Blood pressure targets Recommendation 3.1.1: WesuggestthatadultswithhighBPandCKDbetreatedwithatargetsystolicbloodpressure (SBP) of <120 mm Hg, when tolerated, using standardized of ce BP measurement (2B). Practice Point 3.1.1: It is potentially hazardous to apply the recommended SBP target of <120 mm Hg to BP mea- surements obtained in a non-standardized manner. Practice Point 3.1.2: Clinicians can reasonably offer less intensive BP-lowering therapy in patients with very limited life expectancy or symptomatic postural hypotension. 3.2 Treatment with antihypertensive drugs, including RAS inhibitors (RASi) Recommendation 3.2.1: We recommend starting renin-angiotensin-system inhibitors (RASi) (angiotensin-con- verting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB]) for people with high BP, CKD, and severely increased albuminuria (G1 G4, A3) without diabetes (1B). Recommendation 3.2.2: We suggest starting RASi (ACEi or ARB) for people with high BP, CKD, and moderately increased albuminuria (G1 G4, A2) without diabetes (2C). Recommendation 3.2.3: We recommend starting RASi (ACEi or ARB) for people with high BP, CKD, and moderately-to-severely increased albuminuria (G1 G4, A2 and A3) with diabetes (1B). Practice Point 3.2.1: It may be reasonable to treat people with high BP, CKD, and no albuminuria, with or without diabetes, with RASi (ACEi or ARB). Practice Point 3.2.2: RASi (ACEi or ARB) should be administered using the highest approved dose that is tolerated to achieve the bene ts described because the proven bene ts were achieved in trials using these doses. Practice Point 3.2.3: Changes in BP, serum creatinine, and serum potassium should be checked within 2-4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium. Practice Point 3.2.4: Hyperkalemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi.


Practice Point 3.2.4: Hyperkalemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi. Practice Point 3.2.5: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose. Practice Point 3.2.6: Consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure (estimated glomerular ltration rate [eGFR] <15 ml/min per 1.73 m2 ). Practice Point 3.2.7: Mineralocorticoid receptor antagonists are effective for management of refractory hypertension but may cause hyperkalemia or a reversible decline in kidney function, particularly among patients with low eGFR. 3.3. Role of dual therapy with RASi Recommendation 3.3.1: We recommend avoiding any combination of ACEi, ARB, and direct renin inhibitor (DRI) therapy in patients with CKD, with or without diabetes (1B). summary of recommendation statements and practice points www.kidney-international.org Chapter 4: Blood pressure management in kidney transplant recipients (CKD G1T G5T) Practice Point 4.1: Treat adult kidney transplant recipients with high BP to a target BP of <130 mm Hg systolic and <80 mm Hg diastolic using standardized of ce BP measurement (see Recommendation 1.1). Recommendation 4.1: We recommend that a dihydropyridine calcium channel blocker (CCB) or an ARB be used as the rst-line antihypertensive agent in adult kidney transplant recipients (1C). Chapter 5: Blood pressure management in children with CKD Recommendation 5.1: We suggest that in children with CKD, 24-hour mean arterial pressure (MAP) by ABPM should be lowered to 50th percentile for age, sex, and height (2C).


Chapter 5: Blood pressure management in children with CKD Recommendation 5.1: We suggest that in children with CKD, 24-hour mean arterial pressure (MAP) by ABPM should be lowered to 50th percentile for age, sex, and height (2C). Practice Point 5.1: We suggest monitoring BP once a year with ABPM, and monitoring every 3 6 months with stan- dardized auscultatory of ce BP in children with CKD. Practice Point 5.2: In children with high BP and CKD, when ABPM is not available, manual auscultatory of ce BP obtained in a protocol-driven standardized setting targeting achieved SBP <90th percentile for age, sex, and height of normal children is a reasonable approach. Practice Point 5.3: Use ACEi or ARB as rst-line therapy for high BP in children with CKD. These drugs lower proteinuria and are usually well tolerated, but they carry the risk of hyperkalemia and have adverse fetal risks for pregnant women. www.kidney-international.org summary of recommendation statements and practice points Chapter 1: Blood pressure measurement This chapter makes recommendations on how to measure BP among adults aged $18 years with CKD. Please refer to Chapter 5 for details of BP measurement in children. The evidence review for this chapter encompassed only a search for existing systematic reviews on BP measurement in the general population. An independent systematic review was not undertaken by the ERT. Throughout this chapter, standardized of ce BP refers to measurements obtained according to recommended prepa- ration procedures (Figure 21,2 ), regardless of the type of equipment used. In contrast, routine of ce BP refers to measurements obtained without following these recom- mended preparation procedures and is often also called casual of ce BP.


In contrast, routine of ce BP refers to measurements obtained without following these recom- mended preparation procedures and is often also called casual of ce BP. Once the appropriate preparations for standardized of ce BP have been made, BP may be measured by an automated oscillometric device or manually using an auscultatory method. An oscillometric BP device may be preferable to a manual BP device for standardized of ce BP measurement (see Practice Point 1.1.), but the main emphasis is on the importance of measuring BP according to recommended preparation procedures (Figure 2). Manual BP may be measured with either a mercury or aneroid sphygmoma- nometer. However, aneroid devices require frequent calibra- tion: every 6 months for wall-mounted and every 2 4 weeks for handheld devices.3,4 Oscillometric devices generally require less-frequent calibration (e.g., every 1 2 years, based on manufacturer recommendations), than aneroid devices.3 1 Have the patient relax, sitting in a chair (feet on floor, back supported) for > 5 min 2 The patient should avoid caffeine, exercise, and smoking for at least 30 min before measurement 3 Ensure patient has emptied his/her bladder 4 Neither the patient nor the observer should talk during the rest period or during the measurement 5 Remove all clothing covering the location of cuff placement 6 Measurements made while the patient is sitting or lying on an examining table do not fulfill these criteria 1 Use a BP measurement device that has been validated, and ensure that the device is calibrated periodically 2 Support the patient s arm (e.g.


, every 1 2 years, based on manufacturer recommendations), than aneroid devices.3 1 Have the patient relax, sitting in a chair (feet on floor, back supported) for > 5 min 2 The patient should avoid caffeine, exercise, and smoking for at least 30 min before measurement 3 Ensure patient has emptied his/her bladder 4 Neither the patient nor the observer should talk during the rest period or during the measurement 5 Remove all clothing covering the location of cuff placement 6 Measurements made while the patient is sitting or lying on an examining table do not fulfill these criteria 1 Use a BP measurement device that has been validated, and ensure that the device is calibrated periodically 2 Support the patient s arm (e.g., resting on a desk) 3 Position the middle of the cuff on the patient s upper arm at the level of the right atrium (the midpoint of the sternum) 4 Use the correct cuff size, such that the bladder encircles 80% of the arm, and note if a larger- or smaller-than-normal cuff size is used 5 Either the stethoscope diaphragm or bell may be used for auscultatory readings 1 At the first visit, record BP in both arms. Use the arm that gives the higher reading for subsequent readings 2 Separate repeated measurements by 1 2 min 3 For auscultatory determinations, use a palpated estimate of radial pulse obliteration pressure to estimate SBP. Inflate the cuff 20 30 mm Hg above this level for an auscultatory determination of the BP level 4 For auscultatory readings, deflate the cuff pressure 2 mm Hg per second, and listen for Korotkoff sounds 1 Record SBP and DBP.


Inflate the cuff 20 30 mm Hg above this level for an auscultatory determination of the BP level 4 For auscultatory readings, deflate the cuff pressure 2 mm Hg per second, and listen for Korotkoff sounds 1 Record SBP and DBP. If using the auscultatory technique, record SBP and DBP as onset of the first Korotkoff sound and disappearance of all Korotkoff sounds, respectively, using the nearest even number 2 Note the time of most recent BP medication taken before measurements Use an average of 2 readings obtained on 2 occasions to estimate the individual s level of BP Provide patients with the SBP/DBP readings verbally and in writing Properly prepare the patient Use proper technique for BP measurements Take the proper measurements needed for diagnosis and treatment of elevated BP Properly document accurate BP readings Average the readings Provide BP readings to patient Figure 2 | Checklist for standardized of ce blood pressure measurement. BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure. Modi cation for pediatrics: BP in infants should be taken while supine and the use of the bell is recommended.1 Reprinted from the Journal of the American College of Cardiology, Volume 71, Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, Pages e127 e248, 2018 with permission from the American College of Cardiology Foundation and the American Heart Association, Inc.2 chapter 1 www.kidney-international.org Some oscillometric devices can be programmed to auto- matically provide a period of rest followed by multiple BP readings with a single activation, a method known as auto- mated of ce BP (AOBP).


2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, Pages e127 e248, 2018 with permission from the American College of Cardiology Foundation and the American Heart Association, Inc.2 chapter 1 www.kidney-international.org Some oscillometric devices can be programmed to auto- matically provide a period of rest followed by multiple BP readings with a single activation, a method known as auto- mated of ce BP (AOBP). AOBP can be performed either with the patient alone (i.e., unattended) or with a healthcare provider/technician present (i.e., attended), whereas the other of ce BP methods all require a healthcare provider to be present to perform the measurement. We suggest that AOBP is the preferred method of standardized of ce BP measure- ment (see Practice Point 1.2), but we have no preference for unattended versus attended measurement. Recommendation 1.1: We recommend standardized of ce BP measurement in preference to routine of- ce BP measurement for the management of high BP in adults (1B). This recommendation places a relatively higher value on con- sistency with the BP measurement methods used to de ne BP targets in prior large clinical outcome trials. It also places a higher value on avoidance of misclassi cation to prevent over- treatment or undertreatment of high BP. This recommendation places a lower value on the increased burden to patients, pro- viders, and staff. This recommendation is strong because, in the Work Group s opinion, the importance of of ce BP measured using a standardized versus a routine, non-standardized approach outweighs any potential burden to its implementation. Key information Balance of bene ts and harms.


