methods for guideline development Table 16 | Existing major guidelines and recommendations on hypertension and anti-hypertensive agents in CKD Year Group Target CKD population Recommended BP goal (mm Hg) Recommended preferred anti-hypertensive agent(s) 2003 Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure143 Stage 3 CKD, macroalbuminuria, kidney-transplant recipients o130/80 CKD 3 or macroalbuminuria: ACE-I or ARB in combination with a diuretic Kidney-transplant recipients: No particular class of agents superior 2003 World Health Organization/International Society of Hyper- tension Statement on Management of Hypertension243 http://www.who.int/cardiovascular_diseases/guidelines/ hypertension_guidelines.pdf Type 1 DM with nephropathy Type 2 DM with nephropathy Non-diabetic nephropathy o130/80 Type 1 DM with nephropathy: ACE-I Type 2 DM with nephropathy: ARB Non-diabetic nephropathy: ACE-I 2003 European Society of Hypertension European Society of Cardiology Guidelines for the Management of Arterial DM, CKD o130/80 (if urine protein 41 g/d is present, lower target to lower protein if possible) CKD: Diuretic Type 1 DM with nephropathy: ACE-I Type 2 DM with nephropathy: ARB Non-diabetic nephropathy: ACE-I Proteinuria: ACE-I or ARB 2006 Caring for Australasians with Renal Impairment (CARI) Guidelines: Prevention of Progression of Kidney Disease http://www.cari.org.au/ckd_prevent_list_published.php DM, CKD CKD in general: if urine protein 41 g/d if urine protein 0.25 1 g/d if urine protein o0.25 g/d DKD: o130/85 for patients 450 years of age o120/70 75 for those o50 years of age Non-DKD: Regimens including ACE-I more effective than those not including ACE-I in slowing CKD progression in non-DKD Combination therapy of ACE-I and ARB slows progression of non-DKD more effectively than either single agent ACE-I more effective than beta-blockers and dihydropyridine CCB in slowing progression of CKD Beta-blockers more effective than dihydro- pyridine CCB in slowing CKD progression, especially in the presence of proteinuria DKD: ACE-I for all patients with diabetes and hypertension ACE-I for all patients with diabetes and microalbuminuria or overt nephropathy, independent of BP and GFR ARB provides specific renoprotection in diabetic nephropathy, beyond their anti-hypertensive benefit There is insufficient evidence that ACE-I and ARB combination are of additive specific benefit in diabetic nephropathy, beyond additional anti-hypertensive benefit 2008 Canadian Society of Nephrology Guidelines on Management of CKD238 DM, CKD o130/80 Non-DKD: ACE-I or ARB should be included in the regimen if urine ACR 430 mg/mmol ACE-I, ARB, thiazides, long-acting CCB, or beta- blockers (for patients older than 60 years) should be included in the regimen if urine ACR o30 mg/mmol (o300 mg/g) DKD: ACE-I or ARB should be included in the regimen 2009 Reappraisal of European Guidelines on Hypertension Management: a European Society of Hypertension Task Force Document353 DM, CKD Initiate treatment for systolic BP 4130 and diastolic ACE-I or ARB, but combination therapy with other agents most likely needed to control BP 2009 Japanese Society of Hypertension Guidelines for the Management of Hypertension452 For those with urine protein ACE-I or ARB should be the first choice of therapy and dose should be titrated by urinary albumin excretion (o30 mg/g for diabetic nephropathy and o300 mg/g for glomerulonephritis) For diuretics, thiazides should be used if GFR , and loop diuretics should Table 16 continued on following page methods for guideline development account explicit judgments about the relative importance of each outcome. The resulting four final categories for the quality of overall evidence were: A , B , C or D (Table 12). Assessment of the net health benefit across all important clinical outcomes. The net health benefit was determined on the basis of the anticipated balance of benefits and harms across all clinically important outcomes (Table 13). The assessment of net benefit also involved the judgment of the Work Group and the ERT. Grading the strength of the recommendations. The strength of a recommendation is graded as level 1 or level 2. Table 14 shows the KDIGO nomenclature for grading the strength of a recommendation and the implications of each level for patients, clinicians, and policy makers. Recommendations can be for or against doing something. Table 15 shows that the strength of a recommendation is determined not only by the quality of the evidence but also by other, often complex judgments regarding the size of the net medical benefit, values, and preferences, and costs. Formal decision analyses including cost analysis were not conducted. Ungraded statements. This category was designed to allow the Work Group to issue general advice. Typically an ungraded statement meets the following criteria: it provides guidance based on common sense; it provides reminders of the obvious; and it is not sufficiently specific to allow for application of evidence to the issue and therefore it is not based on systematic evidence review. Common examples include recommendations about frequency of testing, referral to specialists, and routine medical care. We strove to minimize the use of ungraded recommendations. This grading scheme, with two levels for the strength of a recommendation together with four levels of grading the quality of the evidence, as well as the option of an ungraded statement for general guidance, was adopted by the KDIGO Board in December 2008. The Work Group took on the primary role of writing the recommendations and rationale and retained final responsibility for the content of the guideline statements and the accompanying narrative. The ERT reviewed draft recommendations and grades for consistency with the conclusions of the evidence review. Format for guideline recommendations. Each chapter contains one or more specific 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. The recom- mendation statements and grades are followed by a brief background with relevant definitions of terms and then the rationale starting with a chain of logic, which consists of declarative sentences summarizing the key points of the Table 16 | Continued Year Group Target CKD population Recommended BP goal (mm Hg) Recommended preferred anti-hypertensive agent(s) 2011 The Renal Association (UK) CKD Guidelines396 http://www.renal.org/Clinical/GuidelinesSection/ Detection-Monitoring-and-Care-of-Patients-with-CKD.aspx CKD For the majority, systolic BP: o140 mm Hg (target range 120 139 mm Hg) and diastolic BP: o90 mm Hg for the majority ACE-I or ARB For those with DM or proteinuria X1g/24 h, systolic BP: o130 mm Hg (target range 120 129 mm Hg) and diastolic BP: o80 mm Hg unless the risks are considered to outweigh the potential benefits Antihypertensive therapy should be individualized and lowering the systolic blood pressure to o120 mm Hg should be avoided 2012 Canadian Hypertension Education Program Recommendations http://www.hypertension.ca/chep-recommendations Non-DKD and DKD CKD in general: o140/90 Non-DKD: ACE-I or ARB (if ACE-I intolerant) as a first choice agent if urine ACR 430 mg/mmol (4300 mg/g) or urine protein 4500 mg/24 h DKD: For patients with persistent microalbuminuria (urine ACR 42 mg/mmol [420 mg/g] in men and 42.8 mg/mmol [428 mg/g] in women), ACE-I or or ARB is recommended as initial therapy DM with microalbuminuria or overt nephropathy o130/80 ACE-I or ARB should be considered for patients with microalbuminaria or macroalbuminaria. If ACE-I or ARB is not tolerated, then diuretics, CCBs, and beta- blockers should be considered ACE-I, angiotensin-converting enzyme inhibitor; ACR, albumin/creatinine ratio; ARB, angiotensin-receptor blocker; BP, blood pressure; CCB, calcium-channel blocker; CKD, chronic kidney disease; DKD, diabetic kidney disease; DM, diabetes mellitus; GFR, glomerular filtration rate. methods for guideline development Table 17 | The Conference on Guideline Standardization (COGS) checklist for reporting clinical practice guidelines Topic Description Discussed in KDIGO Management of Blood Pressure in Chronic Kidney Disease Guideline 1. Overview material Provide a structured abstract that includes the guideline s release date, status (original, revised, updated), and print and electronic sources. Abstract and Methods for Guideline Development. 