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American Journal of Kidney Diseases

Clinical Value of Ambulatory Blood Pressure Monitoring in CKD

  • Alexander G. Logan
    Correspondence
    Address for Correspondence: Alexander G. Logan, MD, FRCP(C), Mount Sinai Hospital, 60 Murray St, Room L5-254, Toronto, ON M5T 3L9, Canada.
    Affiliations
    Department of Medicine, Mount Sinai Hospital, Division of Nephrology, University Health Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto; and Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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Published:September 22, 2022DOI:https://doi.org/10.1053/j.ajkd.2022.07.002
      Related Article, p. ∗∗∗
      Accurate measurement and classification of blood pressure (BP) are essential in managing hypertensive patients with chronic kidney disease (CKD). Guidelines and scientific statements recommend ambulatory BP monitoring (ABPM) or, when not available, home BP measurements (HBPM) to confirm the presence of hypertension and identify patients with white-coat or masked hypertension.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • 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.
      ,
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      Because BP follows a circadian pattern, ABPM can also be used to assess diurnal BP profile, with key parameters being nighttime (sleep) BP and nocturnal BP dipping pattern (sleep-awake BP cycle). The prognostic superiority of out-of-office BP measurements over standard office-based readings has been amply demonstrated in many observational studies.
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      In patients with hypertension and CKD who are not receiving dialysis, ambulatory BP—whether it be mean 24-hour, daytime, or nighttime—is associated with hypertension-mediated target organ damage, cardiovascular (CV) events, progressive kidney disease (often leading to kidney failure), and mortality, and the adverse prognosis is robust even after adjustments for traditional risk factors including office BP.
      • Drawz P.E.
      • Beddhu S.
      • Kramer H.J.
      • Rakotz M.
      • Rocco M.V.
      • Whelton P.K.
      Blood pressure measurement: a KDOQI perspective.
      CKD patients with white-coat hypertension are not at substantially higher risk for a CV event than normotensive patients,
      • Drawz P.E.
      • Beddhu S.
      • Kramer H.J.
      • Rakotz M.
      • Rocco M.V.
      • Whelton P.K.
      Blood pressure measurement: a KDOQI perspective.
      ,
      • Rahman M.
      • Wang X.
      • Bundy J.D.
      • et al.
      Prognostic significance of ambulatory BP monitoring in CKD: a report from the chronic renal insufficiency cohort (CRIC) study.
      while masked hypertension, a common finding in CKD cohorts, confers the same level of risk for adverse outcomes as sustained hypertension.
      • Rahman M.
      • Wang X.
      • Bundy J.D.
      • et al.
      Prognostic significance of ambulatory BP monitoring in CKD: a report from the chronic renal insufficiency cohort (CRIC) study.
      Reduced nocturnal BP dipping (also referred to as nondipping) is highly prevalent in hypertensive patients with CKD, accounting for more than 60% of participants in most studies and almost 90% of those with advanced CKD.
      • Rahman M.
      • Wang X.
      • Bundy J.D.
      • et al.
      Prognostic significance of ambulatory BP monitoring in CKD: a report from the chronic renal insufficiency cohort (CRIC) study.
      • Pogue V.
      • Rahman M.
      • Lipkowitz M.
      • et al.
      Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease.
      • Agarwal R.
      • Sinha A.D.
      • Cramer A.E.
      • et al.
      Chlorthalidone for hypertension in advanced chronic kidney disease.
      Loss of the normal diurnal variation in BP is associated with markers of kidney dysfunction, such as reduced glomerular filtration rate (GFR), albuminuria, and impaired sodium excretion, and predicts progressive deterioration in GFR (often defined as a 50% decrease) and kidney failure, even after adjusting for office BP.
      • Drawz P.E.
      • Beddhu S.
      • Kramer H.J.
      • Rakotz M.
      • Rocco M.V.
      • Whelton P.K.
      Blood pressure measurement: a KDOQI perspective.
      ,
      • Rahman M.
      • Wang X.
      • Bundy J.D.
      • et al.
      Prognostic significance of ambulatory BP monitoring in CKD: a report from the chronic renal insufficiency cohort (CRIC) study.
      These relationships have been shown to be log-linear and continuous, with no threshold level where risk increases suddenly.
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      To facilitate the clinical application of ABPM, threshold levels of ambulatory BP that are the risk equivalent to office BP levels were derived from prospective observational studies with CV end points
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      and nondipping BP pattern was arbitrarily defined as a decrease in nocturnal BP relative to daytime BP of <10%.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • 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.
      In the article by Borrelli et al

