Meta-analysis was conducted by the Cochrane Kidney and Transplant Evidence Review Team as part of the guideline evidence review. *Includes patients both with and without high blood pressure. CCB, calcium channel blocker; CI, con dence interval; CyP, cytochrome P450 3A5 polymorphism; M-H, Mantel-Haenszel. chapter 4 www.kidney-international.org higher; 95% CI: 2.79 higher 7.74 higher) compared to pla- cebo over a mean follow-up of 15.3 months (Supplementary ). The tradeoff or harms with these interventions include well-known adverse events for both dihydropyridine CCB ) and ARB (e.g., anemia, acute decline in kidney function, hyperkalemia336 ). The evidence review found that, compared to placebo or no treatment, ACEi, alpha-blockers, beta-blockers, and MRAs had no signi cant effect on mortality, graft loss, or CV events (Supplementary Table S35,332,337 349 Supplementary Table S36,350 Supplementary Table S37,351 Supplementary Table S38352 ). With regard to ACEi there was trial evidence showing that these agents were effective at reducing BP and proteinuria in kidney transplant recipients (Supplementary Table S35). However, there was no signi - cant effect of ACEi on all-cause mortality or graft loss, and their use was associated with a signi cant increase in adverse events in the kidney transplant population, including angioedema, cough, hyperkalemia, and anemia (Supplementary Table S35). Quality of evidence. The ERT updated a Cochrane sys- and evaluated the quality of the evidence based on RCTs only (Supplementary Tables S33 S39). The evidence for the use of an ARB or CCB compared to placebo or no treatment is considered low quality because of a serious risk of bias (unclear randomization sequence generation and allocation concealment) and imprecision around the effect estimates. Overall, there were very few graft failure events, which introduces greater fragility in the effect estimates.


Overall, there were very few graft failure events, which introduces greater fragility in the effect estimates. For example, there were only a total of 25 graft failure outcomes among the 786 participants over a mean of 37 months of follow-up in the ARB trials. Values and preferences. Kidney transplant recipients place a high priority on allograft survival. The SONG Kidney Transplantation (SONG-Tx) group was established to deter- mine which outcomes to measure in transplant trials.305 The SONG-Tx methodology included a Delphi survey that was completed by 461 patients or caregivers and 557 health pro- fessionals from 79 countries. They also held 3 consensus conferences in which patients and caregivers partici- Kidney allograft survival was unequivocally the dominant priority for patients, caregivers, and health pro- From the patient s perspective, there was a prevailing dread of returning to dialysis, and they focused on Preventing graft loss was the top priority, even over death, as the patients were more concerned with quality than quantity of life.305 The SONG-Tx work provides strong rationale for the use of interventions that will reduce graft failure. It is the opinion of the Work Group that most well-informed transplant pa- tients would have the same values and preferences for the avoidance of graft loss, as was evident from the SONG-Tx work. Thus, we believe that nearly all well-informed trans- plant patients would accept the tradeoffs of side effects of a CCB or an ARB in exchange for the possible bene t of pro- longed graft survival. Resource use and other costs. This recommendation as- sumes that an antihypertensive agent will be started for the treatment of high BP, and the guideline is to facilitate the decision on the choice of the agent. In most countries, generic CCBs and generic ARBs are inexpensive.


In most countries, generic CCBs and generic ARBs are inexpensive. In resource-limited settings, these drugs are most likely to be available at even lower cost. Given the high nancial and human cost of graft failure, and the relatively low cost of CCB or ARB, it is likely that the initiation of a CCB or ARB would be cost-effective.353 However, a formal economic analysis evaluating different antihypertensive agents in the kidney transplantation setting has not been Considerations for implementation. High BP can be dif cult to control in kidney transplant recipients, and most patients will require more than 1 antihypertensive agent.299 301 This recommendation is for the selection of an initial antihy- pertensive agent with the understanding that other medi- cations may be required to achieve BP control. Patients with evidence of volume overload and high BP should be treated with diuretics before considering an ARB or CCB. Women trying to conceive or who are pregnant should be treated with a CCB, which is generally safe during preg- nancy and lactation, whereas ARB is contraindicated in these conditions. In kidney transplant recipients with pro- teinuria and high BP, ARB should be considered rst given the known proteinuria-lowering effects of these In the early posttransplant period, ARBs should be avoided until kidney transplant function stabilizes, as the acute negative effect of an ARB on GFR can be confused with other causes of graft dysfunction (e.g., rejection). For most other subgroups of transplant patients (e.g., elderly, diabetic), an ARB or CCB should be considered as the rst-line antihypertensive agent. Most, if not all patient subgroups, would value graft survival as a high-priority outcome. The choice of class (i.e., ARB vs. CCB) and speci c agent should be based on local availability and cost.


, ARB vs. CCB) and speci c agent should be based on local availability and cost. Rationale This recommendation places a higher value on preventing kidney allograft loss and a lower value on the risk of medication-related side effects. There are many advantages of using an ARB or CCB for high BP in kidney transplant recipients, including physician familiarity with these agents, well-known side-effect pro les, availability, and low costs. This recommendation is strong because, in the judgment of the Work Group, the potential prevention of transplant www.kidney-international.org chapter 4 failure far outweighs potential risks and burden associated with its implementation. The Work Group also judged that most transplant patients would take a CCB or an ARB given the potential bene t, and only a small proportion would not. Finally, the Work Group judged that the majority, if not all, of clinicians would be comfortable in starting a CCB or ARB due to the familiarity with these agents and their well-known safety pro les. Research recommendations Future research should include:  Adequately powered RCT to evaluate CV and kidney effects of targeting SBP <120 mm Hg versus <130 mm Hg SBP among patients with kidney transplants.  Adequately powered RCT to evaluate CV and kidney effects of ARB versus dihydropyridine CCB among patients with kidney transplants. chapter 4 www.kidney-international.org Chapter 5: Blood pressure management in children with CKD Recommendation 5.1: We suggest that in children with CKD, 24-hour mean arterial pressure (MAP) by ABPM should be lowered to 50th percentile for age, sex, and height (2C). This recommendation is weak, according to GRADE, because the potential risks for adverse events from BP lowering may vary depending on the underlying cause of CKD in children.


This recommendation is weak, according to GRADE, because the potential risks for adverse events from BP lowering may vary depending on the underlying cause of CKD in children. In particular, risks of dehydration, hypotension, and possible AKI may be greater in children with underlying urologic disease that may be associated with xed urine output despite intercurrent gastrointestinal (GI) illness and uid loss or decreased uid intake. There may also be burden due to limitations in available resources associated with BP monitoring via 24-hour ABPM. It places a high value on reduction in kidney disease progression and kidney failure and use of the same BP measurement tech- nique by ABPM as in the single RCT that forms the evidence base. It places a relatively low value on the lack of evidence demonstrating that the clinical bene ts of BP lowering extend to populations characterized by different causes of CKD, level of albuminuria, race and ethnicity, and on the costs and incon- venience associated with BP monitoring using ABPM. Key information Balance of bene ts and harms. This recommendation relies heavily on the data from a single trial (the Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CKD in Pediatric Patients [ESCAPE] trial) of 385 participants in which intensi ed BP control (targeting 24-hour MAP <50th percentile of normal children) was compared to standard BP control (targeting 24-hour MAP 50th 99th percentile of normal children; Supplementary Table S401,142,355 ). This study showed a probable bene t in slowing kidney disease progression and no greater risk of adverse events, such as hypotension or acute decrease in GFR. This study in children was not powered for, and did not demonstrate, differences in the critical outcome of all-cause mortality.


This study in children was not powered for, and did not demonstrate, differences in the critical outcome of all-cause mortality. In the ESCAPE trial, targeting the intensi ed BP control required a larger number of antihypertensive agents than the conventional target, which may be a burden for some children. Certain subgroups, those with glomerular disorders, GFR <45 ml/ , and those with PCR >1.5 g/g (150 mg/ mmol) seemed to bene t the most. Of note, based on this observation, the 2016 European Society of Hypertension guideline recommends targeting the 75th percentile of MAP of normal children in a CKD patient with no proteinuria, and the 50th percentile if an individual has proteinuria.356 This is based on a subgroup analysis of the ESCAPE data, which suggested that those children with a PCR <0.5 g/g (50 mg/ mmol) did not have a signi cant bene t from strict BP control. Therefore, the risk bene t ratio associated with this treatment strategy may differ in different subpopulations. There may be a higher risk of adverse events with aggressive BP control in individuals who are prone to become dehydrated and are at risk of AKI.


There may be a higher risk of adverse events with aggressive BP control in individuals who are prone to become dehydrated and are at risk of AKI. This is especially relevant to children with CKD and congenital anomalies of the kidney and urinary tract (CAKUT) who may be unable to concentrate urine and have a salt-losing nephropathy.357 On the other hand, there are potential CV end-organ bene ts, such as less left ventricular hypertrophy.358 The single RCT of BP control and kidney failure outcomes in the pediatric CKD population utilized 24-hour MAP as the Additionally, the AHA Scienti c Statement on pediatric ABPM currently considers ABPM as the gold stan- dard metric for the assessment of BP in children, as stronger associations have been reported between ABPM and target organ damage in children compared with clinic BP values.359 Targeting BP control by ABPM in children with CKD is also recommended by the American Academy of Pediatrics However, in clinics that do not have the capacity to provide ABPM, performance of standardized, protocol-driven manual BP measurement using an aneroid sphygmoma- nometer is a reasonable alternative. Such standardized manual BP measurement provides prognostic information similar to that provided by ABPM.360,361 Data from the Chronic Kidney Disease in Children Study (CKiD) further demonstrate that manual auscultatory clinic BPs taken in a protocol-driven setting are not inferior to ambulatory BP in the discrimination of BP-related adverse outcomes in children However, it must be emphasized that, despite their prognostic utility, RCTs targeting standardized manual BP with meaningful clinical outcomes are not available in children. Proper technique is essential for BP measurement. BP should be measured in the right arm using standard practices, similar to the method used for adults (see Figure 2 in Chapter 1).