2. Focus Describe the primary disease/condition and intervention/ service/technology that the guideline addresses. Indicate any alternative preventative, diagnostic or therapeutic interventions that were considered during development. Management of blood pressure and the use of anti-hypertensive agents in adults and children with CKD ND, including those with kidney transplants. 3. Goal Describe the goal that following the guideline is expected to achieve, including the rationale for development of a guideline on this topic. This clinical practice guideline is intended to assist the practitioner caring for patients with non-dialysis CKD and hypertension and to prevent deaths, CVD events, and progression to kidney failure while optimizing patients quality of life. 4. User/setting Describe the intended users of the guideline (e.g., provider types, patients) and the settings in which the guideline is intended to be used. Providers: Nephrologists (adult and pediatric), Internists, and Pediatricians. Patients: Adults and children with CKD at risk for hypertension. Policy Makers: Those in related health fields. 5. Target population Describe the patient population eligible for guideline recommendations and list any exclusion criteria. Adults and children with CKD, not on dialysis; kidney transplant recipients. 6. Developer Identify the organization(s) responsible for guideline development and the names/credentials/potential conflicts of interest of individuals involved in the guideline s development. Organization: KDIGO Names/credentials/potential conflicts of interest of individuals involved in the guideline s development are disclosed in the Biographic and Disclosure Information. 7. Funding source/sponsor Identify the funding source/sponsor and describe its role in developing and/or reporting the guideline. Disclose potential conflict of interest. KDIGO is supported by the following consortium of sponsors: 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. No funding is accepted for the development or reporting of specific guidelines. All stakeholders could participate in open review. 8. Evidence collection Describe the methods used to search the scientific literature, including the range of dates and databases searched, and criteria applied to filter the retrieved evidence. Topics were triaged either to a) systematic review, b) systematic search followed by narrative summary, or c) narrative summary. For systematic reviews on treatment with different anti-hypertensive agents or to different BP targets, we searched for RCTs in MEDLINE, Cochrane Central Registry for trials, and Cochrane database of systematic reviews. Screening criteria are outlined in the Methods for Guideline Development chapter. The search was updated through January 2011 and supplemented by articles identified by Work Group members through February 2012. We also searched for pertinent existing guidelines and systematic reviews. grading criteria Describe the criteria used to rate the quality of evidence that supports the recommendations and the system for describing the strength of the recommendations. Recommendation strength communicates the importance of adherence to a recommendation and is based on both the quality of the evidence and the magnitude of anticipated benefits and harms. Quality of individual studies was graded in a three-tiered grading system (see Table 10). Quality of evidence and strength of recommendations were graded following the GRADE approach (Tables 12 and 14). The Work Group could provide general guidance in unngraded statements. 10. Method for synthesizing evidence Describe how evidence was used to create recommendations, e.g., evidence tables, meta-analysis, decision analysis. For systematic review topics, summary tables and evidence profiles were generated. For recommendations on treatment interventions, the steps outlined by GRADE were followed. 11. Prerelease review Describe how the guideline developer reviewed and/or tested the guidelines prior to release. The guideline had undergone internal review at the 2010 KDIGO Board of Directors meeting and external public review in July 2011. Public review comments were compiled and fed back to the Work Group, which considered comments in its revision of the guideline. 12. Update plan State whether or not there is a plan to update the guideline and, if applicable, an expiration date for this version of the guideline. There is no date set for updating. The need for updating of the guideline will depend on the publication of new evidence that would change the quality of the evidence or the estimates for the benefits and harms. Results from registered ongoing studies and other publications will be reviewed periodically to evaluate their potential to impact on the recommendations in this guideline. Table 17 continued on following page methods for guideline development evidence base and the judgments supporting the recommen- dation. This is followed by a narrative in support of the rationale. In relevant sections, research recommendations suggest future research to resolve current uncertainties. Comparison with other guidelines We tabulated recommendations from other key English- language guidelines pertinent to the use of blood-pressure lowering agents in individuals with CKD (Table 16). This served to inform topic selection and scope. Also, after recommendations had been drafted, the Work Group reviewed them in the context of the existing guideline recommendations to avoid unnecessary or unwarranted discrepancies. Limitations of approach Although the literature searches were intended to be comprehensive, they were not exhaustive. MEDLINE was the only database searched. Hand searches of journals were not performed, and review articles and textbook chapters were not systematically searched. However, important studies known to domain experts that were missed by the electronic literature searches were added to retrieved articles and reviewed by the Work Group. Review of guideline development process Several tools and checklists have been developed to assess the quality of the methodological process for guideline develop- ment. These include the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria,446 the Conference on Guideline Standardization (COGS) checklist,447 and the Institute of Medicine s recent Standards for Systematic and Clinical Practice Guideines We Can Trust.449 Table 17 and Supplementary Appdenix 2 online show, respectively, the COGS criteria and the Institute of Medicine standards, and how each one of them is addressed in this Guideline. SUPPLEMENTARY MATERIAL Supplementary Appendix 1. Online search strategies. Supplementary Appendix 2. Concurrence with Institute of Medicine standards for systematic reviews and for guidelines. Supplementary material is linked to the online version of the paper at http://www.kdigo.org/clinical_practice_guidelines/bp.php Table 17 | Continued Topic Description Discussed in KDIGO Management of Blood Pressure in Chronic Kidney Disease Guideline 13. Definitions Define unfamiliar terms and those critical to correct application of the guideline that might be subject to misinterpretation. Abbreviations and Acronyms. 