This recommendation is strong because, in the Work Group s opinion, the importance of of ce BP measured using a standardized versus a routine, non-standardized approach outweighs any potential burden to its implementation. Key information Balance of bene ts and harms. This recommendation relies heavily on the importance of standardized of ce BP mea- surement protocols that are consistent with large randomized controlled trials (RCTs) with clinically important outcomes that have been used to de ne BP targets. Standardized of ce BP measurements allow for extrapolation of the RCT ndings to clinical practice and avoid overtreatment or undertreat- ment of high BP that may occur if non-standardized mea- surements are used. The negative aspects of standardized of ce BP measurement, including the increased burden on patient, provider, staff time, and clinic space, are outweighed by the bene ts. Quality of evidence. There is moderate-quality evidence that routine of ce BP is generally, but not invariably, higher than standardized of ce BP, regardless of whether manual or oscillometric devices are used. However, there is strong evidence that the relationship between routine of ce BP and standardized of ce BP is highly variable among individuals. Thus, it is not possible to apply a correction factor to translate a given routine BP value to standardized of ce BP. Values and preferences. Appropriate BP management re- quires proper BP measurements. All large randomized BP outcome trials used standardized of ce BP measurements. In the opinion of the Work Group, the importance of measuring BP in a manner that is consistent with the RCTs far outweighs the additional burdens and costs for providers, staff, and patients. Increased costs are due to personnel and clinic time utilization.


Increased costs are due to personnel and clinic time utilization. Routine of ce BP measurements are generally higher than standardized of ce BP measurements.5,6 Therefore, the use of routine of ce BP measurements for BP management could lead to overtreatment of BP and possibly result in a higher incidence of hypotension-related adverse events. Conversely, for some persons for whom routine of ce BP is lower than standardized of ceBP,useofroutineof ceBPcouldleadtoundertreatmentof high BP and result in a higher risk of future cardiovascular (CV) events. Routine and standardized BP measurements have poor agreement, including those in the CKD population.5,6 It is therefore not possible to convert a routine of ce BP into a standardized of ce BP using a correction factor in an individual. Thus, in the opinion of the Work Group, most well-informed patients would accept the additional time required for stan- dardized of ce BP measurement. Resource use and costs. Standardized of ce BP does not necessarily require additional equipment beyond the existing BP measurement devices. However, standardized of ce BP takes longer to perform than routine of ce BP, given the need to follow proper preparatory procedures (Figure 2). There- fore, there may be an increased time burden on patients, providers, and staff. This approach also requires staff training and retraining to ensure that a standardized BP measurement approach is followed. Adequate access to a quiet clinic space that allows for an adequate rest period prior to BP mea- surement may also be an issue in certain settings. However, in the opinion of the Work Group, this recommendation is likely to be cost-effective as it may avert consequences of over- treatment and undertreatment, though an economic analysis has not been published. Considerations for implementation.


However, in the opinion of the Work Group, this recommendation is likely to be cost-effective as it may avert consequences of over- treatment and undertreatment, though an economic analysis has not been published. Considerations for implementation. The use of standardized of ce BP over routine of ce BP holds true for all patients, regardless of age, sex, race, or CKD severity. Rationale This chapter is an addition since the KDIGO 2012 BP guide- line. This recommendation places a relatively higher value on consistency with BP measurement methods used in prior outcome trials examining different BP targets, and on mini- mizing overtreatment or undertreatment of BP that may result from routine, non-standardized of ce BP measurements. This recommendation places a lower value on the increased time required to perform standardized BP measurements. This recommendation is consistent with other recent guidelines that also underscore the importance of standard- ized of ce BP measurement (e.g., American College of Car- diology [ACC]/American Heart Association [AHA],2,7 and European Society of Cardiology [ESC]8 ). Practice Point 1.1: An oscillometric BP device may be preferable to a manual BP device for standardized of ce BP measurement; however, standardization emphasizes adequate preparations for BP measurement, not the type of equipment. www.kidney-international.org chapter 1 Oscillometric BP devices may be preferred over manual BP devices, as the former minimizes potential sources of inac- curacies in BP measurements that can occur with human errors associated with manual BP measurement such as those resulting from hearing impairment, an improper de ation rate, or terminal-digit bias.9 Manual BP devices are also acceptable when oscillometric devices are unavailable. The main emphasis is on the importance of obtaining standardized BP measurements that are made ac- cording to recommended preparation procedures (Figure 2).


The main emphasis is on the importance of obtaining standardized BP measurements that are made ac- cording to recommended preparation procedures (Figure 2). RCTs and prospective cohort studies used standardized of ce BP measured with either oscillometric (in newer studies) or manual devices (in older studies; Figure 310 13 ). Studies that directly compared standardized of ce BP measured using an oscillometric device versus a manual de- vice do not suggest overt differences in readings between these 2 types of devices (Supplementary Table S414 16 ). Moreover, all BP measurement devices are validated and calibrated against mercury sphygmomanometers, so they would be ex- pected to give similar BP readings. Therefore, BP levels from trials that have used different types of standardized of ce BP measurements should, in general, be comparable. The negative aspects of oscillometric BP devices are the potentially higher cost of the device compared with a manual device, the requirement of an electric power source, and lack of availability in some settings. In choosing a device, one that has been validated for accuracy and precision against a mer- cury sphygmomanometer should be selected. Several national medical or hypertension associations have established a vali- dated device listing that has information on oscillometric devices that are suitable for use.17 19 Providers working in areas where oscillometric BP devices are not available may use a manual BP device, but proper calibration of these BP de- vices is required as noted above. Regardless of the type of BP device used, proper prepa- ration and BP measurement techniques are paramount (Figure 2). Practice Point 1.2: Automated of ce BP (AOBP), either attended or unattended, may be the preferred method of standardized of ce BP measurement.


Practice Point 1.2: Automated of ce BP (AOBP), either attended or unattended, may be the preferred method of standardized of ce BP measurement. In the opinion of the Work Group, AOBP may increase the likelihood of adherence to proper preparation measures, as the AOBP devices can be programmed to include a rest period. AOBP devices can also automatically take multiple BP measurements and provide an average BP measurement. Thus, BP measured with AOBP can be either attended (i.e., with a healthcare provider in the room) or unattended (i.e., without a provider in the room). Although a recent meta- analysis suggested that unattended AOBP measurements result in lower average BPs than attended measurements,20 the differences were notably small when restricted to studies that randomized the order in which unattended and attended standardized measurements were made.18,21 25 Several large trials, including Systolic Blood Pressure Intervention Trial (SPRINT), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), and Action to Control Cardiovascular Risk in Diabetes (ACCORD), used AOBP as the BP measurement method (Figure 3). Of note, the SPRINT protocol did not specify whether AOBP should be performed while attended or unattended.


Of note, the SPRINT protocol did not specify whether AOBP should be performed while attended or unattended. A post hoc analysis of SPRINT data found that while a majority of sites did perform unattended AOBP, many performed attended AOBP or some combination of Study Method/device Type of study Year Framingham MDRD UKPDS AASK ADVANCE CRIC ACCORD ONTARGET CKD JAC SPRINT Population General ) ) ) Recent lacunar stroke (baseline eGFR 80 ; 16% CKD) CVD or T2D (baseline SCr 1.05 mg/dl [93 mol/l]; ) ) High CVD risk (baseline SCr 1.07 mg/dl [95 mol/l]; ) Observational Clinical trial Clinical trial Clinical trial Clinical trial Observational Clinical trial Clinical trial Clinical trial Observational Clinical trial Manual Manual Automated Manual Manual Manual and automated Automated/Omron Automated/Colin electronic device Automated/Omron Manual Automated/Omron Figure 3 | Blood pressure measurement method and device used in select RCTs and prospective observational studies. AASK, African American Study of Kidney Disease and Hypertension; ACCORD, Action to Control Cardiovascular Risk in Diabetes; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modi ed Release Controlled Evaluation; CKD-JAC, Chronic Kidney Disease Japan Cohort; CRIC, Chronic Renal Insuf ciency Cohort; MDRD, Modi cation of Diet in Renal Disease; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; SPRINT, Systolic Blood Pressure Intervention Trial; SPS3, Secondary Prevention of Small Subcortical Strokes Trial; UKPDS, United Kingdom Prospective Diabetes Study. Adapted with modi cations with permission of the American Society of Nephrology from BP measurement in clinical practice: time to SPRINT to guideline-recommended protocols. Drawz PE, Ix JH, volume 29, Copyright 2018, permission conveyed through Copyright Clearance Center, Inc.10 ONTARGET was published in 2008.11 The BP measurement approach used in the trial was subsequently published in the 2012 article referenced above.


Drawz PE, Ix JH, volume 29, Copyright 2018, permission conveyed through Copyright Clearance Center, Inc.10 ONTARGET was published in 2008.11 The BP measurement approach used in the trial was subsequently published in the 2012 article referenced above. de Galan et al.12 Peralta et al.13 CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular ltration rate; RCT, randomized controlled trial; SCr, serum creatinine; T2D, type 2 diabetes. chapter 1 www.kidney-international.org unattended and attended measurements.26 Nonetheless, similar BP levels and CV disease risk reduction were observed in the intensive group in SPRINT participants, whether the measurement technique used was primarily attended or unattended. Unattended AOBP measurements may have some practical advantages over attended standardized BP measurements, such as discouraging talking by the patients and freeing clinic staff to complete other duties during the BP measurement process. Practice Point 1.3: Oscillometric devices can be used to measure BP among patients with atrial brillation. It is a misperception that oscillometric devices do not measure BP accurately among patients with atrial brillation. Prior studies comparing BP measured using oscillometric devices versus auscultatory techniques suggest that oscillo- metric devices provide a valid systolic BP (SBP) assessment in patients with atrial brillation.27 Although oscillometric de- vices may be less accurate for estimating diastolic BP (DBP) than auscultatory techniques, the population with atrial brillation is, on average, older, and the emphasis in older adults has been on SBP.28 Recommendation 1.2: We suggest that out-of-of ce BP measurements with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) be used to complement standardized of ce BP readings for the management of high BP (2B). This recommendation places a relatively higher value on detecting a potential difference in BP status based on of ce versus out-of-of ce BP (Figure 4).