BP should be measured in the right arm using standard practices, similar to the method used for adults (see Figure 2 in Chapter 1). The AAP 2017 Clinical Practice guidelines also provide considerable detail on correct BP measurement methods.1 When possible, in the clinic, the use of auscultatory BP is preferred, as normative BP data in children are obtained using this technique, and there are signi cant differences between values obtained by oscillometric and auscultatory measurements, with oscillometric measures being slightly www.kidney-international.org chapter 5 higher on average.1,3,362 Regardless, RCT data targeting either oscillometric or auscultatory BP measurements obtained in the clinic setting in children are lacking.363 For practical purposes, the initial BP measurement in a clinic setting may be oscillometric using a calibrated machine that has been validated for use in the pediatric population.1,3 However, conversion from oscillometric to ascultatory measurement on an individual basis is dif cult. In individuals at particularly high risk for elevated BP (e.g., those with glomerular dis- readings should then be con rmed by auscultation. Use of HBPM in children requires further study and has not been endorsed for the diagnosis of hypertension by the AAP Clinical Practice Guideline. When performed, elec- tronic upper-arm cuff monitors, which have been clinically validated in children, should be used with appropriate cuff size. Validation status for oscillometric BP devices in the pediatric age group can be checked at stridebp.org. HBPM should be performed for 7 days (not less than 3), with duplicate morning and evening measurements after 5 mi- nutes of sitting at rest and 1 minute between measurements (total of at least 12 readings per week).


HBPM should be performed for 7 days (not less than 3), with duplicate morning and evening measurements after 5 mi- nutes of sitting at rest and 1 minute between measurements (total of at least 12 readings per week). These preparations have been suggested to be useful in the initial evaluation of untreated children with suspected hypertension, and for children with treated hypertension before each follow-up visit to the healthcare provider.365 The advantages of HBPM include the ability to obtain multiple BP measure- ments outside the of ce setting, its relative ease of use, and perhaps higher acceptance by patients and families. Similar to standardized of ce BP measurements and in contrast to ABPM, however, no prospective RCTs targeting HBPM to improve clinical outcomes are available in children. Reliable factors converting standardized of ce BP to home BP or ABPM are also not available in children. Additionally, clin- ical validation of newer, more automated BP devices in children is necessary. Quality of evidence. The quality of the evidence is low for the outcomes of annual GFR loss and ESKD, as the recom- mendation of a target of <50th percentile MAP by ABPM in children was based on a single RCT with study limitations (Supplementary Table S40142 ). The quality of the evidence for the mortality outcome was very low because of study limi- tations and very serious imprecision because death is a rare event in children. Nonetheless, multiple smaller interven- tional trials and observational studies with multiple mean- ingful outcomes for children have consistently shown bene ts of BP lowering.


Nonetheless, multiple smaller interven- tional trials and observational studies with multiple mean- ingful outcomes for children have consistently shown bene ts of BP lowering. For example, observational data from CKiD, published in abstract form, suggest that MAP targets at <90th percentile are bene cial for children with either glomerular or non-glomerular causes of CKD, and lower MAP at <50th percentile may have an additional bene t.366 Therefore, a range of MAP targets, including the 50th 90th percentile, may also be considered. Values and preferences. The Work Group judged that the prevention of kidney failure and progressive kidney function loss would be of high value to nearly all well-informed patients or caregivers. Published patient-reported outcome data from the SONG Kids study reported that children with kidney disease and caregivers rated kidney function as an important outcome, whereas BP control was also rated as an important outcome by caregivers.367 In the judgment of the Work Group, most patients would value these clinical bene ts despite the inconvenience and potential risk of harms associated with aggressive BP management (e.g., multiple medications, more-frequent dosing, possible adverse events if dehydrated, and the burden of monitoring with 24-hour ABPM). Patients for whom medication burden or the burden of ABPM monitoring are particularly important concerns may be more inclined not to follow this recommendation. Resource use and costs. In the judgment of the Work Group, the potential bene ts associated with ABPM outweigh the costs and inconvenience associated with its implementa- tion. Patients and families in areas where ABPM is unavailable or less affordable will be less inclined to follow this recom- mendation and may choose to use clinic-based auscultatory BP monitoring instead. Consideration for implementation.


Patients and families in areas where ABPM is unavailable or less affordable will be less inclined to follow this recom- mendation and may choose to use clinic-based auscultatory BP monitoring instead. Consideration for implementation. There are no data that suggest differences in bene cial effects of BP lowering be- tween males and females, or children of different ethnic backgrounds or races. However, compared to nonproteinuric kidney diseases, children with proteinuria may derive more clinical bene ts from intensive BP lowering.142 Implementation of ABPM for monitoring treatment of hypertension is challenging.368 Some children have dif culty wearing the monitors and completing the full 24 hours of measurements. Monitors are not always available when needed; they require time from a parent or other adult to return the monitor to the clinic and are expensive. With this in mind, there are certain situations in which there is a low probability of nding elevated BP by ABPM. For example, individuals with clinic BP at #25th percentile are unlikely to have elevated ABPM. Individual practitioners may, therefore, consider less-frequent ABPM monitoring if this level of clinic BP is achieved.360 There are additional challenges on how these guidelines apply to children who are too young to undergo ABPM or to children <120 centimeters in height, for whom no normative ABPM data exist. Additionally, for those on ACEi or ARB, it is important for families to understand how to monitor their children to prevent complications, such as dehydration, hy- potension, and AKI. Rationale The Work Group considered the balance between bene ts and harms, evidence quality, values and preferences, as well as resource utilization in making this recommendation.


Rationale The Work Group considered the balance between bene ts and harms, evidence quality, values and preferences, as well as resource utilization in making this recommendation. Primary evidence comes from the ESCAPE trial in which children with baseline CKD with eGFR 20 80 ml/min per 1.73 m2 hour average ambulatory MAP >95th percentile were ran- domized to <50th percentile versus 50th 90th percentile of MAP in the nomogram of healthy children. Both arms received ramipril. The primary composite endpoint of 50% chapter 5 www.kidney-international.org GFR decline and ESKD favored the intensive BP arm (HR: Existing guidelines from other organizations include the 2016 ESH guidelines for management of high BP in chil- dren and adolescents, which promote the use of ausculta- tory of ce measurements and BP targets in children with CKD of <75th percentile of normal children (and <50th percentile if proteinuric). This recommendation is based on a post hoc analysis from the ESCAPE study.142 Obser- vational data on standardized auscultatory of ce moni- toring in the CKiD cohort suggest achieved of ce SBP and DBP <90th percentile offers protection against kidney function decline, compared to of ce SBP and DBP >90th percentile in children with CKD, with potential additional bene t of even lower of ce BP levels in children with non- glomerular forms of CKD.369 Additionally, observational data illustrate that higher levels of proteinuria are most strongly associated with poor BP control and worsening BP Targeting BP control by ABPM in children with CKD is also recommended by the AAP. The AAP 2017 Pediatric Hyper- tension guideline recommends that children or adolescents with both CKD and hypertension should be treated to lower 24-hour MAP to <50th percentile of the distribution of BP of healthy children, as measured using ABPM.


The AAP 2017 Pediatric Hyper- tension guideline recommends that children or adolescents with both CKD and hypertension should be treated to lower 24-hour MAP to <50th percentile of the distribution of BP of healthy children, as measured using ABPM. They further recommend that, regardless of apparent control of BP ac- cording to of ce measurements, children and adolescents with CKD and a history of hypertension should have BP assessed by ABPM at least yearly. Additionally, this guideline recommends that children and adolescents with CKD, hypertension, and proteinuria should be treated with an ACEi or ARB, largely based on observational data.1 In the ESCAPE trial, children in both arms of the trial were given a xed-dose ACEi; therefore, the effect of ACEi per se could not be delineated. Key differences between the current and prior KDIGO recommendations in children with CKD include that the prior KDIGO guideline made a recommendation for the initiation of antihypertensive medication when the of ce SBP or DBP is consistently above the 90th percentile for age, sex, and height, whereas in the current guideline, all children with CKD and MAP consistently above the 50th percentile should be treated.


Key differences between the current and prior KDIGO recommendations in children with CKD include that the prior KDIGO guideline made a recommendation for the initiation of antihypertensive medication when the of ce SBP or DBP is consistently above the 90th percentile for age, sex, and height, whereas in the current guideline, all children with CKD and MAP consistently above the 50th percentile should be treated. The use of medications is included in this update only as a practice point, as direct trial evidence supporting their use does not exist, and the prior recommendation was based on limited indirect evidence, primarily data from CKiD that showed better BP control with use of ACEi or ARB.371 Compared to standard-of-care therapy, ACEi in children with CKD did not lower BP or protect against GFR decline, although it has been reported to have a bene cial effect on proteinuria and left ventricular hypertrophy in small Practice Point 5.1: We suggest monitoring BP once a year with ABPM, and monitoring every 3 6 months with stan- dardized auscultatory of ce BP in children with CKD. Practice Point 5.2: In children with high BP and CKD, when ABPM is not available, manual auscultatory of ce BP obtained in a protocol-driven standardized setting target- ing achieved SBP <90th percentile for age, sex, and height of normal children is a reasonable approach. Practice Point 5.3: Use ACEi or ARB as rst-line therapy for high BP in children with CKD. These drugs lower pro- teinuria and are usually well tolerated, but they carry the risk of hyperkalemia and have adverse fetal risks for pregnant women.


These drugs lower pro- teinuria and are usually well tolerated, but they carry the risk of hyperkalemia and have adverse fetal risks for pregnant women. (For Rationale of above practice points, please see text of Research recommendations  Develop normative reference values for ABPM in pediatric populations that include various races and ethnicities, as differences in normative values by race or ethnicity might inform appropriate targets for BP treatment in childhood CKD.  Identify the best BP measurement technique and setting to de ne hypertension and BP targets for pediatric CKD patients.  Ascertain when antihypertensive medications should be initiated.  Conduct RCTs that de ne targets for treatment when ABPM cannot be obtained repeatedly, for example, with home-based or of ce-based auscultatory or oscillometric BP, with kidney disease progression and CVD as outcomes. www.kidney-international.org chapter 5 Methods for guideline development Aim This is an update of the KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease (CKD) published in 2012.141 In September 2017, KDIGO held a Contro- versies Conference to determine whether there was suf cient new evidence to support updating any of the guideline recommendations. It was decided that a guideline update was required.374 The objective of this project was to update the evidence-based clinical practice guideline for the management of BP in patients with CKD. The guideline development methods are described below. Overview of the process This guideline adhered to international best practice for guideline development (Appendix B: Supplementary Tables S2 and S3).375,376 This guideline has been conducted and reported in accordance with the AGREE II reporting checklist.377 The processes under- taken for the development of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD are described below.


