The higher the quality of evidence, the more likely a strong recommendation is
warranted.
Values and preferences The more variability in values and preferences, or the more uncertainty in val-
ues and preferences, the more likely a weak recommendation is warranted.
Resource use and other considerations The higher the resource use associated with a recommendation, the less likely
a strong recommendation is warranted.
Appendix Table 2. Factors That Influence the Grading for Quality of Evidence
Quality of Evidence Meaning
High (A) We are very confident that the true effect lies close to the estimate of the effect.
Moderate (B) The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low (C) The true effect may be substantially different from the estimate of the effect.
Very low (D) The estimate of the effect is very uncertain and may be far from the true effect.
Annals of Internal Medicine Annals.orgAppendix Table 3. Implications of Strong Versus Weak Recommendations
Strength Implications for Patients Implications for Clinicians Implications for Policy
Level 1, Strong: Most people in your situation Most patients should receive the The recommendation can be
“We recommend” would want the recommended recommended course of evaluated as a candidate for
course of action, and only a action. developing a policy or per-
small proportion would not. formance measure.
Level 2, Weak: The majority of people in your Different choices will be appro- The recommendation is likely to
“We suggest” situation would want the priate for different patients. require substantial debate and
recommended course of Each patient needs help to involvement of stakeholders
action, but many would not. arrive at a management deci- before policy can be
sion consistent with her or his determined.
values and preferences.
Appendix Table 4. Research Recommendations for BP
Measurement
There are several areas in which more research is needed specifically for
the CKD population:
Identify if procedures for standardized BP measurement can be simpli-
fied, such as using a shorter rest period (e.g., 1 or 2 min) or shorter
interval between BP measurements (e.g., 15 or 30 s).
Compare standardized unattended vs. standardized attended automated
office BP in routine clinical practice.
Determine the optimal interval for repeating ABPM and HBPM among
individuals not receiving and receiving antihypertensive medications.
Determine the proportion of patients with CKD who have white coat
hypertension, masked hypertension, white coat effect, and masked
uncontrolled hypertension using a BP threshold of 120 mm Hg instead
of 140 mm Hg and whether these phenotypes are associated with
increased risk for cardiovascular disease.
Assess the cost-effectiveness of ABPM and HBPM, separately, for identify-
ing white coat hypertension, masked hypertension, white coat effect,
and masked uncontrolled hypertension.
Conduct RCTs comparing treatment based on ABPM or HBPM vs. stand-
ardized office BP measurements. Treatment based on ABPM or HBPM
includes not treating patients with white coat hypertension, not intensi-
fying treatment for white coat effect, treating masked hypertension,
and intensifying treatment for masked uncontrolled hypertension.
ABPM = ambulatory BP monitoring; BP = blood pressure; CKD =
chronic kidney disease; HBPM = home BP monitoring; RCT = random-
ized controlled trial
Annals.org Annals of Internal MedicineAppendix Table 5. Research Recommendations for BP
Targets
Information is needed on how patient values and preferences influence
decisions related to BP-lowering therapy. This would be an ideal topic
for the SONG initiative.
Conduct adequately powered RCTs to examine the effects of intensive
BP control among patients with CKD with concomitant diabetes, con-
comitant severely increased proteinuria (>1 g/d), or very low GFR (15 butYou can also read