This recommendation places a relatively higher value on detecting a potential difference in BP status based on of ce versus out-of-of ce BP (Figure 4). In the judgment of the Work Group, the potential bene ts of additional information obtained from out-of-of ce BP measurements outweigh the additional costs and increased patient burden that these measurements impose. We suggest using an initial ABPM to supplement standardized of ce BP and HBPM for ongoing management of BP. Although ABPM may be the better measurement method, HBPM is more prac- tical for routine out-of-of ce assessment. HBPM may be particularly important for the management of BP when a clinic visit is not practical, for example, in the coronavirus disease 2019 (COVID-19) pandemic. For individuals not taking antihyper- tensive medication identi ed as having white-coat hyperten- sion, annual out-of-of ce BP assessments may be useful. For individuals taking antihypertensive medication, 1 week of daily HBPM prior to each of ce visit may be useful to complement standardized of ce BP for clinical management decisions. This is a weak recommendation according to GRADE, since there are no large RCTs comparing the effects of lower versus higher BP goals on clinical outcomes in adults that used out-of-of ce measurements to guide the BP intervention. Hence, the BP target using out-of-of ce measurements is unknown. Furthermore, it may not be feasible to implement ABPM and HBPM in many settings. Providers working in areas where ABPM is not available may choose to use HBPM instead of an initial ABPM procedure. Patients who nd ABPM and HBPM to be uncomfortable and inconvenient may prefer not to use such devices. Key information Balance of bene ts and harms.


Patients who nd ABPM and HBPM to be uncomfortable and inconvenient may prefer not to use such devices. Key information Balance of bene ts and harms. This recommendation places a relatively higher value on assessing a patient s broader BP pro le than relying solely on standardized of ce BP mea- surements. Observational studies indicate that the diagnosis of high BP and BP control status differs for a high proportion of adults when BP is measured in the of ce versus outside the of ce, which can lead to detection of masked hypertension, masked uncontrolled hypertension, white-coat hyperten- sion, and the white-coat effect (Figure 4). Further, obser- vational studies indicate a stronger association of out-of-of ce BP measurements with CV and kidney outcomes than of ce BP measurements in the general population and CKD.29 31 Masked hypertension and masked uncontrolled hyper- tension are present among 9% 30% of adults without high BP based on of ce measurements and are associated with higher risk for CV disease and kidney outcomes compared with sustained normotension and sustained controlled hy- pertension, respectively. White-coat hypertension and the white-coat effect are present among 15% 30% of adults with high BP based on of ce measurements. In a recent meta- analysis, white-coat hypertension was associated with a Not taking antihypertensive medication White-coat hypertension Sustained hypertension Normotension Masked hypertension Hypertension based on standardized office BP Hypertension based on out-of-office BP Yes Yes No No Taking antihypertensive medication White-coat effect Sustained uncontrolled hypertension Sustained controlled hypertension Masked uncontrolled hypertension Hypertension based on standardized office BP Hypertension based on out-of-office BP Yes Yes No No Figure 4 | Blood pressure patterns informed by out-of-of ce blood pressure measurements in addition to standardized of ce blood pressure measurement.


In a recent meta- analysis, white-coat hypertension was associated with a Not taking antihypertensive medication White-coat hypertension Sustained hypertension Normotension Masked hypertension Hypertension based on standardized office BP Hypertension based on out-of-office BP Yes Yes No No Taking antihypertensive medication White-coat effect Sustained uncontrolled hypertension Sustained controlled hypertension Masked uncontrolled hypertension Hypertension based on standardized office BP Hypertension based on out-of-office BP Yes Yes No No Figure 4 | Blood pressure patterns informed by out-of-of ce blood pressure measurements in addition to standardized of ce blood pressure measurement. www.kidney-international.org chapter 1 modest increased risk for CV disease, compared to sustained However, this risk was substantially lower than the risk for participants with sustained hypertension.31 Additionally, the white-coat effect was not associated with increased risk for CV disease when compared to the risk for people with sustained controlled hypertension.29 The prevalences of white-coat hypertension, masked hypertension, the white-coat effect, and masked uncon- trolled hypertension are each high among patients with Identi cation of white-coat hypertension and masked hypertension for patients not taking antihypertensive medication, and the white-coat effect and masked uncon- trolled hypertension for patients taking antihypertensive medication may have potential treatment implications (see Rationale section). However, it remains to be determined whether initiation of antihypertensive medication among patients with white-coat hypertension and masked hyper- tension, or intensi cation of antihypertensive medication among patients with the white-coat effect and masked uncontrolled hypertension improves outcomes (see Research Recommendations). This recommendation places a relatively lower value on the potential lack of device availability, costs, and patient and staff burden. Quality of evidence.


This recommendation places a relatively lower value on the potential lack of device availability, costs, and patient and staff burden. Quality of evidence. There are systematic reviews in the general population showing that high out-of-of ce BP is associated with CV disease risk independent of of ce BP.36 Although there are no systematic reviews in CKD patients, the results from individual studies in CKD are generally consistent with the general population data in that BP differs when measured outside the of ce versus in the of ce setting, and out-of-of ce readings provide additional prognostic Therefore, there is no reason to suspect that ndings in the general population would not apply to patients with CKD also. The systematic reviews and meta- analyses of general population studies provide moderate- quality evidence because of the inherent limitations of observational studies, but the evidence quality is upgraded from low because of the strength of associations of out-of- of ce BP measurements with critically important outcomes. However, no single outcome trial targeting out-of-of ce BP has been reported so far in CKD populations. Values and preferences. This recommendation places a relatively higher value on providing complementary infor- mation to standardized of ce BP that may affect clinical de- cisions. There is a modest correlation between BP measured in the of ce and outside of the of ce using ABPM or HBPM. However, these BP measurements should not be considered interchangeable. Importantly, there have been no large RCTs with clinical outcomes using ABPM or HBPM to de ne BP targets. Therefore, at present, ABPM and HBPM cannot be used alone to guide therapy. The recommendation places a relatively lower value on the potential lack of device avail- ability, costs, and patient burden.


The recommendation places a relatively lower value on the potential lack of device avail- ability, costs, and patient burden. In the opinion of the Work Group, many but not all patients and providers will value the information provided by ABPM and HBPM. Prior studies have found that a majority of patients prefer HBPM to ABPM. HBPM has been reported by patients to result in fewer disturbances in their daily activities and to be more comfortable than ABPM.37 39 The Work Group recognizes that some patients will nd both ABPM and HBPM to be uncomfortable and/or inconvenient, and such patients may choose to forgo measurement using these devices. Resource use and costs. This recommendation stems from studies showing that ABPM is cost-saving and cost-effective for the management of high BP in the general population. Although studies were not conducted in CKD, there is no reason to expect that the cost-savings would be any different in the CKD population.40,41 In contrast, the cost- effectiveness of HBPM for management of high BP is Persons with limited nancial resources, or those treated in health systems where ABPM and HBPM are less available or affordable, may be less inclined to follow this recommendation. Consideration for implementation. The use of ABPM or HBPM will depend on the resources available. Staff should be trained to conduct ABPM and to teach patients proper HBPM techniques. This recommendation holds true for all patients, regardless of age, sex, race, or CKD severity.


This recommendation holds true for all patients, regardless of age, sex, race, or CKD severity. ABPM requires recalibration every 1 2 years, based on There are no standardized protocols for calibrating HBPM devices; however, when it is suspected that home measurements are inaccurate, providers should ask their patients to bring their HBPM device to the of ce to compare BP values on these devices with those ob- tained from a calibrated device.42 Rationale This recommendation places a high value on informing an individual s overall BP pro le and identifying persons with high CV disease risks related to high BP. This recommenda- tion places a relatively lower value on the potential lack of device availability, cost, and patient burden. Observational studies indicate that the diagnosis of high BP and BP control status differs for a high proportion of adults when BP is measured in the of ce versus outside the of ce. Also, observational studies indicate a stronger associ- ation of out-of-of ce BP measurements with CV and kidney outcomes than of ce BP measurements in the general pop- ulation and CKD. Identi cation of white-coat hypertension, masked hy- pertension, the white-coat effect, and masked uncontrolled hypertension has potential treatment implications. Antihy- pertensive medication initiation and intensi cation may be considered for patients with substantial masked hypertension and masked uncontrolled hypertension, respectively, whereas for those with substantial white-coat hypertension and the white-coat effect the choice may be made to defer initiation and defer intensi cation of antihypertensive medication, respectively, especially in individuals with symptoms associ- ated with documented out-of-of ce hypotension. However, the Work Group acknowledges the lack of RCTs that chapter 1 www.kidney-international.org speci cally address whether and how best to treat BP pro les identi ed by out-of-of ce BP measurements.


However, the Work Group acknowledges the lack of RCTs that chapter 1 www.kidney-international.org speci cally address whether and how best to treat BP pro les identi ed by out-of-of ce BP measurements. HBPM also has the advantage of empowering individuals to take ownership of their medical care, hence promoting adherence to therapy. Research recommendations There are several areas in which more research is needed speci cally for the CKD population:  Identify if procedures for standardized BP measurement can be simpli ed, such as using a shorter rest period (e.g., 1 or 2 minutes) or a shorter interval between BP measure- ments (e.g., 15 or 30 seconds).  Compare standardized unattended versus standardized attended AOBP in routine clinical practice.  Determine the optimal interval for repeating ABPM and HBPM among individuals not taking and taking antihy- pertensive medications.  Determine the proportion of CKD patients with white- coat hypertension, masked hypertension, the white-coat effect, and masked uncontrolled hypertension using a BP threshold of 120 mm Hg instead of 140 mm Hg, and whether these phenotypes are associated with increased risk for CV disease.  Assess the cost-effectiveness of ABPM and HBPM, sepa- rately, for identifying white-coat hypertension, masked hypertension, the white-coat effect, and masked uncon- trolled hypertension.  Conduct RCTs comparing treatment based on ABPM or HBPM versus standardized of ce BP measurements. Treatment based on ABPM or HBPM includes not treating patients with white-coat hypertension, not intensifying treatment for the white-coat effect, treatment of masked hypertension, and intensifying treatment for masked un- controlled hypertension.