      Borrelli S, Garofalo C, Gabbai FB, et al. Isolated effect of dipping status and ambulatory blood pressure control on cardiovascular and renal risk in CKD patients: a multicenter cohort study. Am J Kidney Dis. Published online June 13, 2022. doi:10.1053/j.ajkd.2022.04.010

      published in the current issue of AJKD, the investigators explored the use of 2 closely related ABPM parameters, ambulatory BP (daytime and nighttime BP) and dipping status, expressed as categorical variables, to evaluate the prognosis of treated patients with hypertension and CKD who were not receiving kidney replacement therapy (dialysis or transplant). Few studies with CV and kidney outcomes have used both BP parameters in the same sample to determine their relative importance in predicting outcomes. Identifying the best BP index of risk and in what circumstances provides an opportunity to develop and test a more focused approach to treatment.
      Borrelli et al categorized the 906 hypertensive patients with CKD (stages 2-5) in their study into 1 of 4 mutually exclusive groups: ambulatory BP above or at goal (defined as daytime and nighttime systolic BP <135 mm Hg and <120 mm Hg, respectively) and nondipping or dipping (defined as night-to-day ratio of systolic BP <0.9 based on a single 24-hour ABPM performed at baseline). Study participants were followed for a median of 7.8 years. Outcomes were a kidney progression outcome (defined as a composite of ≥50% decline in estimated GFR or initiation of maintenance dialysis) and all CV events. In total there were 315 kidney progression events and 220 CV events. In line with past studies
      • Rahman M.
      • Wang X.
      • Bundy J.D.
      • et al.
      Prognostic significance of ambulatory BP monitoring in CKD: a report from the chronic renal insufficiency cohort (CRIC) study.
      • Pogue V.
      • Rahman M.
      • Lipkowitz M.
      • et al.
      Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease.
      • Agarwal R.
      • Sinha A.D.
      • Cramer A.E.
      • et al.
      Chlorthalidone for hypertension in advanced chronic kidney disease.
      the prevalence of nondipping was 70% and nondippers above ambulatory BP target were older, were predominantly men, had a history of diabetes or prior CV disease, and had lower estimated GFR, more proteinuria, and higher nighttime BP than dippers not at ambulatory BP goal. Not surprisingly, these patients were at highest risk for kidney disease progression and CV events. The novel findings of the study were the increased kidney as well as CV risk of nondippers at ambulatory BP goal compared to normotensive dippers, and that the increased level of risk was virtually identical to that of dippers with uncontrolled hypertension. The authors concluded that nocturnal nondipping BP pattern is an independent risk factor for adverse events among hypertensive patients with CKD and should be considered a target for therapeutic intervention to restore normal dipping status.
      Despite the encouraging results, ascertaining dipping status as a treatment target is still controversial for several reasons. First, dipping status derived from a single 24-hour ABPM recording, as in the current study, is poorly reproducible.
      • McGowan N.J.
      • Gough K.
      • Padfield P.L.
      Nocturnal dipping is reproducible in the long term.
      This has led guideline committees and others to recommend repeat testing or extending monitoring to 48 hours to confirm the presence of nondipping.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • 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.
      ,
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      Second, observation studies can only identify links; as such, they do not imply a reduction in adverse effects of nondipping with successful treatment.
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      ,
      • Drawz P.E.
      • Beddhu S.
      • Kramer H.J.
      • Rakotz M.
      • Rocco M.V.
      • Whelton P.K.
      Blood pressure measurement: a KDOQI perspective.
      Moreover, successful treatment of nondipping, for example by bedtime administration of antihypertensive medications, is invariably accompanied by a decrease in nocturnal BP, making it difficult to tease out the relative contributions of these highly correlated variables to any observed benefits.
      • Hermida R.C.
      • Ayala D.E.
      • Mojón A.
      • Fernández J.R.
      Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD.
      ,
      • Tiwari V.
      • Chaudhary A.R.
      • Dasgupta S.
      • et al.
      Effect of chronotherapy of antihypertensives in chronic kidney disease: a randomized controlled trial.
      Third, in a meta-analysis of prospective studies involving patients with hypertension, dipping status remained significantly associated with total mortality or composite CV end points even with adjustment for 24-hour BP, but its inclusion did not greatly improve the model fit beyond the 24-hour BP readings.
      • Hansen T.W.
      • Li Y.
      • Boggia J.
      • Thijs L.
      • Richart T.
      • Staessen J.A.
      Predictive role of the nighttime blood pressure.
