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volume 2 | issue 5 | DECEMBER 2012 http://www.kidney-international.org Official Journal of the International Society of Nephrology KDIGOClinicalPracticeGuidelinefortheManagementofBloodPressure inChronicKidneyDisease KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease KDIGO gratefully acknowledges the following consortium of sponsors that make our initiatives possible: Abbott, Amgen, Bayer Schering Pharma, Belo Foundation, Bristol-Myers Squibb, Chugai Pharmaceutical, Coca-Cola Company, Dole Food Company, Fresenius Medical Care, Genzyme, Hoffmann-LaRoche, JC Penney, Kyowa Hakko Kirin, NATCO The Organization for Transplant Professionals, NKF-Board of Directors, Novartis, Pharmacosmos, PUMC Pharmaceutical, Robert and Jane Cizik Foundation, Shire, Takeda Pharmaceutical, Transwestern Commercial Services, Vifor Pharma, and Wyeth. Sponsorship Statement: KDIGO is supported by a consortium of sponsors and no funding is accepted for the development of specific guidelines. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease Tables v KDIGO Board Members vi Reference Keys vii Abbreviations and Acronyms viii Notice Foreword Work Group Membership Abstract Summary of Recommendation Statements Chapter 1: Introduction Chapter 2: Lifestyle and pharmacological treatments for lowering blood pressure in CKD ND patients Chapter 3: Blood pressure management in CKD ND patients without diabetes mellitus Chapter 4: Blood pressure management in CKD ND patients with diabetes mellitus Chapter 5: Blood pressure management in kidney transplant recipients (CKD T) Chapter 6: Blood pressure management in children with CKD ND Chapter 7: Blood pressure management in elderly persons with CKD ND Chapter 8: Future directions and controversies Methods for Guideline Development Biographic and Disclosure Information Acknowledgments References http://www.kidney-international.org contents & 2012 KDIGO VOL 2 | ISSUE 5 | DECEMBER 2012 TABLES Table 1. Relationship among categories for albuminuria and proteinuria Table 2. Selected calcium-channel blockers Table 3. Questions for future research Table 4. Existing guidelines on ambulatory BP monitoring (ABPM) and home BP monitoring Table 5.


Existing guidelines on ambulatory BP monitoring (ABPM) and home BP monitoring Table 5. Systematic review topics and screening criteria Table 6. Hierarchy of outcomes Table 7. Relevant systematic reviews and meta-analyses Table 8. Literature yield Table 9. Work products for BP guideline Table 10. Classification of study quality Table 11. GRADE system for grading quality of evidence Table 12. Final grade for overall quality of evidence Table 13. Balance of benefits and harms Table 14. KDIGO nomenclature and description for grading recommendations Table 15. Determinants of strength of recommendation Table 16. Existing major guidelines and recommendations on hypertension and anti-hypertensive agents in CKD Table 17.