Treatment based on ABPM or HBPM includes not treating patients with white-coat hypertension, not intensifying treatment for the white-coat effect, treatment of masked hypertension, and intensifying treatment for masked un- controlled hypertension. www.kidney-international.org chapter 1 Chapter 2: Lifestyle interventions for lowering blood pressure in patients with CKD not receiving dialysis 2.1 Sodium intake Recommendation 2.1.1: We suggest targeting a sodium intake <2 g of sodium per day (or <90 mmol of sodium per day, or <5 g of sodium chloride per day) in patients with high BP and CKD (2C). This recommendation places a relatively high value on data from both the CKD population and the general population demon- strating that reductions in dietary sodium intake induce short- term reductions in BP and other evidence suggesting that these bene ts will reduce the need for antihypertensive medications. The Work Group placed lower value on the limited available data evaluating the effects of dietary sodium intake on clinical outcomes, including kidney failure, mortality, and CV disease endpoints in CKD patients. The recommendation is weak ac- cording to GRADE because of the low-quality evidence sup- porting the bene ts of low-sodium intake speci cally in the hypertensive CKD population; yet, many well-informed patients would agree to follow the guidance. This represents a change from the recommendation (1C) in the 2012 guideline based on the opinion of the current Work Group members, but it is consistent with the KDIGO 2020 Guideline for the Management of Patients with Diabetes and CKD. Key information Balance of bene ts and harms. In most populations worldwide, estimated average sodium intake is much higher than the proposed target of sodium intake <2 g (<90 mmol) per day for the general population.


In most populations worldwide, estimated average sodium intake is much higher than the proposed target of sodium intake <2 g (<90 mmol) per day for the general population. Recent meta-analyses of RCTs in non-CKD populations demonstrate a graded bene t in both BP and CV disease risk reduction with reductions in sodium intake. Importantly, even more- modest reductions in sodium intake that did not reach the <2 g per day target were associated with these Indeed, achieved mean sodium intake typically was in the 3.0 3.5 g/d range, and the low target of <2 g/d was reached in few participants. In CKD populations, this recommendation is driven by short-term studies of moderate- quality evidence evaluating SBP and DBP, but not CV events, as endpoints. It is unknown whether sodium intakes far below 2 g per day are safe or not. The Work Group notes that there are instances in which recommendations in the general population may not apply to the CKD population. For example, rarely, CKD patients may have salt-wasting kidney disease in which case this recom- mendation may not apply. In some instances, salt substitutes are used for the purpose of maintaining food-taste prefer- ences in people practicing dietary sodium restriction. These substitutes often replace sodium with potassium salts. Clinical trials of potassium-containing salt substitutes systematically exclude patients with CKD, so bene ts and harms of potassium-containing salt substitutes in CKD are not avail- able. Potassium-containing salt substitutes differ from foods rich in potassium, as such foods may have other health bene ts, thus extrapolating data from potassium intake in the diet may not be informative to potassium-containing salt substitutes.


Potassium-containing salt substitutes differ from foods rich in potassium, as such foods may have other health bene ts, thus extrapolating data from potassium intake in the diet may not be informative to potassium-containing salt substitutes. Although there is still controversy about the risk bene t ratio of potassium intake, observational studies often found that a higher potassium intake may be associated with a lower risk for all-cause death, CV disease, and CV death. However, at advanced stages of CKD (G4 and G5), a high potassium intake may be associated with higher risk.44 46 The Work Group suggests caution in using potassium-containing salt substitutes in CKD populations, especially in those with advanced CKD, hyporeninemic hypoaldosteronism, or hyperkalemia from other causes until more data on the safety and ef cacy of their use in CKD become available (see Practice Point 2.1.2). Quality of evidence. The Cochrane systematic reviews upda- ted for this guideline found low-to-moderate-quality evidence demonstrating that dietary sodium reduction results in short- term reductions in BP in CKD populations.47,48 This was evident for both SBP and DBP in CKD without diabetes (moderate; Supplementary Table S549 58 ); Type 1 diabetes (T1D) and CKD (low; Supplementary Table S659 63 ); Type 2 diabetes (T2D) and CKD (low; Supplementary Table S764 69 ); and diabetes and severely increased albuminuria (low; Supplementary Tables S8 and S9,63,66,68,69 ). These data were considered in the context of a substantial body of evidence con rming short-term bene ts in SBP and DBP reduction in the general population.


These data were considered in the context of a substantial body of evidence con rming short-term bene ts in SBP and DBP reduction in the general population. In the general population, the magnitude of BP lowering may be greater in persons with high BP, which is more prevalent in CKD patients.43 There is also moderate strength of evidence from sys- tematic reviews that lowering of sodium intake reduces CV disease in the general population.43 The systematic review conducted for this guideline found no RCT data evaluating the effects of dietary sodium reduction on clinical outcomes, including kidney failure (formerly known as end-stage kidney disease [ESKD]), CV disease, or mortality in CKD pop- ulations. However, the Work Group agrees that there is no reason to believe that the epidemiologic ndings in the gen- eral population would be different in CKD populations. chapter 2 www.kidney-international.org Further, persons with CKD frequently take angiotensin- converting enzyme inhibitors (ACEi) or angiotensin II re- ceptor blockers (ARB) compared to non-RASi therapy, and the kidney and CV bene ts of these medications may be enhanced if accompanied by a low-sodium diet compared to a Values and preferences. This recommendation places a relatively high value on the bene ts of using a non- pharmacologic method to lower BP and minimize additional medications. The recommendation places a relatively high value on data from the general population, demonstrating that reductions in dietary sodium intake induce short-term reductions in BP, and other evidence suggests that these bene ts likely extend to people with CKD. The Work Group placed lower value on the limited available data evaluating the effects of dietary sodium reduction on clinical outcomes, including kidney failure, mortality, and CV disease endpoints in CKD patients.


The Work Group placed lower value on the limited available data evaluating the effects of dietary sodium reduction on clinical outcomes, including kidney failure, mortality, and CV disease endpoints in CKD patients. The Work Group also considered the secondary bene ts of dietary sodium reduction in reducing pill burden and medication-related side effects. However, in the judgment of the Work Group, some individuals may prefer additional medications to the burden and decreased palatability of foods when following a low-sodium diet. Although forti ed salt is an important treatment for iodine de ciency in some countries, the Work Group judged that the bene ts of implementing this recommendation in CKD patients likely outweigh its risks. The recommendation is weak because, in controlled trials, only a minority of patients reached a target intake of <2 g (<90 mmol) of sodium per day, and effects on important clinical outcomes in CKD are uncertain. However, the Work Group believes that the bene ts of the recommendation likely exceed the harms and that many well-informed patients would try to follow the advice. Resource use and costs. Processed foods are generally higher in salt and often are less expensive than fresh food alterna- tives. Yet, a higher sodium intake associated with processed foods is likely to necessitate additional antihypertensive medications, greater pill burden, and associated healthcare costs. The Work Group also recognizes that, although feasible, following a low-sodium diet is challenging in many Western food environments. However, this recommendation may not only bene t individual patients, but also may in uence public health interventions and policymakers to consider targeting reductions of sodium in the food supply.


However, this recommendation may not only bene t individual patients, but also may in uence public health interventions and policymakers to consider targeting reductions of sodium in the food supply. Although this may require buy-in from key stakeholders, policy changes, and investment of public health resources, the Work Group believes that the health bene ts of such changes are also likely to be experienced by a wider population than those with CKD alone. Considerations for implementation. This recommendation places high value on evidence linking short-term changes in sodium intake with reductions in BP in CKD populations, and extrapolation of long-term bene ts from the general population. Although there is limited evidence from RCTs about the long-term bene ts or harms of sodium reduction in CKD populations per se, the Work Group agrees, with few exceptions, that there is little evidence or likelihood that health bene ts observed in the general population should not apply to CKD patients. On the contrary, there is reason to believe that the health bene ts of dietary sodium reduction may be particularly bene cial in CKD patients. Persons with CKD are commonly hypertensive, and systematic reviews have suggested that the magnitude of BP reduction for a given degree of reduction in dietary sodium intake is magni ed in hypertensive individuals, particularly if usual sodium intake is high.43 CKD populations also have high risk of CV disease and may therefore have a greater absolute risk reduction of such events with dietary sodium reduction, if the relative bene ts in the general population are indeed applicable to CKD.


Persons with CKD are commonly hypertensive, and systematic reviews have suggested that the magnitude of BP reduction for a given degree of reduction in dietary sodium intake is magni ed in hypertensive individuals, particularly if usual sodium intake is high.43 CKD populations also have high risk of CV disease and may therefore have a greater absolute risk reduction of such events with dietary sodium reduction, if the relative bene ts in the general population are indeed applicable to CKD. Finally, ACEi and ARBs are commonly used in CKD patients, and post hoc analyses of RCTs demonstrate that low-sodium intake may enhance the effects of these medications on kidney and CV outcomes.70 The Work Group agrees that decreasing dietary sodium intake is likely to also be appropriate in children with CKD, albeit with modi ed targets. Speci c targets are not available from prior studies for children with CKD, but the Work Group believes that adjusting the <2 g (<90 mmol) daily target for body weight in children would be reasonable.71 The Work Group considered the speci c target of sodium intake of <2 g (<90 mmol) daily and found no evidence showing different health bene ts or harms at different sodium intake targets in CKD populations per se. Existing interven- tion studies targeting BP in CKD populations typically targeted <2 g or <2.3 g daily in the low-sodium arms, which are similar to targets recommended for the general popula- Therefore, the present guideline was created in the absence of data suggesting superiority or inferiority of other targets in CKD populations. Further, for concordance across guidelines from various organizations that might facilitate policy decisions, Work Group members agree a target of <2.0 g per day should be recommended for CKD populations.