Overview of the process This guideline adhered to international best practice for guideline development (Appendix B: Supplementary Tables S2 and S3).375,376 This guideline has been conducted and reported in accordance with the AGREE II reporting checklist.377 The processes under- taken for the development of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD are described below.  Appointing Work Group members and the ERT  Finalizing guideline development methodology  De ning scope and topics of the guideline  Formulating clinical questions identifying the Population, Intervention, Comparator, Outcome, Methods (PICOM)  Selecting topics for systematic evidence review and linking to existing Cochrane Kidney and Transplant systematic reviews  Developing and implementing literature search strategies  Selecting studies according to prede ned inclusion criteria  Data extraction and critical appraisal of the literature  Evidence synthesis and meta-analysis  Grading the quality of the evidence for each outcome across studies  Grading the strength of the recommendation, based on the quality of the evidence, and other considerations  Finalizing guideline recommendations and supporting rationale  Public review in January 2020  Guideline update  Finalizing and publishing the guideline The development process was followed in the majority of the guideline chapters. Some chapters, in particular Chapter 3, required an iterative process, whereby the initial evidence review deliverables were revised to re ect issues raised during the Work Group meeting in January 2019. These additional reviews and clari cations were provided to the Work Group coauthors to ensure that the draft of the Chapter re ected available evidence. Commissioning of Work Group and ERT. The KDIGO Co- Chairs appointed the Work Group Co-Chairs, who then assembled the Work Group, to include content experts in adult and pediatric nephrology, blood pressure management, epidemiology, and public health.


The KDIGO Co- Chairs appointed the Work Group Co-Chairs, who then assembled the Work Group, to include content experts in adult and pediatric nephrology, blood pressure management, epidemiology, and public health. Cochrane Kidney and Transplant was contracted to conduct systematic evidence review and provide expertise in guideline development methodology. The ERT consisted of adult and pediatric nephrologists, and methodologists with expertise in evidence synthesis, and guideline development. The ERT coordinated the methodological and analytical processes of guideline development, including literature searching, data extraction, critical appraisal, evidence synthesis and meta-analysis, grading the quality of the evidence per outcome, and grading the quality of the evidence for the recommendations. The Work Group was responsible for writing the recommendations and underlying rationale, as well as grading the strength of the recommendation. The KDIGO Co-Chairs, KDIGO Methods Chair, Work Group Co-Chairs, and the ERT had a one-day meeting in Houston, Texas, USA in February 2018 to discuss the previous guideline and the ndings from the KDIGO Controversies Conference on Blood Pressure in Chronic Kidney Disease,374 and nalize the guideline development process. Guideline topics from the previous guideline and new guideline topics were linked with appropriate clinical questions to underpin the systematic evidence review. The draft guideline topics and review topics were nalized with feedback from the Work Group. De ning scope and topics and formulating key clinical questions. The guideline Work Group, with assistance from the ERT, determined the overall scope of the guideline. A preliminary list of topics and key clinical questions was informed by the pre- vious KDIGO guideline141 and the KDIGO Controversies Confer- ence on Blood Pressure in CKD.374 Logical frameworks were developed to present a visual representation of the clinical question and facilitate discussion about the scope of the guideline.


A preliminary list of topics and key clinical questions was informed by the pre- vious KDIGO guideline141 and the KDIGO Controversies Confer- ence on Blood Pressure in CKD.374 Logical frameworks were developed to present a visual representation of the clinical question and facilitate discussion about the scope of the guideline. The majority of clinical questions for this guideline were based upon RCTs to avoid bias by design. However, for questions of critical importance, systematic reviews of the general population were included. Clinical questions adhered to the PICOM format (a list of critical and important outcomes was compiled after voting from the Work Group [Table 1]). The Work Group and the ERT further re ned the clinical questions to nalize inclusion and exclusion criteria to guide literature searching and data extraction. Clinical questions were mapped to existing Cochrane Kidney and Trans- plant systematic reviews. These systematic reviews were updated accordingly. For clinical questions that did not map with any Cochrane Kidney and Transplant systematic reviews, de novo sys- tematic reviews were undertaken. The previous guideline was reviewed to ensure all identi ed studies were included in the evi- Details of the PICOM questions and associated Cochrane Kidney and Transplant systematic reviews are provided in Table 2. All evidence reviews were conducted in accordance to the Cochrane Handbook,383 and guideline development adhered to the standards of GRADE.384 Literature searches and article selection. Searches for RCTs utilized the Cochrane Kidney and Transplant Registry of studies. The Cochrane Kidney and Transplant Registry of studies is a database of RCTs in kidney disease that is maintained by information specialists.


The Cochrane Kidney and Transplant Registry of studies is a database of RCTs in kidney disease that is maintained by information specialists. The database is populated by monthly searches of the Cochrane Central Register of Controlled Trials, weekly searches of MEDLINE methods for guideline development www.kidney-international.org OVID, yearly searches of Embase OVID, hand-searching of major kidney and transplant conference proceedings, searches of trial registries, including clinicaltrials.gov and the International Clinical Trials Register search portal. The updated search examined the medical databases MEDLINE, Cochrane Central Registry of Controlled Trials, and Embase. For review topics that matched existing Cochrane Kidney and Transplant systematic reviews, an updated search for the review using the Cochrane Kidney and Transplant Registry of studies was conducted. The Cochrane Kidney and Transplant Registry of studies was searched for clinical questions that included only RCTs and were not linked to any existing Cochrane systematic review. For clinical questions that included other study types, such as systematic reviews on non-CKD populations, the medical literature databases MED- LINE and Embase were searched. The search strategies are provided in Appendix A: Supplementary Table S1. The titles and abstracts resulting from the searches were screened by 2 ERT members who independently assessed retrieved abstracts, and if necessary, the full text, to determine which studies satis ed the inclusion criteria. Disagreement about inclusion was resolved by discussion with a third member of the ERT. A total of 6863 citations were screened. Of these, 290 RCTs, 35 reviews, and 14 observational studies were included in the evidence review (Figure 8). Data extraction. Data extraction was performed independently by 2 members of the ERT. Unclear data were clari ed by contacting the author of the study report, and any relevant data obtained in this manner were included.


Unclear data were clari ed by contacting the author of the study report, and any relevant data obtained in this manner were included. The ERT designed data extraction forms to capture data on study design, study participant characteristics, intervention and comparator characteristics, and critical and important outcomes. Any differences in extraction between mem- bers of the ERT were resolved through discussion. A third reviewer was included if consensus could not be achieved. Critical appraisal of studies. The majority of reviews undertaken were intervention reviews that included RCTs. For these reviews, the Cochrane Risk of Bias tool was used to assess individual study limitations based on the following items383 :  Was there adequate sequence generation (selection bias)?  Was allocation adequately concealed (selection bias)?  Was knowledge of the allocated interventions adequately pre- vented during the study (detection bias)?  Participants and personnel (performance bias)  Outcome assessors (detection bias)  Were incomplete outcome data adequately addressed (attrition bias)?  Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?  Was the study apparently free of other problems that could put it at risk of bias? For some topics, for which there were no RCTs in the CKD population, the ERT conducted reviews of existing systematic re- views. AMSTAR 2 was used to critically appraise systematic re- For systematic reviews of diagnostic test accuracy studies, the QUADAS-2 tool was used to assess study limitations.386 All critical appraisal was conducted independently by 2 ERT members, with disagreements regarding the risk of bias adjudications resolved by consultation with a third review author. Evidence synthesis and meta-analysis. Measures of treatment effect.


AMSTAR 2 was used to critically appraise systematic re- For systematic reviews of diagnostic test accuracy studies, the QUADAS-2 tool was used to assess study limitations.386 All critical appraisal was conducted independently by 2 ERT members, with disagreements regarding the risk of bias adjudications resolved by consultation with a third review author. Evidence synthesis and meta-analysis. Measures of treatment effect. Dichotomous outcomes (all-cause mortality, CV mortality, kidney failure, CV events [MI, stroke, HF], dementia or cognitive impairment, doubling serum creatinine, AKI, falls, fatigue, body weight, and BP) results were expressed as RR with 95% CI. When continuous scales of measurement were used to assess the effects of treatment, such as body weight, the mean difference (MD) with 95% CI was used. Data synthesis. Data were pooled using the Mantel-Haenszel random-effects model for dichotomous outcomes, and the inverse variance random-effects model for continuous outcomes. The random-effects model was chosen because it provides a conservative estimate of effect in the presence of known and Assessment of heterogeneity. Heterogeneity was assessed by visual inspection of forest plots of standardized mean effect sizes and of risk ratios, and c2 tests. A P value of <0.05 was used to denote statistical heterogeneity, and an I2 was calculated to measure the proportion of total variation in the estimates of treatment effect that was due to heterogeneity beyond chance.384 We used conventions of interpre- tation as de ned by Higgins et al. (2003).387 Assessment of publication bias. We made every attempt to minimize publication bias by including unpublished studies (for example, by searching online trial registries). To assess publication bias, we used funnel plots of the log odds ratio (effect vs. standard error of the effect size) when a suf cient number of studies were Other reasons for the asymmetry of funnel plots were considered.


