KDIGO 2021 CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF BLOOD PRESSURE IN CHRONIC KIDNEY DISEASE KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease S3 Tables, gures, and supplementary material S7 KDIGO Executive Committee S8 Reference keys S9 CKD nomenclature S10 Conversion factors and Glossary of terms for blood pressure management S11 Abbreviations and acronyms S14 Updates to the KDIGO guideline format S18 Work Group membership S23 Summary of recommendation statements and practice points S26 Chapter 1: Blood pressure measurement S32 Chapter 2: Lifestyle interventions for lowering blood pressure in patients with CKD not receiving dialysis S37 Chapter 3: Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis S55 Chapter 4: Blood pressure management in kidney transplant recipients (CKD S59 Chapter 5: Blood pressure management in children with CKD S62 Methods for guideline development S71 Biographic and disclosure information The development and publication of this guideline were supported by KDIGO. The opinions or views expressed in this professional education supplement are those of the authors and do not necessarily re ect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may re ect their clinical experience or may be derived from the professional literature or other clinical sources. Because of the differences between in vitro and in vivo systems and between laboratory animal models and clinical data in humans, in vitro and animal data may not necessarily correlate with clinical results. contents www.kidney-international.org VOL 99 | ISSUE 3S | MARCH 2021 TABLES S63 Table 1. Hierarchy of outcomes S64 Table 2. Clinical questions and systematic review topics in the PICOM format S68 Table 3. Classi cation for certainty and quality of the evidence S69 Table 4. GRADE system for grading quality of evidence S69 Table 5. KDIGO nomenclature and description for grading recommendations S69 Table 6. Determinants of the strength of recommendation FIGURES S14 Figure 1. Updates to the KDIGO guideline format S26 Figure 2. Checklist for standardized of ce blood pressure measurement S28 Figure 3. Blood pressure measurement method and device used in select RCTs and prospective observational studies S29 Figure 4. Blood pressure patterns informed by out-of-of ce blood pressure measurements in addition to standardized of ce blood pressure measurement S47 Figure 5. SPRINT research treatment algorithm for the intensive group (goal SBP <120 mm Hg) S48 Figure 6. Cardiovascular events in patients with CKD G3 G4, A3 without diabetes S56 Figure 7. CCB versus placebo/no treatment for the outcome of graft loss S68 Figure 8. Search yield and study ow diagram SUPPLEMENTARY MATERIAL Supplementary File (PDF) Appendix A. Search strategies Table S1. Search strategies for systematic review topics Appendix B. Concurrence with Institute of Medicine (IOM) standards for guideline development Table S2. Guideline development checklist IOM standards for development of trustworthy clinical practice guidelines Table S3. Adapted systematic review reporting standards checklist IOM standards for systematic reviews Appendix C. Data supplement - Summary of ndings (SoF) tables cited in the guideline text Table S4. General population studies comparing auscultatory versus oscillometric blood pressure measurement devices Table S5. Adults with CKD without diabetes, low-salt diet versus usual or normal-salt diet Table S6. Adults with type 1 diabetes and CKD, low-salt diet versus normal-salt diet Table S7. Adults with type 2 diabetes and CKD, low-salt diet versus usual diet Table S8. Adults with diabetes and CKD with moderately increased albuminuria, low-salt diet versus normal- salt diet Table S9. Adults with diabetes and CKD with severely increased albuminuria, low-salt diet versus normal-salt diet Table S10. Adults with CKD, any exercise to improve blood pressure versus control (no exercise/placebo exercise) Table S11. Adults with CKD, low blood pressure target ( 120 mm Hg) versus standard blood pressure target Table S12. Adults with CKD and increased proteinuria/albuminuria, low blood pressure target versus standard diastolic blood pressure target Table S13. Adults with CKD, low blood pressure target versus standard blood pressure target Table S14. Adults with CKD without diabetes, low blood pressure target versus standard blood pressure target Table S15. Adults with CKD without diabetes, ACEi versus placebo or standard of care Table S16. Adults with CKD without diabetes, ARB versus placebo or standard of care Table S17. Adults with CKD without diabetes, aldosterone antagonist versus placebo or standard care www.kidney-international.org contents Table S18. Adults with CKD without diabetes, beta-blockers versus RASi Table S19. Adults with CKD without diabetes, calcium channel blocker versus placebo Table S20. Adults with CKD without diabetes, direct renin inhibitors versus RASi Table S21. Adults with diabetes and CKD, ACEi versus placebo or standard care Table S22. Adults with diabetes and CKD, ARB versus placebo or standard care Table S23. Adults with diabetes and CKD, ARB versus ACEi Table S24. Adults with diabetes and CKD, aldosterone antagonists versus placebo or standard care Table S25. Adults with diabetes and CKD, beta-blocker versus ACEi Table S26. Adults with diabetes and CKD, calcium channel blocker versus placebo Table S27. Adults with diabetes and CKD, diuretics D ACEi or ARB versus placebo, standard of care, or no treatment Table S28. Adults with diabetes and CKD, aliskiren versus ACEi or ARB. Table S29. Adults with type 2 diabetes and CKD, aliskiren D ACEi or ARB versus placebo D ACEi or ARB Table S30. Adults with diabetes and CKD, calcium channel blocker versus ACEi or ARB Table S31. Adults with CKD, dual RASi therapy versus single RASi therapy Table S32. Network meta-analysis of adults with CKD, dual RASi therapy versus single RASi therapy Table S33. Kidney transplant recipients, calcium channel blockers versus placebo or no treatment Table S34. Kidney transplant recipients, ARB versus placebo or no treatment Table S35. Kidney transplant recipients, ACEi versus placebo, no treatment, or non-antihypertensive treatment Table S36. Kidney transplant recipients, alpha-blocker versus placebo or no treatment Table S37. Kidney transplant recipients, beta-blocker versus placebo or no treatment Table S38. Kidney transplant recipients, mineralocorticoid receptor antagonists versus placebo Table S39. Kidney transplant recipients, ACEi or ARB versus placebo, no treatment, or standard of care Table S40. Children with CKD, intensi ed blood pressure control (MAP <50th percentile) versus conventional blood pressure control (MAP 50th 99th percentile) Appendix D. Data supplement - Additional SoF tables developed as part of the evidence review Table S41. Correlation of blood pressure measurement techniques in patients with CKD Table S42. Accuracy of blood pressure measurement techniques in the general population Table S43. Systematic reviews of approaches to blood pressure measurement in the general population and associations with clinical outcomes Table S44. Systematic reviews of economic evaluations of differing approaches to BP measurement in the general population Table S45. Adults with diabetes and CKD and habitual low-salt intake, higher dietary salt intake (through NaCl supplement) versus regular-salt intake Table S46. Adults with diabetes and habitual high-salt intake, higher dietary salt intake (through NaCl supplement) versus regular salt intake Table S47. Adults with CKD, aerobic exercise to improve blood pressure versus control (no exercise/placebo) Table S48. Adults with CKD, mix of resistance and cardiovascular exercise versus control (no exercise/placebo) Table S49. Adults with CKD without