14. Recommendations and rationale State the recommended action precisely and the specific circumstances under which to perform it. Justify each recommendation by describing the linkage between the recommendation and its supporting evidence. Indicate the quality of evidence and the recommendation strength, based on the criteria described in Topic 9. Each guideline chapter contains recommendations for blood pressure management of CKD patients. Each recommendation builds on a supporting rationale with evidence tables if available. The strength of the recommendation and the quality of evidence are provided in parenthesis within each recommendation. 15. Potential benefits and harms Describe anticipated benefits and potential risks associated with implementation of guideline recommendations. The benefits and harm for each comparison of interventions are provided in summary tables and summarized in evidence profiles. The estimated balance between potential benefits and harm was considered when formulating the recommendations. 16. Patient preferences Describe the role of patient preferences when a recommendation involves a substantial element of personal choice or values. Many recommendations are level 2 or discretionary, which indicates a greater need to help each patient arrive at a management decision consistent with her or his values and preferences. 17. Algorithm Provide (when appropriate) a graphical description of the stages and decisions in clinical care described by the guideline. No overall algorithm. considerations Describe anticipated barriers to application of the recommendations. Provide reference to any auxiliary documents for providers or patients that are intended to facilitate implementation. Suggest review criteria for measuring changes in care when the guideline is implemented. These recommendations are global. Review criteria were not suggested because implementation with prioritization and development of review criteria have to proceed locally. Furthermore, most recommendations are discretionary, requiring substantial discussion among stakeholders before they can be adopted as review criteria. Suggestions were provided for future research. BP, blood pressure; CKD, chronic kidney disease; CKD ND, non dialysis-dependent CKD; CVD, cardiovascular disease; GRADE, Grading of Recommendations Assessment, Development and Evaluation; KDIGO, Kidney Disease: Improving Global Outcomes; RCT, randomized controlled trial. methods for guideline development Biographic and disclosure information Gavin J Becker, MD, FRACP (Work Group Co-Chair), is Professor and Director of Nephrology at the Royal Melbourne Hospital and Clinical Director of Renal and Endocrinology Services at Melbourne Health. He maintains an active role in numerous professional societies including serving as a current member of the International Society of Nephrology (ISN) Executive Committee, Cochrane Renal Collaboration Advisory Board and Co-Chair of the World Health Organization ICD-11Renal Diseases Working Group. He is a Past President of the Asian Pacific Society of Nephrology. Dr Becker has published over 300 papers, chapters and books and presently serves as Associate Editor for Nephrology Dialysis Transplantation. He has served as Editor of Nephrology, Associate Editor or on the editorial boards of the Journal of the American Society of Nephrology, Clinical Journal of the American Society of Nephrology, American Journal of Kidney Diseases, Nephron, and Journal of Nephrology. His research interests center on the progression of kidney failure, development of guidelines for renal care, promotion of renal physician education and the development of nephrology in the Asian Pacific region. In recognition for his work, he was awarded the International Distinguished Medal by the US National Kidney Foundation in 2002. He was also a recipient of an Honorary Fellowship of the Ceylon College of Physicians in 2003, the Oshima Award from the Asian Pacific Society of Nephrology in 2005 and Chairman s Best of Health Award from Melbourne Health in 2002 and again in 2009. Dr Becker reported no relevant financial relationships David C Wheeler, MD, FRCP (Work Group Co-Chair), holds an academic position in Nephrology (Reader) at University College London, UK and is an Honorary Consultant Nephrologist at the Royal Free Hospital. His research is focused on the cardiovascular complications of CKD and the role of vascular risk factors in progression of kidney damage. Dr Wheeler is a member of the International Steering Committee of the Study of Heart and Renal Protection (SHARP) and was UK National Coordinator for the trial. He is involved in several other randomized trials and observational studies involving patients with CKD. Dr Wheeler is Co-Chair of KDIGO, having served previously on its Executive Committee and Board. He received an International Distinguished Medal from the US National Kidney Foundation in recognition of his contribu- tion to guideline development. In the UK, he has been elected President of the Renal Association for the term 2012 2014. Dr Wheeler has served on the editorial boards of American Journal of Kidney Diseases and Journal of the American Society of Nephrology and is presently Co-Editor for Nephrology Dialysis Transplantation. Advisor/Consultant: Amgen Honoraria: Abbott; Amgen; Fresenius; Otsuka; Shire Travel Stipend: Amgen; Merck Sharp & Dohme; Shire Grant/Research Support: Abbott; Genzyme Dick de Zeeuw, MD, PhD, earned his MD from the University of Groningen in 1975. He completed his PhD thesis in 1980 on the topic of renal hypertension at the Renal Department of the Groningen University. He later obtained training in clinical and experimental renal research at the Renal Department in Groningen and clinical pharmacology at the University of Dallas (1984 1985) and was board certified in 1996 at the University of Groningen. Dr de Zeeuw is currently Professor and Chair of the Department of Clinical Pharmacology with a joint appointment in the Department of Nephrology. He has served on the editorial board of several international journals, including Clinical Nephrology, Current Opinion in Nephrology and Hypertension, Journal of Geriatric Urology and Nephrology, Journal of Hypertension, Journal of the Renin-Angiotensin-Aldosterone System, Kidney International, NDT Plus, and Nephron. Dr de Zeeuw is Director of the Groningen University Institute for Drug Exploration (GUIDE), and member of ISN Council. His research interests include: optimizing current therapies and finding new therapeutical approaches to reduce the progressive loss of cardiovascular and renal function, both in diabetic and non-diabetic renal disease. The role of albuminuria/proteinuria and microalbuminuria as biomar- kers for cardiac and renal disease progression has been his particular interest, not only in trying to establish the independent causal role of albumin leakage in renal and CVD progression, but also to establish intervention strategies that lower albuminuria/proteinuria with the supposed organ protective results. In his albuminuria quest he initiated large cohort studies such as PREVEND (in general population) and GIANTT (type 2 diabetes), and is involved in the leadership of several clinical trials on preventing diabetic car- diovascular and renal disease progression such as RENAAL (angiotensin II receptor antagonist), PLANET (statin), TREAT (darbepoetin), VITAL (vitamin D), SUN (sulodex- ide), ALTITUDE (renin-inhibition), CANVAS (SGLT2-in- hibition), RADAR (atrasentan) and BEACON (bardoxolone). biographic and disclosure information http://www.kidney-international.org & 2012 KDIGO Unraveling the reasons for individual therapy resistance and creating a response score to evaluate the total effect of drugs are the topics that he judges to be of important focus for the next decade. He has authored more than 440 international scientific publications and more than 60 book chapters, and received the Lennart Hansson Memorial Lecture Award from the European Society of Hypertension, the International Distinguished Medal from the US National Kidney Foundation, and a special lecture award from the Japanese Society of Nephrology. Advisor/Consultant: Abbott; Amgen; Astellas; AstraZeneca; Bristol-Myers