Existing major guidelines and recommendations on hypertension and anti-hypertensive agents in CKD Table 17. The Conference on Guideline Standardization (COGS) checklist for reporting clinical practice guidelines Additional information in the form of supplementary materials can be found online at http://www.kdigo.org/clinical_practice_guidelines/bp.php http://www.kidney-international.org contents & 2012 KDIGO Kidney International Supplements (2012) 2, v v KDIGO Board Members Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs Kai-Uwe Eckardt, MD Immediate Past Co-Chair Bertram L Kasiske, MD KDIGO Co-Chair David C Wheeler, MD, FRCP KDIGO Co-Chair Omar I Abboud, MD, FRCP Sharon Adler, MD, FASN Rajiv Agarwal, MD Sharon P Andreoli, MD Gavin J Becker, MD, FRACP Fred Brown, MBA, FACHE Daniel C Cattran, MD, FRCPC Allan J Collins, MD, FACP Rosanna Coppo, MD Josef Coresh, MD, PhD Ricardo Correa-Rotter, MD Adrian Covic, MD, PhD Jonathan C Craig, MBChB, MM (Clin Epi), DCH, FRACP, PhD Angel de Francisco, MD Paul de Jong, MD, PhD Ana Figueiredo, RN, MSc, PhD Mohammed Benghanem Gharbi, MD Gordon Guyatt, MD, MSc, BSc, FRCPC David Harris, MD Lai Seong Hooi, MD Enyu Imai, MD, PhD Lesley A Inker, MD, MS, FRCP Michel Jadoul, MD Simon Jenkins, MBE, FRCGP Suhnggwon Kim, MD, PhD Martin K Kuhlmann, MD Nathan W Levin, MD, FACP Philip K-T Li, MD, FRCP, FACP Zhi-Hong Liu, MD Pablo Massari, MD Peter A McCullough, MD, MPH, FACC, FACP Rafique Moosa, MD Miguel C Riella, MD Adibul Hasan Rizvi, MBBS, FRCP Bernardo Rodriquez-Iturbe, MD Robert Schrier, MD Justin Silver, MD, PhD Marcello Tonelli, MD, SM, FRCPC Yusuke Tsukamoto, MD Theodor Vogels, MSW Angela Yee-Moon Wang, MD, PhD, FRCP Christoph Wanner, MD Elena Zakharova, MD, PhD NKF-KDIGO GUIDELINE DEVELOPMENT STAFF Kerry Willis, PhD, Senior Vice-President for Scientific Activities Michael Cheung, MA, Guideline Development Director Sean Slifer, BA, Guideline Development Manager Kidney International Supplements (2012) 2, vi vi http://www.kidney-international.org & 2012 KDIGO CONVERSION FACTORS OF METRIC UNITS TO SI UNITS Parameter Metric units Conversion factor SI units Blood urea nitrogen mg/ml 0.357 mmol/l Creatinine (serum) mg/dl 88.4 mmol/l Creatinine clearance ml/min 0.01667 ml/s Note: Metric unit  conversion factor SI unit.


Grade Quality of evidence Meaning A High We are confident that the true effect lies close to that of 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 will be far from the truth. CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE USED BY KDIGO CKD categories Definition CKD CKD of any stage (1 5), with or without a kidney transplant, including both non-dialysis dependent CKD (CKD 1 5 ND) and dialysis-dependent CKD (CKD 5D) CKD ND Non-dialysis-dependent CKD of any stage (1 5), with or without a kidney transplant (i.e., CKD excluding CKD 5D) CKD T Non-dialysis-dependent CKD of any stage (1 5) with a kidney transplant Specific CKD Stages CKD 1, 2, 3, 4 Specific stages of CKD, CKD ND, or CKD T CKD 3-4, etc. Range of specific stages (e.g., both CKD 3 and CKD 4) CKD 5D Dialysis-dependent CKD 5 CKD 5HD Hemodialysis-dependent CKD 5 CKD 5PD Peritoneal dialysis-dependent CKD 5 Implications Grade* Patients Clinicians Policy 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. 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.


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. *The additional category Not Graded was used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence. The most common examples include recommendations regarding monitoring intervals, counseling, and referral to other clinical specialists. The ungraded recommendations are generally written as simple declarative statements, but are not meant to be interpreted as being stronger recommendations than Level 1 or 2 recommendations. NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS Within each recommendation, the strength of recommendation is indicated as Level 1, Level 2, or Not Graded, and the quality of the supporting evidence is shown as A, B, C, or D. Reference Keys CKD Stage Description GFR (ml/min per 1.73 m2 ) 1 Kidney damage with normal or increased GFR Z90 2 Kidney damage with mild decreased GFR 60 89 3 Moderate decreased GFR 30 59 4 Severe decreased GFR 15 29 Kidney failure o15 (or dialysis) CKD, chronic kidney disease; GFR, glomerular filtration rate. CKD 1 5T notation applies to kidney transplant recipients. a 5D if dialysis (HD or PD).