To assess publication bias, we used funnel plots of the log odds ratio (effect vs. standard error of the effect size) when a suf cient number of studies were Other reasons for the asymmetry of funnel plots were considered. Subgroup analysis and investigation of heterogeneity. Subgroup analysis was undertaken to explore whether there were clinical dif- ferences between the studies that may have systematically in uenced the differences that were observed in the critical and important outcomes. However, subgroup analyses are hypothesis-forming rather than hypothesis-testing and should be interpreted with caution. The following subgroups were considered: severity of CKD, primary kidney disease, elderly age/presence of comorbidities, presence of proteinuria or albuminuria, diabetes, number of antihypertensives, lifestyle behaviors/health behaviors. The test of subgroup differences used the I2 statistic and a P value of 0.1 (noting that this is a weak test).383 Sensitivity analysis. The following sensitivity analyses were considered: Table 1| Hierarchy of outcomes Hierarchy Outcomes Critical outcomes  All-cause mortality  Cardiovascular mortality  Kidney failure (formerly known as ESKD)  Cardiovascular events (MI, stroke, HF)  Dementia or cognitive impairment Important outcomes  Doubling serum creatinine  AKI  Falls  Fatigue  Body weight  Blood pressure Outcomes of limited importance  eGFR or creatinine clearance  Proteinuria AKI, acute kidney injury; eGFR, estimated glomerular ltration rate; ESKD, end-stage kidney disease; HF, heart failure; MI, myocardial infarction. The critical and important outcomes were voted on by the Work Group using an adapted Delphi process (1 9 Likert scale). Critical outcomes median was rated 7 9, and important outcomes were rated 4 6 on the 9-point scale.


Critical outcomes median was rated 7 9, and important outcomes were rated 4 6 on the 9-point scale. www.kidney-international.org methods for guideline development Table 2| Clinical questions and systematic review topics in the PICOM format Guideline Chapter 1 Blood pressure measurement Clinical question In patients with CKD, what is the diagnostic accuracy of various BP measurement techniques compared to standardized auscultatory of ce-based BP? Population Patients with CKD (CKD G1 G5 without kidney transplant, and kidney transplant recipients) Index test Oscillometric (of ce-based) BP (unattended or attended), ambulatory BP, home oscillometric monitors Reference standard Auscultatory of ce-based BP monitoring Outcomes Sensitivity, speci city, negative predictive value, positive predictive value Study design Systematic reviews SoF table Supplementary Table S41 Clinical question In the general population, what is the diagnostic accuracy of various BP measurement techniques (oscillometric of ce and home BP, ambulatory BP) compared to standardized auscultatory of ce-based BP in diagnosing high BP? Population General population Index test Oscillometric (of ce-based) BP (unattended or attended), ambulatory BP, home oscillometric monitors Reference standard Auscultatory of ce-based BP monitoring Outcomes Sensitivity, speci city, negative predictive value, positive predictive value Study design Systematic reviews SoF table Supplementary Tables S4, S42, and S43 Clinical question In the general population, what is the association among various approaches to measuring BP including in the clinic (standardized vs. non-standardized), at home, and ambulatory with classi cation of BP and long-term outcomes?


Population General population Index test Oscillometric (of ce-based) BP (unattended or attended), ambulatory BP, home oscillometric monitors Reference standard Auscultatory of ce-based BP monitoring Outcomes Sensitivity, speci city, negative predictive value, positive predictive value Study design Systematic reviews SoF table Supplementary Tables S4, S42, and S43 Clinical question In the general population, what is the association among various approaches to measuring BP including in the clinic (standardized vs. non-standardized), at home, and ambulatory with classi cation of BP and long-term outcomes? Population General population Index test Oscillometric (of ce-based) BP (unattended or attended), ambulatory BP, home oscillometric monitors Reference standard Auscultatory of ce-based BP monitoring Outcomes Cost-effectiveness Study design Systematic reviews SoF table Supplementary Tables S43 and S44 Guideline Chapter 2 Lifestyle interventions for lowering blood pressure in patients with CKD not receiving dialysis Clinical question In adults with CKD without diabetes, does reducing protein intake compared to usual protein intake improve clinically relevant outcomes and decrease adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) without diabetes Intervention Low-protein diet Comparator Usual-protein diet Outcomes Outcomes listed in Table 1 Study design RCTs Cochrane review Hahn D, et al. Low protein diets for non-diabetic adults with chronic kidney disease (Review). Cochrane Database of Systematic Reviews. 2020:10;CD001892.378 SoF table Supplementary Tables S49 and S50 Clinical question In adults with CKD without diabetes, does reducing dietary salt intake compared to usual dietary salt intake improve clinically relevant outcomes and decrease adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) without diabetes Intervention Low-salt diet Comparator Usual salt diet Outcomes Outcomes listed in Table 1 Additional outcomes sodium excretion, serum creatinine, BP Study design RCTs Cochrane review McMahon EJ, et al. Altered dietary salt intake for people with chronic kidney disease (Review).


Altered dietary salt intake for people with chronic kidney disease (Review). Cochrane Database of SoF table Supplementary Table S5 Clinical question In adults with CKD and diabetes, does reducing dietary salt intake compared to usual dietary salt intake improve clinically relevant outcomes and decrease adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and diabetes (T1D and T2D) Intervention Low-salt diet Comparator Usual salt diet Outcomes Outcomes listed in Table 1 Additional outcomes body mass index Study design RCTs Cochrane review No relevant Cochrane Kidney and Transplant review SoF table Supplementary Tables S6 S9, S45, and S46 Clinical question What are the bene ts and harms of dietary interventions/patterns among adults with CKD, including people with kidney failure treated with kidney transplantation? Population Adults with CKD (CKD G1 G5 including kidney transplant recipient) Intervention Dietary modi cations (including dietary advice or lifestyle management) methods for guideline development www.kidney-international.org Guideline Chapter 2 Lifestyle interventions for lowering blood pressure in patients with CKD not receiving dialysis Comparator Standard of care (including lifestyle advice) or any other dietary pattern Outcomes Outcomes listed in Table 1 Additional outcomes BP Study design RCTs Cochrane review Palmer SC, et al. Dietary interventions for adults with chronic kidney disease. Cochrane Database of Systematic Reviews. SoF table Supplementary Tables S51 S53 and S90 Clinical question In adults with CKD and hypertension, does exercise improve clinically relevant outcomes and decrease adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and high BP Intervention Any exercise intervention greater than 8 weeks duration (to examine the effects of regular ongoing physical exercise training) Comparator Standard of care Outcomes Outcomes listed in Table 1 Additional outcomes fat mass, BP, quality of life Study design RCTs Cochrane review Heiwe S and Jacobson SH.


Population Adults with CKD (CKD G1 G5 without kidney transplant) and high BP Intervention Any exercise intervention greater than 8 weeks duration (to examine the effects of regular ongoing physical exercise training) Comparator Standard of care Outcomes Outcomes listed in Table 1 Additional outcomes fat mass, BP, quality of life Study design RCTs Cochrane review Heiwe S and Jacobson SH. Exercise training for adults with chronic kidney disease (Review). Cochrane Database of Systematic Reviews. 2011:10;CD00323.380 SoF table Supplementary Tables S10, S47, and S48 Guideline Chapter 3 Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis Clinical question In patients with CKD, does lower (intensive) BP targets compared to standard BP targets improve clinical ef cacy outcomes and reduce adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and with or without diabetes (T1D and T2D) Intervention Lower BP target (<140/80 mm Hg, <130/80 mm Hg, <120 mm Hg, MAP <92 mm Hg target) Comparator Standard BP target (including MAP target 102 107 mm Hg) Outcomes Critical and important outcomes listed in Table 1 Study design RCTs Cochrane review None relevant SoF table Supplementary Tables S11 S14, S54 S59, and S75 S78 Clinical question In patients with CKD, does RAS inhibition compared to placebo/no treatment or standard of care improve clinical ef cacy outcomes and reduce adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and with and without diabetes (T1D and T2D) Intervention ACEi, ARB, aldosterone antagonists Comparator Placebo/standard of care Outcomes Critical and important outcomes listed in Table 1 Study design RCTs Cochrane review Strippoli GFM, et al. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database of Systematic Reviews. 2006:4;CD006257.259 Sharma P, et al.


Cochrane Database of Systematic Reviews. 2006:4;CD006257.259 Sharma P, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database of Systematic Reviews. 2011:10;CD007751.281 Chung EYM, Ruospo M, Natale P, et al. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database of Systematic Reviews. 2020;10:CD007004.193 SoF table Supplementary Tables S15 S17, S21 S24, and S60 S62 Clinical question In patients with CKD, does non-RAS inhibition compared to placebo or RAS inhibition improve clinical ef cacy outcomes and reduce adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and with and without diabetes (T1D and T2D) Intervention Non-RAS inhibition (alpha-blockers, beta-blockers, CCBs, DRIs, diuretics) Comparator Placebo or RASi Outcomes Critical and important harms listed in Table 1 Study design RCTs Cochrane review None relevant Clinical question In patients with CKD, does dual-RAS inhibition compared to mono-RAS inhibition improve clinical ef cacy outcomes and reduce adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) and with and without diabetes (T1D and T2D) Intervention Dual RAS inhibition Comparator Mono RAS inhibition Outcomes Critical and important harms listed in Table 1 Study design RCTs Cochrane review Strippoli GFM, et al. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database of Systematic Reviews. 2006:4;CD006257.259 Sharma P, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database of Systematic Reviews.


Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database of Systematic Reviews. 2011:10;CD007751.281 (Continued on following page) Table 2| (Continued) Clinical questions and systematic review topics in the PICOM format www.kidney-international.org methods for guideline development Guideline Chapter 3 Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis SoF table Supplementary Tables S31, S32, and S80 Clinical question In patients with CKD and chronic hyperkalemia, do potassium binders compared to placebo or standard of care improve clinically relevant outcomes, and decrease adverse effects? Population Adults with CKD (CKD G1 G5 without kidney transplant) with chronic hyperkalemia Intervention Potassium binders Comparator Placebo/standard of care Outcomes Critical and important harms listed in Table 1 Additional outcomes reported hospitalization, hypokalemia, SBP, and DBP Study design RCTs Cochrane review Natale P, et al. 2020. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database of Systematic Reviews. 2020:6:CD013165.381 SoF table Supplementary Tables S73, S74, and S88 Guideline Chapter 4 Blood pressure management in kidney transplant recipients Clinical question In kidney transplant recipients, does reducing protein intake compared to usual protein intake improve clinically relevant outcomes and decrease adverse effects? Population Kidney transplant recipients Intervention Low-protein diet Comparator Usual protein diet Outcomes Outcomes listed in Table 1 Study design RCTs Cochrane review None relevant SoF table None Clinical question In kidney transplant recipients, does reducing dietary salt intake compared to usual salt intake improve clinically relevant outcomes and decrease adverse effect?


