Low sodium diet or lifestyle modification and change in BP Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials Dickinson et al.53 Cochrane CENTRAL MEDLINE Embase References used to check and supplement reference list of ERT systematic review Systematic review of long term effects of advice to reduce dietary salt in adults Hooper et al.62 Cochrane CENTRAL MEDLINE Embase CAB abstracts CVRCT registry SIGLE Further search on sodium restriction and BP: Cochrane CENTRAL MEDLINE Embase Up to July 2002 References used to check and supplement reference list of ERT systematic review Topic 2. BP target and kidney outcomes Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient level meta-analysis Jafar et al.96 MEDLINE References used to check and supplement reference list of ERT systematic review Topic 3. ACE-I or ARB on CVD and CKD progression RAS blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinuria: a meta-analysis Balamuthusamy et al.97 OVID MEDLINE Embase References used to check and supplement reference list of ERT systematic review Angiotensin receptor blockers as anti-hypertensive treatment for patients with diabetes mellitus: meta-analysis of controlled double-blind randomized trials Siebenhofer et al.450 Cochrane CENTRAL MEDLINE Embase Cochrane Controlled Trials Register PubMed DARE NHSEED HTA References used to check and supplement reference list of ERT systematic review Topic 4. ACE-I or ARB on CKD progression Effect of inhibitors of the renin-angiotensin system and other anti-hypertensive drugs on renal outcomes: systematic review and meta-analysis Casas et al.451 Cochrane CENTRAL MEDLINE Embase References used to check and supplement reference list of ERT systematic review Topic 5. ACE-I on CKD progression in CKD without DM Angiotensin-converting enzyme inhibitors and progression of non-diabetic renal disease.


ACE-I on CKD progression in CKD without DM Angiotensin-converting enzyme inhibitors and progression of non-diabetic renal disease. A meta-analysis of patient-level data Jafar et al.141 MEDLINE References used to check and supplement reference list of ERT systematic review Topic 6. Anti-hypertensive agents in kidney-transplant recipients Anti-hypertensives for kidney-transplant recipients: Systematic review and meta-analysis of randomized controlled trials Cross et al.301 Cochrane Renal Group Specialized Register Cochrane CENTRAL MEDLINE Embase Up to July 1, 2008 References used to check and supplement reference list of ERT systematic review ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; ERT, evidence review team; RAS, renin angiotensin system. Table 8 | Literature yield Studies included in summary tables Intervention Abstracts identified Articles retrieved Studies with data extracted DKD Non-DKD Transplant General population studies in summary tables Summary tables Agents DKD, diabetic kidney disease. methods for guideline development July 2002, the search for the current KDIGO Guideline included publications since January 2002. Search strategies were developed by the ERT with input from the Work Group. The text words or medical subject headings (MeSH) that were included are provided in the Supplementary Appendix 1 online. Non-human studies and those focusing on dialysis, pregnancy, neonates, malignant hypertension, acute kidney injury, or drug pharmacology were excluded. The MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched by the ERT to capture all RCTs on the use of BP-lowering agents in CKD. The first search was conducted in November 2009 and was subsequently updated in April and August of 2010; the final update was done in January 2011.


The first search was conducted in November 2009 and was subsequently updated in April and August of 2010; the final update was done in January 2011. Additional focused searches were conducted to identify RCTs evaluating lifestyle interventions of salt restriction, weight loss, and diet and exercise in CKD and to look for reviews of adverse effects of anti-hypertensive agents. The ERTrelied on Work Group members to identify large, general population RCTs reporting on subgroup analyses based on CKD, GFR, or proteinuria status. Additional pertinent articles were added from the reference lists of JNC 7 and relevant meta-analyses and systematic reviews (Table 7). The search yield was also supplemented by articles provided by Work Group members through February 2012. A total of 10, 657 citations were initially screened. Journal articles reporting original data, meta-analyses, and systematic reviews were selected for evidence review. Editorials, letters, abstracts, unpublished reports, and articles published in non peer-reviewed journals were not included. The Work Group also decided to exclude publications from journal supplements because of potential differences in the process of how they get solicited, selected, reviewed, and edited compared to peer-reviewed publications. Post hoc analyses were also excluded, however, after discussion with the Work Group, it was decided that exception would be made for post-trial observational follow-up reports from RCTs looking at BP targets as BP interventions may take longer time to influence outcomes. These studies were downgraded one level to designate that they are of lesser quality than the original RCT. The overall search yield along with the number of abstracts identified and articles reviewed for each topic are presented in Table 8. Data extraction Data extraction was done by the ERT.