Further, for concordance across guidelines from various organizations that might facilitate policy decisions, Work Group members agree a target of <2.0 g per day should be recommended for CKD populations. Rationale This recommendation places a relatively higher value on studies in CKD populations demonstrating that short-term dietary sodium reduction interventions lower BP, and consistency with ndings of similar interventions in the general population. The recommendation also places a higher value on dietary sodium- reduction strategies as a readily available, non-pharmacologic intervention to lower BP in CKD populations. Relatively lower value was placed on the challenges in following a low-sodium diet in many current food environments. This recommenda- tion is made despite low-to-moderate-quality evidence in CKD populations per se, especially for hard clinical endpoints, because in the judgment of the Work Group, relative bene ts of efforts to lower dietary sodium intake will outweigh risks and healthcare costs in most patients. Although there is a lack of RCT data on use of potassium- containing salt substitutes in CKD populations, Work Group members are concerned about the risk of hyperkalemia that www.kidney-international.org chapter 2 these salt substitutes may pose to persons with advanced CKD, as well as observational data suggesting that higher dietary potassium intake may be associated with increased risk of CVand kidney outcomes in CKD populations.45,46 The Work Group acknowledges that there is also evidence to the contrary in people at high CV risk in the general popula- Therefore, the present recommendation for sodium reduction refers to dietary sodium reduction without substi- tution with potassium until further studies can discern risks and bene ts of salt-substitution strategies speci cally in CKD. Practice Point 2.1.1: Dietary sodium restriction is usually not appropriate for patients with sodium-wasting nephropathy.


Practice Point 2.1.1: Dietary sodium restriction is usually not appropriate for patients with sodium-wasting nephropathy. Practice Point 2.1.2: The Dietary Approaches to Stop Hy- pertension (DASH)-type diet or use of salt substitutes that are rich in potassium may not be appropriate for patients with advanced CKD or those with hyporeninemic hypo- aldosteronism or other causes of impaired potassium excretion because of the potential for hyperkalemia. (For Rationale of above practice points, please see text of 2.2 Physical activity Recommendation 2.2.1: We suggest that patients with high BP and CKD be advised to undertake moderate-intensity physical activity for a cumula- tive duration of at least 150 minutes per week, or to a level compatible with their cardiovascular and physical tolerance (2C). This recommendation places a relatively higher value on evi- dence suggesting that physical activity lowers BP, improves quality of life, and improves CV health in CKD patients. The recommendation places lower value on the time investment required for physical activity and the potential for physical ac- tivity to cause adverse events in CKD patients. The recom- mendation is weak according to GRADE because of the low quality of evidence supporting the bene ts of physical activity, speci cally in hypertensive CKD populations. Key information Balance of bene ts and harms. The recommendation is driven by low-quality evidence demonstrating that physical activity may decrease BP and body weight and improve quality of life in CKD patients. The recommendation was also supported by the larger body of evidence in the general population, demonstrating the BP-lowering and other health bene ts of regular physical activity. The Work Group recognizes a higher prevalence of comorbidity and frailty in CKD compared to the general population and is uncertain about whether regular physical activity increases or decreases adverse events.


The Work Group recognizes a higher prevalence of comorbidity and frailty in CKD compared to the general population and is uncertain about whether regular physical activity increases or decreases adverse events. Nonetheless, the Work Group believes that most CKD patients would bene t from regular physical activity. Quality of evidence. Intervention studies and systematic re- views in the general population have rmly established the effects of regular physical activity on BP lowering, improved strengthening, physical tness, lower body weight, and lower risks of dysglycemia and diabetes. In populations with CKD, however, the evidence is much more limited. Our systematic review in CKD populations found low-quality evidence from 1 study conducted over 12 months showing that physical activity may improve SBP and DBP, and low-quality evidence from the same study showing that physical activity may improve eGFR These ndings, however, were inconsistent with other studies suggesting little or no differences.76 82 The updated Cochrane systematic review nds that physical activity decreases weight and improves the mental components of quality of life in CKD.83 patients from 6 studies, the systematic review found very low-quality evidence supporting the association of physical activity with increased study-reported adverse events (including pain, kidney infection, hypotension, dizziness, etc.), an important consideration given the high burden of comorbidity and frailty in CKD populations (Supplementary ). Observational data also show a dose response relationship between greater levels of physical activity and lower risk of mortality in CKD patients.84 Overall, the available literature did not allow differentiation between resistive and aerobic physical activity, or between supervised and unsupervised physical activity programs, leading to uncertainty about the critical elements of physical activity interventions in CKD populations. Nevertheless, it was the opinion of the Work Group that recommendations for the general population are likely to apply in CKD. Values and preferences.


Nevertheless, it was the opinion of the Work Group that recommendations for the general population are likely to apply in CKD. Values and preferences. This recommendation places a relatively high value on physical activity as a nonpharmacologic intervention, with substantial evidence for BP lowering, im- provements in dysglycemia, and other CV and health bene ts in the general population. The high prevalence of hypertension, dysglycemia, and CV disease in CKD populations suggests that the absolute bene t of physical activity may be especially high in people with CKD if the established relative bene ts in the general population are indeed applicable to CKD. The higher potential for bene t is possibly offset by the high prevalence of comorbidity and frailty in CKD populations, which might limit the level of physical activity CKD patients can achieve and in- crease the risk of adverse events. However, the data on critical outcomes are not available, and those for other health bene ts and risks are limited in CKD populations, leading to a weak recommendation. The Work Group recognizes that some patients may have limited ability to exercise due to severe cardiorespiratory ill- nesses and physical or cognitive limitations, and may not be able to achieve physical activity levels recommended for the general population. In such individuals, targets can be indi- vidualized by patients and healthcare providers. The Work Group judged that most patients would bene t from efforts to perform physical activity regularly, even if not achieving the targets set for the general population. Patients in whom chapter 2 www.kidney-international.org physical activity is less feasible due to comorbidity may be less inclined to follow the recommendation, as with those who place a lower potential value on the uncertain bene ts asso- ciated with physical activity. Resource use and costs.


Patients in whom chapter 2 www.kidney-international.org physical activity is less feasible due to comorbidity may be less inclined to follow the recommendation, as with those who place a lower potential value on the uncertain bene ts asso- ciated with physical activity. Resource use and costs. Although a formal cost bene t analysis has not been performed, the Work Group judged that encouraging physical activity is likely to be a good use of resources. Some individuals may choose to perform physical activity in structured environments such as a gymnasium with guidance and supervision from exercise professionals, which could incur costs. However, simple and widely available recreational and leisure-time activities are likely to lead to health bene ts for CKD patients as well. Considerations for implementation. Moderate physical ac- tivity may include recreational and leisure-time activities such as walking and cycling, household chores, and playing sports in the context of daily family and community life. Some patients with musculoskeletal limitations, frailty, high risks of falls, cognitive impairment, or severe cardiorespiratory disease may not be able to achieve physical activity targets set for the general population, but efforts to increase physical activity levels to modi ed targets, in the Work Group s opinion, are likely to translate to health bene ts nonetheless. The speci c type, frequency, duration, and intensity of physical activity that maximizes health bene ts in CKD patients are unknown. However, the Work Group found no reason to believe that interventions with proven health bene ts in the general population would not also provide health bene ts in CKD populations. Rationale There are limited data in CKD populations on the risks and bene ts of physical activity interventions. The quality of evi- dence is low or very low.


The quality of evi- dence is low or very low. Nonetheless, short-term studies suggest that physical activity interventions lower BP, decrease weight, and improve the mental aspects of quality of life. These data are consistent with a substantial body of evidence demonstrating that physical activity improves BP, dysglycemia, cardiopulmonary tness, physical function, and mood in the general population. Prevalence of hypertension and diabetes, and risk of CV disease are extremely high in CKD populations, suggesting that the absolute bene t of physical activity in- terventions may be enhanced in CKD if the relative bene ts are equivalent to those observed in the general population. Exer- cise programs have also been shown to improve health out- comes in other chronic disease conditions, including CV disease and chronic obstructive pulmonary disease. These factors led the Work Group to believe that physical activity is likely to be bene cial in CKD populations as well, despite the low-quality direct evidence currently available. There are limited data on the optimal type or intensity of physical activity in CKD populations. The Work Group reviewed physical activity targets set forth by the World Health Organization (WHO)71 and the recently released AHA/ACC lifestyle guidelines for primary prevention of CV These targets were not developed to speci cally address physical activity in populations with chronic diseases; however, the Work Group believes there is no evidence or plausibility to suggest that these recommendations are not applicable to CKD patients. The Work Group also consulted with the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. In an effort to align guidelines, the target set forth by the AHA/ACC guidelines of moderate- intensity physical activity for a cumulative duration of at least 150 minutes per week was adopted.


In an effort to align guidelines, the target set forth by the AHA/ACC guidelines of moderate- intensity physical activity for a cumulative duration of at least 150 minutes per week was adopted. This target is applicable to hypertensive CKD patients if their healthcare providers consider that the individual patient s comorbidities and exercise tolerance allow it. For others, the degree of physical activity should be individualized according to their cognitive, CV, and physical tolerance, and adjusted, as these limitations change over time. Practice Point 2.2.1: Consider the cardiorespiratory tness status, physical limitations, cognitive function, and risk of falls when deciding on the implementation and intensity of physical activity interventions in individual patients. Practice Point 2.2.2: The form and intensity of physical activity should be considered and modi ed as necessary in individual patients. There may still be important health bene ts even if physical activity falls below targets pro- posed for the general population. (For Rationale of above practice points, please see text of 2.3 Other lifestyle interventions The Work Group recognizes that several other lifestyle in- terventions, including weight loss among those who are overweight or obese, reducing alcohol consumption among those who drink heavily, and adopting a heart-healthy diet pattern have been demonstrated in RCTs to lower BP in the general population. These lifestyle interventions may also have BP-lowering bene ts in patients with CKD, and it may be reasonable to consider them when they can be applied safely and without side effects. Insuf cient data on the risks or bene ts of these interventions on BP in CKD populations per se precluded speci c recommendations in this guideline.