Population Kidney transplant recipients Intervention Low-protein diet Comparator Usual protein diet Outcomes Outcomes listed in Table 1 Study design RCTs Cochrane review None relevant SoF table None Clinical question In kidney transplant recipients, does reducing dietary salt intake compared to usual salt intake improve clinically relevant outcomes and decrease adverse effect? Population Kidney transplant recipients Intervention Low-salt diet Comparator Usual salt diet Outcomes Outcomes listed in Table 1 Additional outcomes sodium excretion, serum creatinine, BP Study design RCTs Cochrane review None relevant SoF table Supplementary Table S89 Clinical question What are the bene ts and harms of dietary interventions/patterns among kidney transplant recipients? Population Kidney transplant recipients Intervention Dietary modi cations (including dietary advice or lifestyle management) Comparator Standard of care (including lifestyle advice) or any other dietary pattern Outcomes Outcomes listed in Table 1 Additional outcomes BP Study design RCTs Cochrane review Palmer SC, et al. Dietary interventions for adults with chronic kidney disease. Cochrane Database of Systematic Reviews. SoF table Supplementary Table S90 Clinical question In kidney transplant recipients and high BP, does exercise improve clinically relevant outcomes and decrease adverse effects? Population Kidney transplant recipients and high BP Intervention Any exercise intervention greater than 8 weeks duration (to examine the effects of regular ongoing physical exercise training) Comparator Standard of care Outcomes Outcomes listed in Table 1 Additional outcomes body mass index, BP, quality of life Study design RCTs Cochrane review Heiwe S and Jacobson SH. Exercise training for adults with chronic kidney disease (Review). Cochrane Database of Systematic Reviews. 2011:10;CD00323.380 SoF table Supplementary Table S91 Clinical question In kidney transplant recipients does lower (intensive) BP target compared to standard BP targets improve clinical ef cacy outcomes and reduce adverse effects?


2011:10;CD00323.380 SoF table Supplementary Table S91 Clinical question In kidney transplant recipients does lower (intensive) BP target compared to standard BP targets improve clinical ef cacy outcomes and reduce adverse effects? Population Kidney transplant recipients, adult and children Intervention Lower BP target Comparator Standard BP target Outcomes Critical and important outcomes listed in Table 1 Study design RCTs Table 2| (Continued) Clinical questions and systematic review topics in the PICOM format methods for guideline development www.kidney-international.org  Repeating the analysis, excluding unpublished studies  Repeating the analysis taking account of the risk of bias, as speci ed  Repeating the analysis, excluding any very long or large studies to establish how much they dominate the results  Repeating the analysis, excluding studies using the following l- ters: language of publication, source of funding (industry vs. other), and country in which the study was conducted. However, the available data were insuf cient to determine the in u- ence of these factors on the effect size of critical and important outcomes. Grading the quality of the evidence and the strength of a guideline recommendation. GRADING the quality of the evidence for each outcome across studies. The overall quality of the evidence related to each critical and important outcome was assessed using the GRADE approach,384,388 which assesses the quality of the evidence for each outcome. For outcomes that are based on data from RCTs, the initial grade for the quality of the evidence is considered to be high. For observational studies, the initial quality of the evidence is low.


For observational studies, the initial quality of the evidence is low. The quality of the evidence is lowered in the event of study limitations; important inconsistencies in results across Guideline Chapter 4 Blood pressure management in kidney transplant recipients Cochrane review None relevant SoF table None Clinical question In kidney transplant recipients, what antihypertensive agents improve ef cacy outcomes and reduce adverse effects? Population Kidney transplant recipients, adult and children Intervention RAS inhibition (ACEi, ARB, aldosterone antagonists), and non-RAS inhibition (alpha-blockers, beta-blockers, CCBs, diuretics, DRI) Comparator Placebo or standard of care Outcomes Critical and important outcomes listed in Table 1 Other outcomes reported: BP Study design RCTs Cochrane review Cross NB, et al. Antihypertensive treatment for kidney transplant recipients. Cochrane Database of Systematic Reviews. SoF table Supplementary Tables S33 S39 and S92 S106 Clinical question In kidney transplant recipients with chronic hyperkalemia, do potassium binders compared to placebo or standard of care improve clinically relevant outcomes and decrease adverse effects? Population Kidney transplant recipients with chronic hyperkalemia Intervention Potassium binders Comparator Placebo/standard of care Outcomes Critical and important harms listed in Table 1 Study design RCTs Cochrane review Natale P, et al. 2020. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database of Systematic Reviews. 2020:6:CD013165.381 SoF table None Guideline Chapter 5 Blood pressure management in children with CKD Clinical question In children with CKD, does a lower BP target compared to a higher BP target improve ef cacy outcomes and reduce adverse effects?


2020:6:CD013165.381 SoF table None Guideline Chapter 5 Blood pressure management in children with CKD Clinical question In children with CKD, does a lower BP target compared to a higher BP target improve ef cacy outcomes and reduce adverse effects? Population Children with CKD Intervention Lower BP target Comparator Standard BP target Outcomes Critical and important outcomes listed in Table 1 Study design RCTs Cochrane review None relevant SoF table Supplementary Table S40 Clinical question In children with CKD, what antihypertensive agents compared to standard of care improve ef cacy outcomes and reduce adverse effects? Population Children with CKD (CKD G1 G5 without kidney transplant and kidney transplant recipients) and diabetes (T1D and T2D) Intervention RAS inhibition (ACEi, ARB, aldosterone antagonists), and non-RAS inhibition (alpha-blockers, beta-blockers, CCBs, diuretics, DRI) Comparator Placebo or standard of care Outcomes Critical and important outcomes listed in Table 1 Additional outcomes: BP, serum creatinine Study design RCTs Cochrane review Bagga A, et al. Antihypertensive agents for children with chronic kidney disease (Protocol). Cochrane Database of Systematic SoF table Supplementary Table S107 ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BP, blood pressure; CCB, calcium channel blocker; CKD, chronic kidney disease; DBP, diastolic blood pressure; DRI, direct renin inhibitor; MAP, mean arterial pressure; RAS(i), renin-angiotensin system (inhibitor); RCT, randomized controlled trial; SBP, systolic blood pressure; SoF, summary of ndings; T1D, type 1 diabetes; T2D, type 2 diabetes. Table 2| (Continued) Clinical questions and systematic review topics in the PICOM format www.kidney-international.org methods for guideline development studies; indirectness of the results, including uncertainty about the population, intervention, and outcomes measured in trials and their applicability to the clinical question of interest; imprecision in the evidence review results; and concerns about publication bias.


Table 2| (Continued) Clinical questions and systematic review topics in the PICOM format www.kidney-international.org methods for guideline development studies; indirectness of the results, including uncertainty about the population, intervention, and outcomes measured in trials and their applicability to the clinical question of interest; imprecision in the evidence review results; and concerns about publication bias. For imprecision, data were benchmarked against optimal information size, low event rates in either arm, CIs that indicate appreciable bene t and harm (25% decrease and 25% increase in the outcome of interest), and sparse data (only 1 study), all indicating concerns about the precision of the results.388 The nal grade for the quality of the evidence for an outcome could be high, moderate, low, or very low (Table 3). For observational studies and other study types, it is possible for the quality of the evidence to be upgraded from a rating of low quality, according to the speci ed criteria. For further details on the GRADE approach for rating quality of the evidence, see Table 4. Summary of ndings (SoF) tables. The SoF tables were developed to include a description of the population and the intervention and comparator. In addition, the SoF tables included results from the data synthesis as relative and absolute effect estimates. The grading of the quality of the evidence for each critical and important outcome is also provided in the SoF table. The SoF tables were generated using MAGICapp, an online software application designed to support guideline development, and they are available in the Data Supplement Appendix C and Appendix D (https://kdigo.org/ guidelines/blood-pressure-in-ckd/). Developing the recommendations. The recommendations were drafted by the Work Group Co-Chairs and Work Group members. Recommendations were revised in a multistep process during a face-to-face meeting (New Orleans, LA, USA, January 2019) and by e-mail communication.


Recommendations were revised in a multistep process during a face-to-face meeting (New Orleans, LA, USA, January 2019) and by e-mail communication. The nal draft was sent for external public review, and reviewers provided open-ended responses. Based on the external stakeholder feedback, the draft was further revised by Work Group Co-Chairs and members. All Work Group members provided feedback on initial and nal drafts of the recommendation statement and guideline text and approved the nal version of the guideline. The ERT also provided a descriptive Primary evidence Search October 2018, updated September 2019, updated April 2020 Cochrane Kidney and Transplant Registry, MEDLINE, Embase - 6156 study reports retrieved - 148 observational studies Included RCTs Dietary protein 21 RCTs Dietary and supplementary salt 30 RCTs Dietary patterns 5 RCTs Exercise interventions 11 RCTs Blood pressure targets in CKD 11 RCTs Renin angiotensin system inhibitors in adults 76 RCTs Non-renin angiotensin system inhibitors 37 RCTs Blood pressure targets in transplant recipients 1 RCT Antihypertensive therapy in transplant recipients 82 RCTs Blood pressure targets in children 1 RCT Antihypertensive therapy in children 2 RCTs Potassium binders 13 RCTs Included studies 290 RCTs (n 61000) Systematic reviews - 7 CKD narrative reviews - 3 general population diagnostic test accuracy reviews - 20 general population narrative reviews - 5 general population cost-effectiveness reviews 14 observational studies Full-text screening 524 citations excluded Systematic reviews of blood pressure measurement techniques Search February 2019, updated April 2020 Cochrane Kidney and Transplant Registry - 559 reports retrieved Figure 8 | Search yield and study ow diagram. CKD, chronic kidney disease; RCT, randomized controlled trial. Table 3| Classi cation for certainty and quality of the evidence Grade Quality of evidence Meaning A High We are con dent that the true effect is close to the estimate of the effect.