Squibb; HemoCue; Johnson & Johnson; Merck Sharp & Dohme; Novartis; Reata; Takeda; Vitae Toshiro Fujita, MD, is Professor and Chairman of the Department of Internal Medicine and Chief of the Depart- ment of Nephrology and Endocrinology at the University of Tokyo. He qualified in medicine in 1972 at the Keio University School of Medicine, Japan and remained in Keio until 1976, during which time he completed his medical internship and residency. Between 1976 and 1978, he was a Research and Clinical Fellow at National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. Upon his return to Japan, he was appointed Assistant Professor of Internal Medicine, firstly at the University of Tsukuba and later at the University of Tokyo School of Medicine. Since 1995, Professor Fujita has been Chairman of the Department of Internal Medicine at the Graduate School of Medicine and Faculty of Medicine, University of Tokyo, and is Chief of the Department of Nephrology and Endocrinology at the University of Tokyo Hospital. In 1980, Fujita and Bartter at NIH demonstrated the pathophysiology of salt-sensitive hypertension (Am J Med 1980). Since then, he has been continuing research on renal and metabolic aspects of hypertension. His research interests include nephrology, endocrinology, metabolic science and cardioangiology. Dr Fujita s group has reported the involve- ment of aldosterone/mineralocorticoid receptor (MR) activa- tion in salt-sensitive hypertension and metabolic syndrome. Recently, they found an alternative pathway of MR activation: modification of MR function by Rac1 GTPase (Nat Med 2008). Most recently, his group clarified the involvement of aberrant renal b adrenergic receptor-WNK4 pathway in salt- induced hypertension (Nat Med 2011). A renowned expert in his field, Professor Fujita has been actively contributing to professional associations and scien- tific publications and his contribution to the study of hypertension and kidney diseases has been widely recognized. In 2009, Professor Fujita was awarded Arthur Corcoran Lecture Award by the Council for High Blood Pressure Research, American Heart Association (AHA). Over the past 30 years, Professor Fujita has published over 500 scientific articles and has been a member of the Committee of the High Blood Pressure Council, AHA. Professor Fujita is currently serving as a Consulting Editor for Hypertension and an Editorial Board member for Diabetes. He was Past President of the Japanese Society of Hypertension (2003 2005), the Japanese Society of Internal Medicine (2004 2006), the Japanese Society of Endocrinology (2006 2007), and the Japanese Society of Nephrology (2009 2010). He was also Vice-President, International Society of Hypertension (2008 2010). Speaker: Astellas; Boehringer Ingelheim; Daiichi Sankyo; Merck; Mitsubishi Tanabe; Mochida; Novartis; Pfizer; Takeda Grant/Research Support: Astellas; Boehringer Ingelheim; Daiichi Sankyo; Merck; Mitsubishi Tanabe; Mochida; Novartis; Pfizer; Takeda Susan L Furth, MD, PhD, is Chief, Divison of Pediatric Nephrology at Children s Hospital of Philadelphia and Professor, Department of Pediatrics and Epidemiology, Perelman School of Medicine at University of Pennsylvania School of Medicine, where she is also currently a Senior Scholar and faculty member at the institution s Center for Clinical Epidemiology and Biostatistics. Dr Furth received her medical degree from University of Pennsylvania and doctorate degree from Johns Hopkins University School of Hygiene and Public Health. She maintains a longstanding interest in the studies of children and adolescents with kidney disease, particularly their risk factors and consequences, including pediatric hypertension. As Principal Investigator of CKiD, she directs a multidisciplinary team for one of the largest multicenter, prospective cohort studies of children with CKD to better identify risk factors for CKD progression, neurocognitive deficits and CVD. Dr Furth is also a recipient of an National Institute of Diabetes and Digestive and Kidney Diseases Investigator Award in Clinical Research to mentor fellows and junior faculty on the evaluation of hypertension and risk of kidney dysfunction using national pediatric data. In addition to being a peer reviewer for 20 academic journals, Dr Furth has authored over 100 publications and served as a thesis advisor to more than 30 students. As an acknowledgment for her contribution, Dr Furth was awarded Pediatric Leaders for the 21st Century by the American Society of Pediatric Nephrology and American Academy of Pediatrics and is currently President of the Society for Pediatric Research. Dr Furth reported no relevant financial relationships Hallvard Holdaas, MD, PhD, is senior consultant in Nephrology at Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Norway, where he also received his training in transplant medicine. His primary research interests are immunosuppression, dyslipidemia, and CVD in renal transplant recipients. He was the principal investigator in the ALERT trial (fluvastatin) and co- investigator in the AURORA and SHARP trials. Dr Holdaas is a member of numerous professional organizations including American Society of Nephrology, American Society of Transplantation, European Dialysis and biographic and disclosure information Transplant Association and European Society for Organ Transplantation. He has published more than 170 original articles, reviews and book chapters in the fields of nephrology, dialysis and transplantation. Advisor/Consultant: Merck (Schering Plough); Novartis; Speaker: AstraZeneca; Bristol-Myers Squibb; Novartis Shanthi Mendis, MBBS, MD, FRCP, FACC, is Senior Advisor for Cardiovascular Diseases and Coordinator, Chronic Disease Prevention and Management at the World Health Organization (WHO) in Geneva, Switzerland. Prior to taking up the position in WHO, she was Professor of Medicine at Peradeniya Medical School in Sri Lanka from 1991 2000. As a specialist in cardiology and public health with expertise in policy development, she has written extensively on the prevention and management of CVD in a global context. In particular, she has advocated for the development of national policies and strategies to combat non-communicable diseases which strike disproportionately in low- and middle-income countries. Dr Mendis reported no relevant financial relationships Suzanne Oparil, MD, is Professor of Medicine, Professor of Cell, Developmental and Integrative Biology, and Physiology & Biophysics, and Director of the Vascular Biology and Hypertension Program of the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham. She earned her medical degree at Columbia University College of Physicians and Surgeons, New York and completed her medical residency at Columbia Presbyterian Hospital and cardiology fellowship at Massachusetts General Hospital. Dr Oparil is Past President of the American Heart Association (AHA) and American Society of Hypertension, and a member of numerous editorial boards, societies and important advisory positions with the NIH (Co-Chair, JNC 8). She has published over 700 journal articles, books, and book chapters on topics in clinical cardiology, vascular biology and hypertension. Dr Oparil has received a number of honorary memberships, lectureships, and distinguished awards for her contributions to hypertension research, including the Irving Page-Alva Bradley Lifetime Achievement Award, given by the AHA Council for High Blood Pressure Research (2002); the 2008 Harriet Dustan Award, sponsored by the AHA Council for High Blood Pressure Research; the Virginia Frantz 22 Award for Distinguished Women in Medicine (2010) presented by Columbia University College of Physicians and Surgeons; and the ICS Distinguished Lecture Award (2011), sponsored by the Institute of Cardiovascular Sciences. Dr Oparil is a cardiologist with a special interest in the fundamental mechanisms of CVD and in applying this