The Kidney Disease Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline on the Management of Blood Pressure in Chronic Kidney Disease includes new recommendations on BP management for individuals with CKD not receiving dialysis. Two important topics discussed are the importance of standardized office BP measurement and the evidence-based BP target.
A 65-year-old man was referred for management of hypertension. Initial routine laboratory tests showed a serum creatinine of 2.0 mg/dl, corresponding to an eGFR of 34 ml/min per 1.73 m2. After a standardized measurement protocol, his mean office systolic BP was 140 mm Hg and diastolic BP was 90 mm Hg. He used a wrist BP device at home and reported a systolic BP of 130–140 mm Hg and a diastolic BP of 90–100 mm Hg. He was taking amlodipine 5 mg, chlorthalidone 25 mg, and benazepril 20 mg daily. He had a urinalysis showing 2+ proteinuria on dipstick, which was confirmed on repeat testing. His primary care provider expressed concern about being too aggressive in lowering BP as the patient appeared frail and had CKD.
Standardized Office BP Measurement
The KDIGO 2021 BP guideline emphasizes the importance of measuring BP utilizing a standardized approach, consistent with those in large outcome trials (1). The term “standardized” means following a protocol that includes the setting where BP is measured, patient preparation, positioning, not talking during a rest period or measurements, and the measurement of BP itself (Figure 1). Consistent with other BP guidelines, the KDIGO guideline recommends the management of BP be on the basis of multiple measurements taken in the office on more than a single occasion. Not following a protocol (i.e., nonstandardized BP measurements) will yield BP levels that often do not reflect a patient’s regular BP level. There is no substitute for standardized BP levels because nonstandardized BP levels cannot be converted to standardized levels.
The use of an automated oscillometric BP device, as opposed to a manual device, to measure office BP has several advantages. Automated oscillometric BP devices can be programmed to take multiple BP measurements after a prespecified rest period. Similarly, BP measured with these devices can be taken unattended, without a health care provider in the room, preventing the patient and provider from talking during the procedure. Manual devices, especially aneroid manometers, need to be calibrated frequently, but usually are not, and digit preference is common with manual measurements. Even in patients with atrial fibrillation, automated oscillometric BP devices provide reasonably accurate systolic BP readings.
Out-of-office BP measurements with ambulatory BP monitoring or home BP monitoring are recommended to complement standardized office BP readings for the management of high BP. When recommending home BP monitoring, patients should use the standardized approach for measurement with a device that measures brachial artery BP and has been validated.
For patients with high BP and CKD who are not receiving dialysis, a target systolic BP <120 mm Hg is recommended. This recommendation is primarily on the basis of a single high-quality randomized controlled trial, the Systolic Blood Pressure Intervention Trial (SPRINT), which demonstrated that “targeting systolic BP to <120 mm Hg, when measured under standardized conditions” reduces cardiovascular events and mortality in patients with CKD by 25%–30% (2).
Lifestyle interventions including reduction of dietary sodium intake and increase in moderate-intensity physical activity are the initial recommendations for the management of elevated BP and hypertension. When pharmacologic therapy is indicated, lifestyle interventions should be continued. Renin-angiotensin-system inhibitors are recommended for people with high BP, CKD, and moderately or severely increased albuminuria, and may be reasonable for those without albuminuria (Figure 1).
The cardiovascular and mortality risk-reduction benefits of a systolic BP goal of <120 mm Hg for patients with CKD should be weighed against the risk of potential adverse events. Although concerns have been raised that intensive systolic BP lowering leads to syncope, hypotension, electrolyte abnormalities, and AKI (Figure 1), this is not supported by data from randomized trials (2,3). In SPRINT, there was no evidence of a clinically important difference in hypotension, syncope, and bradycardia between participants with CKD randomized to a systolic BP target <120 mm Hg versus <140 mm Hg (2). Although those randomized to a systolic BP target <120 mm Hg were more likely to develop AKI, the overall risk was low (3% per year versus 2% per year among those randomized to a systolic BP target <140 mm Hg) and it tended to resolve without any recognizable long-term adverse effects. Also, an acute/persistent decrease in eGFR with intensive BP lowering is likely due to reversible hemodynamic changes. Intensive BP lowering generally requires more medications, which can contribute to low adherence and higher health care utilization, such as more frequent health care provider visits for medication titration. Adherence can be monitored through standardized questionnaires, and fixed-dose combination medications can be used because they can lead to better adherence and faster achievement of BP goals.