Table 3| Classi cation for certainty and quality of the evidence Grade Quality of evidence Meaning A High We are con dent that the true effect is close to the estimate of the effect. B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. C Low The true effect may be substantially different from the estimate of the effect. D Very low The estimate of effect is very uncertain, and often it will be far from the true effect. methods for guideline development www.kidney-international.org summary of the evidence quality in support of the recommendations. Grading the strength of the recommendations. The strength of a recommendation is graded as strong or weak (Table 5). The strength of a recommendation was determined by the balance of bene ts and harms across all critical and important outcomes, the grading of the overall quality of evidence, patient preferences and values, resources, and other considerations (Table 6). Balance of bene ts and harms. The Work Group and ERT determined the anticipated net health bene t on the basis of expected bene ts and harms across all critical and important out- comes from the underlying evidence review. In addition to the evi- dence review, the ERT assisted Work Group members in evaluating the balance of bene ts and harms arising from key individual studies. The overall quality of evidence. The overall quality of the evidence was based on the certainty of the evidence for all critical and important outcomes, taking into account the relative importance of each outcome to the population of interest. The overall quality of the evidence was graded A, B, C, or D (Table 3).


The overall quality of the evidence was graded A, B, C, or D (Table 3). Table 4| GRADE system for grading quality of evidence Study design Starting grade of the quality of the evidence Step 2 Lower grade Step 3 Raise grade for observational studies RCTs High Study limitations: 2, very serious Strength of association: 1, large effect size (e.g., <0.5 or >2) 2, very large effect size (e.g., <0.2 or >5) Moderate Inconsistency: 2, very serious Evidence of a dose response gradient Observational studies Low Indirectness: 2, very serious All plausible confounding would reduce the demonstrated effect Very low Imprecision: 2, very serious Publication bias: 2, very serious GRADE, Grading of Recommendations Assessment, Development and Evaluation; RCT, randomized controlled trial. Table 5| KDIGO nomenclature and description for grading recommendations Grade Implications Patients Clinicians Policy Level 1 Strong We recommend Most people in your situation would want the recommended course of action, and only a small proportion would not. Most patients should receive the recommended course of action. The recommendation can be evaluated as a candidate for developing a policy or a performance measure. Level 2 Weak We suggest The majority of people in your situation would want the recommended course of action, but many would not. Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences. The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined. Table 6| Determinants of the strength of recommendation Factors Comment Balance of bene ts and harms The larger the difference between the desirable and undesirable effects, the more likely a strong recommendation is provided. The narrower the gradient, the more likely a weak recommendation is warranted.


The narrower the gradient, the more likely a weak recommendation is warranted. Quality of evidence The higher the quality of evidence, the more likely a strong recommendation is warranted. However, there are exceptions for which low or very low quality of the evidence will warrant a strong recommendation. 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. Values and preferences were obtained from the literature, where possible, or were assessed by the judgment of the Work Group when robust evidence was not identi ed. Resources and other considerations The higher the costs of an intervention that is, the more resources consumed the less likely a strong recommendation is warranted. www.kidney-international.org methods for guideline development Patient preferences and values. No patients or caregivers were involved in the Work Group. The Work Group, from their experi- ence in managing BP in patients with CKD and their understanding of the best available scienti c literature, made judgments on the preferences and values of patients. Formal qualitative evidence syn- thesis on patient priorities and preferences was not undertaken. Resources and other considerations. Healthcare and non- healthcare resources, including all inputs in the treatment were considered in grading the strength of a recommendation. The following resources were considered: direct healthcare costs, non-healthcare resources (e.g., transportation and social services), informal caregiver resources (e.g., time of family and caregivers), and changes in productivity. Economic evaluations, including cost-effectiveness analysis, were not conducted for any of the guideline topics. However, the ERT conducted searches for systematic reviews of cost-effectiveness studies in support of selected topics, such as BP measurement techniques.


However, the ERT conducted searches for systematic reviews of cost-effectiveness studies in support of selected topics, such as BP measurement techniques. Practice points In addition to graded recommendations, KDIGO guidelines now include practice points to help clinicians better evaluate and implement the guidance from the expert Work Group. Practice points are consensus statements about a speci c aspect of care, and they supplement recommendations for which a larger quantity of evidence was identi ed. These were used when no formal systematic evidence review was undertaken, or there was insuf cient evidence to provide a graded recommendation. Practice points represent the expert judg- ment of the guideline Work Group, but they also may be based on limited evidence. Practice points were sometimes formatted as a table, a gure, or an algorithm to make them easier to use in clinical practice. Format for guideline recommendations Each guideline recommendation provides an assessment of the strength of the recommendation (strong, level 1 or weak, level 2) and the quality of evidence (A, B, C, D). The recommendation state- ments are followed by a short remark, Key information (Balance of bene ts and harms, Quality of evidence, Values and preferences, Resource use and costs, Considerations for implementation), and a rationale. Each recommendation is linked to relevant SoF tables. An underlying rationale supported each practice point. Limitations of the guideline development process The evidence review prioritized RCTs as the primary source of evi- dence. For a select number of clinical questions in this guideline, the ERT undertook a comprehensive evidence review beyond RCTs. However, these reviews were not exhaustive, as specialty or regional databases were not searched, and manual searching of journals was not performed for these reviews.


However, these reviews were not exhaustive, as specialty or regional databases were not searched, and manual searching of journals was not performed for these reviews. In the development of these guidelines, no scoping exercise with patients, searches of the quali- tative literature, or formal qualitative evidence synthesis examining patient experiences and priorities were undertaken. As noted, although resource implications were considered in the formulation of recommendations, formal economic evaluations were not un- dertaken for all topics. methods for guideline development www.kidney-international.org Biographic and disclosure information Alfred K. Cheung, MD (Work Group Co-Chair), is Dialysis Research Foundation Presidential Endowed Chair, Professor of Internal Medicine, Chief of the Division of Nephrology & Hypertension, Execu- tive Director of the Dialysis Program, and Vice-chair for Research in the Department of Internal Medicine at the University of Utah, Salt Lake City, UT, USA. His research has focused on CKD, hemodialysis, vascular access, and hypertension. He has served on various com- mittees in the American Society of Nephrology, the US Na- tional Kidney Foundation, the US Food & Drug Administration, the US Centers for Medicare & Medicaid Services, and as a councilor at the International Society of Nephrology. He has also been a chartered member or ad hoc member of grant review committees for the US National Institutes of Health (NIH) and other research funding orga- nizations. He was interim Co-Editor-in-chief of the Journal of American Society of Nephrology. He co-chaired the Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines on Cardiovascular Disease in Dialysis Patients. Of particular relevance to this task, he was a member of the Steering Committee and the Principal Inves- tigator of the Utah Clinical Center Network in the Systolic Blood Pressure Intervention Trial (SPRINT) sponsored by the NIH.


Of particular relevance to this task, he was a member of the Steering Committee and the Principal Inves- tigator of the Utah Clinical Center Network in the Systolic Blood Pressure Intervention Trial (SPRINT) sponsored by the NIH. Consultancy: Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate Grant/research support: National Institutes of Health for SPRINT* *Monies paid to institution. Johannes F.E. Mann, MD (Work Group Co-Chair), is a professor of medicine at the University of Erlangen-N rnberg, Erlangen, Germany, and head of the KfH Kidney Centre, Munich, Germany. He is also an international scholar at the Population Health Research Institute, McMaster University, Hamilton, Can- ada. He is board-certi ed in internal medicine, nephrology, intensive care, and pharmacology. His work focused initially on the physiology of the RAS in experimental animals and later on the role of this system in the diseases of the kidney and the heart. From there, his interest moved to the treatment of progressive kidney dis- eases. The latter included steering, adjudication, and data safety monitoring board memberships in outcome trials, namely AIPRI, HOPE, MICRO-HOPE, HOPE-TOO, RENAL-ONTARGET, RENAL-TRANSCEND, ASCEND, DIABHYCAR, ORIGIN, LEADER, SONAR, SOUL, FLOW, DAPA-CKD. His scienti c work includes about 270 original papers. Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius Medical Care, Novo Nordisk, and Vifor Fresenius Medical Care Renal Pharma Grant/research support: Boehringer Ingelheim, Canadian Institutes Health Research, European Union, Idorsia, Novo Nordisk, Sandoz, and Sano Speaker bureaus: AstraZeneca, B. Braun, Fresenius Medical Care, Novartis, Novo Nordisk, and Roche Tara I. Chang, MD, MS, is an associate professor of medicine, division chief, and director of clinical research in the Division of Nephrology at Stanford University School of Medicine in Palo Alto, CA, USA.


Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius Medical Care, Novo Nordisk, and Vifor Fresenius Medical Care Renal Pharma Grant/research support: Boehringer Ingelheim, Canadian Institutes Health Research, European Union, Idorsia, Novo Nordisk, Sandoz, and Sano Speaker bureaus: AstraZeneca, B. Braun, Fresenius Medical Care, Novartis, Novo Nordisk, and Roche Tara I. Chang, MD, MS, is an associate professor of medicine, division chief, and director of clinical research in the Division of Nephrology at Stanford University School of Medicine in Palo Alto, CA, USA. She received her medi- cal degree at the University of Michigan before completing her internal medi- cine residency at the University of Cal- ifornia, San Francisco, CA, USA, and her nephrology fellowship at Stanford. Dr. Chang maintains an active clin- ical research program that focuses on improving cardio- vascular outcomes among patients with CKD. Dr. Chang s research projects involve clinical epidemiology and clinical trials. She recently served as a US national leader for the Canagli ozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. Dr. Chang is a member of the KDIGO Executive Committee and is actively involved with the American Society of Nephrology and the US National Kidney Foundation. Her other re- sponsibilities include serving as an associate editor for the American Heart Journal, and as a member of the editorial boards of Kidney360, the Clinical Journal of the American Society of Nephrology, and the Journal of Human Hypertension.