diabetes, low-protein versus normal-protein diet Table S50. Adults with CKD without diabetes, very low protein versus normal-protein diet Table S51. Adults with CKD, high base (non-acidic) fruit and vegetable diet versus usual diet with bicarbonate supplement Table S52. Adults with CKD and diabetes, carbohydrate-restricted low-iron available polyphenol-enriched (CR- LIPE) diet versus usual diet (standard protein restricted diet [0.8 g/kg/d], isocaloric for ideal body weight maintenance) Table S53. Adults with CKD, intensive dietary counselling versus usual (health) care contents www.kidney-international.org Table S54. Adults with diabetes and CKD, low blood pressure target versus standard blood pressure target Table S55. Adults with diabetes and CKD, low blood pressure target ( 120 systolic mm Hg) versus standard blood pressure target ( 140 systolic mm Hg) Table S56. Adults with diabetes and CKD, low blood pressure target (<80 diastolic mm Hg) versus standard blood pressure target (80-89 diastolic mm Hg) Table S57. Adults with diabetes and CKD, low blood pressure target (<130/80 mm Hg) plus multifactorial care versus usual care Table S58. Adults with CKD and low proteinuria (PCR 0.22 g/g and PE <0.3 g/d), low MAP target (<92 mm Hg) versus standard MAP target (102 107 mm Hg) Table S59. Adults with CKD and high proteinuria (PCR >0.22 g/g and PE >0.3 g/d), low MAP target (<92 mm Hg) versus standard MAP target (102 107 mm Hg) Table S60. Adults with CKD, ACEi versus placebo or standard of care Table S61. Adults with CKD, ARB versus placebo or standard of care Table S62. Adults with CKD, aldosterone antagonist versus placebo or standard of care Table S63. Adults with CKD, beta-blocker versus placebo or standard of care Table S64. Adults with CKD, beta-blocker versus RASi Table S65. Adults with CKD, calcium channel blockers versus placebo Table S66. Adults with CKD, calcium channel blockers versus RASi Table S67. Adults with CKD, direct renin inhibitor versus placebo Table S68. Adults with CKD, direct renin inhibitor versus RASi Table S69. Adults with CKD, direct renin inhibitor D ACEi or ARB versus placebo or standard of care Table S70. Adults with CKD, diuretics versus RASi Table S71. Older adults with CKD (65 85 years old), high-dose ARB versus calcium channel blocker combined with ARB Table S72. Adults with CKD, type 2 diabetes, and moderately increased albuminuria, calcium channel blockers D RAS blockade versus RAS blockade Table S73. Adults with CKD and chronic hyperkalemia, potassium binder versus placebo Table S74. Adults with CKD and chronic hyperkalemia, calcium polystyrene sulphonate (CPS) versus sodium polystyrene sulphonate (SPS) Table S75. Adults with CKD without diabetes, lower MAP (<92 mm Hg) target versus higher MAP (102 107 mm Hg) target Table S76. Adults with CKD and proteinuria (>1g/24 h for at least 3 months) without diabetes, low blood pressure target (<130/80 mm Hg) versus standard diastolic blood pressure target (<90 mm Hg) Table S77. Adults with CKD without diabetes, lower blood pressure target ( 120 mm Hg) versus standard blood pressure target Table S78. Adults 75 years of age with CKD without diabetes, lower blood pressure target ( 120 mm Hg) versus standard blood pressure target Table S79. Adults with CKD without diabetes, calcium channel blockers versus RASi Table S80. Adults with diabetes and CKD, ACEi or ARB monotherapy versus dual (ACEi D ARB) therapy Table S81. Adults with diabetes and CKD, diuretics D ACEi or ARB versus ACEi or ARB Table S82. Adults with diabetes and CKD, diuretics D calcium channel blockers versus ACEi or ARB D calcium channel blockers Table S83. Adults with diabetes and CKD, diuretics D ACEi or ARB versus ACEi or ARB D calcium channel blockers Table S84. Adults with diabetes and CKD, diuretics D ACEi or ARB D beta-blockers versus placebo plus standard of care Table S85. Adults with CKD, type 2 diabetes, and moderately increased albuminuria, calcium channel blocker versus ARB plus diuretics www.kidney-international.org contents Table S86. Adults with CKD, type 2 diabetes and albuminuria (AER >100 mg/24 h), direct renin inhibitor versus placebo Table S87. Adults with diabetes and CKD, aliskiren versus ACEi or ARB Table S88. Adults with diabetes, chronic hyperkalemia, and CKD, high-dose potassium binder versus low-dose potassium binder Table S89. Kidney transplant recipients, low-salt diet versus usual or normal-salt diet Table S90. Kidney transplant recipients, Mediterranean diet versus low-fat diet Table S91. Kidney transplant recipients, any exercise to control blood pressure versus control (no exercise/ placebo exercise) Table S92. Kidney transplant recipients, ACEi versus calcium channel blockers Table S93. Kidney transplant recipients, ARB versus calcium channel blockers Table S94. Kidney transplant recipients, ACEi versus ARB Table S95. Kidney transplant recipients, ACEi D calcium channel blockers versus ACEi alone Table S96. Kidney transplant recipients, ACEi D calcium channel blockers versus calcium channel blockers alone Table S97. Kidney transplant recipients, ACEi D ARB versus ACEi alone Table S98. Kidney transplant recipients, ACEi D ARB versus ARB alone Table S99. Kidney transplant recipients, ACEi D ARB versus placebo or no treatment Table S100. Kidney transplant recipients, ACEi versus alpha-blocker Table S101. Kidney transplant recipients, ACEi versus beta-blocker Table S102. Kidney transplant recipients, ARB versus beta-blocker Table S103. Kidney transplant recipients, calcium channel blockers versus beta-blocker Table S104. Kidney transplant recipients, ARB versus direct renin inhibitor Table S105. Kidney transplant recipients, calcium channel blockers versus thiazide Table S106. Kidney transplant recipients, ACEi or ARB versus placebo, no treatment, or standard of care Table S107. Children with CKD, ACEi versus standard treatment contents www.kidney-international.org KDIGO EXECUTIVE COMMITTEE Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs David C. Wheeler, MD, FRCP Immediate Past Co-Chair Michel Jadoul, MD KDIGO Co-Chair Wolfgang C. Winkelmayer, MD, MPH, ScD KDIGO Co-Chair Mustafa Arici, MD Tara I. Chang, MD, MS Jennifer E. Flythe, MD, MPH Masafumi Fukagawa, MD, PhD Morgan E. Grams, MD, MPH, PhD Fan Fan Hou, MD, PhD Meg Jardine, MBBS, PhD Markus Ketteler, MD, FERA Magdalena Madero, MD Jolanta Ma yszko, MD, PhD Ikechi G. Okpechi, MBBS, FWACP, PhD Rukshana Shroff, MD, FRCPCH, PhD Laura Sol , MD Paul E. Stevens, MB, FRCP Sydney C.W. Tang, MD, PhD, FRCP, FACP, FHKCP, FHKAM Marcello A. Tonelli, MD, SM, MSc, FRCPC Christina M. Wyatt, MD KDIGO Staff John Davis, Chief Executive Of cer Danielle Green, Executive Director Michael Cheung, Chief Scienti c Of cer Melissa Thompson, Chief Operating Of cer Amy Earley, Guideline Development Director Kathleen Conn, Director of Communications Tanya Green, Events Director Coral Cyzewski, Events Coordinator www.kidney-international.org KDIGO executive committee Reference keys NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS Within each recommendation, the strength of recommendation is indicated as Level 1 or Level 2, and the quality of the supporting evidence is shown as A, B, C, or D. Grade Implications Patients Clinicians Policy Level 1 Strong We recommend Most people in your situation would want the recommended course of action, and only a small proportion would not. Most patients should receive the recommended course of action. The recommendation can be evaluated as a candidate for developing a policy or a performance measure. Level 2 Weak We suggest The majority of people in your situation would want the recommended course of action, but many would not. Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences. The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined. Grade Quality of evidence Meaning A High We are con dent that the true effect is close to the estimate of the effect. B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. C Low The true effect may be substantially different from the estimate of the effect. D Very low The estimate of effect is very uncertain, and often it will be far from the true effect. reference keys www.kidney-international.org CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE USED BY KDIGO CKD is de ned as abnormalities of kidney structure or function, present for > 3 months, with implications for health. CKD is classi ed based on Cause, GFR category (G1 G5), and Albuminuria category (A1-A3), abbreviated as CGA. Green, low risk (if no other markers of kidney disease, no CKD); yellow, moderately increased risk; orange, high risk; red, very high risk. GFR, glomerular ltration rate. www.kidney-international.org CKD nomenclature CONVERSION FACTORS OF CONVENTIONAL UNITS TO SI UNITS Conventional unit Conversion factor SI Unit Creatinine mg/dl 88.4 mmol/l Creatinine clearance ml/min 0.01667 ml/s Note: Conventional unit  conversion factor SI unit. ALBUMINURIA CATEGORIES IN CKD Category AER (mg/24 h) ACR (approximate equivalent) Termsa (mg/mmol) (mg/g) ACR, albumin-creatinine ratio; AER, albumin excretion rate; CKD, chronic kidney disease. a Formerly known as normoalbuminuria, microalbuminuria, and macroalbuminuria. b Relative to young adult level. c Including nephrotic syndrome (albumin excretion usually >2200 mg/24 h [ACR >2200 mg/g; >220 mg/mmol]). GLOSSARY OF TERMS FOR BLOOD PRESSURE MEASUREMENT Terms De nition Standardized of ce blood pressure This is the recommended method for measuring blood pressure in the current revised guideline. Blood pressure measurement following all guideline-recommended preparations as presented in Figure 2. The device used is not part of the de nition. Routine of ce blood pressure Blood pressure measured in the provider s of ce. Preparation before measurement and the device used are not part of the de nition. The values are often inconsistent between providers performing the measurements. In addition, it does not bear a reliable relationship with standardized of ce blood pressure. Manual blood pressure Blood pressure obtained using a manual auscultatory blood pressure cuff, instead of an automated method, with either a mercury or aneroid sphygmomanometer. Preparation before the measurement is not part of the de nition. Automated of ce blood pressure (AOBP) Blood pressure obtained in the provider s of ce using an automated device that is programmed to start only after a set resting period and measured several times with xed intervals between measurements. An average reading is then provided as the output. Preparation before measurement and attendance by the provider are not part of the de nition. Ambulatory blood pressure monitoring (ABPM) Blood pressure obtained on a frequent intermittent basis (i.e., 15 30 min per 24 h) using an automated wearable device, usually outside the provider s of ce or medical facilities. Home blood pressure monitoring (HBPM) Blood pressure obtained at the patient s home with an automated oscillometric or manual auscultatory device, usually excluding ABPM. Preparation before measurement, person taking the measurement, and the device used are not part of the de nition, although they are often performed by the patient herself/himself with an automated device. conversion factors www.kidney-international.org Abbreviations and acronyms ABPM ambulatory blood pressure monitoring ACEi angiotensin-converting enzyme inhibitor(s) ACR albumin-creatinine ratio AOBP automated of ce blood pressure AKI acute kidney injury ARB angiotensin II receptor blocker BP blood pressure CCB calcium channel blocker CI con dence interval CKD chronic kidney disease CV cardiovascular DBP diastolic blood pressure DRI direct renin inhibitor eGFR estimated glomerular ltration rate ERT Evidence Review Team ESKD end-stage kidney disease GFR glomerular ltration rate GI gastrointestinal GRADE Grading of Recommendations Assessment, Development, and Evaluation HBPM home blood pressure monitoring HF heart failure HR hazard ratio i.v. intravenous KDIGO Kidney Disease: Improving Global Outcomes MACE major adverse cardiovascular events MAP mean arterial pressure MI myocardial infarction MRA mineralocorticoid receptor antagonist NSAID nonsteroidal anti-in ammatory drug(s) OR odds ratio PCR protein-creatinine ratio p.o. oral RAS renin-angiotensin system RASi renin-angiotensin system inhibitor(s) RCT randomized controlled trial RR relative risk SBP systolic blood pressure UKPDS United Kingdom Prospective Diabetes Study Group www.kidney-international.org abbreviations and acronyms Notice SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon literature searches last conducted in October 2018, supplemented with additional evidence through September 2019. The search was updated in April 2020 with additional analyses conducted as required. It is designed to assist decision-making. It is not intended to de ne a standard of care and should not be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians consider the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Health care professionals using these recommendations should decide how to apply them to their own clinical practice. SECTION II: DISCLOSURE Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived con icts of interest that may arise from an outside relationship or a personal, professional, or business interest of a member of the Work Group. All members of the Work Group are required to complete, sign, and submit a disclosure and attestation form showing all such relationships that might be perceived as or are actual con icts of interest. This document is updated annually, and information is adjusted accordingly. All reported information is published in its entirety at the end of this document in the Work Group members Disclosure section and is kept on le at KDIGO. Copyright  2021, KDIGO. Published by Elsevier on behalf of the International Society of Nephrology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Single copies may be made for personal use as allowed by national copyright laws. Special rates are available for educational institutions that wish to make photocopies for nonpro t educational use. No part of this publication may be reproduced, amended, or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without explicit permission in writing from KDIGO. Details on how to seek reprints, permission for reproduction or translation, and further information about KDIGO s permissions policies can be obtained by contacting Melissa Thompson, Chief Operating Of cer, at melissa.thompson@kdigo.org. To the fullest extent of the law, neither KDIGO, Kidney International, nor the authors, contributors, or editors assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. notice www.kidney-international.org Foreword With the growing awareness that chronic kidney disease (CKD) is a major global health problem, Kidney Disease: Improving Global Outcomes (KDIGO) was established in 2003 with its stated mission to improve the care and out- comes of patients with kidney disease worldwide through promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines. Since 2003, KDIGO has developed a catalog of clinical practice guidelines informing the care of patients with, or at risk of, developing kidney diseases. Currently, KDIGO is updating 2 existing guidelines on the Management of Blood Pressure in CKD and Glomerular Diseases, respectively. In addition, KDIGO has recently published its rst guideline related to Diabetes Management in CKD. High blood pressure (BP) is closely related to adverse kidney and cardiovascular outcomes in CKD. Thus, KDIGO published