CKD 1 5T notation applies to kidney transplant recipients. a 5D if dialysis (HD or PD). STAGES OF CHRONIC KIDNEY DISEASE Kidney International Supplements (2012) 2, vii vii http://www.kidney-international.org & 2012 KDIGO Kidney International Supplements (2012) 2, viii viii Abbreviations and Acronyms AASK African American Study of Kidney Disease and Hypertension ABCD Appropriate Blood Pressure Control in Diabetes ABPM Ambulatory blood pressure monitoring ACCF American College of Cardiology Foundation ACCORD Action to Control Cardiovascular Risk in Diabetes ACE-I Angiotensin-converting enzyme inhibitor ACR Albumin/creatinine ratio ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AER Albumin excretion rate AGREE Appraisal of Guidelines for Research and Evaluation AHA American Heart Association ALLHAT Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALTITUDE Aliskiren Trial in Type 2 Diabetes Using Cardio- vascular and Renal Disease Endpoints ARB Angiotensin-receptor blocker BMI Body mass index BP Blood pressure CAD Coronary artery disease CASE J Candesartan Antihypertensive Survival Evaluation in Japan CI Confidence interval CKD Chronic kidney disease CKD-EPI CKD Epidemiology Collaboration CKD ND Non dialysis-dependent CKD of any stage CKD T Non dialysis-dependent CKD of any stage with a kidney transplant CKD 5D Dialysis-dependent CKD 5 CKiD Chronic Kidney Disease in Children CNI Calcineurin inhibitor COGS Conference on Guideline Standardization CPG Clinical practice guideline CRIC Chronic Renal Insufficiency Cohort CVD Cardiovascular disease DCCT/EDIC Diabetes Control and Complications Trial/Epide- miology of Diabetes Interventions and Complications DRI Direct renin inhibitor EDC Pittsburgh Epidemiology of Diabetes Complica- tions Study ERT Evidence review team ESCAPE Effect of Strict Blood Pressure Control and ACE- Inhibition on Progression of Chronic Renal Failure in Pediatric Patients EUROPA European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease FDA Food and Drug Administration GFR Glomerular filtration rate GRADE Grading of Recommendations Assessment, Development and Evaluation HOPE Heart Outcomes Prevention Evaluation HOT Hypertension Optimal Treatment HR Hazard ratio HYVET Hypertension in the Very Elderly Trial ICD International Classification of Diseases IDNT Irbesartan Diabetic Nephropathy Trial INVEST International Verapamil SR Trandolapril study JATOS Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients JNC Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure KDIGO Kidney Disease: Improving Global Outcomes KDOQI Kidney Disease Outcomes Quality Initiative KEEP Kidney Early Evaluation Program MAP Mean arterial pressure MDRD Modification of Diet in Renal Disease MRFIT Multiple Risk Factor Intervention trial mTOR Mammalian target of rapamycin NHANES National Health and Nutrition Examination Survey NICE National Institute for Health and Clinical Excellence NIH National Institutes of Health NKF National Kidney Foundation NSAID Nonsteroidal anti-inflammatory drug ONTARGET Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint trial PCR Protein/creatinine ratio PEACE Prevention of Events with Angiotensin-Convert- ing Enzyme Inhibitor Therapy PREVEND IT Prevention of Renal and Vascular Endstage Disease Intervention Trial PROGRESS Perindopril Protection Against Recurrent Stroke Study RAAS Renin-angiotensin-aldosterone system RCT Randomized controlled trial REIN-2 Ramipril Efficacy in Nephropathy 2 RENAAL Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan RR Relative risk SCr Serum creatinine SD Standard deviation SECRET Study on Evaluation of Candesartan Cilexetil after Renal Transplantation SHEP Systolic Hypertension in the Elderly Program SPRINT Systolic Blood Pressure Intervention Trial Steno-2 Intensified Multifactorial Intervention in Patients With Type 2 Diabetes and Microalbuminuria STONE Shanghai Trial of Nifedipine in the Elderly Syst-Eur Systolic Hypertension in Europe TRANSCEND Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease UKPDS United Kingdom Prospective Diabetes Study VALISH Valsartan in Elderly Isolated Systolic Hypertension WHO World Health Organization http://www.kidney-international.org & 2012 KDIGO Notice SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon systematic literature searches last conducted in January 2011, supplemented with additional evidence through February 2012.