Her other re- sponsibilities include serving as an associate editor for the American Heart Journal, and as a member of the editorial boards of Kidney360, the Clinical Journal of the American Society of Nephrology, and the Journal of Human Hypertension. Consultancy: Bayer, Gilead, Janssen Research and Develop- ment, Novo Nordisk, Tricida, and Vascular Dynamics Advisory boards: AstraZeneca and Fresenius Medical Care Renal Therapies Group Grant/research support: AstraZeneca and Satellite Healthcare www.kidney-international.org biographic and disclosure information William C. Cushman, MD, FAHA, FACP, is the medical director of the Department of Preventive Medicine, and a professor of preventive medicine, medicine, and physiology at the Uni- versity of Tennessee Health Science Center (UTHSC) in Memphis, TN, USA. He was trained at the University of Mississippi School of Medicine in Jack- son, Mississippi, USA. After serving on the faculty there and as staff at the Department of Veterans Affairs (VA) Medical Center, he moved to the UTHSC and the VA in Memphis, Tennessee. He retired from the VA in 2020 to assume his current position at UTHSC. Dr. Cushman is recognized for his expertise in hyperten- sion. He was a VA champion for the 2014 and 2020 US VA/ DoD Hypertension Clinical Practice Guideline committees, and was on the leadership committees for the Joint National Committee (JNC) 7 and JNC 8 US hypertension guidelines. He has participated in the leadership for many National Heart, Lung and Blood Institute, VA, and industry-sponsored clinical trials in hypertension and diabetes. He has authored more than 300 journal article and book chapter publications and has received several awards, including the 2010 VA Clinical Science Research and Development Barnwell Award, the 2017 Inter-American Society of Hypertension Lifetime Achievement Award, and the 2018 American Heart Associa- tion s Council on Hypertension Irvine Page-Alva Bradley Lifetime Achievement Award.


He has authored more than 300 journal article and book chapter publications and has received several awards, including the 2010 VA Clinical Science Research and Development Barnwell Award, the 2017 Inter-American Society of Hypertension Lifetime Achievement Award, and the 2018 American Heart Associa- tion s Council on Hypertension Irvine Page-Alva Bradley Lifetime Achievement Award. Grant/research support: National Institutes of Health* and Eli Lilly* *Monies paid to institution. Susan L. Furth, MD, PhD, is Vice- chair of the Department of Pediatrics, associate Chair for Academic Affairs, and professor of pediatrics and epide- miology at the University of Pennsyl- vania, Philadelphia, PA, USA. She is chief of the nephrology division at Children s Hospital of Philadelphia, Philadelphia, PA, USA. She is the principal investigator of the Chronic Kidney Disease in Children (CKiD) Study, the largest multicenter prospective cohort study of children with CKD ever conducted in North America, now in its 16th year. She also leads the Pediatric Center of Excellence in Nephrology at the Chil- dren s Hospital of Philadelphia. She has authored over 250 publications, and in 2020, she was awarded the Maureen Andrew Mentor Award by the Society for Pediatric Research. Grant/research support: National Institutes of Health* *Monies paid to institution. Fan Fan Hou, MD, PhD, is a nephrologist and professor of medicine at the Southern Medical University in Guangzhou, China. She is an acade- mician of the Chinese Academy of Sciences and a member of the Third World Academy of Sciences. Dr. Hou received her nephrology training at the Brigham and Women s Hospital and Harvard Medical School in Boston, MA, USA. She assumed her current position as chief of nephrology at Nanfang Hos- pital, Southern Medical University, Guangzhou, China in 1999.


She assumed her current position as chief of nephrology at Nanfang Hos- pital, Southern Medical University, Guangzhou, China in 1999. Dr. Hou has been serving as Chair of the National Clinical Research Center for Kidney Disease since 2013. She is currently a councilor of the International Society of Nephrology and an Executive Committee member of KDIGO. Dr. Hou is a clinician scientist with an interest in kidney disease, speci cally the intervention of CKD and mechanisms underlying CKD progression. She had served as a steering committee member of international clinical trials, including ALBUM, SONAR, DAPA-CKD, and principal investigator of several national trials such as ESBARI, ROAD, and CSPPT- CKD. Dr. Hou has published hundreds of papers in peer- reviewed journals such as the New England Journal of Medi- cine, the Journal of the American Medical Association, Nature Medicine, the Journal of the American Society of Nephrology, and Kidney International. Consultancy: AstraZeneca Joachim H. Ix, MD, MAS, received his medical degree from the Uni- versity of Chicago, Pritzker School of Medicine, IL, USA. He trained in internal medicine and nephrology and subsequently joined the faculty at University of California San Francisco, CA, USA. He was recruited to University of California San Diego, CA, USA, in 2007 and has served as chief of the Division of Nephrology-Hypertension at University of Cali- fornia San Diego since 2013. Dr. Ix s research interests broadly focus on the overlap between kidney disease and vascular disease. His work has primarily utilized epidemiologic methods and clinical trials to understand disease patterns that overlap between kidney and vascular disease, and to test novel therapies to improve vascular disease in the kidney patient.


His work has primarily utilized epidemiologic methods and clinical trials to understand disease patterns that overlap between kidney and vascular disease, and to test novel therapies to improve vascular disease in the kidney patient. He is particularly interested in the effects of blood pressure control on kidney disease and its complications and is a principal investigator of an NIH award focused on this topic. He also served as the San Diego Site principal investigator and a member of the CKD working group within the SPRINT trial. Dr. Ix has co-authored over 370 peer-reviewed scienti c papers, has previously served as an associate editor for the Journal of the American Society of Nephrology and Circulation. biographic and disclosure information www.kidney-international.org In 2020, he received the Shaul G. Massry Award from the US National Kidney Foundation. Consultancy: AstraZeneca and Sani t Grants/research support: Baxter International* and National Institutes of Diabetes and Digestive and Kidney Diseases* Travel expenses: American Society of Nephrology and Insti- tute of Medicine *Monies paid to institution. Gregory A. Knoll, MD, MSc, FRCPC, is head of the Division of Nephrology at the Ottawa Hospital and a professor of medicine at the University of Ottawa, Canada. He currently holds the University of Ottawa Chair in Clinical Transplantation Research and is a senior scientist with the Clinical Epidemiology Program of the Ottawa Hospital Research Institute. He completed his nephrology fellowship at the University of Ottawa, followed by a kidney transplant fellowship at the University of Alabama at Bir- mingham, USA. Following this training, he took further graduate work and received a master s degree in epidemi- ology. For over 15 years, he was the medical director of kidney transplantation at the Ottawa Hospital. He assumed his cur- rent position as head of the nephrology division in 2016.


He assumed his cur- rent position as head of the nephrology division in 2016. He is a past president of the Canadian Society of Transplantation. Dr. Knoll is involved in ongoing studies related to cardiac screening in kidney transplant candidates, systematic reviews on immunosuppressive strategies, and measuring quality in transplantation. He was the lead author on the Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. He also served as the Co-Chair of the KDIGO Clinical Practice Guideline on Evaluation and Management of Candidates for Kidney Transplantation. Grant/research support: Canadian Institutes of Health Research* *Monies paid to institution. Paul Muntner, PhD, MHS, FASH, FAHA, is associate dean for research and a professor of epidemiology at the Uni- versity of Alabama at Birmingham (UAB), AL, USA. Additionally, he is the co-director of the UAB Pharmacoepi- demiology and Economics Research Unit. He earned a master s degree in biostatistics and a doctorate in epidemi- ology from the Johns Hopkins University, Baltimore, MD, USA. Since 2015, Dr. Muntner has served as the director for the UAB American Heart Association Strategically Focused Research Network hypertension center. He is the principal investigator on grants from the US National Heart, Lung, and Blood Institute. From 2015 to 2018, he was Vice-chair of the Statistics Committee for the American Heart Association and chaired the 2019 American Heart Association Scienti c Statement on blood pressure measurement. His research has focused on the prevention and treatment of cardiovascular disease and its risk factors. Dr. Muntner has an extensive bibliography in clinical and population hypertension, including over 500 peer-reviewed journal articles.


Dr. Muntner has an extensive bibliography in clinical and population hypertension, including over 500 peer-reviewed journal articles. Consultancy: Amgen Grant/research support: Amgen and National Institutes of Health Roberto Pecoits-Filho, MD, PhD, FASN, FACP, is a senior research sci- entist at Arbor Research Collaborative for Health in Ann Arbor, MI, USA, and a professor of medicine at the Ponti cal Catholic University of Paran in Curi- tiba, Brazil. As a clinician, he has broad activities in internal medicine and nephrology based at the university- af liated hospitals, where he was chief of the Department of Internal Medicine between 2010 and 2016, and the director of the residency program in nephrology from 2013 to 2016. Dr. Pecoits-Filho is the principal investigator for CKDOPPS, a multinational study on practice patterns and outcomes in CKD, and acts as a scien- ti c leader for clinical trials in nephrology with George Clinical, Sydney, Australia. Dr. Pecoits-Filho received his medical degree and trained in internal medicine and nephrology in Curitiba, Brazil, before completing a research nephrology fellowship at the University of Missouri, Columbia, MO, USA, and a PhD from the University of Sao Paulo, Brazil. He was a visiting scholar for extended periods at the Karolinska Institute in Sweden and the George Institute in Australia. He has participated as a principal investigator, regional leader, and on steering com- mittees in multinational clinical trials. Dr. Pecoits-Filho served as a member of the Executive Committee of the ISN (2017 2019), the SONG Initiative (2017 present), and KDIGO (2016 2018). Consultancy: Akebia, AstraZeneca, Fresenius Medical Care, and Novo Nordisk Grant/research support: Fresenius Medical Care* Speaker bureaus: AstraZeneca and Novo Nordisk *Monies paid to institution.