its rst guideline for the management of BP in CKD in 2012. The guideline was derived from a signi cant effort by the Work Group to summarize the evidence on this topic available through 2011. Since 2011, new evidence has emerged, which has important implications to be considered for future guideline updates. To this end, KDIGO convened a Controversies Conference to examine this new evidence as it relates to the management and treatment of high BP in CKD. The KDIGO Controversies Conference on Blood Pressure in CKD assembled a global panel of multidisciplinary clinical and scienti c experts to identify key issues relevant to the updating of the KDIGO 2012 Blood Pressure guideline. The objective of this conference was to assess the current state of knowledge related to the optimal means for measuring BP, management of high BP in CKD patients, with and without diabetes (including older adults), as well as the pediatric and kidney transplant subpopulations. A guideline update was recommended and commissioned following this Contro- versies Conference. In keeping with KDIGO s policy for transparency and rigorous public review during the guideline development process, the guideline scope was made available for open commenting prior to the start of the evidence review. The feedback received on the Scope of Work draft was carefully considered by the Work Group members. The guideline draft was also released for public review by external stakeholders. The Work Group has critically reviewed the feedback from the public input and revised the guideline as appropriate for the nal publication. We thank Alfred K. Cheung, MD and Johannes F.E. Mann, MD for leading this important initiative, and we are especially grateful to the Work Group members who provided their time and expertise to this endeavor. In addition, this Work Group was ably assisted by colleagues from the independent Evidence Review Team (ERT) led by Jonathan Craig, MBChB, DipCH, FRACP, M Med (Clin Epi), PhD; Martin Howell, PhD; and David Tunnicliffe, PhD, who made this guideline possible. KDIGO recently appointed Marcello Tonelli, MD, SM, MSc, FRCPC as its rst Guideline Methods Chair. He was tasked with improving KDIGO guideline methodology by reinforcing the linkage between the recommendations and the corresponding evidence, standardizing the guideline format, reducing unnecessary length, and enhancing the utility of the guideline for its users. To meet these goals, Dr. Tonelli suggested KDIGO work with MAGICapp, a web-based publishing platform for evidence-based guidelines. The program uses a prede ned format and allows for both direct linkage of the evidence to the recommendation statement, and the generation of patient decision aids directly from the evidence syntheses used to support the guideline. In addition, he also introduced the concept of practice points, a new form of guidance in addi- tion to recommendations. For cases in which a systematic review was not done, or was performed but did not nd suf cient evidence to warrant a recommendation, a practice point was used to provide guidance to clinicians. Practice points do not necessarily follow the same format as recom- mendations for example, they may be formatted as tables, gures, or algorithms and are not graded for strength or evidence quality. With Dr. Tonelli s guidance and expertise, and through the use of MAGICapp, and the adoption of practice points, KDIGO has aligned the update of the Blood Pressure in CKD Guideline with the current state of the evidence, creating a highly useful document that is rich in guidance while main- taining the high-quality standards and rigor for which KDIGO is best known. The update to the KDIGO guideline format is discussed below in greater detail by Dr. Tonelli (Figure 1). In summary, we are con dent that this guideline will prove useful to clinicians around the world who are treating people with high BP and kidney disease. Once again, we thank the Work Group members and all those who contributed to this very important KDIGO activity. Michel Jadoul, MD Wolfgang C. Winkelmayer, MD, ScD KDIGO Co-Chairs www.kidney-international.org foreword Figure 1 | Updates to the KDIGO guideline format. CKD, chronic kidney disease; eGFR, estimated glomerular ltration rate; FAQ, frequently asked questions; GFR, glomerular ltration rate; GI, gastrointestinal; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HbA1c, glycated hemoglobin; KDIGO, Kidney Disease: Improving Global Outcomes; RCT, randomized controlled trial. foreword www.kidney-international.org Figure 1 | (Continued) www.kidney-international.org foreword Figure 1 | (Continued) foreword www.kidney-international.org Figure 1 | (Continued) www.kidney-international.org foreword Work Group membership WORK GROUP CO-CHAIRS Alfred K. Cheung, MD University of Utah Salt Lake City, UT, USA Johannes F.E. Mann, MD KfH Kidney Center University Hospital, Friedrich Alexander University Erlangen-Nuremberg, Germany WORK GROUP Tara I. Chang, MD, MS Stanford University Palo Alto, CA, USA William C. Cushman, MD, FAHA, FACP University of Tennessee Health Science Center Memphis, TN, USA Susan L. Furth, MD, PhD Perelman School of Medicine University of Pennsylvania The Children s Hospital of Philadelphia Philadelphia, PA, USA Fan Fan Hou, MD, PhD Nanfang Hospital Southern Medical University Guangzhou, Guangdong, China Joachim H. Ix, MD, MAS University of California San Diego Veterans Affairs San Diego Healthcare System San Diego, CA, USA Gregory A. Knoll, MD, MSc, FRCPC The Ottawa Hospital Ottawa Hospital Research Institute Ottawa, Canada Paul Muntner, PhD, MHS, FASH, FAHA University of Alabama at Birmingham Birmingham, AL, USA Roberto Pecoits-Filho, MD, PhD, FASN, FACP Arbor Research Collaborative for Health Ann Arbor, MI, USA Ponti cal Catholic University of Paran Curitiba PR, Brazil Mark J. Sarnak, MD, MS Tufts University Boston, MA, USA Sheldon W. Tobe, MD, FRCPC, FRCP, FACP, FAHA, MScCH (HPTE) University of Toronto Toronto, Ontario, Canada Northern Ontario School of Medicine Sudbury, Ontario, Canada Charles R.V. Tomson, MA, BM, Bch, DM, FRCP Consultant Nephrologist Freeman Hospital Newcastle upon Tyne Hospitals NHS Trust Newcastle upon Tyne, UK METHODS CHAIR Marcello A. Tonelli, MD, SM, MSc, FRCPC Work Group membership www.kidney-international.org j (Continued) EVIDENCE REVIEW TEAM Cochrane Kidney and Transplant, Sydney, Australia Jonathan C. Craig, MBChB, DipCH, FRACP, M Med (Clin Epi), PhD, Evidence Review Team Director Suetonia C. Palmer, MBChB, FRACP, PhD, Evidence Review Team Co-Director Giovanni F.M. Strippoli, MD, MPH, M Med (Clin Epi), PhD, Evidence Review Team Co-Director Martin Howell, PhD, Assistant Project Director David J. Tunnicliffe, PhD, Evidence Review Project Team Leader and Project Manager Fiona Russell, PhD, Cochrane Kidney and Transplant, Managing Editor Gail Y. Higgins, BA, Grad Ed, Grad Dip LibSc, Information Specialist Tess E. Cooper, MPH, MSc (Evidence-based Health Care), Research Associate Nicole Evangelidis, MPH, MPhil, Research Associate Brydee Cashmore, MPH, Research Associate Rabia Khalid, MND, Research Associate Claris Teng, BPsych (Hons), Research Associate Cochrane Kidney and Transplant recognizes the contribution of authors (Elisabeth Hodson, Emma McMahon, Patrizia Natale, Narelle Willis) who have updated their reviews for this guideline. MAGICAPP LIAISON Lyubov Lytvyn, BSc, MSc www.kidney-international.org Work Group membership Abstract The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease (CKD) represents an update to the 2012 KDIGO guideline on this topic. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, and antihypertensive therapies in CKD patients not receiving dialysis, including special populations such as kidney transplant recipients and children. In addition, this guideline introduces a chapter dedicated to proper blood pressure measurement. The goal of the guideline is to serve as a useful resource for clinicians and patients by providing actionable recommendations with useful infographics based on a rigorous formal systematic review. Another aim is to propose research recommendations for areas in which there are gaps in knowledge. The guideline targets clinicians treating high blood pressure and CKD, while taking into account policy and resource implications. Development of this guideline update followed an explicit process of evidence review. Treatment approaches and guideline recom- mendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Limitations of the evidence are discussed, and areas of future research are presented. Keywords: albuminuria; ambulatory blood pressure monitoring; angiotensin-converting enzyme inhibitor; angiotensin II receptor blocker; antihypertensive agents; automated of ce blood pressure; blood pressure measurement; blood pressure targets; children; chronic kidney disease; creatinine; diabetes; dietary sodium; evidence-based; guideline; home blood pressure monitoring; hyperkalemia; KDIGO; kidney transplant recipient; lifestyle; mineralocorticoid receptor antag- onist; of ce blood pressure; physical activity; potassium; proteinuria; renin-angiotensin system; standarized of ce blood pressure; systematic review; weight loss CITATION In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1 S87. This guideline, including all statements and evidence, will be published simultaneously on MAGICapp (https://kdigo.org/guidelines/blood-pressure-in-ckd/). This online format will facil- itate rapid updates as new evidence emerges. abstract www.kidney-international.org Introduction The original KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease in the chronic kidney disease (CKD) population not receiving dialysis was published in 2012. Since then, completion of the SPRINT trial and the revision of blood pressure (BP) guide- lines by many guideline task forces around the world have prompted the re-examination of the KDIGO 2012 Guideline for the Management of Blood Pressure. Upon invitation by the KDIGO Executive Committee, a Work Group consisting of a subset of the members of the original guideline panel and some new members was formed in 2018. The Cochrane Kidney and Transplant group from Australia was selected as the Evidence Review Team (ERT) for the update, and a new online publishing software, MAGICapp, was introduced with the aim to create a living guideline that is consistently kept up-to-date. A Controversies Conference was held in Edinburgh in September 2017 to help better identify the emerging evidence, ongoing controversies, and unsettled questions in relation to BP management in CKD. The conclusions from this confer- ence helped to frame the Scope of Work for the Guideline update. It was decided that since the de nition, management, and nuances of high BP in the maintenance dialysis popula- tion are signi cantly different from those in the CKD popu- lation not receiving dialysis, the Work Group should con ne its purview to the latter population in keeping with the 2012 guideline. The chapters from the original guidelines have been reor- ganized. The section on pharmacologic agents in the original chapter on Lifestyle and pharmacologic treatments for lowering blood pressure in CKD ND patients has been signi cantly streamlined and separated. The lifestyle chapter, Chapter 2, now focuses on dietary sodium restriction and physical activities. The use of renin-angiotensin inhibitors (RASi) is now included in the current Chapter 3 under the broad topic of BP management in CKD patients, while readers are referred to standard textbooks for descriptions of various BP-lowering drugs. The original Chapter 3 on BP management in CKD patients without diabetes and the original Chapter 4 on CKD patients with diabetes are now consolidated into the current Chapter 3, which covers both subgroups, with the literature on patients with diabetes and without, combined and synthesized. The current Chapter 3 also includes guidance related to older adults with CKD, which was in a separate chapter in the original guideline. Since older adults comprised a substantial proportion of the cohort in the SPRINT trial, it forms a major basis for the current recommendation of the BP target. Finally, the respective chapters on kidney transplant recipients and children with CKD have both been retained and updated. The Work Group has identi ed 2 major areas that warrant particular attention in this guideline update because of new evidence and interests that have emerged since the publication of the original guideline. These 2 areas are: (i) BP measurement (Chapter 1) and (ii) BP targets within the domain of BP management in CKD patients not receiving dialysis (Chapter 3). These 2 issues are closely related as the systolic BP (SBP) target of <120 mm Hg recommended in Chapter 3 is contingent upon proper BP measurement technique following recommended rigorous procedures. This lower SBP target is largely based on its car- dioprotective, survival, and potential cognitive bene ts. There are no new data supporting the renoprotective bene ts of targeting SBP <120 mm Hg. The overall evidence for kidney protection at this low SBP level is almost non-existent, but it is somewhat more convincing for CKD patients with pro- teinuria and long-term follow-up. There are certain subpopulations in CKD in which the evidence supporting the SBP target of <120 mm Hg is less rigorous; hence, the risk bene t ratios in those instances are less certain. These subpopulations include those with diabetes, advanced CKD (G4 and G5), signi cant protein- uria, very low diastolic blood pressure (DBP), white-coat hypertension, and at extreme ages (younger or older). Thus, randomized controlled trials (RCTs) in these subpopulations are necessary. The term high BP is used throughout the document to denote BP above the target. For most patients with CKD not receiving dialysis, the target is SBP <120 mm Hg. For kidney transplant recipients (Chapter 4), the target SBP is <130 mm Hg, and target diastolic BP (DBP) is <80 mm Hg. For children with CKD (Chapter 5), a mean arterial pressure (MAP, calculated as DBP 1/3  pulse pressure) #50th percentile for age, sex, and height is the primary target. The Work Group fully emphasizes that individualization of management, including consideration of the patient s characteristics, tolerability, and preferences is crucial, as it is in other areas of medical management. However, the Work Group also feels that some guidance should be provided to practitioners and that these practitioners should be aware of the strengths and weaknesses of the evidence underlying the recommendations. Evidence in all chapters has been care- fully gathered and scrutinized by the ERT, including areas in which the Work Group decided that update or revision of the guideline is unnecessary. This guideline focuses exclu- sively on high BP and does not discuss other health-related issues of CKD, such as smoking or obesity. We also do not discuss bene ts and harms of physical activity or diet beyond their effects on BP. As in many other KDIGO guidelines, recommendations for further research are an integral component as it will facilitate the update and revision of future guidelines on BP management in CKD. www.kidney-international.org introduction The Co-Chairs would like to recognize all the efforts of the Work Group, ERT, and KDIGO staff. We greatly appreciate the dedication and work of the entire team, as well as the public comments, and the collaboration of the KDIGO Dia- betes guideline team. Our goal is to help improve the care of patients with high BP and CKD, and