information to the development of novel treatments. Her research ranges from molecular and cellular studies to whole animal studies to clinical trials. She has made a number of innovative discoveries with major clinical impact: 1) observing that angiotensin-converting enzyme (ACE) is involved in vascular disease, leading to the development of ACE-Is; 2) identifying endothelin as the major mediator of pulmonary hypertension and pulmonary vascular disease, leading to the development of a class of drugs for patients with pulmonary hypertension; and 3) defining novel pathways by which blood vessels are protected from injury by estrogens, providing crucial information on potential targets for future gene therapy. She has made many significant contributions to vascular biology and hypertension research. Advisor/Consultant: BackBeat Medical; Bayer; Boehringer Ingelheim; Daiichi Sankyo; Eli Lilly; Forest Laboratories; Medtronic; Merck; NicOx; Novartis;Omron Healthcare; Pfizer Grant/Research Support: Daiichi Sankyo; Merck; Novartis; Takeda Vlado Perkovic, MBBS, FRACP, FASN, PhD, is Executive Director, George Clinical at The George Institute for International Health and Staff Specialist in Nephrology and Hypertension at the Royal North Shore and Sydney Adventist Hospitals. Dr Perkovic received his medical and doctorate degrees from University of Melbourne and completed his training in nephrology and general medicine at the Royal Melbourne Hospital. His research interests include elucidat- ing the roles of BP and lipid management and their impact on CVD in CKD patients. In this vein, Dr Perkovic is a committee member of the ALTITUDE and SHARP trials and an organizer of the Cardiovascular Guideline Group for Caring for Australasians with Renal Impairment (CARI). As an author of over 75 publications, Dr Perkovic also serves as a peer reviewer to numerous journals and a grant reviewer for the National Health and Medical Research Council. Advisor/Consultant: Abbott; Baxter; Boehringer Ingelheim; Johnson & Johnson; Vitae Honoraria: AstraZeneca; Roche; Servier Grant/Research Support: Baxter; Johnson & Johnson Cibele Isaac Saad Rodrigues, MD, PhD, is a full Professor of Nephrology at the Faculdade de Cie ncias Me dicas e da Sau de Pontif cia Universidade Cato lica de Sa o Paulo (PUC-SP), Brazil where she also graduated and completed her Residency in Internal Medicine and Nephrology. She obtained her master s and doctorate degrees in Nephrology at the Federal University of Sa o Paulo, Brazil. Currently she is the academic coordinator of Santa Lucinda Hospital in Sorocaba Sa o Paulo, coordinator of the Hypertension Department of the Brazilian Society of Nephrology, and member of the Scientific Council of the Brazilian Society of Hypertension. From 2001 to 2009 she was the dean of the Centro de Cie ncias Me dicas e Biolo gicas (PUC-SP) and President of the Administration Council of Santa Lucinda Hospital. Her primary research biographic and disclosure information interests are hypertension, diabetic nephropathy and CKD. Professor Rodrigues has published more than 40 journal articles and contributed 15 book chapters in the field of nephrology and hypertension. She is a member of numerous professional organizations in Brazil and abroad, and has served as peer reviewer for many scientific journals and an advisory committee member to various organizations. Dr Rodrigues reported no relevant financial relationships Mark J Sarnak, MD, MS, is Professor of Medicine at Tufts University of School of Medicine in Boston, Massachusetts, USA and Director of Research in the Division of Nephrology at Tufts Medical Center. He obtained his medical degree from Columbia University College of Physicians and Surgeons and s degree in clinical care research from Tufts University of Medicine. His current research encompasses various topics including the role of aging in CKD, the relationship between cognition and CKD, and CVD in CKD. He has lectured extensively on the epidemiology and management of traditional and non-traditional cardiovascular risk factors in CKD. Dr Sarnak has authored more than 175 publications and is a peer reviewer for more than a dozen journals. He was Co-Editor for American Journal of Kidney Disease between 2006 2007 and presently serves on the Editorial Board of the Annals of Internal Medicine. Among the recent honors he has received include Best Teacher Award for the Medical Residents in 2008, Excellence in Teaching in the Medical Clerkship in 2009, and an acknowledgment in Boston Magazine Best Doctors in both 2010 and 2011. Dr Sarnak reported no relevant financial relationships Guntram Schernthaner, MD, became Professor of Medicine at the University of Vienna, Austria in 1987. Since 1988 he has been Head of the Department of Medicine I at the Rudolfstiftung Hospital in Vienna and between 1982 and 1988 he served as Head of the Division of Metabolism & Endocrinology at the University of Vienna. Professor Schernthaner s main research interests are diabetes mellitus (including diabetic nephropathy, diabetic retinopathy, insulin resistance, CVD, hemostasis, immunotherapy of type 1 diabetes, gestational diabetes), hypertension and morbid obesity. Professor Schernthaner has held various prestigious positions, including serving as Council Member and Vice- President of the European Society for Clinical Investigation; President of the Austrian Diabetes Association; President of the first Joint Congress of the German and Austrian Diabetes Associations; Council Member of the European Diabetes Association; and President of the 32nd European Diabetes Congress (EASD, Vienna 1996). Professor Schernthaner has authored more than 350 publications in peer-reviewed journals and has presented invited lectures at many international congresses, symposia and universities in more than 50 countries. According to the Citation Index of Web of Science his papers were cited 8300 times, with a Hirsch index of 43. He was also the principal investigator of more than 40 studies (e.g., Canadian- Cyclosporin Trial; Diapep277 Study; IDNT; IRMA 2; QUARTET; PROactive; GUIDE; ORIGIN; LEAD-6; DIRECT; EUREXA; DURATION; GENERATION). Professor Schernthaner was awarded the Bertram Award of the German Diabetes Association in 1982 and the Albert Renold Medal of the European Association for the Study of Diabetes in 1997. He is currently the Liaison Editor for Diabetology for Nephrology Dialysis Transplantation. Dr Schernthaner reported no relevant financial relationships Charles R V Tomson, DM, FRCP, completed his under- graduate studies at Cambridge University and attended medical school at University of Oxford. Dr Tomson has worked as a Consultant Nephrologist at Southmead Hospital since April 1991. Between 1997 and 2004 he was course director for the Renal Association s Advanced Nephrology Course, and between 1998 and 2002 he was Secretary of the Renal Association s Audit and Standards Subcommittee, developing the 3rd edition of the Association s Standards document. In 2001 he set up and chaired the group that developed the first UK guidelines on identification, manage- ment and referral of patients with CKD. In 2004 5 he was a Health Foundation Quality Improvement Fellow at the Institute for Healthcare Improvement in Boston, USA. From 2006 2010 he was Chairman of the UK Renal Registry, which measures and reports on the quality of care achieved by all renal centers in the UK. He became President of the Renal Association in May 2010. Dr Tomson reported no relevant financial relationships Carmine Zoccali, MD, is Director of the Division of Nephrology, Hypertension and Renal Transplantation and Chief of the Clinical Epidemiology of Renal Diseases and Hypertension Unit of the National Research Council-IBIM at Riuniti Hospital, Calabria. He is Professor of Nephrology at the Postgraduate School of Nephrology, Universities of Palermo and Messina, Sicily, Italy. Having trained in medicine at the