It is designed to provide information and assist decision making. It is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Every health-care professional making use of these recommendations is responsible for evaluating the appropriateness of applying them in any particular clinical situation. The recommendations for research contained within this document are general and do not imply a specific protocol. SECTION II: DISCLOSURE Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived conflicts of interest that may arise as a result of 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 or actual conflicts 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 Biographic and Disclosure Information section, and is kept on file at the National Kidney Foundation (NKF), Managing Agent for KDIGO. http://www.kidney-international.org & 2012 KDIGO Copyright &2012 by KDIGO. All rights reserved. Single photocopies 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 non-profit educational use.


Special rates are available for educational institutions that wish to make photocopies for non-profit 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 permission for reproduction or translation, and further information about KDIGO s permissions policies can be obtained by contacting Danielle Green, KDIGO Managing Director, at danielle.green@kdigo.org To the fullest extent of the law, neither KDIGO, Kidney International Supplements, National Kidney Foundation (KDIGO Managing Agent) 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. Foreword It is our hope that this document will serve several useful purposes. Our primary goal is to improve patient care. We hope to accomplish this, in the short term, by helping clinicians know and better understand the evidence (or lack of evidence) that determines current practice. By providing comprehensive evidence-based recommendations, this guideline will also help define areas where evidence is lacking and research is needed. Helping to define a research agenda is an often neglected, but very important, function of clinical practice guideline development. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and the strength of recommendations.


We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and the strength of recommendations. In all, there were no recommendations in this guideline for which the overall quality of evidence was graded A, whereas 4 (23.5%) were graded B, 3 (17.7%) were graded C, and 10 (58.8%) were graded D. Although there are reasons other than quality of evidence that underpin a grade 1 or 2 recomm- endation, in general, there is a correlation between the quality of overall evidence and the strength of the recommendation. Thus, there were 8 (47.1%) recommendations graded 1 and 9 (52.9%) graded 2. There were no recommendations graded were 1D. There were no recommendations graded 2A or 2B, 4 (19.1%) statements that were not graded. Some argue that recommendations should not be made when evidence is weak. However, clinicians still need to make decisions in their daily practice, and they often ask, What do the experts do in this setting? We opted to give guidance, rather than remain silent. These recommendations are often rated with a low strength of recommendation and a low quality of evidence, or were not graded. It is important for the users of this guideline to be cognizant of this (see Notice). In every case these recommendations are meant to be a place for clinicians to start, not stop, their inquiries into specific management questions pertinent to the patients they see in daily practice. We wish to thank Dr Gavin Becker who co-chaired the Work Group with David Wheeler, along with all of the Work Group members who volunteered countless hours of their time developing this guideline. We also thank the Evidence Review Team members and staff of the National Kidney Foundation who made this project possible.


We also thank the Evidence Review Team members and staff of the National Kidney Foundation who made this project possible. Finally, we owe a special debt of gratitude to the many KDIGO Board members and individuals who volunteered time reviewing the guide- line, and making very helpful suggestions.