The overall search yield along with the number of abstracts identified and articles reviewed for each topic are presented in Table 8. Data extraction Data extraction was done by the ERT. The ERT, in consultation with the Work Group, designed forms to capture data on design, methodology, sample characteristics, interventions, comparators, outcomes, results, and limita- tions of individual studies. Methodology and outcomes were also systematically graded (see the section on grading below) and recorded during the data extraction process. Summary tables Summary tables were developed for each comparison of interest (Table 9). Studies included in the evidence base for the KDOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease1 were also incorporated if they fulfilled the inclusion criteria for the current KDIGO Guideline. Summary tables contain outcomes of interest, relevant population characteristics, description of intervention and comparator, results, and quality grading for each outcome. Categorical and continuous outcomes were summarized separately. Studies done exclusively in patients of a single race or ethnicity and studies reporting effect modifications by baseline urine protein level were annotated.


Studies done exclusively in patients of a single race or ethnicity and studies reporting effect modifications by baseline urine protein level were annotated. Studies were also Table 9 | Work products for BP guideline* Topic Summary table of RCTs Evidence profile Diet or lifestyle modification Exercise + (single study) BP targets in CKD without DM BP target in adults + + (3 studies) BP target in children + (single study) Adverse events of target RCTs + a Agents in CKD without DM, non-transplant ACE-I or ARB versus CCB + + (7 studies) ACE-I or ARB versus placebo + + (6 studies) High-dose ACE-I versus low-dose ACE-I + + (2 studies) ACE-I versus ARB + + (3 studies) ACE-I versus beta-blocker + (single study) High-dose ARB versus low-dose ARB + + (3 studies) (ACE-I + CCB) versus ACE-I + (single study) (ACE-I + CCB) versus CCB + (single study) Beta-blocker versus CCB + (single study) CCB versus CCB + (single study) Central-acting agent versus CCB + (single study) Adverse events of agent RCTs + a Agents in CKD with DM, non-transplant Aldosterone antagonist versus placebo + (single study) ACE-I or ARB versus CCB + + (7 studies) ACE-I or ARB versus placebo + + (9 studies) ACE-I versus ARB + + (3 studies) ARB versus ARB + + (3 studies) CCB versus placebo + (single study) Direct renin inhibitor versus placebo + (single study) Endothelin antagonist versus endothelin antagonist + (single study) Endothelin antagonist versus placebo + (single study) Adverse events of agents in RCTs + a Agents in CKD in kidney transplant recipient ACE-I versus ARB + (single study) ARB versus placebo + (single study) ACE-I versus CCB + + (2 studies) CCB versus placebo + + (3 studies) Adverse events of agent RCTs + a CKD subgroups from general population studies BP target + (1 study) ACE-I + diuretic versus placebo in DM + (4 studies) ACE-I or ARB versus control + (5 studies) ACE + ARB or ARB versus ACE-I + (1 study) ARB versus CCB + (1 study) CCB versus control + (2 studies) ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BP, blood pressure; CCB, calcium-channel blocker; CKD, chronic kidney disease; DM, diabetes mellitus; RCTs, randomized controlled trials; +, work product is indicated for the topic of interest; , work product is not indicated for the topic of interest.