      In keeping with this finding, a recent randomized controlled trial of patients with advanced CKD and poorly controlled hypertension showed that the addition of chlorthalidone, a long-acting thiazide diuretic, to existing drug therapy significantly reduced ambulatory daytime and nighttime BP in parallel but did not substantially lower the high percentage of participants with nondipping BP pattern.
      • Agarwal R.
      • Sinha A.D.
      • Cramer A.E.
      • et al.
      Chlorthalidone for hypertension in advanced chronic kidney disease.
      Finally, nondipping expressed as a categorical variable is not a robust measure in assessing benefits. This was apparent in chronobiology studies in which bedtime dosing of antihypertensive medications greatly improved the dipping ratio (a continuous variable) and clinical outcomes but only re-established a normal nocturnal BP dipping pattern in about one-third of patients.
      • Hermida R.C.
      • Ayala D.E.
      • Mojón A.
      • Fernández J.R.
      Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD.
      ,
      • Tiwari V.
      • Chaudhary A.R.
      • Dasgupta S.
      • et al.
      Effect of chronotherapy of antihypertensives in chronic kidney disease: a randomized controlled trial.
      There is a growing support for out-of-office BP measurements, not only for diagnosis, but, importantly, for monitoring antihypertensive treatment after its initiation. Measurement options include ABPM, HBPM, and, more recently, small wearable devices, although the latter is still hampered by issues around accuracy, reproducibility, and calibration.
      • Kario K.
      Management of hypertension in the digital era. Small wearable monitoring devices for remote blood pressure monitoring.
      Guidelines recommend both ABPM and HBPM and view them as complementary procedures.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • 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.
      HBPM allows patients to monitor their BP regularly over an extended period of time and is a powerful monitoring tool when coupled with a BP telemonitoring system that provides feedback support in real time from a multidisciplinary clinical team.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • 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.
      ,
      • Omboni S.
      • McManus R.J.
      • Bosworth H.B.
      • et al.
      Evidence and recommendations on the use of telemedicine for the management of arterial hypertension. An international expert position paper.
      It is particularly valuable in situations where there are frequent changes in antihypertensive drug treatment to improve BP control or in response to medication side effects. ABPM is less well suited for repeated monitoring because of inconvenience, cost (not a recoverable expense in many jurisdictions), and poorer patient acceptance.
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      ,
      • Parati G.
      • Omboni S.
      • Bilo G.
      Why is out-of-office blood pressure measurement needed?.
      Indeed, position papers and scientific statements envisage a more limited role of ABPM in the long-term management of hypertension. Situations where ABPM seems to have advantages over HBPM include assessment for nocturnal hypertension in patients at risk such as those with more advanced CKD, diabetes, or obstructive sleep apnea; evaluation of patients with symptomatic hypotension, especially when associated with severe supine hypertension; and ascertaining therapeutic coverage over 24 hours.
      • Parati G.
      • Omboni S.
      • Bilo G.
      Why is out-of-office blood pressure measurement needed?.
      ,
      • Muntner P.
      • Shimbo D.
      • Carey R.M.
      • et al.
      Measurement of blood pressure in humans. A scientific statement from the American Heart Association.
      A major limitation of both ABPM and HBPM as the primary measurement tool in managing hypertension is the lack of clinical trials with hard outcomes using BP from these procedures to determine eligibility for treatment and goals of therapy. Current drug treatment parameters are founded on the results of multiple clinical trials that exclusively used office-based BP measurements. As such, they are widely accepted and will likely continue to inform clinical decision making until new evidence indicates otherwise.
      • Huang Q.-F.
      • Yang W.-Y.
      • Asayama K.
      • et al.
      Ambulatory blood pressure monitoring to diagnose and manage hypertension.
      ,
      • Parati G.
      • Omboni S.
      • Bilo G.
      Why is out-of-office blood pressure measurement needed?.
      ,
      • Muntner P.
      • Shimbo D.
      • Carey R.M.
      • et al.
      Measurement of blood pressure in humans. A scientific statement from the American Heart Association.

      Article Information

      Support

      Funding from the Canadian Institutes of Health Research (Catalyst Grant: FRN 155481). The funder of the research grant had no role in defining the content of the editorial.

      Financial Disclosure

      The author declares that he has no other relevant financial interests.

      Peer Review

      Received July 3, 2022, in response to an invitation from the journal. Direct editorial input from an Associate Editor and a Deputy Editor. Accepted in revised form July 27, 2022.

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