we hope this update to the guideline will succeed in doing so for the global nephrology community. Alfred K. Cheung, MD Johannes F.E. Mann, MD Blood Pressure Guideline Update Co-Chairs introduction www.kidney-international.org Summary of recommendation statements and practice points The term high BP is used throughout the document to denote BP above the target for a particular population under consideration. For most adult patients with CKD not receiving dialysis, the target is SBP <120 mm Hg (Chapter 3). For adult kidney transplant recipients, the target remains SBP <130 mm Hg/DBP <80 mm Hg (Chapter 4). For pediatric populations, MAP (calculated as DBP 1/3  pulse pressure) targets are age-dependent (Chapter 5). Given that these targets vary according to the subpopulation of interest, we have avoided the term hypertension when referring to treatment decisions, as the term hypertension requires a single numerical de nition and does not necessarily facilitate BP management. Chapter 1: Blood pressure measurement Recommendation 1.1: We recommend standardized of ce BP measurement in preference to routine of ce BP measurement for the management of high BP in adults (1B). Practice Point 1.1: An oscillometric BP device may be preferable to a manual BP device for standardized of ce BP measurement; however, standardization emphasizes adequate preparations for BP measurement, not the type of equipment. Practice Point 1.2: Automated of ce BP (AOBP), either attended or unattended, may be the preferred method of stan- dardized of ce BP measurement. Practice Point 1.3: Oscillometric devices can be used to measure BP among patients with atrial brillation. Recommendation 1.2: We suggest that out-of-of ce BP measurements with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) be used to complement standardized of ce BP readings for the management of high BP (2B). Chapter 2: Lifestyle interventions for lowering blood pressure in patients with CKD not receiving dialysis 2.1. Sodium intake Recommendation 2.1.1: We suggest targeting a sodium intake <2 g of sodium per day (or <90 mmol of sodium per day, or <5 g of sodium chloride per day) in patients with high BP and CKD (2C). Practice Point 2.1.1: Dietary sodium restriction is usually not appropriate for patients with sodium-wasting nephropathy. Practice Point 2.1.2: The Dietary Approaches to Stop Hypertension (DASH) type diet or use of salt substitutes that are rich in potassium may not be appropriate for patients with advanced CKD or those with hyporeninemic hypoaldosteronism or other causes of impaired potassium excretion because of the potential for hyperkalemia. 2.2. Physical activity Recommendation 2.2.1: We suggest that patients with high BP and CKD be advised to undertake moderate- intensity physical activity for a cumulative duration of at least 150 minutes per week, or to a level compatible with their cardiovascular and physical tolerance (2C). Practice Point 2.2.1: Consider the cardiorespiratory tness status, physical limitations, cognitive function, and risk of falls when deciding on the implementation and intensity of physical activity interventions in individual patients. www.kidney-international.org summary of recommendation statements and practice points Practice Point 2.2.2: The form and intensity of physical activity should be considered and modi ed as necessary in in- dividual patients. There may still be important health bene ts even if physical activity falls below targets proposed for the general population. Chapter 3: Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis 3.1. Blood pressure targets Recommendation 3.1.1: WesuggestthatadultswithhighBPandCKDbetreatedwithatargetsystolicbloodpressure (SBP) of <120 mm Hg, when tolerated, using standardized of ce BP measurement (2B). Practice Point 3.1.1: It is potentially hazardous to apply the recommended SBP target of <120 mm Hg to BP mea- surements obtained in a non-standardized manner. Practice Point 3.1.2: Clinicians can reasonably offer less intensive BP-lowering therapy in patients with very limited life expectancy or symptomatic postural hypotension. 3.2 Treatment with antihypertensive drugs, including RAS inhibitors (RASi) Recommendation 3.2.1: We recommend starting renin-angiotensin-system inhibitors (RASi) (angiotensin-con- verting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB]) for people with high BP, CKD, and severely increased albuminuria (G1 G4, A3) without diabetes (1B). Recommendation 3.2.2: We suggest starting RASi (ACEi or ARB) for people with high BP, CKD, and moderately increased albuminuria (G1 G4, A2) without diabetes (2C). Recommendation 3.2.3: We recommend starting RASi (ACEi or ARB) for people with high BP, CKD, and moderately-to-severely increased albuminuria (G1 G4, A2 and A3) with diabetes (1B). Practice Point 3.2.1: It may be reasonable to treat people with high BP, CKD, and no albuminuria, with or without diabetes, with RASi (ACEi or ARB). Practice Point 3.2.2: RASi (ACEi or ARB) should be administered using the highest approved dose that is tolerated to achieve the bene ts described because the proven bene ts were achieved in trials using these doses. Practice Point 3.2.3: Changes in BP, serum creatinine, and serum potassium should be checked within 2-4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium. Practice Point 3.2.4: Hyperkalemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi. Practice Point 3.2.5: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose. Practice Point 3.2.6: Consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure (estimated glomerular ltration rate [eGFR] <15 ml/min per 1.73 m2 ). Practice Point 3.2.7: Mineralocorticoid receptor antagonists are effective for management of refractory hypertension but may cause hyperkalemia or a reversible decline in kidney function, particularly among patients with low eGFR. 3.3. Role of dual therapy with RASi Recommendation 3.3.1: We recommend avoiding any combination of ACEi, ARB, and direct renin inhibitor (DRI) therapy in patients with CKD, with or without diabetes (1B). summary of recommendation statements and practice points www.kidney-international.org Chapter 4: Blood pressure management in kidney transplant recipients (CKD G1T G5T) Practice Point 4.1: Treat adult kidney transplant recipients with high BP to a target BP of <130 mm Hg systolic and <80 mm Hg diastolic using standardized of ce BP measurement (see Recommendation 1.1). Recommendation 4.1: We recommend that a dihydropyridine calcium channel blocker (CCB) or an ARB be used as the rst-line antihypertensive agent in adult kidney transplant recipients (1C). Chapter 5: Blood pressure management in children with CKD Recommendation 5.1: We suggest that in children with CKD, 24-hour mean arterial pressure (MAP) by ABPM should be lowered to 50th percentile for age, sex, and height (2C). Practice Point 5.1: We suggest monitoring BP once a year with ABPM, and monitoring every 3 6 months with stan- dardized auscultatory of ce BP in children with CKD. Practice Point 5.2: In children with high BP and CKD, when ABPM is not available, manual auscultatory of ce BP obtained in a protocol-driven standardized setting targeting achieved SBP <90th percentile for age, sex, and height of normal children is a reasonable approach. Practice Point 5.3: Use ACEi or ARB as rst-line therapy for high BP in children with CKD. These drugs lower proteinuria and are usually well tolerated, but they carry the risk of hyperkalemia and have adverse fetal risks for pregnant women. www.kidney-international.org summary of recommendation statements and practice points Chapter 1: Blood pressure measurement This chapter makes recommendations on how to measure BP among adults aged $18 years with CKD. Please refer to Chapter 5 for details