University of Rome, he completed specialist training in renal diseases, hypertension, internal medicine and clinical epidemiology. Dr Zoccali s research interests cover hypertension, cardio- vascular complications in chronic renal failure, kidney disease progression and the epidemiology of chronic renal failure. He has contributed over 600 publications in these areas, including more than 400 papers in international peer- reviewed journals with a Hirsch index of 52. Dr Zoccali founded NDT-Educational in 2004 and directed its online educational resources between 2004 2009, and he is presently the Editor-in-Chief of Nephrology Dialysis Transplantation. Dr Zoccali also holds editorial positions in several national and international nephrology journals including Clinical Nephrology, Clinical biographic and disclosure information Journal of the American Society of Nephrology, Hypertension, Journal of the American Society of Nephrology, Journal of Hypertension, Journal of Nephrology, Kidney International, Nephron Clinical Practice, and PlosOne. An ex-officio council member of the European Renal Association European Dialysis and Transplant Association (ERA-EDTA), and of their selection committee, he is a member of numerous other nephrology societies. He was also Chairman of the European Dialysis and Transplant Registry (2003 2009), President of the Italian Society of Nephrology (2007 2008) and member of the KDIGO Board of Directors. Dr Zoccali reported no relevant financial relationships KDIGO CHAIRS Bertram L Kasiske, MD, is Professor of Medicine at the University of Minnesota, USA. He received his medical degree from the University of Iowa and completed his Internal Medicine residency and fellowship training in Nephrology at Hennepin County Medical Center where he is currently Director of Nephrology. Dr Kasiske is former Deputy Director of the United States Renal Data System and former Editor-in-Chief of American Journal of Kidney Diseases. He has served as Secretary/Treasurer and on the Board of Directors of the American Society of Transplantation, and on the Organ Procurement and Transplantation Network/United Network of Organ Sharing Board of Directors, and the Scientific Advisory Board of the US National Kidney Foundation. He is currently serving on the Board of Councilors of the International Society of Nephrology. He is the Principal Investigator for a National Institutes of Health-sponsored, multi-center study of long term outcomes after kidney donation and he is the Director of the Scientific Registry of Transplant Recipients. He has over 160 scientific publications in major peer reviewed journals, and 230 review articles, editorials and textbook chapters. Dr Kasiske is also a recipient of the US National Kidney Foundation s Garabed Eknoyan Award in 2003. Advisor/Consultant: Litholink Grant/Research Support: Bristol-Myers Squibb; Merck (Schering Plough) David C Wheeler, MD, FRCP (see biography earlier) EVIDENCE REVIEW TEAM Katrin Uhlig, MD, MS, is the Director, Guideline Develop- ment at the Tufts Center for Kidney Disease Guideline Development and Implementation, Boston, MA, Associate Professor of Medicine at Tufts University School of Medicine, and a staff nephrologist at Tufts Medical Center. Dr Uhlig completed her training in internal medicine, nephrology, and rheumatology in Germany (Aachen University Hospital and Munich University Hospital) and the USA (Georgetown University Medical Center and Tufts Medical Center). Since 2001, she has been participating in or directing the evidence review for KDOQI and KDIGO guidelines. As Director of Guideline Development, Dr Uhlig has a substantial role in coordinating the ERT. She orchestrates and supervises the guideline development process and didactic curriculum that provides Work Group members with formal instruction on topics related to guideline development. As project director on individual guidelines, she directs and supervises the collection, evaluation, grading, and synthesis of evidence and the drafting and revisions of the final evidence report. She provides methodological guidance and training to Work Group members at meetings regarding topic refinement, key question formulation, data extraction, study assessment, evidence grading, and recommendation formulation. She provides nephrology expertise in the interpretation and review of guideline recommendations and evidence reports. In this capacity, Dr Uhlig possesses unique knowledge as a methods expert in evidence synthesis and critical literature appraisal in the domain of nephrology. In 2005, she co-chaired the KDIGO Evidence Rating Group to develop a consensus on grading of KDIGO guidelines and also co-chaired the KDIGO Consensus Conference on Guideline Methodology in October 2007. From 2006 to 2007, she served as Co-Editor of American Journal of Kidney Diseases. Her teaching and research focus includes evidence-based medicine, systematic review, clinical practice guideline development, and critical literature appraisal. Dr Uhlig lectures on guideline topics and is a co- instructor of an annual course on meta-analysis in the Master of Science Program at the Sackler School of Graduate Biomedical Sciences at Tufts University. Dr Uhlig reported no relevant financial relationships Ashish Upadhyay, MD, is Assistant Professor, Renal Section and Associate Director, Internal Medicine Residency Program at Boston University School of Medicine, Boston, MA, USA. Dr Upadhyay was previously Assistant Professor at Tufts University School of Medicine and staff physician in the William B Schwartz, MD, Division of Nephrology at Tufts Medical Center. He joined the ERT in July 2009 and served as the Assistant Project Director for the KDIGO Management of Blood Pressure in CKD and Anemia in CKD Guidelines. Dr Upadhyay coordinated and assisted in the collection, evalua- tion, grading, and synthesis of evidence, and played a critical role in the revisions of the final evidence report. He also provided methodological guidance and training of Work Group members on topic refinement, key question formula- tion, data extraction, study assessment, evidence grading, and recommendation formulation. Dr Upadhyay s past research involved studying kidney disease epidemiology in the Framing- ham Heart Study. He has published in areas ranging from arterial stiffness in CKD and inflammation in kidney disease to dialysis complications and epidemiology of hyponatremia. Dr Upadhyay reported no relevant financial relationships biographic and disclosure information Amy Earley, BS, is a project coordinator at the Tufts Center for Kidney Disease Guideline Development and Implementa- tion in Boston, MA, USA. She is key in coordinating the guideline development activities within the ERT, especially in the development of the evidence reports for all guidelines. Ms Earley also heads the actual evidence review, which includes running searches, screening, data extraction, drafting of tables and methods sections, proofing of guideline drafts and critical literature appraisals. She participates in the conduct of research projects at the Center and actively collaborates with other members of the Center on indepen- dent research topics and manuscript submissions. Ms Earley reported no relevant financial relationships Shana Haynes, MS, DHSc, is a research assistant at the Tufts Center for Kidney Disease Guideline Development and Implementation in Boston, MA, USA. She participates in all aspects of evidence review and guideline development. She screens abstracts and articles, extracts data, and assists in the drafting and editing of evidence tables. Dr Haynes also assists in the development of clinical practice guidelines and conducts systematic reviews and critical literature appraisals. Dr Haynes reported no relevant financial relationships Jenny Lamont, MS, is a project manager and medical writer at the Tufts Center for Kidney Disease Guideline Develop- ment and