There is no recommended target diastolic BP value in patients with CKD because few trials have compared intensive versus standard diastolic BP lowering. Recognizing that a wide pulse pressure is common in patients with CKD, one can extrapolate that targeting a systolic BP <120 mm Hg will likely lead to a diastolic BP <70 mm Hg.
There are possible exceptions to the recommended target systolic BP <120 mm Hg. These are scenarios whereby the evidence is uncertain for the benefits of intensive BP lowering outweighing the harms. These include patients with lower eGFR (CKD G4 and G5), diabetes, baseline systolic BP 120–129 mm Hg (4), etiology of CKD (5), proteinuria, extremes of age (6), very frail or nursing home residents, “white-coat” hypertension, and severe hypertension.
Frailty, which is more common among adults with versus without CKD, is a risk factor for falls, hospitalization, nursing home placement, and death. There is no evidence that intensive systolic BP lowering leads to, or worsens, frailty. In SPRINT, a higher frailty index was associated with a higher risk for self-reported and injurious falls and hospitalization (7). However, a systolic BP target of <120 mm Hg versus <140 mm Hg resulted in lower rates of cardiovascular disease and death among frail and not frail participants. These data suggest frailty should not be a barrier for intensive systolic BP lowering.
It should be noted, however, that not all guidelines recommend a target systolic BP of <120 mm Hg. For example, the American College of Cardiology/American Heart Association BP guideline recommends a target systolic BP <130 mm Hg for individuals with CKD not receiving dialysis (8).
The KDIGO guideline supports the common dictum that “individualization is key.” For instance, for those with very limited life expectancy or symptomatic postural hypotension, a higher systolic BP reading may be appropriate. An approach of shared decision making between health care providers and patients should be followed.
The patient was advised to check his BP on his upper arm at home using an oscillometric BP device, two times in the morning and two times in the evening for 1 week. In addition, while advising him to continue adherence to lifestyle modifications, benazepril was increased to 40 mg and amlodipine to 10 mg daily in a single-pill combination, along with chlorthalidone 25 mg daily. In a recent randomized trial including adults with an eGFR of 15 to <30 ml/min per 1.73 m2, chlorthalidone titrated up to 50 mg versus placebo lowered systolic BP by 10.5 mm Hg over 12 weeks (9). During a follow-up visit, his BP was recorded at 115/70 mm Hg. He remained asymptomatic and his laboratory studies were unremarkable.
E.V. Lerma reports having employment with Associates in Nephrology; reports having consultancy agreements with Akebia, Bayer, Otsuka, Travere Therapeutics, and Vifor; ownership interest in Fresenius Joint Venture; receiving royalty/ honoraria from Elsevier, McGraw-Hill, Springer, UpToDate, and Wolters Kluwer; serving as editorial board member of American Journal of Kidney Diseases, ASN Kidney News, International Urology and Nephrology, Journal of Clinical Lipidology, Journal of Vascular Access, Peritoneal Dialysis International, Prescribers Letter, Renal and Urology News, and Reviews in Endocrinology and Metabolic Disorders; serving as a Visual Abstract Editor for CJASN, Kidney 360, and Peritoneal Dialysis International; speakers bureau for AstraZeneca, Bayer, Otsuka, and Vifor; and KDIGO Knowledge Translation Lead. P. Muntner reports having consultancy agreements with Amgen Inc. and reports receiving research funding from Amgen Inc. W.C. Cushman reports receiving research funding from Eli Lilly and ReCor.
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