of BP measurement in children. The evidence review for this chapter encompassed only a search for existing systematic reviews on BP measurement in the general population. An independent systematic review was not undertaken by the ERT. Throughout this chapter, standardized of ce BP refers to measurements obtained according to recommended prepa- ration procedures (Figure 21,2 ), regardless of the type of equipment used. In contrast, routine of ce BP refers to measurements obtained without following these recom- mended preparation procedures and is often also called casual of ce BP. Once the appropriate preparations for standardized of ce BP have been made, BP may be measured by an automated oscillometric device or manually using an auscultatory method. An oscillometric BP device may be preferable to a manual BP device for standardized of ce BP measurement (see Practice Point 1.1.), but the main emphasis is on the importance of measuring BP according to recommended preparation procedures (Figure 2). Manual BP may be measured with either a mercury or aneroid sphygmoma- nometer. However, aneroid devices require frequent calibra- tion: every 6 months for wall-mounted and every 2 4 weeks for handheld devices.3,4 Oscillometric devices generally require less-frequent calibration (e.g., every 1 2 years, based on manufacturer recommendations), than aneroid devices.3 1 Have the patient relax, sitting in a chair (feet on floor, back supported) for > 5 min 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 1 Use a BP measurement device that has been validated, and ensure that the 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 1 At the first visit, record BP in both arms. Use the arm that gives the higher reading for subsequent readings 2 Separate repeated measurements by 1 2 min 3 For auscultatory determinations, use a palpated estimate of radial pulse 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 1 Record SBP and DBP. If using the auscultatory technique, record SBP and DBP as 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 Use an average of 2 readings obtained on 2 occasions to estimate the individual s level of BP Provide patients with the SBP/DBP readings verbally and in writing Properly prepare the patient Use proper technique for BP measurements Take the proper measurements needed for diagnosis and treatment of elevated BP Properly document accurate BP readings Average the readings Provide BP readings to patient Figure 2 | Checklist for standardized of ce blood pressure measurement. BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure. Modi cation for pediatrics: BP in infants should be taken while supine and the use of the bell is recommended.1 Reprinted from the Journal of the American College of Cardiology, Volume 71, Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, Pages e127 e248, 2018 with permission from the American College of Cardiology Foundation and the American Heart Association, Inc.2 chapter 1 www.kidney-international.org Some oscillometric devices can be programmed to auto- matically provide a period of rest followed by multiple BP readings with a single activation, a method known as auto- mated of ce BP (AOBP). AOBP can be performed either with the patient alone (i.e., unattended) or with a healthcare provider/technician present (i.e., attended), whereas the other of ce BP methods all require a healthcare provider to be present to perform the measurement. We suggest that AOBP is the preferred method of standardized of ce BP measure- ment (see Practice Point 1.2), but we have no preference for unattended versus attended measurement. Recommendation 1.1: We recommend standardized of ce BP measurement in preference to routine of- ce BP measurement for the management of high BP in adults (1B). This recommendation places a relatively higher value on con- sistency with the BP measurement methods used to de ne BP targets in prior large clinical outcome trials. It also places a higher value on avoidance of misclassi cation to prevent over- treatment or undertreatment of high BP. This recommendation places a lower value on the increased burden to patients, pro- viders, and staff. This recommendation is strong because, in the Work Group s opinion, the importance of of ce BP measured using a standardized versus a routine, non-standardized approach outweighs any potential burden to its implementation. Key information Balance of bene ts and harms. This recommendation relies heavily on the importance of standardized of ce BP mea- surement protocols that are consistent with large randomized controlled trials (RCTs) with clinically important outcomes that have been used to de ne BP targets. Standardized of ce BP measurements allow for extrapolation of the RCT ndings to clinical practice and avoid overtreatment or undertreat- ment of high BP that may occur if non-standardized mea- surements are used. The negative aspects of standardized of ce BP measurement, including the increased burden on patient, provider, staff time, and clinic space, are outweighed by the bene ts. Quality of evidence. There is moderate-quality evidence that routine of ce BP is generally, but not invariably, higher than standardized of ce BP, regardless of whether manual or oscillometric devices are used. However, there is strong evidence that the relationship between routine of ce BP and standardized of ce BP is highly variable among individuals. Thus, it is not possible to apply a correction factor to translate a given routine BP value to standardized of ce BP. Values and preferences. Appropriate BP management re- quires proper BP measurements. All large randomized BP outcome trials used standardized of ce BP measurements. In the opinion of the Work Group, the importance of measuring BP in a manner that is consistent with the RCTs far outweighs the additional burdens and costs for providers, staff, and patients. Increased costs are due to personnel and clinic time utilization. Routine of ce BP measurements are generally higher than standardized of ce BP measurements.5,6 Therefore, the use of routine of ce BP measurements for BP management could lead to overtreatment of BP and possibly result in a higher incidence of hypotension-related adverse events. Conversely, for some persons for whom routine of ce BP is lower than standardized of ceBP,useofroutineof ceBPcouldleadtoundertreatmentof high BP and result in a higher risk of future cardiovascular (CV) events. Routine and standardized BP measurements have poor agreement, including those in the CKD population.5,6 It is therefore not possible to convert a routine of ce BP into a standardized of ce BP using a correction factor in an individual. Thus, in the opinion of the Work Group, most well-informed patients would accept the additional time required for stan- dardized of ce BP measurement. Resource use and costs. Standardized of ce BP does not necessarily require additional equipment beyond the existing BP measurement devices. However, standardized of ce BP takes longer to perform than routine of ce BP, given the need to follow proper preparatory procedures (Figure 2). There- fore, there may be an increased time burden on patients, providers, and staff. This approach also requires staff training and retraining to ensure that a standardized BP measurement approach is followed. Adequate access to a quiet clinic space that allows for an adequate rest period prior to BP mea- surement may also be an issue in certain settings. However, in the opinion of the Work Group, this recommendation is likely to be cost-effective as it may avert consequences of over- treatment and undertreatment, though an economic analysis has not been published. Considerations for implementation. The use of standardized of ce BP over routine of ce BP holds true for