Insuf cient data on the risks or bene ts of these interventions on BP in CKD populations per se precluded speci c recommendations in this guideline. Research recommendations  Conduct clinical trials evaluating different dietary sodium reduction strategies for prevention of clinical endpoints of critical importance for CKD populations, including kidney failure, CV disease, and mortality.  There are inconsistencies among the studies examining the relationship of dietary sodium intake with health outcomes in persons with diabetes.45,46,85 Additional research is required to investigate the consistency of effects of dietary sodium changes on health bene ts and harms across different causes and severities of CKD.  It is unknown if there is a minimum dietary sodium level in CKD below which health risks are increased. Most of these www.kidney-international.org chapter 2 data derive from studies evaluating sodium intake using spot urine sodium measurements. There is current con- troversy about the accuracy of assessing sodium intake us- ing random spot urine specimens, and potential increased risk of adverse health outcomes at the low- sodium intake range when assessed by this method.86 Additional research is required in both sodium-intake assessment methodology in CKD, and to evaluate the health impacts of very low-sodium intakes in CKD populations.  Recent small, single-center clinical trials evaluating chronic oral sodium bicarbonate supplementation versus placebo have not found changes in BP.87 89 These ndings raise the possibility that the anion associated with sodium intake may in uence the BP response. Future research is required to determine if relationships of sodium intake with BP are in uenced by the accompanying anion.  In the general population, potassium-containing salt sub- stitutes have been demonstrated to lower BP.


In the general population, potassium-containing salt sub- stitutes have been demonstrated to lower BP. Persons with CKD have been systematically excluded from clinical trials evaluating potassium-based salt substitutes, and some, albeit not all, observational data in CKD populations demonstrate that higher potassium intake is associated with higher risk of CKD progression and CV disease. Whether using potassium-containing salt substitutes may have health bene ts or unique risks when applied to CKD populations requires future study.  Persons of African ancestry are disproportionately repre- sented in CKD populations. Prior systematic reviews sug- gest that reductions in sodium intake may result in larger reductions in BP in persons of African and Asian ancestry, compared to Caucasians.90 Whether such racial differences can also be found in CKD populations is uncertain and should be evaluated in future studies.  There is a paucity of data on factors that could identify individual CKD patients who have the greatest or least BP bene t from physical activity interventions, and also those that are at greater risk for harm. Identi cation of these factors and algorithms to tailor physical activity intensity and supervision to individual CKD patients is needed.  Iodine supplements are added to salt in some countries. Future studies are required to determine whether restricting sodium intake in CKD populations may contribute to iodine de ciency in these settings. chapter 2 www.kidney-international.org Chapter 3: Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis 3.1 Blood pressure targets Recommendation 3.1.1: We suggest that adults with high BP and CKD be treated with a target systolic blood pressure (SBP) of <120 mm Hg, when toler- ated, using standardized of ce BP measurement (2B).


chapter 2 www.kidney-international.org Chapter 3: Blood pressure management in patients with CKD, with or without diabetes, not receiving dialysis 3.1 Blood pressure targets Recommendation 3.1.1: We suggest that adults with high BP and CKD be treated with a target systolic blood pressure (SBP) of <120 mm Hg, when toler- ated, using standardized of ce BP measurement (2B). The recommendation is based on a single high-quality RCTwith important bene ts in the study cohort that included a sub- stantial number of CKD patients, even though the recommen- dation is considered weak by GRADE standards. This recommendation assumes that standardized of ce BP measure- ment has been taken according to Recommendation 1.1. The recommendation suggests that the majority of people would want the recommended course of action, but some, particularly in the subgroups mentioned below, may not, because adjusting BP-lowering therapy to achieve this target SBP causes potential bene ts and harms that may vary with comorbidities, severity of CKD, existing treatment burden, and the presence of white- coat or masked hypertension. The statement is weak because it is based primarily on a subgroup from 1 RCT; however, the subgroup was prespeci ed from a very high-quality trial. This recommendation does not apply to patients with CKD who have a kidney transplant; this guideline does not apply to those receiving dialysis. Key information Balance of bene ts and harms. There is evidence that tar- geting SBP to <120 mm Hg, when measured under stan- dardized conditions, reduces CV events and all-cause mortality in CKD (Supplementary Table S1191 93 ). In most people with high BP, including the frail and elderly, these bene ts appear to outweigh the risks of harm (e.g., hypotension and acute kidney injury [AKI]).


In most people with high BP, including the frail and elderly, these bene ts appear to outweigh the risks of harm (e.g., hypotension and acute kidney injury [AKI]). However, empirical evidence demonstrating how individuals would weigh these bene ts and harms is lacking. These bene ts extend to patients with or without CKD. Still, there is less certainty that the bene ts outweigh the harms with the following scenarios:  CKD G4 and G5: For people with a lower GFR, there is less certainty around the bene t of lower BP target and po- tential risk of harm, compared to people with higher GFRs.  Diabetes: The bene ts of intensive BP lowering are less certain among patients with concomitant diabetes and CKD, compared to patients with CKD without diabetes.  Individuals with SBP of 120 129 mm Hg: Observational data suggest that individuals with SBP of 120 129 mm Hg are at higher CV risk than those with SBP <120 mm Hg.94 Lowering the SBP from 120 129 mm Hg to <120 mm Hg may therefore be bene cial hypothetically. However, RCTs in CKD targeting SBP <120 mm Hg have not included individuals with SBP of 120 129 mm Hg. Therefore, the recommendation of lowering SBP from 120 129 mm Hg to <120 mm Hg by pharmacologic or non-pharmacologic means is tentative.  People with very low baseline DBP (e.g., <50 mm Hg), particularly in the presence of coronary artery disease: In theory, it is possible that intensive BP lowering will increase the risk of myocardial infarction (MI) in this subgroup because coronary perfusion depends on DBP. However, in SPRINT, the subgroup with the lowest DBP at baseline had similar CV and survival bene ts from intensive SBP reduction as those with higher baseline DBP.


However, in SPRINT, the subgroup with the lowest DBP at baseline had similar CV and survival bene ts from intensive SBP reduction as those with higher baseline DBP.  Etiology of CKD: There is no evidence that CV bene ts of a lower target BP in CKD varies with its etiology. However, kidney bene ts in autosomal dominant polycystic kidney disease may be greater with an SBP of 95 110 mm Hg than  Proteinuria: Proteinuria may no longer be an effect modi- er of BP target with an SBP target of <120 mm Hg.  Older age: The ratio of bene ts to harms of intensive BP reduction in CKD patients at the upper spectrum of age (e.g., >90 years old) is less certain, although people with a mean age of 83  3 years seemed to derive CV, survival, and  Younger age: The ratio of bene ts to harms of intensive BP reduction in people at the younger spectrum of age (e.g., <50 years old), who may have low absolute risks of CV disease and all-cause death, is less certain.  The very frail and those residing in a nursing home: Frailty did not appear to modify the bene cial effects of intensive SBP lowering.  White-coat hypertension: If of ce BP, even when measured under standardized conditions, is higher than daytime ambulatory or home BP, the risks of additional BP- lowering treatment to achieve of ce BP <120 mm Hg may be higher, with less certainty of bene ts. Nonetheless, it should be noted that patients with white-coat hyperten- sion were not excluded in SPRINT and other major outcome trials.


Nonetheless, it should be noted that patients with white-coat hyperten- sion were not excluded in SPRINT and other major outcome trials. www.kidney-international.org chapter 3  Severe hypertension, such as SBP $180 mm Hg on no or 1 antihypertensive drug, or $150 mm Hg on >4 antihyper- tensive drugs, because such patients were not included in SPRINT. Uncertainty in risk bene t ratios in the various scenarios above does not necessarily imply that intensive SBP lowering is not warranted. It only re ects the lack of RCT data to support or refute the ratios. If the patient cannot tolerate SBP <120 mm Hg despite a slow, gradual decrease in SBP over months, efforts should be made to maintain SBP <130 mm Hg, <140 mm Hg, or an even higher tolerated SBP goal. Individualization based on trial and error prevails, as in many aspects of medical practice. The importance of standardized BP measurement when applying this guideline cannot be overemphasized. Routine, non-standardized of ce BP mea- surements often, but not invariably, overestimate BP compared to measurements under standardized conditions (Chapter 1). Importantly, the extent to which routine mea- surements overestimate or underestimate standardized of ce BP is highly variable between and within patients; therefore, no correction factor can be used to convert routine BP to standardized BP measurement by calculation. The use of routine measurements to adjust BP-lowering therapy confers a serious risk of overtreatment and sometimes undertreat- ment. It should be emphasized that the most important aspect of standardized BP measurement is preparation prior to the measurement and not the equipment used (Chapter 1). Heterogeneity in primary outcomes among various RCTs.


It should be emphasized that the most important aspect of standardized BP measurement is preparation prior to the measurement and not the equipment used (Chapter 1). Heterogeneity in primary outcomes among various RCTs. It should be noted that the medium-sized trials that exclusively enrolled CKD patients and examined target BP levels, such as the Modi cation of Diet in Renal Disease (MDRD) trial,97 the African American Study of Kidney Disease and Hypertension and the Blood-Pressure Control for Renoprotection in Patients with Non-diabetic Chronic had used kidney events as the primary outcomes and had relatively few non-kidney events during the trial. In contrast, the larger trials that did not exclusively enroll CKD patients, such as the Systolic Hypertension in the Elderly Program (SHEP) trial,100 the Secondary Prevention of Small Subcortical Strokes (SPS3) the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,92 and the Systolic Blood Pressure Intervention Trial (SPRINT),93 used CV events as the primary outcomes and had relatively few kidney events, although there might be a sizeable number of CKD patients in the latter trials. These dichotomies and the heterogeneity in the characteristics of the study cohorts create challenges in data synthesis to provide an evidence base for practice recommendations in CKD. Cardiovascular outcomes. General population. In the general population, there is extensive evidence that the reduction in the risk of CV events is proportional to the SBP reduction achieved, with the absolute bene ts being greater in those with higher baseline risk of CV disease, and with no differ- ence in proportional risk reductions across groups de ned according to higher or lower baseline SBP.102 106 The meta- analysis of 21 RCTs by Xie et al.