Implementation in Boston, MA, USA. She participates in all aspects of evidence review and guideline development, assists in the preparation of talks and manu- scripts, and edits KDIGO draft guidelines currently in progress. Ms Lamont reported no relevant financial relationships biographic and disclosure information Acknowledgments A special debt of gratitude is owed to the KDIGO Co-Chairs Kai-Uwe Eckardt, Bertram Kasiske, David Wheeler and the KDIGO Board for their invaluable guidance throughout the development of this guideline. In particular, we thank the ERT members: Katrin Uhlig, Ashish Upadhyay, Amy Earley, Shana Haynes, and Jenny Lamont for their substantial contribution to the rigorous assessment of the available evidence. We are also especially grateful to the Work Group members for their expertise throughout the entire process of literature review, data extraction, meeting participation, the critical writing and editing of the statements and rationale, which made the publication of this guideline possible. The generous gift of their time and dedication is greatly appreciated. Finally, and on behalf of the Work Group, we gratefully acknowledge the careful assessment of the draft guideline by external reviewers. The Work Group considered all of the valuable comments made and, where appropriate, suggested changes were incorporated into the final publica- tion. The following individuals provided feedback during the public review of the draft guideline: Omar Abboud; Yerado Abrahamian; Daniel Abramowicz; Patricia Abreu; Nasrulla Abutaleb; Tekin Akpolat; Mona Al- Rukhaimi; Mershed Al Samara; Annette Alfonzo; Maria Almerinda Ribeiro Alves; Bulent Altun; Rui Alves; Alessandro Amore; Christos Argyropoulos; Mustafa Arici; Mariano Arriola; Suheir Assady; George L Bakris; Breda Pee ovnik Balon; Antoine Barbari; Rashad S Barsoum; Donald Batisky; Ezequiel Bellorin-Font; Craig Belsha; Dibyendu Bhattachar- yya; Rudy Bilous; Tammy Brady; Rafael Burgos-Calderon; Niels Henrik Buus; Sue Cary; Jiang-Hua Chen; Massimo Cirillo; Peter Clausen; Fre de ric Collart; Giuseppe Conte; Rosanna Coppo; Olivier Coustere; Ana Maria Cusumano; Jane S Davis; Rodrigo Daza; Angel de Francisco; Rodrigo Bueno de Oliveira; Roge rio Baumgratz de Paula; Jean-Yves De Vos; Sheila Deziel; Janis Dionne; Kenneth Donaldson; Tilman B Dru eke; Jesus Egido; Robert Ekart; Sandro Feriozzi; Francisco Ferna ndez-Vega; Ana Figueiredo; Joseph T Flynn; Ricardo Fonseca; Ping Fu; Guillermo Garcia Garcia; Colin Geddes; Mathieu Ghadanfar; Richard J Glassock; Elaine Mary Joyce Go; Jane Goddard; Dr. Gokulnath; Eliezer Golan; J Michael Gonzalez-Campoy; Suzanne Gore; Manuel Gorostidi; Alaciel Melissa Palacios Guille n; Chuan-Ming Hao; Jeff Harder; Rebecca Hays; Lee A Hebert; Brenda R Hemmelgarn; Hideki Hirakata; Eero Honkanen; Lai Seong Hooi; Enyu Imai; Dmytro Ivanov; Helena Jardim; Andrzej Jaroszynski; Simon Jenkins; Gu lc in Kantarcy ; Frederick Kaskel; Mika Kastarinen; Johannes Kessel; Arif Khwaja; Vera Koch; Jean-Marie Krzesinski; Dirk Kuypers; Nadiya Lakhani; Edmund J Lamb; Stewart Lambie; Marc B Lande; Benjamin Laskin; Keith Lau; Edgar V Lerma; Vicki Levidiotis; Nathan W Levin; Visnja Lezaic; Hao Li; Rong-Shan Li; Robert Liebl; Petrica Ligia; Zhang-Suo Liu; Zhi-Hong Liu; Gerard London; Attilio Losito; Francesca Mallamaci; Braden Manns; Roberto Ramirez Marmolejo; Alberto Mart nez-Castelao; Timothy Mathew; Cecilia Mengarelli; Kaj Metsa rinne; Kevin Meyers; Sergio A Mezzano; Roberto Minutolo; Gabriel Mircescu; Kirtida Mistry; Mark M Mitsnefes; Gerardo Oscar Mogni; Jose M Morales; Sameh Morgan; Eugen Mota; Judit Nagy; Mooppil Nandakumar; Andrew S Narva; Alicia M Neu; Abdou Niang; Javier Nieto; Gregorio T Obrador; Adrian Oksa; Marcelo Orias; Alberto Ortiz; Sreejith Parameswaran; Sonia Pasquali; Saime Paydas; Jose Carlos Rodriguez Pe rez; Frida L Plavnik; Claudio Ponticelli; Roberto Pontremoli; Troels Ring; Francisco Rivera; S Adibul Hasan Rizvi; Nicola s Roberto Robles; Michael V Rocco; Guillermo Rosa-Diez; Jaroslav Rosenberger; Luis M Ruilope; Rafael Santamaria; Sergio Santos; Adalbert Schiller; Francesco Scolari; Julian Segura; Christine Sethna; Deepak Sharma; Kumar Sharma; Robert Shay; Michael G Shlipak; Alexander Shutov; Justin Silver; Karin Skov; Itzchak Slotki; Neil Smith; Elaine Spalding; Susan P Steigerwalt; Graham Stewart; Stephanie Stewart; Tennille Tan; James Tattersall; Irma Tchokhonelidze; Peter Thomson; Ilkka Tikkanen; Rui Toledo-Barros; Natalia Tomilina; Howard Trachtman; Jamie Traynor; Hernan Trimarchi; Yusuke Tsukamoto; Alexey Tsygin; Kriang Tung- sanga; Harun Ur Rashid; Joseph A Vassalotti; Rowan Walker; Jianxin Wan; Angela Yee-Moon Wang; Talia Weinstein; Colin T White; Rong Wang; Viktoria Woronik; Elke Wuehl; Chang- Ying Xing; Elena Zakharova; Nadia Zalunardo; Weiming Zhang; Ming-Hui Zhao; Kim Zuber; Alessandro Zuccala . Participation in the review does not necessarily consti- tute endorsement of the content of this report by the above individuals, or the organization or institution they represent. Gavin J Becker, MD, FRACP David C Wheeler, MD, FRCP Work Group Co-Chairs acknowledgments http://www.kidney-international.org & 2012 KDIGO References 1. National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43: S1 S290. 2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1 S266. 3. Levey AS, Atkins R, Coresh J et al. Chronic kidney disease as a global public health problem: approaches and initiatives a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007; 72: 247 259. 4. Levin NW, Kotanko P, Eckardt KU et al. Blood pressure in chronic kidney disease stage 5D-report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int 2010; 77: 273 284. 5. Agarwal R, Sinha AD. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis. Hypertension 2009; 53: 860 866. 6. Heerspink HJ, Ninomiya T, Zoungas S et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet 2009; 373: 1009 1015. 7. KDIGO GN Work Group. KDIGO clinical practice guideline for glome- rulonephritis. Kidney inter, Suppl 2012; 2: 139 274. 8. Magee LA, Abalos E, von Dadelszen P et al. Control of hypertension in pregnancy. Curr Hypertens Rep 2009; 11: 429 436. 9. Chobanian AV, Bakris GL, Black HR et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treat- ment of High Blood Pressure. Hypertension 2003; 42: 1206 1252. 10. Pickering TG, Hall JE, Appel LJ et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation 2005; 111: 697 716. 11. Agarwal R, Andersen MJ. Prognostic importance of clinic and home blood pressure recordings in patients with chronic kidney disease. Kidney Int 2006; 69: 406 411. 12. Andersen MJ, Khawandi W, Agarwal R. Home blood pressure monitoring in CKD. Am J Kidney Dis 2005; 45: 994 1001. 13. Wuhl E, Hadtstein C, Mehls O et al. Home, clinic, and ambulatory blood pressure monitoring in children with chronic renal failure. Pediatr Res 2004; 55: 492 497. 14. Wuhl E, Trivelli A, Picca S et al. Strict blood-pressure control and progres- sion of renal failure in children. N Engl J Med 2009; 361: 1639 1650. 15. Powers BJ, Olsen MK, Smith VA et al. Measuring blood pressure for decision making and quality reporting: where and how many measures? Ann Intern Med 2011; 154: 781 788, W-289 W-790. 16. Astor BC, Matsushita K, Gansevoort RT et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int 2011; 79: 1331 1340. 17. Gansevoort RT, Matsushita K, van der Velde M et al. Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int 2011; 80: 93 104. 18. Matsushita K, van der Velde M, Astor BC et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovas- cular mortality in general population cohorts: a collaborative meta- analysis. Lancet 2010; 375: 2073 2081. 19. van der Velde M, Matsushita K, Coresh J et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all- cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 2011; 79: 1341 1352. 20. Levey AS, de Jong PE, Coresh J et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int 2011; 80: 17 28. 