Consultancy: Akebia, AstraZeneca, Fresenius Medical Care, and Novo Nordisk Grant/research support: Fresenius Medical Care* Speaker bureaus: AstraZeneca and Novo Nordisk *Monies paid to institution. Mark J. Sarnak, MD, MS, is chief of the Division of Nephrology at Tufts Medical Center and the Gerald J. and Dorothy R. Friedman Professor of Medicine at Tufts University School of Medicine, Boston, MA, USA. Dr. Sarnak s primary research interest is in cardiovascular disease in CKD. He has also focused on cognitive function, novel biomarkers, and hyper- tension in CKD. Dr. Sarnak s research is funded by the NIH. www.kidney-international.org biographic and disclosure information He is a previous recipient of the Shaul Massry Award from the US National Kidney Foundation. Dr. Sarnak has a long record of national and international leadership positions in nephrology. He was Co-Chair and lead author of a review commissioned by the Kidney Council of the American Heart Association, CKD as a Risk Factor for Cardiovascular Disease. He chaired the subgroup covering CKD patients without diabetes on the previous KDIGO Blood Pressure Guideline. He chaired the Kidney Disease Outcomes Quality Initiative Commentary on the KDIGO Clinical Practice Guideline for Lipid Management in CKD, and most recently, he co-chaired the KDIGO Controversies Conference on Coronary Artery and Valvular Disease in CKD. Dr. Sarnak is a previous recipient of a K24 Midcareer Career Award in Patient-Oriented Research and has men- tored more than 20 research fellows and 9 junior faculty members. He has published more than 350 articles, including more than 85 peer-reviewed, non-review articles, with his mentee as the rst author. His mentees now include professors of medicine and chiefs of divisions of nephrology at other institutions. Consultancy: Akebia*, Bayer, and Cardurion Pharmaceuticals Grant/research support: National Institutes of Health* *Monies paid to institution.


Consultancy: Akebia*, Bayer, and Cardurion Pharmaceuticals Grant/research support: National Institutes of Health* *Monies paid to institution. Sheldon W. Tobe, MD, FRCPC, FRCP, FACP, FAHA, MScCH (HPTE), received his medical de- gree in 1985 from the University of Calgary, Alberta, Canada. Dr. Tobe trained in internal medicine and nephrology at the University of Toronto, Ottawa, Canada. He is a professor of medicine at both the University of Toronto and the Northern Ontario School of Medicine and the Nephrology Postgraduate Fellowship Di- rector at the University of Toronto. Dr. Tobe was previously the director of the nephrology division at Sunnybrook Research Institute. His clinical activities focus on hemodialysis and patients with CKD and hypertension. His main research interests are implementation science for the dissemination of cardiovascular-focused clinical practice guidelines. Dr. Tobe was Chair of the Canadian Hypertension Education Program from 2005 to 2012 and is a Co-Chair of the Canadian Car- diovascular Harmonized National Guidelines Endeavor (C- CHANGE). He also chairs the diabetes subgroup of Hyper- tension Canada s clinical practice guidelines. Dr. Tobe serves on the Board of Directors of the American Society of Hy- pertension Specialists Program. Dr. Tobe has had continuous peer-reviewed funding for 25 years. Dr. Tobe has received many teaching awards and other career distinctions, has published over 150 peer-reviewed articles, and has led and participated in peer-reviewed, investigator-initiated, and multi-centered international research collaborations. Consultancy: AstraZeneca Grant/research support: Bayer* Speaker bureaus: AstraZeneca and Janssen *Monies paid to institution. Charles R.V. Tomson, MA, BM, Bch, DM, FRCP, received his un- dergraduate training at Cambridge and Oxford, UK, and underwent clinical training in Nottingham, Newcastle upon Tyne, and Leicester, UK, before taking up consultant posts at St Barts, Lon- 2014), and Newcastle upon Tyne (2014 2018).


Tomson, MA, BM, Bch, DM, FRCP, received his un- dergraduate training at Cambridge and Oxford, UK, and underwent clinical training in Nottingham, Newcastle upon Tyne, and Leicester, UK, before taking up consultant posts at St Barts, Lon- 2014), and Newcastle upon Tyne (2014 2018). He has authored or coauthored 36 book chapters and over 250 journal articles on a wide range of topics including hypertension, CKD, and cardiovascular complications of kid- ney disease. His involvement in guideline development started with the third edition of the Renal Association Clinical Practice Guidelines. He was a member of the group that produced the KDIGO 2012 Management of Blood Pressure in CKD guide- line. He was a Health Foundation Quality Improvement Fellow at the Institute for Healthcare Improvement in Boston from 2003 to 2004, a placement that led to a keen interest in the translation of evidence into reliable practice and in shared decision-making. He was Chair of the UK Renal Registry (2006 2010), president of the Renal Association (2010 2012), and is a current trustee of Kidney Research UK. He retired from clinical practice in 2018 but returned during the COVID-19 pandemic. Travel: Attendance at a London Hatter Institute meeting organized by The Lancet and University College London with arm s length funding from pharmaceutical companies. KDIGO Chairs Michel Jadoul, MD, received his medi- cal degree in 1983 at the Universit Catholique de Louvain (UCLouvain) in Brussels, Belgium. Dr. Jadoul trained in internal medicine and nephrology under the mentorship of Professor Charles van Ypersele de Strihou. He has served as Chair at the Department of Nephrology of the Cliniques Universitaires Saint-Luc since 2003 and is currently a full clinical professor at UCLouvain.


He has served as Chair at the Department of Nephrology of the Cliniques Universitaires Saint-Luc since 2003 and is currently a full clinical professor at UCLouvain. Dr. Jadoul s clinical activities focus on the follow-up of hemodialysis and CKD patients, and his main research interests include b2-microglobulin amyloid- osis, hepatitis C, and other complications (e.g., falls, bone fractures, sudden death) in hemodialysis patients, as well as cardiovascular complications after kidney transplantation and various causes of kidney disease (e.g., drug-induced). Dr. Jadoul has coauthored over 260 scienti c papers, most of them published in major nephrology journals. He is biographic and disclosure information www.kidney-international.org currently serving as a theme editor of Nephrology Dialysis Transplantation, and he is also a country co-investigator for the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2001 present). In 2008, he received the international distin- guished medal from the US National Kidney Foundation. He was previously a member of the KDIGO Executive Committee (2010 2015) and the ERA-EDTA Council (2013 2016). Presently, Dr. Jadoul is a KDIGO Co-Chair. Consultancy: Astellas*, AstraZeneca*, Merck Sharp & Dohme*, Mundipharma*, and Vifor Fresenius Medical Care Renal Pharma* Expert testimony: Vifor Fresenius Medical Care Renal Pharma* Grants / research support: Amgen*, Janssen-Cilag*, Otsuka*, and Roche* Speaker bureaus: Amgen*, Menarini*, Merck Sharp & Dohme*, Mundipharma, and Vifor Fresenius Medical Care Renal Pharma* Travel: Amgen* and Sano * *Monies paid to institution. Wolfgang C. Winkelmayer, MD, MPH, ScD, is the Gordon A. Cain Chair of Nephrology and professor of medicine at Baylor College of Medicine in Houston, TX, USA. Dr. Winkelmayer received his medical degree (1990) from the Univer- sity of Vienna, Austria, and later earned a Master of Public Health in healthcare management (1999) and a Doctor of Science in health policy (2001) from Harvard University, Cambridge, MA, USA.


Dr. Winkelmayer received his medical degree (1990) from the Univer- sity of Vienna, Austria, and later earned a Master of Public Health in healthcare management (1999) and a Doctor of Science in health policy (2001) from Harvard University, Cambridge, MA, USA. He then spent 8 years on the faculty of Brigham and Women s Hospital and Harvard Medical School, where he established himself as a proli c investigator and leader in the discipline of comparative-effectiveness research as it pertains to patients with kidney disease. From 2009 to 2014, he was the director of clinical research in the Division of Nephrology at Stanford University School of Medicine, Palo Alto, CA, USA. He assumed his current position as chief of nephrology at Baylor College of Medicine in September 2014. His main areas of research interest include comparative effectiveness and safety research of treatment strategies for anemia, as well as of various interventions for cardiovascular disease in patients with kidney disease. Dr. Winkelmayer is a member of the American Society of Clinical Investigation. His clinical passion lies in providing quality kidney care to the predominantly disadvantaged and un(der)insured population in the public safety net health system of Harris County, Texas. Dr. Winkelmayer has authored over 300 peer-reviewed pub- lications, and he has a particular interest in medical pub- lishing. He currently serves as associate editor for the Journal of the American Medical Association, was a co-editor of the American Journal of Kidney Disease from 2007 to 2016, and has been appointed to several other editorial boards of leading nephrology and epidemiology journals. He also volunteers his time toward important initiatives of the American Society of Nephrology (e.g., Public Policy Board), and he joined KDIGO volunteer leadership as an executive committee member in 2015 and has served as its Co-Chair since 2016.


, Public Policy Board), and he joined KDIGO volunteer leadership as an executive committee member in 2015 and has served as its Co-Chair since 2016. Consultancy: Akebia, Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Relypsa, and Vifor Fresenius Medical Care Renal Pharma Methods Chair Marcello Tonelli, MD, SM, MSc, FRCPC, is senior associate dean (clinical research) at the Cumming School of Medicine in Calgary, Alberta, Canada. He is associate vice president (health research) at the University of Calgary. He received his medical degree from the University of Western Ontario, Canada, a Master of Science in epidemiology from Harvard University, Cambridge, MA, USA, and a Master of Science in health policy from Imperial College London, UK. He is a nephrologist and professor at the University of Calgary. Dr. Tonelli has served in the past as president of the Ca- nadian Society of Nephrology, councilor of the ISN, and a member of the KDIGO Executive Committee. Dr. Tonelli is Chair emeritus of the Canadian Task Force for Preventive Health Care, a national panel of experts that makes recom- mendations about preventive health services to Canada s 36,000 family physicians. A unique aspect of Dr. Tonelli s research program includes partnering with regional, provincial, and national decision makers to ensure that the ndings will be used to produce rational health policy. Speaker bureaus: B. Braun* *Monies donated to charity. Evidence Review Team Jonathan C. Craig, MBChB, DipCH, FRACP, M Med (Clin Epi), PhD, Evidence Review Team Director, is an interna- tionally recognized clinician and scientist and holds the position of vice president and executive dean of the College of Medicine & Public Health at Flinders Univer- sity, Adelaide, South Australia.