Finally, we owe a special debt of gratitude to the many KDIGO Board members and individuals who volunteered time reviewing the guide- line, and making very helpful suggestions. Bertram L Kasiske, MD David C Wheeler, MD, FRCP KDIGO Co-Chair KDIGO Co-Chair http://www.kidney-international.org & 2012 KDIGO Work Group Membership http://www.kidney-international.org & 2012 KDIGO WORK GROUP CO-CHAIRS Gavin J Becker, MD, FRACP Royal Melbourne Hospital Melbourne, Australia David C Wheeler, MD, FRCP University College London London, United Kingdom WORK GROUP Dick de Zeeuw, MD, PhD University Medical Center Groningen Groningen, Netherlands Toshiro Fujita, MD University of Tokyo School of Medicine Tokyo, Japan Susan L Furth, MD, PhD The Children s Hospital of Philadelphia Philadelphia, PA, USA Hallvard Holdaas, MD, PhD Hospital Rikshospitalet Oslo, Norway Shanthi Mendis, MBBS, MD, FRCP, FACC World Health Organization Geneva, Switzerland Suzanne Oparil, MD University of Alabama Birmingham, AL, USA Vlado Perkovic, MBBS, FRACP, FASN, PhD George Institute for International Health Sydney, Australia Cibele Isaac Saad Rodrigues, MD, PhD Catholic University of Sa o Paulo Sa o Paulo, Brazil Mark J Sarnak, MD, MS Tufts Medical Center Boston, MA, USA Guntram Schernthaner, MD Rudolfstiftung Hospital Vienna, Austria Charles R V Tomson, DM, FRCP Southmead Hospital Bristol, United Kingdom Carmine Zoccali, MD CNR-IBIM Clinical Research Unit, Ospedali Riuniti Reggio Calabria, Italy EVIDENCE REVIEW TEAM Tufts Center for Kidney Disease Guideline Development and Implementation, Tufts Medical Center, Boston, MA, USA: Katrin Uhlig, MD, MS, Project Director; Director, Guideline Development Ashish Upadhyay, MD, Assistant Project Director Amy Earley, BS, Project Coordinator Shana Haynes, MS, DHSc, Research Assistant Jenny Lamont, MS, Project Manager In addition, support and supervision were provided by: Ethan M Balk, MD, MPH; Program Director, Evidence Based Medicine Abstract The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease aims to provide guidance on blood pressure management and treatment for all non-dialysis-dependent CKD patients and kidney transplant recipients.


Bertram L Kasiske, MD David C Wheeler, MD, FRCP KDIGO Co-Chair KDIGO Co-Chair http://www.kidney-international.org & 2012 KDIGO Work Group Membership http://www.kidney-international.org & 2012 KDIGO WORK GROUP CO-CHAIRS Gavin J Becker, MD, FRACP Royal Melbourne Hospital Melbourne, Australia David C Wheeler, MD, FRCP University College London London, United Kingdom WORK GROUP Dick de Zeeuw, MD, PhD University Medical Center Groningen Groningen, Netherlands Toshiro Fujita, MD University of Tokyo School of Medicine Tokyo, Japan Susan L Furth, MD, PhD The Children s Hospital of Philadelphia Philadelphia, PA, USA Hallvard Holdaas, MD, PhD Hospital Rikshospitalet Oslo, Norway Shanthi Mendis, MBBS, MD, FRCP, FACC World Health Organization Geneva, Switzerland Suzanne Oparil, MD University of Alabama Birmingham, AL, USA Vlado Perkovic, MBBS, FRACP, FASN, PhD George Institute for International Health Sydney, Australia Cibele Isaac Saad Rodrigues, MD, PhD Catholic University of Sa o Paulo Sa o Paulo, Brazil Mark J Sarnak, MD, MS Tufts Medical Center Boston, MA, USA Guntram Schernthaner, MD Rudolfstiftung Hospital Vienna, Austria Charles R V Tomson, DM, FRCP Southmead Hospital Bristol, United Kingdom Carmine Zoccali, MD CNR-IBIM Clinical Research Unit, Ospedali Riuniti Reggio Calabria, Italy EVIDENCE REVIEW TEAM Tufts Center for Kidney Disease Guideline Development and Implementation, Tufts Medical Center, Boston, MA, USA: Katrin Uhlig, MD, MS, Project Director; Director, Guideline Development Ashish Upadhyay, MD, Assistant Project Director Amy Earley, BS, Project Coordinator Shana Haynes, MS, DHSc, Research Assistant Jenny Lamont, MS, Project Manager In addition, support and supervision were provided by: Ethan M Balk, MD, MPH; Program Director, Evidence Based Medicine Abstract The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease aims to provide guidance on blood pressure management and treatment for all non-dialysis-dependent CKD patients and kidney transplant recipients. Guideline development followed an explicit process of evidence review and appraisal.