In the general population, there is extensive evidence that the reduction in the risk of CV events is proportional to the SBP reduction achieved, with the absolute bene ts being greater in those with higher baseline risk of CV disease, and with no differ- ence in proportional risk reductions across groups de ned according to higher or lower baseline SBP.102 106 The meta- analysis of 21 RCTs by Xie et al. concluded that the absolute bene ts of lowering SBP were greater and the number-needed-to-treat was smaller in trials where all enrolled patients had vascular disease, diabetes, or kidney In this meta-analysis, on-treatment BP averaged 133/76 mm Hg on intensive treatment and 140/81 mm Hg on less-intensive treatment. Outcomes in patients with and without albuminuria at baseline were not reported separately. SPRINT provides further evidence that intensive SBP lowering reduces CV events and death in those at high CV risk.


SPRINT provides further evidence that intensive SBP lowering reduces CV events and death in those at high CV risk. Those bene ts targeting SBP <120 mm Hg compared to <140 mm Hg in SPRINT extended to CKD, the elderly, and those with frailty.91,107 In a prespeci ed analysis, the bene ts of targeting SBP <120 mm Hg in SPRINT included a signi cant reduction in the combined endpoint of probable dementia and mild cognitive impairment, with no interaction with baseline CKD.108 Secondary analyses further suggest that the bene cial effect of intensive BP lowering on the incidence of mild cognitive impairment per se may extend to those with and those who are aged 80 years or older.96 A recent meta-analysis of 74 RCTs with broader inclusion criteria than those discussed above102,105,106 concluded that the effect of BP lowering differed by baseline BP with no clear effect on death or CV disease in participants with no prior coronary heart disease and SBP <140 mm Hg at baseline.109 This nding has been used by some guideline groups, such as the National Institute for Health and Care Excellence (NICE) in the United Kingdom, to justify a more conservative approach to BP-lowering therapy than that advocated in the present guideline. However, the inclusion of large numbers of trials comparing antihypertensive drugs versus placebo, not lower versus higher BP target, and importantly, those in which BP measurement technique was less precisely speci ed makes drawing conclusions challenging.109 Adults with CKD. A meta-analysis from the Blood Pressure Lowering Treatment Trialists Collaboration, which included trials of antihypertensive drugs versus placebo and trials of different BP targets, found that the proportional reduction in CV events with more intensive BP treatment was independent of the presence or absence of CKD.110 In their meta-analysis, Ettehad et al.


A meta-analysis from the Blood Pressure Lowering Treatment Trialists Collaboration, which included trials of antihypertensive drugs versus placebo and trials of different BP targets, found that the proportional reduction in CV events with more intensive BP treatment was independent of the presence or absence of CKD.110 In their meta-analysis, Ettehad et al. also reported a risk reduction for CVevents with intensive BP lowering in those with CKD, but the size of the risk reduction was less than that in those without CKD.105 SPRINT intentionally included a CKD subgroup a priori and examined an SBP target of <120 mm Hg, as recom- mended in the present guideline, versus <140 mm Hg. In the primary analysis of the entire cohort of 9361 participants, SPRINT demonstrated bene ts for the primary CV outcome (hazard ratio [HR]: 0.75; 95% con dence interval [CI]: 0.64 0.89) and for all-cause death (HR: 0.73; 95% CI: 0.60 0.90) across all subgroups with no heterogeneity, including those with or without CKD de ned as eGFR 20 to <60 ml/min per , with proteinuria <1 g/d.91,93 Indeed, in the sub- group with CKD (median albumin-creatinine ratio [ACR]: ), the CV bene t chapter 3 www.kidney-international.org missed signi cance of P < 0.05 (HR: 0.81; 95% CI: 0.63 1.05), while the mortality bene t was nominally signi cant. That said, SPRINT was not powered for subgroup analyses, especially given that it ended early because of the substantial CV disease and mortality bene t. It should be noted that large RCTs with major clinical outcomes are rarely powered for a speci c subgroup, even for age or sex. Trial results should be interpreted for the entire study cohort, with effect modi ca- tion by factors de ning subgroups examined in secondary analysis.


Trial results should be interpreted for the entire study cohort, with effect modi ca- tion by factors de ning subgroups examined in secondary analysis. Such effect modi cation was not noticed for CKD in SPRINT. Regardless, SPRINT is the largest trial testing 2 BP targets in CKD with approximately 2600 CKD patients. Although SPRINT excluded patients with diabetes, polycystic kidney disease, or proteinuria $1 g/d, those with glomeru- lonephritis not taking immunosuppressive medications were not excluded. Three other trials comparing different BP targets, powered for kidney outcomes as primary outcomes, generated far too few CV events or death outcomes (MDRD, AASK, REIN-2). However, a meta-analysis by Malhotra et al., examining death as an outcome exclusively in the CKD subgroups of the large hypertension treatment RCTs, also found a bene t of lower target BP.111 Older adults with or without CKD. There are meta-analyses and systematic reviews based on the general population of older adults, including patients with CKD, addressing the impact of lower BP targets. Garrison et al. analyzed RCTs conducted in hypertensive adults aged 65 years or older and reported outcomes for higher SBP (150 160 mm Hg) or DBP (95 105 mm Hg), compared to a lower treatment target SPRINT was excluded from this analysis because its lower target was lower than the inclusion criteria of the meta-analysis. Its inclusion may have changed the results of the meta-analysis. Based on this meta-analysis, there was insuf cient evidence to determine whether a lower SBP target provides meaningful differences in bene ts or harms to older adults. However, there are very few major trials and relatively few events in this meta-analysis. In contrast, Bavishi et al.


However, there are very few major trials and relatively few events in this meta-analysis. In contrast, Bavishi et al. included RCTs in a meta-analysis comparing intensive versus standard or less-intensive BP control in older adults ($65 years) and provided long-term CV and safety outcomes.113 SPRINT met the inclusion criteria for this review. There were reductions in major CV events, CV mortality, and heart failure (HF), but a possible increase in AKI and serious adverse events. No analysis of the older population with CKD was described in these studies. There is only one large study analyzing the effects of lower BP targets in CKD patients older than 75 years. A post hoc analysis of that speci c subgroup in SPRINT showed that the low BP target (SBP <120 mm Hg) reduced the primary CV outcome (HR: 0.64; 95% CI: 0.45 0.92), all-cause death (HR: 0.64; 95% CI: 0.43 0.96), and the composite of primary CV disease outcome or all-cause death (HR: 0.66; 95% CI: 0.49 There was no description of potential harm of achieving lower targets in this subgroup of older adults with CKD, although the risk bene t ratio in the entire CKD cohort and in the entire subcohort older than 75 years in SPRINT was favorable. Even in the age group 80 years and older, subgroup analysis in SPRINT showed that intensive BP lowering decreased the risk of CV events (HR: 0.66; 95% CI: Adults with diabetes and CKD. Among patients with concomitant diabetes and CKD, the bene ts of intensive BP lowering are less certain than those with CKD without dia- betes. All previous studies in diabetes with and without CKD have favored more, instead of less, intensive BP reduction ). In their meta-analysis, Ettehad et al.


All previous studies in diabetes with and without CKD have favored more, instead of less, intensive BP reduction ). In their meta-analysis, Ettehad et al. reported that the reduction in major CV events remained proportional to the BP reduc- tion achieved among trial participants with diabetes, but that the proportional risk reductions were smaller than the re- ductions in those without diabetes.105 In contrast, in the meta-analysis of intensive versus less-intensive BP-lowering therapy among patients with CKD, Malhotra et al. found no evidence of heterogeneity in bene cial effects on mortality with respect to the presence or absence of diabetes.111 Brunstr m et al. conducted a systematic review and meta- analysis of RCTs that included at least 100 patients with diabetes, and found that BP reduction decreased MI, stroke, CV mortality, ESKD, and all-cause mortality if baseline SBP was >150 mm Hg; there was decreased MI, HF, and all-cause mortality if baseline SBP was 140 to 150 mm Hg, but para- doxically, increased CV mortality was observed if baseline SBP was <140 mm Hg.118 Two major caveats should be noted regarding these meta- analyses in diabetes. First, these meta-analyses differ sub- stantially from each other in their respective inclusion criteria. Brunstr m et al. and Ettehad et al. included RCTs that compared antihypertensives to placebo, and different BP targets. Ettehad et al. included RCTs of head-to-head com- parisons of antihypertensive agents to examine the effect of 10 mm Hg reduction in SBP on clinical outcomes. Second, none of the trials conducted prior to ACCORD and SPRINT examined an SBP target as low as <120 mm Hg. Nonetheless, they collectively suggest that SBP lowering decreases the CV event rate and perhaps mortality and kidney outcomes.


Nonetheless, they collectively suggest that SBP lowering decreases the CV event rate and perhaps mortality and kidney outcomes. The ACCORD trial that enrolled exclusively patients with diabetes did not show a difference in the prespeci ed primary endpoint of composite CV events between the intensive SBP target (<120 mm Hg) and standard SBP target (<140 mm Hg), but it did demonstrate a signi cant reduction in stroke (HR: 0.59; 95% CI: 0.39 0.89), a prespeci ed sec- ondary outcome, with intensive SBP lowering.92 However, ACCORD included few patients with CKD, as patients with serum creatinine >1.5 mg/dl (132 mmol/l) were excluded, and those with CKD were mostly proteinuric with well-preserved Therefore, there is little direct evidence from ACCORD alone to guide a recommendation for patients with diabetes and CKD. Nonetheless, there was no statistical interaction between CKD and intensive BP lowering on the reduction in stroke risk.119 www.kidney-international.org chapter 3 In contrast to ACCORD, SPRINT included a substantial number (n 2646) of participants with CKD. Although SPRINTspeci cally excluded patients with diabetes, 42% (n 3898) of the cohort had prediabetes, de ned as baseline fasting serum glucose >100 mg/dl [5.6 mmol/l]. A post hoc analysis of SPRINT comparing participants with and without prediabetes found that the CV and survival bene ts of intensive SBP reduction (<120 mm Hg) were similar in the 2 subgroups.120 Other secondary analyses of ACCORD data further suggest that intensive SBP lowering is bene cial. A combined post hoc analysis of SPRINT and ACCORD suggested similar CV bene ts of intensive BP-lowering therapy in the presence or absence of diabetes.121 ACCORD was not only a BP trial, but it also employed a rather complex study design.