21. Lewington S, Clarke R, Qizilbash N et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903 1913. 22. Lewis JB. Blood pressure control in chronic kidney disease: is less really more? J Am Soc Nephrol 2010; 21: 1086 1092. 23. Ahmed AK, Kamath NS, El Kossi M et al. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant 2010; 25: 3977 3982. 24. de Zeeuw D, Lambers-Heerspink H. Drug dosing for renoprotection: maybe it s time for a drug efficacy-safety score? J Am Soc Nephrol 2009; 20: 688 689. 25. Mason NA, Bailie GR, Satayathum S et al. HMG-coenzyme a reductase inhibitor use is associated with mortality reduction in hemodialysis patients. Am J Kidney Dis 2005; 45: 119 126. 26. Fellstrom BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395 1407. 27. Wanner C, Krane V, Marz W et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238 248. 28. Muntner P, He J, Astor BC et al. Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease: results from the atherosclerosis risk in communities study. J Am Soc Nephrol 2005; 16: 529 538. 29. Li Z, Lacson E, Jr., Lowrie EG et al. The epidemiology of systolic blood pressure and death risk in hemodialysis patients. Am J Kidney Dis 2006; 48: 606 615. 30. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis 2007; 49: S1 S179. 31. Acelajado MC, Oparil S. Hypertension in the elderly. Clin Geriatr Med 2009; 25: 391 412. 32. Covic A, Gusbeth-Tatomir P, Goldsmith DJ. Arterial stiffness in renal patients: an update. Am J Kidney Dis 2005; 45: 965 977. 33. London GM, Guerin AP, Verbeke FH et al. Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 2007; 18: 613 620. 34. Ohya Y, Iseki K, Iseki C et al. Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort. Am J Kidney Dis 2006; 47: 790 797. 35. Pannier B, Guerin AP, Marchais SJ et al. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension 2005; 45: 592 596. 36. Toussaint ND, Lau KK, Strauss BJ et al. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 2008; 23: 586 593. 37. Cockcroft JR, Wilkinson IB, Evans M et al. Pulse pressure predicts cardiovascular risk in patients with type 2 diabetes mellitus. Am J Hypertens 2005; 18: 1463 1467; discussion 1468 1469. 38. Domanski MJ, Davis BR, Pfeffer MA et al. Isolated systolic hypertension: prognostic information provided by pulse pressure. Hypertension 1999; 34: 375 380. 39. Schram MT, Kostense PJ, Van Dijk RA et al. Diabetes, pulse pressure and cardiovascular mortality: the Hoorn Study. J Hypertens 2002; 20: 1743 1751. 40. Messerli FH, Mancia G, Conti CR et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006; 144: 884 893. 41. Somes GW, Pahor M, Shorr RI et al. The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med 1999; 159: 2004 2009. 42. Denardo SJ, Gong Y, Nichols WW et al. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Am J Med 2010; 123: 719 726. 43. Oates DJ, Berlowitz DR, Glickman ME et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc 2007; 55: 383 388. 44. Benvenuto LJ, Krakoff LR. Morbidity and mortality of orthostatic hypotension: implications for management of cardiovascular disease. Am J Hypertens 2011; 24: 135 144. http://www.kidney-international.org references & 2012 KDIGO 45. Wu JS, Yang YC, Lu FH et al. Population-based study on the prevalence and correlates of orthostatic hypotension/hypertension and orthostatic dizziness. Hypertens Res 2008; 31: 897 904. 46. Alderman MH. Salt, blood pressure, and human health. Hypertension 2000; 36: 890 893. 47. Jones DW, Kim JS, Andrew ME et al. Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey. J Hypertens 1994; 12: 1433 1437. 48. Whelton SP, Chin A, Xin X et al. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136: 493 503. 49. Chen L, Davey Smith G, Harbord RM et al. Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med 2008; 5: e52. 50. Brown CD, Higgins M, Donato KA et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res 2000; 8: 605 619. 51. The Obesity in Asia Collaboration. Is central obesity a better discriminator of the risk of hypertension than body mass index in ethnically diverse populations? J Hypertens 2008; 26: 169 177. 52. Whitlock G, Lewington S, Sherliker P et al. Body-mass index and cause- specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373: 1083 1096. 53. Dickinson HO, Mason JM, Nicolson DJ et al. Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials. J Hypertens 2006; 24: 215 233. 54. Navaneethan SD, Yehnert H, Moustarah F et al. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009; 4: 1565 1574. 55. Buchwald H, Estok R, Fahrbach K et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122: 248 256 e245. 56. James WP, Caterson ID, Coutinho W et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363: 905 917. 57. Topol EJ, Bousser MG, Fox KA et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo- controlled trial. Lancet 2010; 376: 517 523. 58. Kalantar-Zadeh K, Abbott KC, Salahudeen AK et al. Survival advantages of obesity in dialysis patients. Am J Clin Nutr 2005; 81: 543 554. 59. Pifer TB, McCullough KP, Port FK et al. Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS. Kidney Int 2002; 62: 2238 2245. 60. Hoogeveen EK, Halbesma N, Rothman KJ et al. Obesity and mortality risk among younger dialysis patients. Clin J Am Soc Nephrol 2012; 7: 280 288. 61. World Health Organization. Prevention of Cardiovascular Disease: Guide- lines for Assessment and Management of Total Cardiovascular Risk. 2007. 62. Hooper L, Bartlett C, Davey Smith G et al. Systematic review of long term effects of advice to reduce dietary salt in adults. BMJ 2002; 325: 628. 63. Esnault VL, Ekhlas A, Delcroix C et al. Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents. J Am Soc Nephrol 2005; 16: 474 481. 64. Phillips CO, Kashani A, Ko DK et al. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med 2007; 167: 1930 1936. 65. Slagman MC, Waanders F, Hemmelder MH et al. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ 2011; 343: d4366. 66. Vogt L, Waanders F, Boomsma F et al. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 2008; 19: 999 1007. 67. Ekinci EI, Clarke S, Thomas MC et al. Dietary salt intake and mortality in patients with type 2 diabetes. Diabetes Care 2011; 34: 703 709. 68. Thomas MC, Moran J, Forsblom C et al. The association between dietary sodium intake, ESRD, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 2011; 34: 861 866. 69. Chen JL, Lerner D, Ruthazer R et al. Association of physical activity with mortality in chronic kidney disease. J Nephrol 2008; 21: 243 252. 70. O Hare AM, Tawney K, Bacchetti P et al. Decreased survival among sedentary patients undergoing dialysis: results from the dialysis morbidity and mortality study wave 2. Am J Kidney Dis 2003; 41: 447 454. 71. Stack AG, Molony DA, Rives T et al. Association of physical activity with mortality in the US dialysis population. Am J Kidney Dis 2005; 45: 690 701. 72. World Health Organization. International Guide for Monitoring Alcohol Consumption and Related Harm. 2000. 73. Jee SH, Miller ER, 3rd, Guallar E et al. The effect of magnesium supplemen- tation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens 2002; 15: 691 696. 74. Campbell F, Dickinson HO, Critchley JA et al. A systematic review of fish-oil supplements for the prevention and treatment of hypertension. Eur J Prev Cardiol 2012 (in press). 75. Donadio JV, Jr., Bergstralh EJ, Offord KP et al. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med 1994; 331: 1194 1199. 76. Swan SK, Olyaei A, Sica D. Clinical pharmacology for the nephrologist. NephSap 2010; 9: 220 264. 77. Agarwal R, Andersen MJ. Blood pressure recordings within and outside the clinic and cardiovascular events in chronic kidney disease. Am J Nephrol 2006; 26: 503 510. 78. Davidson MB, Hix JK, Vidt DG et al. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. Arch Intern Med 2006; 166: 846 852. 79. Minutolo R, Agarwal R, Borrelli S et al. 