Guideline development followed an explicit process of evidence review and appraisal. Treatment approaches are addressed in each chapter and guideline recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. Ongoing areas of controversies and limitations of the evidence are discussed and additional suggestions are also provided for future research. Keywords: blood pressure; chronic kidney disease; clinical practice guideline; evidence-based recommendation; KDIGO; systematic review CITATION In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney inter., Suppl. 2012; 2: 337 414. http://www.kidney-international.org & 2012 KDIGO Summary of Recommendation Statements http://www.kidney-international.org & 2012 KDIGO Chapter 2: Lifestyle and pharmacological treatments for lowering blood pressure in CKD ND patients GENERAL STRATEGIES 2.1: Individualize BP targets and agents according to age, co-existent cardiovascular disease and other co-morbidities, risk of progression of CKD, presence or absence of retinopathy (in CKD patients with diabetes) and tolerance of treatment. (Not Graded) 2.2: Inquire about postural dizziness and check for postural hypotension regularly when treating CKD patients with BP-lowering drugs. (Not Graded) LIFESTYLE MODIFICATION 2.3: Encourage lifestyle modification in patients with CKD to lower BP and improve long-term cardiovascular and other outcomes: 2.3.1: We recommend achieving or maintaining a healthy weight (BMI 20 to 25). (1D) 2.3.2: We recommend lowering salt intake to o90 mmol (o2 g) per day of sodium (corresponding to 5 g of sodium chloride), unless contraindicated. (1C) 2.3.3: We recommend undertaking an exercise program compatible with cardiovascular health and tolerance, aiming for at least 30 minutes 5 times per week.


(1C) 2.3.3: We recommend undertaking an exercise program compatible with cardiovascular health and tolerance, aiming for at least 30 minutes 5 times per week. (1D) 2.3.4: We suggest limiting alcohol intake to no more than two standard drinks per day for men and no more than one standard drink per day for women. (2D) Chapter 3: Blood pressure management in CKD ND patients without diabetes mellitus 3.1: We recommend that non-diabetic adults with CKD ND and urine albumin excretion o30 mg per 24 hours (or equivalent*) whose office BP is consistently 4140 mm Hg systolic or 490 mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently r140 mm Hg systolic and r90 mm Hg diastolic. (1B) 3.2: We suggest that non-diabetic adults with CKD ND and urine albumin excretion of 30 to 300 mg per 24 hours (or equivalent*) whose office BP is consistently 4130 mm Hg systolic or 480 mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently r130 mm Hg systolic and r80 mm Hg diastolic. (2D) 3.3: We suggest that non-diabetic adults with CKD ND and urine albumin excretion 4300 mg per 24 hours (or equivalent*) whose office BP is consistently 4130 mm Hg systolic or 480 mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently r130 mm Hg systolic and r80 mm Hg diastolic. (2C) 3.4: We suggest that an ARB or ACE-I be used in non-diabetic adults with CKD ND and urine albumin excretion of 30 to 300 mg per 24 hours (or equivalent*) in whom treatment with BP-lowering drugs is indicated.


(2C) 3.4: We suggest that an ARB or ACE-I be used in non-diabetic adults with CKD ND and urine albumin excretion of 30 to 300 mg per 24 hours (or equivalent*) in whom treatment with BP-lowering drugs is indicated. (2D) 3.5: We recommend that an ARB or ACE-I be used in non-diabetic adults with CKD ND and urine albumin excretion 4300 mg per 24 hours (or equivalent*) in whom treatment with BP-lowering drugs is indicated. (1B) *Approximate equivalents for albumin excretion rate per 24 hours expressed as protein excretion rate per 24 hours, albumin/creatinine ratio, protein/ creatinine ratio, and protein reagent strip results are given in Table 1, Chapter 1. Chapter 4: Blood pressure management in CKD ND patients with diabetes mellitus 4.1: We recommend that adults with diabetes and CKD ND with urine albumin excretion o30 mg per 24 hours (or equivalent*) whose office BP is consistently 4140 mm Hg systolic or 490 mm Hg diastolic be treated with BP- lowering drugs to maintain a BP that is consistently r140 mm Hg systolic and r90 mm Hg diastolic. (1B) 4.2: We suggest that adults with diabetes and CKD ND with urine albumin excretion 430 mg per 24 hours (or equivalent*) whose office BP is consistently 4130 mm Hg systolic or 480 mm Hg diastolic be treated with BP- lowering drugs to maintain a BP that is consistently r130 mm Hg systolic and r80 mm Hg diastolic. (2D) 4.3: We suggest that an ARB or ACE-I be used in adults with diabetes and CKD ND with urine albumin excretion of 30 to 300 mg per 24 hours (or equivalent*). (2D) 4.4: We recommend that an ARB or ACE-I be used in adults with diabetes and CKD ND with urine albumin excretion 4300 mg per 24 hours (or equivalent*).