a Included in evidence profile for other outcomes. methods for guideline development categorized by baseline proteinuria status in summary tables for the CKD with diabetes mellitus topic. For studies not exclusively examining CKD population, only those reporting analysis by CKD subgroups were tabulated. Studies including both diabetes mellitus and non-diabetes mellitus populations were included in summary tables for the CKD without diabetes mellitus topic unless results of subgroup analysis by diabetes mellitus status was provided. Work Group members proofed all summary table data and quality assessments. Summary tables are available at www.kdigo.org. Evidence profiles Evidence profiles were constructed to assess the quality and record quality grades and descriptions of effect for each outcome across studies, as well as the quality of overall evidence and description of net benefits or harms of the intervention or comparator across all outcomes. These profiles aim to make the evidence synthesis process transparent. Decisions in the evidence profiles were based on data from the primary studies listed in corresponding summary tables and on judgments of the ERT and the Work Group. When the body of evidence for a particular comparison of interest consisted of only one study, the summary table provided the final level of synthesis and an evidence profile was not generated. Evidence profiles were also not created for studies that did not exclusively examine CKD population. Each evidence profile was initially con- structed by the ERT and then reviewed, edited, and approved by the Work Group. The work products created by the ERT for summarizing the evidence base are listed in Table 9. Grading of quality of evidence for outcomes of individual studies Methodological quality. Methodological quality (internal validity) refers to the design, conduct, and reporting of outcomes of a clinical study.


Methodological quality (internal validity) refers to the design, conduct, and reporting of outcomes of a clinical study. A previously devised three-level classification system for quality assessment was used to grade the overall study quality and quality of all relevant outcomes in the study (Table 10). Variations of this system have been used in most KDOQI and all KDIGO guidelines and have been recommended for the US Agency for Healthcare Research and Quality Evidence-based Practice Center program.444 Each study was given an overall quality grade based on its design, methodology (randomization, allocation, blinding, definition of outcomes, appropriate use of statistical methods, etc.), conduct (dropout percentage, outcome assessment methodologies, etc.) and reporting (internal consistency, clarity, thoroughness and precision, etc.). Each reported outcome was then evaluated and given an individual grade depending on the quality of reporting and methodo- logical issues specific to that outcome. However, the quality Table 10 | Classification of study quality Good quality Low risk of bias and no obvious reporting errors; complete reporting of data. Must be prospective. If study of intervention, must be RCT. Fair quality Moderate risk of bias, but problems with study or paper are unlikely to cause major bias. If study of intervention, must be prospective. Poor quality High risk of bias or cannot exclude possible significant biases. Poor methods, incomplete data, reporting errors. Prospective or retrospective. RCT, randomized controlled trial.


Poor methods, incomplete data, reporting errors. Prospective or retrospective. RCT, randomized controlled trial. Table 11 | GRADE system for grading quality of evidence Step 1: Starting grade for quality of evidence based on study design Step 2: Reduce grade Step 3: Raise grade Final grade for quality of evidence and definition Randomized trials = High Observational study = Low Study quality 1 level if serious limitations 2 levels if very serious limitations Consistency 1 level if important inconsistency Directness 1 level if some uncertainty 2 levels if major uncertainty Other 1 level if sparse or imprecise datac 1 level if high probability of reporting bias Strength of association +1 level if stronga , no plausible confounders +2 levels if very strongb , no major threats to validity Other +1 level if evidence of a dose response gradient +1 level if all residual plausible confounders would have reduced the observed effect High = Further research is unlikely to change confidence in the estimate of the effect Moderate = Further research is likely to have an important impact on confidence in the estimate of effect, and may change the estimate Low = Further research is very likely to have an important impact on confidence in the estimate, and may change the estimate Any other evidence = Very Low Very Low = Any estimate of effect is very uncertain GRADE, Grading of Recommendations Assessment, Development and Evaluation. a Strong evidence of association is defined as significant relative risk of 42 (o0.5) based on consistent evidence from two or more observational studies, with no plausible confounders. b Very strong evidence of association is defined as significant relative risk of 45 (o0.2) based on direct evidence with no major threats to validity. c Sparse if there is only one study or if total N o500.