all patients, regardless of age, sex, race, or CKD severity. Rationale This chapter is an addition since the KDIGO 2012 BP guide- line. This recommendation places a relatively higher value on consistency with BP measurement methods used in prior outcome trials examining different BP targets, and on mini- mizing overtreatment or undertreatment of BP that may result from routine, non-standardized of ce BP measurements. This recommendation places a lower value on the increased time required to perform standardized BP measurements. This recommendation is consistent with other recent guidelines that also underscore the importance of standard- ized of ce BP measurement (e.g., American College of Car- diology [ACC]/American Heart Association [AHA],2,7 and European Society of Cardiology [ESC]8 ). Practice Point 1.1: An oscillometric BP device may be preferable to a manual BP device for standardized of ce BP measurement; however, standardization emphasizes adequate preparations for BP measurement, not the type of equipment. www.kidney-international.org chapter 1 Oscillometric BP devices may be preferred over manual BP devices, as the former minimizes potential sources of inac- curacies in BP measurements that can occur with human errors associated with manual BP measurement such as those resulting from hearing impairment, an improper de ation rate, or terminal-digit bias.9 Manual BP devices are also acceptable when oscillometric devices are unavailable. The main emphasis is on the importance of obtaining standardized BP measurements that are made ac- cording to recommended preparation procedures (Figure 2). RCTs and prospective cohort studies used standardized of ce BP measured with either oscillometric (in newer studies) or manual devices (in older studies; Figure 310 13 ). Studies that directly compared standardized of ce BP measured using an oscillometric device versus a manual de- vice do not suggest overt differences in readings between these 2 types of devices (Supplementary Table S414 16 ). Moreover, all BP measurement devices are validated and calibrated against mercury sphygmomanometers, so they would be ex- pected to give similar BP readings. Therefore, BP levels from trials that have used different types of standardized of ce BP measurements should, in general, be comparable. The negative aspects of oscillometric BP devices are the potentially higher cost of the device compared with a manual device, the requirement of an electric power source, and lack of availability in some settings. In choosing a device, one that has been validated for accuracy and precision against a mer- cury sphygmomanometer should be selected. Several national medical or hypertension associations have established a vali- dated device listing that has information on oscillometric devices that are suitable for use.17 19 Providers working in areas where oscillometric BP devices are not available may use a manual BP device, but proper calibration of these BP de- vices is required as noted above. Regardless of the type of BP device used, proper prepa- ration and BP measurement techniques are paramount (Figure 2). Practice Point 1.2: Automated of ce BP (AOBP), either attended or unattended, may be the preferred method of standardized of ce BP measurement. In the opinion of the Work Group, AOBP may increase the likelihood of adherence to proper preparation measures, as the AOBP devices can be programmed to include a rest period. AOBP devices can also automatically take multiple BP measurements and provide an average BP measurement. Thus, BP measured with AOBP can be either attended (i.e., with a healthcare provider in the room) or unattended (i.e., without a provider in the room). Although a recent meta- analysis suggested that unattended AOBP measurements result in lower average BPs than attended measurements,20 the differences were notably small when restricted to studies that randomized the order in which unattended and attended standardized measurements were made.18,21 25 Several large trials, including Systolic Blood Pressure Intervention Trial (SPRINT), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), and Action to Control Cardiovascular Risk in Diabetes (ACCORD), used AOBP as the BP measurement method (Figure 3). Of note, the SPRINT protocol did not specify whether AOBP should be performed while attended or unattended. A post hoc analysis of SPRINT data found that while a majority of sites did perform unattended AOBP, many performed attended AOBP or some combination of Study Method/device Type of study Year Framingham MDRD UKPDS AASK ADVANCE CRIC ACCORD ONTARGET CKD JAC SPRINT Population General ) ) ) Recent lacunar stroke (baseline eGFR 80 ; 16% CKD) CVD or T2D (baseline SCr 1.05 mg/dl [93 mol/l]; ) ) High CVD risk (baseline SCr 1.07 mg/dl [95 mol/l]; ) Observational Clinical trial Clinical trial Clinical trial Clinical trial Observational Clinical trial Clinical trial Clinical trial Observational Clinical trial Manual Manual Automated Manual Manual Manual and automated Automated/Omron Automated/Colin electronic device Automated/Omron Manual Automated/Omron Figure 3 | Blood pressure measurement method and device used in select RCTs and prospective observational studies. AASK, African American Study of Kidney Disease and Hypertension; ACCORD, Action to Control Cardiovascular Risk in Diabetes; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modi ed Release Controlled Evaluation; CKD-JAC, Chronic Kidney Disease Japan Cohort; CRIC, Chronic Renal Insuf ciency Cohort; MDRD, Modi cation of Diet in Renal Disease; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; SPRINT, Systolic Blood Pressure Intervention Trial; SPS3, Secondary Prevention of Small Subcortical Strokes Trial; UKPDS, United Kingdom Prospective Diabetes Study. Adapted with modi cations with permission of the American Society of Nephrology from BP measurement in clinical practice: time to SPRINT to guideline-recommended protocols. Drawz PE, Ix JH, volume 29, Copyright 2018, permission conveyed through Copyright Clearance Center, Inc.10 ONTARGET was published in 2008.11 The BP measurement approach used in the trial was subsequently published in the 2012 article referenced above. de Galan et al.12 Peralta et al.13 CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular ltration rate; RCT, randomized controlled trial; SCr, serum creatinine; T2D, type 2 diabetes. chapter 1 www.kidney-international.org unattended and attended measurements.26 Nonetheless, similar BP levels and CV disease risk reduction were observed in the intensive group in SPRINT participants, whether the measurement technique used was primarily attended or unattended. Unattended AOBP measurements may have some practical advantages over attended standardized BP measurements, such as discouraging talking by the patients and freeing clinic staff to complete other duties during the BP measurement process. Practice Point 1.3: Oscillometric devices can be used to measure BP among patients with atrial brillation. It is a misperception that oscillometric devices do not measure BP accurately among patients with atrial brillation. Prior studies comparing BP measured using oscillometric devices versus auscultatory techniques suggest that oscillo- metric devices provide a valid systolic BP (SBP) assessment in patients with atrial brillation.27 Although oscillometric de- vices may be less accurate for estimating diastolic BP (DBP) than auscultatory techniques, the population with atrial brillation is, on average, older, and the emphasis in older adults has been on SBP.28 Recommendation 1.2: We suggest that out-of-of ce BP measurements with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) be used to complement standardized of ce BP readings for the management of high BP (2B). 