(2D) 4.4: We recommend that an ARB or ACE-I be used in adults with diabetes and CKD ND with urine albumin excretion 4300 mg per 24 hours (or equivalent*). (1B) *Approximate equivalents for albumin excretion rate per 24 hours expressed as protein excretion rate per 24 hours, albumin/creatinine ratio, protein/ creatinine ratio, and protein reagent strip results are given in Table 1, Chapter 1. Chapter 5: Blood pressure management in kidney transplant recipients (CKD T) 5.1: We suggest that adult kidney transplant recipients whose office BP is consistently 4130 mm Hg systolic or 480 mm Hg diastolic be treated to maintain a BP that is consistently r130 mm Hg systolic and r80 mm Hg diastolic, irrespective of the level of urine albumin excretion. (2D) 5.2: In adult kidney transplant recipients, choose a BP-lowering agent after taking into account the time after transplantation, use of calcineurin inhibitors, presence or absence of persistent albuminuria, and other co-morbid conditions. (Not Graded) Chapter 6: Blood pressure management in children with CKD ND 6.1: We recommend that in children with CKD ND, BP-lowering treatment is started when BP is consistently above the percentile for age, sex, and height. (1C) 6.2: We suggest that in children with CKD ND (particularly those with proteinuria), BP is lowered to consistently achieve systolic and diastolic readings less than or equal to the 50th percentile for age, sex, and height, unless achieving these targets is limited by signs or symptoms of hypotension. (2D) 6.3: We suggest that an ARB or ACE-I be used in children with CKD ND in whom treatment with BP-lowering drugs is indicated, irrespective of the level of proteinuria.


(2D) 6.3: We suggest that an ARB or ACE-I be used in children with CKD ND in whom treatment with BP-lowering drugs is indicated, irrespective of the level of proteinuria. (2D) Chapter 7: Blood pressure management in elderly persons with CKD ND 7.1: Tailor BP treatment regimens in elderly patients with CKD ND by carefully considering age, co-morbidities and other therapies, with gradual escalation of treatment and close attention to adverse events related to BP treatment, including electrolyte disorders, acute deterioration in kidney function, orthostatic hypotension and drug side effects. (Not Graded) summary of recommendation statements Chapter 1: Introduction There is a strong association between chronic kidney disease (CKD) and an elevated blood pressure (BP) whereby each can cause or aggravate the other. BP control is fundamental to the care of patients with CKD and is relevant at all stages of CKD regardless of the underlying cause. Clinical practice guidelines (CPGs) have been published on this topic by many authoritative bodies over the past decade, the most comprehensive being the National Kidney Foundation s (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines on Hypertension and Antihyper- tensive Agents in Chronic Kidney Disease, which was based on evidence collected up to 2001 (http://www.kidney.org/ The Kid- ney Disease: Improving Global Outcomes (KDIGO) Board believed that it would be clinically useful to update this CPG to incorporate the evidence gathered since then. KDIGO therefore commissioned an evidence review to include the recent literature and assembled a Work Group with the mandate of writing an updated guideline relevant to an international audience. This KDIGO Guideline, entitled Management of Blood Pressure in Chronic Kidney Disease, is the result of these efforts.