c Sparse if there is only one study or if total N o500. Imprecise if there is a low event rate (0 or 1 event) in either arm or confidence interval spanning a range 41. Adapted by permission from Macmillan Publishers Ltd, Kidney International. Uhlig K, Macleod A, Craig J et al. Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 70: 2058 2065;157 accessed http://www.nature.com/ki/journal/v70/n12/pdf/5001875a.pdf. methods for guideline development grade of an individual outcome could not exceed the quality grade for the overall study. Grading the quality of evidence and the strength of a guideline recommendation A structured approach, based on Grading of Recom- mendations Assessment, Development and Evaluation and facilitated by the use of evidence profiles was used to grade the quality of the overall evidence and the strength of recommendations. For each topic, the discussion on grading of the quality of the evidence was led by the ERT, and the discussion regarding the strength of the recommendations was led by the Work Group Co-Chairs. The strength of a recommendation indicates the extent to which one can be confident that adherence to the recommendation will do more good than harm. The quality of a body of evidence refers to the extent to which our confidence in an estimate of effect is sufficient to support a particular recommendation.445 Grading the quality of evidence for each outcome across studies. Following GRADE, the quality of a body of evidence pertaining to a particular outcome of interest was initially categorized on the basis of study design.


Following GRADE, the quality of a body of evidence pertaining to a particular outcome of interest was initially categorized on the basis of study design. For questions of interventions, the initial quality grade was High if the body of evidence consisted of RCTs, Low if it consisted of observational studies, and Very Low if it consisted of studies of other study designs. For questions of interventions, the Work Group decided to use only RCTs. The grade for the quality of evidence for each intervention outcome pair was then lowered if there were serious limitations to the methodological quality of the aggregate of studies, if there were important inconsistencies in the results across studies, if there was uncertainty about the directness of evidence including limited applicability of the findings to the population of interest, if the data were imprecise (a low event rate in either arm or a CI spanning a range 41) or sparse (only 1 study or total No500), or if there was thought to be a high likelihood of bias. The final grade for the quality of the evidence for an intervention outcome pair could be one of the following four grades: High , Moderate , Low or Very Low (Table 11). Grading the overall quality of evidence. The quality of the overall body of evidence was then determined on the basis of the quality grades for all outcomes of interest, taking into Table 14 | KDIGO nomenclature and description for grading recommendations 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.


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. 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. Table 15 | Determinants of strength of recommendation Factor Comment Balance between desirable and undesirable effects The larger the difference between the desirable and undesirable effects, the more likely a strong recommendation is warranted. The narrower the gradient, the more likely a weak recommendation is warranted. Quality of the evidence The higher the quality of evidence, the more likely a strong recommendation is warranted. Values and preferences The more variability in values and preferences, or the more uncertainty in values and preferences, the more likely a weak recommendation is warranted. Costs (resource allocation) The higher the costs of an intervention that is, the more resources consumed the less likely a strong recommendation is warranted.


Costs (resource allocation) The higher the costs of an intervention that is, the more resources consumed the less likely a strong recommendation is warranted. Table 13 | Balance of benefits and harms When there was evidence to determine the balance of medical benefits and harms of an intervention to a patient, conclusions were categorized as follows: K For statistically significant benefit or harm, report as benefit [or harm] of drug X. K For non statistically significant benefit or harm, report as possible benefit [or harm] of drug X. K In instances where studies are inconsistent, report as possible benefit [or harm] of drug X. K No difference can only be reported if a study is not imprecise. K Insufficient evidence is reported if imprecision is a factor. Table 12 | Final grade for overall quality of evidence 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.


D Very low The estimate of effect is very uncertain, and often will be far from the truth. 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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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).


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.


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.


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.


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.


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.


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.


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.


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.


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.


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).


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 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.


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.


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 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 .


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