A combined post hoc analysis of SPRINT and ACCORD suggested similar CV bene ts of intensive BP-lowering therapy in the presence or absence of diabetes.121 ACCORD was not only a BP trial, but it also employed a rather complex study design. The partici- pants were randomized rst to intensive versus less-intensive glycemic control, and then either to intensive versus less- intensive BP control or to the addition of feno brate versus placebo on a background of a statin. The trial of glycemic control was terminated early because of higher all-cause mortality with intensive glycemic control.92 This adverse ef- fect of intensive glycemic control was also demonstrated in the CKD subgroup of ACCORD.119 The ACCORD BP trial reported no statistical interaction between glycemic control and BP control on prespeci ed primary and secondary CV outcomes. However, a more detailed combined analysis of data from ACCORD and SPRINT found that the bene cial effects of intensive SBP control (with both trials targeting <120 mm Hg) on combined CV endpoints and on all-cause mortality were similar in the standard glycemia arm of ACCORD and in SPRINT.122,123 In contrast, intensive SBP control increased CV death, HF, and MI in the intensive glycemia arm.


However, a more detailed combined analysis of data from ACCORD and SPRINT found that the bene cial effects of intensive SBP control (with both trials targeting <120 mm Hg) on combined CV endpoints and on all-cause mortality were similar in the standard glycemia arm of ACCORD and in SPRINT.122,123 In contrast, intensive SBP control increased CV death, HF, and MI in the intensive glycemia arm. These interactions lessened after discontinua- tion of the glycemic intervention.122 In another post hoc analysis among ACCORD participants in the standard gly- cemia arm who had additional CV risk factors that would have met the SPRINT inclusion criteria, intensive BP control provided CV bene ts similar to those seen in SPRINT.124 Similarly, a pooled analysis of individual patient data from 4983 patients with CKD from AASK, MDRD, ACCORD, and SPRINT found a non-signi cant trend to decreased mortality with intensive BP-lowering therapy, but a statistically signif- icant reduction in mortality in a subgroup with eGFR <60 who were not assigned to intensive gly- Collectively, these aforementioned post hoc analyses support the notion that intensive BP control im- proves clinical outcomes even in patients with diabetes and CKD, but glycemic control modulates the effects of intensive BP control on CV outcomes. This evidence is indirect, hence diminishing the certainty of the bene ts and strength of recommendation of targeting SBP <120 mm Hg. Low diastolic blood pressure.


This evidence is indirect, hence diminishing the certainty of the bene ts and strength of recommendation of targeting SBP <120 mm Hg. Low diastolic blood pressure. Numerous observational including those that examine data from RCTs in a post hoc observational manner,128 although not all studies, have suggested a J-shaped curve with very low DBP being associated with an increased risk of CVevents, particularly MI among patients with pre-existing coronary artery disease.94 The validity of these observations is supported by biological plausibility, as low DBP in the setting of coronary stenosis could lead to impaired subendocardial blood ow during diastole. However, this association is heavily confounded, as patients with very low DBP inherently have high CV risks. Beddhu et al. recently showed that in SPRINT participants, baseline DBP indeed bore a U-shaped relationship with mor- tality. However, the CV-protective bene ts of intensive SBP lowering were independent of baseline DBP, including the lowest DBP quintile at baseline with a mean DBP of 61  Whether this bene cial effect of SBP lowering persists at even lower DBP levels (e.g., <45 mm Hg) cannot be determined from these data. Kidney outcomes. Rate of decline in GFR. The effects of intensive BP lowering on GFR are often complicated by an exaggerated early acute GFR decline that is also seen with inhibitors of the renin-angiotensin system (RAS) and the sodium glucose cotransporter-2 (SGLT2) system. This acute eGFR decrease with BP lowering may be mediated, at least in part, by intrarenal hemodynamic changes.


This acute eGFR decrease with BP lowering may be mediated, at least in part, by intrarenal hemodynamic changes. This hypothesis is supported by the following observations: (i) Single-nephron GFR decreases when glomerular blood ow rate drops below the level that can be sustained by (ii) Urinary excretion of various tubular biomarkers during intensive SBP treatment in SPRINT was not indicative of (iii) Albuminuria during follow-up was lower, instead of higher, in the intensive SBP arm than in the standard SBP treatment arm in SPRINT. Similar observations have been reported in ACCORD participants.133 Nonetheless, the overall rate of decline of eGFR was higher rather than lower on intensive treatment in SPRINT in both and non-CKD subgroups,134 In both ACCORD and SPRINT, participants assigned to intensive BP target also developed more incident CKD during follow-up than those assigned to standard BP target.128,134 There was no difference in the rate of doubling of serum creatinine between intensive and standard SBP treatment in SPRINT, but the small number of these discrete events pre- cludes rm conclusions. The difference in the rate of decline of eGFR in SPRINT after the initial 6 months was small (0.47 /yr in the intensive and standard arms, respectively). If this slope persisted long-term, it would take 20 years to cause a 3 ml/min per 1.73 m2 difference in eGFR between intensive and standard SBP treatment. Taking both the bene cial effect on albuminuria and the adverse effect on eGFR into account, the long-term effects of intensive SBP lowering on the kidney cannot be determined from these relatively short-term, on-treatment observations. Progression to kidney failure and effect modi cation by proteinuria. Prior to SPRINT, the largest RCTs addressing the effects of intensive BP control in CKD were MDRD,97 The primary outcome of these 3 trials was progression of kidney disease.


Prior to SPRINT, the largest RCTs addressing the effects of intensive BP control in CKD were MDRD,97 The primary outcome of these 3 trials was progression of kidney disease. During the trial phase, when the chapter 3 www.kidney-international.org participants were under their respective randomized in- terventions, none of these trials showed bene ts or harms on kidney function by intensive BP lowering in the primary analysis of the entire cohort. A caveat of MDRD and AASK is that both trials targeted mean arterial BP (MAP, calculated as DBP 1/3  pulse pressure), rather than SBP or DBP. The lower target was a MAP of <92 mm Hg (equivalent, for example, to 125/75 mm Hg, 140/68 mm Hg, 160/58 mm Hg, or many other combinations of SBPs and DBPs), whereas the higher target was a MAPof <107 mm Hg (equivalent to 140/90 mm Hg, 125/98 mm Hg, etc.). Further, the MAP targets varied in MDRD, depending on the age of the patients.136 A meta-analysis in 2011 conducted by the ERT of the KDIGO 2012 BP guideline found only these 3 studies (MDRD, AASK, and REIN-2) pertinent to the discussion of whether a lower BP target reduced the risk of progression to kidney failure in the presence of proteinuria. They concluded that the evidence was inconclusive.137 Similarly, the current ERT review found no effect modi cation according to the presence of proteinuria (Supplementary Table S1297 ).


They concluded that the evidence was inconclusive.137 Similarly, the current ERT review found no effect modi cation according to the presence of proteinuria (Supplementary Table S1297 ). The evidence that intensive BP reduction reduces the risk of progression to kidney failure is derived mainly from a prede ned subgroup analysis of MDRD (only 54 pa- tients with proteinuria >3 g/d, but large effect size)97,139 and long-term post-treatment follow-up from MDRD138 and A more recent meta-analysis of 11 RCTs of lower versus higher BP goals found that intensive BP reduction was associated with a reduction in kidney failure events (de ned as the composite of doubling of serum creatinine and a >50% reduction in eGFR or ESKD), with effect modi cation by Intensive BP control reduced the risk of kidney failure only among those with baseline proteinuria, de ned as a protein creatinine ratio (PCR) >220 mg/g (22 mg/mmol). The MDRD and AASK studies were major con- tributors to this evidence base. The REIN-2 study compared a higher DBP target of <90 mm Hg with a lower BP target of <130/80 mm Hg by adding felodipine to baseline ramipril therapy in patients with protei- nuric CKD (mean eGFR and proteinuria approximately 35 ml/ min and 3 g/d, respectively) without diabetes.99 no bene t of intensi ed BP control over a mean follow-up of approximately 19 months. However, the study was underpow- ered with a total of only 338 participants and had very small differences in achieved SBP and DBP of only 4 mm Hg and 2 mm Hg, respectively, during the intervention phase. The effects of intensive SBP lowering with target <120 mm Hg are only available in ACCORD and SPRINT.


The effects of intensive SBP lowering with target <120 mm Hg are only available in ACCORD and SPRINT. In ACCORD, which had few CKD patients, there was no dif- ference in progression to ESKD between intensive (59 cases/ 2362 patients) and standard (58 cases/2371 patients) SBP groups. SPRINT excluded patients with proteinuria >1 g/d, and the baseline median ACR was only 13 mg/g (1.3 mg/ mmol) in the CKD subgroup. ESKD events were rare in SPRINT, with a total of only 16 cases in 9361 patients. No reliable conclusions can therefore be reached on the effects of an SBP target <120 mm Hg on progression to kidney failure in patients with CKD from ACCORD or SPRINT (Supplementary Table S1191 93 ). Previous guidelines, including the KDIGO 2012 BP guide- line, recommended more aggressive BP lowering for patients with albuminuria than for those without albuminuria.141 These recommendations were based largely on the subgroup ndings of the MDRD,97 as described above, and in the pedi- atric population, the ESCAPE trial (Chapter 5).142 With the adoption of an SBP target <120 mm Hg for all patients with CKD in the present revised guideline based on the evidence for CV and survival bene ts, separate targets for patients with and without albuminuria are no longer required. There is no evi- dence supporting an even lower target (e.g., <110 mm Hg) for patients with severely increased proteinuria. Mortality. The ERT found 5 RCTs examining the effects of intensive versus less-intensive BP control on mortality in patients with CKD without diabetes (Supplementary ).