This KDIGO Guideline, entitled Management of Blood Pressure in Chronic Kidney Disease, is the result of these efforts. Scope of this guideline This Guideline has been developed to provide advice on the management of BP in patients with non dialysis-dependent CKD (CKD ND) (see Reference Keys). BP. We have avoided using the term hypertension in our title because this implies that there is a BP value above or below which morbidity or mortality changes in a stepwise fashion, hence suggesting that it is possible to set a universal BP target. In reality, it proved difficult to define precise targets appropriate for all CKD subpopulations, consistent with the notion that the ideal BP may differ between patients, once other factors are considered. These factors include specific features of CKD such as the severity of albuminuria or proteinuria, the presence of other risk factors for cardiovascular disease (CVD) and co- morbidities. Another reason for our choice of terminology is that agents introduced primarily to treat high BP may have actions that may not be directly linked to BP-lowering (e.g., the anti-albuminuric effects of angiotensin-converting enzyme inhibitors [ACE-Is] and angiotensin-receptor blockers [ARBs]). Definition of CKD. The Work Group defined CKD according to the standard KDOQI classification system2 as endorsed by KDIGO.3 Populations of interest.


The Work Group defined CKD according to the standard KDOQI classification system2 as endorsed by KDIGO.3 Populations of interest. The populations covered in this guideline are: K Adults with CKD ND without diabetes mellitus K Adults with CKD ND with diabetes mellitus K Adults with CKD ND who have received a kidney transplant (CKD T) K Children with CKD ND K Elderly with CKD ND The scope of this guideline did not include BP manage- ment in patients with dialysis-dependent CKD 5 (CKD 5D) since this has been the topic of a recent KDIGO consensus and has been covered by two recent systematic There are other groups of patients with CKD for whom specific recommendations might be welcome, but who are not represented in sufficient numbers in randomized controlled trials (RCTs) to constitute a sufficiently robust evidence base. The evidence review team (ERT) was asked to present the evidence separately for adults with CKD and diabetes, since these individuals constitute the single largest subgroup of CKD patients in the world. The separation of the evidence base according to diabetes status meant that there were two separate datasets for the Work Group to review. Although the two sets of recommen- dations had much in common, the Work Group decided that they differed sufficiently in detail to warrant two separate chapters. Adults who received a kidney transplant, children, and the elderly were also thought to deserve dedicated chapters, although the evidence base for each of these subpopulations is rather small. The Work Group was unable to identify sufficient evidence to make recommendations according to severity (stage) of CKD, although common sense dictates that pharmacological management should differ at least between mild CKD (patients with normal glomerular filtration rate [GFR]) and advanced CKD (patients with low GFR).


The Work Group was unable to identify sufficient evidence to make recommendations according to severity (stage) of CKD, although common sense dictates that pharmacological management should differ at least between mild CKD (patients with normal glomerular filtration rate [GFR]) and advanced CKD (patients with low GFR). However, the Work Group did consider the modification of drug dosages and risks related to the various classes of BP-lowering agents in the context of CKD in Chapter 2. Clearly there are many other populations that could have been considered. CKD patients with glomerulonephritis are the subject of a recent KDIGO Guideline,7 so they were not considered separately here. Although management of BP in the pregnant CKD patient is an important issue, there is insuf- ficient evidence in this subgroup to allow recommendations to be made.8 Furthermore, the Work Group did not consider the management of BP in patients with acute kidney injury. http://www.kidney-international.org chapter 1 & 2012 KDIGO Interventions. Interventions primarily aiming at modify- ing BP include advice on lifestyle and administration of pharmacological agents that reduce BP. The efficacies of both strategies have been widely studied in the general population with high BP. The pharmacology of anti-hypertensive agents was detailed in the 2004 KDOQI guideline.1 Of the available RCTs that met our inclusion criteria, most involved agents interfering with the renin-angiotensin- aldosterone system (RAAS). Accordingly, these agents may be over-represented in this Guideline, and if so, it is because of the availability of the evidence rather than a deliberate focus by the Work Group. Evidence for interventions Because CKD is common and BP levels are often elevated in CKD populations, the management of BP in CKD patients could have an enormous global impact.