Comparing the 2021 KDIGO vs. 2017 ACC/AHA guidelines for hypertension
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Chronic kidney disease occurs commonly in patients with hypertension and diabetes, and is also associated with acute kidney failure, intrinsic kidney disorders and family history of chronic kidney disease.
Nearly 40% of people aged 65 years and older have chronic kidney disease (CKD), with 2021 Medicare expenditures totaling more than $87 billion. Because CKD is generally a progressive condition, early identification and therapeutic intervention are important to reduce kidney-related disease complications and overall morbidity and mortality.
Hypertension and CKD
BP and kidney function are intimately linked by the relationship between sodium/water handling and hormonal regulation via the renin-angiotensin-aldosterone system (RAAS). Elevated BP and hypertension contribute to CKD by accelerating glomerular hyperfiltration, promoting sympathetic hyperactivity and worsening endothelial dysfunction; it also is a known, significant factor for CVD risk in patients with and without CKD.
In U.S. adults, mortality rates for patients with CKD and hypertension have been consistently higher compared with patients with CKD but without hypertension, across all stages (ie, levels of severity) of CKD. In representative studies of U.S. adults with known CKD, about 70% had hypertension as a prior diagnosis but less than 50% had achieved BP of 130/80 mm Hg or less. Therefore, control and management of hypertension in CKD appropriately deserves attention as a clinical priority.
Hypertension guidelines
Several updated evidence-based guidelines for management of hypertension have been published in recent years, including the 2017 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults. BP goals for patients with CKD vary somewhat between these guidelines (Table 1); recommendations for nonpharmacologic and pharmacologic treatment are more consistent and favor sodium restriction, increased physical activity and selection of thiazide diuretics, calcium antagonists and RAAS inhibitors as first-line antihypertensive medications.
Kidney Disease: Improving Global Outcomes (KDIGO)
The KDIGO Global Network is an international foundation organized to develop and implement clinical practice guidelines across the various conditions specific to the care of those with kidney diseases.
In 2021, the KDIGO Global Network updated its Clinical Practice Guideline on the Management of Blood Pressure in Chronic Kidney Disease. Specifically, the 2021 KDIGO Guideline recommends (level 1, GRADE framework) adopting a standardized, rather than usual, in-office BP measurement for disease monitoring and to guide management decisions. Furthermore, it goes on to suggest (level 2) that most patients with CKD and high BP be treated to a target systolic BP of less than 120 mm Hg, if able to be tolerated. Both recommendations differ in specifics from the 2017 ACC/AHA hypertension guideline.
Standardized BP measurement
The terminology of “standardized BP” refers to results obtained in-office and adhering to steps outlined in the 2019 AHA Scientific Statement on Measurement of BP in Humans, and particularly reinforces the need for proper patient preparation and manner of measurement (Table 3). Emphasis is placed on technique, rather than type of device used or automated vs. manual readings, as well as making treatment decisions to achieve target BP based on these in-office readings. Out-of-office BPs obtained from home or ambulatory BP monitoring is discussed as only supplementary to in-office measurements or when circumstances like the recent COVID-19 pandemic or patient disability render in-person visits impractical.
KDIGO addresses benefits and risks associated with this approach, particularly citing use of optimized BP measurement as the standard in randomized controlled trials including SPRINT, as well as the imprecision of routine (nonstandardized) BPs. Variability between routine and standardized in-office BP is highlighted, especially because it is not at all predictable; therefore, any sort of correlation factor is not provided. Challenges associated with clinical (rather than research) implementation of standardized BP measurement include increased time and preparation steps for patients, additional training of health care providers, and extended time in patient assessment and monitoring. As a practical consideration, the 2021 KDIGO Guideline proposes automated oscillometric BP devices as an option to facilitate adoption and clinical acceptance of standardized BP in practice.
In contrast, the 2017 ACC/AHA hypertension guideline encourages accuracy of BP techniques for in-office measurement (consensus of expert opinion) while also recommending increasing use of out-of-office measurements to confirm patient diagnoses and to titrate medications (based on high-quality evidence from randomized clinical trials). The 2019 AHA Statement on Measurement of BP provides extensive detail on different BP measurement modalities and the evidence that informs their use (Table 2).
BP targets
The 2021 KDIGO BP Guideline specifies systolic BP of less than 120 mm Hg (by standardized measure, above) as the ideal target for patients with CKD, either with or without diabetes, as long as this can be tolerated by the patient. This recommendation is based primarily on findings from the SPRINT trial, which included about one-third of study participants with CKD. Overall, treatment to a lower target resulted in fewer CVD events and deaths in the intervention group compared with a BP target of less than 140 mm Hg, without major positive or negative effect on kidney outcomes. Given the high prevalence of CVD in the general population and a substantially increased CVD risk across the full spectrum of CKD, the KDIGO working group reported there was sufficient benefit to justify the guidance, particularly as there may be additional benefits (eg, improved cognition) associated with such practice. This recommendation is graded as level 2 (weaker quality) as it is based on a single, though robust, randomized study. As such, it may not be suitable for all patients and particularly not for those at risk for acute kidney injury or electrolyte abnormalities, or those likely to experience low diastolic pressures on multidrug regimens.
Risks of intensive BP lowering potentially exceed benefits in several patient groups with CKD, namely those patients on dialysis or after kidney transplantation where quality of life and allograft survival are clear priorities. Therefore, alternative BP targets should be considered for these groups, per expert opinion. Patients with diabetes were notably excluded from SPRINT, though results from this and other trials do not clearly rule out health benefit from lower BP targets in patients with CKD and prediabetes and/or diabetes.
SPRINT trial and controversies
SPRINT was a large NHLBI-sponsored randomized controlled, open-label trial of 9,361 participants conducted across the U.S. Results were published in 2015. Participants were aged at least 50 years, with systolic BP of 130 mm Hg to 180 mm Hg and additional CVD risk factors including CKD with an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m2 to 60 mL/min/1.73 m2, but no diabetes. In the study, the intervention group was randomly assigned to a systolic BP target of less than 120 mm Hg (compared with < 140 mm Hg) using standardized treatment algorithms including all major classes of antihypertensive medication. Outcome adjudicators were not aware of treatment assignments, and stopped the trial early after 3.3 years due to significant decrease in the composite endpoint of CVD events (MI, other ACS, stroke or HF) and death: 1.65% per year vs. 2.19% per year (HR = 0.75; 95% CI, 0.64-0.89; P < .001). Those in the intensive treatment group required an average of 2.8 antihypertensive medications, compared with 1.8 medications in the standard group.
Nearly 30% (n = 2,646) of SPRINT participants had CKD and were included in a prespecified subgroup analysis. In this cohort, patients tended to be older (71.9 years) and male (60%) and had eGFR of 48 mL/min/1.73 m2; Black and Hispanic participants comprised about one-third. CKD status did not result in significant differences in the primary study outcomes compared with the overall group, particularly when comparing all-cause death: 1.61% per year in intensive target group and 2.21% per year in the standard target group (HR = 0.72; 95% CI, 0.53-0.99). For patients aged 75 years and older at study entry, the HRs for outcomes compared favorably for intensive treatment vs. standard treatment (eg, for composite of primary CVD outcome or all-cause death, HR = 0.66; 95% CI, 0.49-0.9). Mean number of BP medications was similar to the overall SPRINT cohorts, averaging 2.9 and 2, respectively.
Kidney outcomes were also studied in the subgroup analysis, without any significant change in decline of eGFR of at least 50% or difference in time to end-stage kidney disease noted between groups. The intensive treatment group included 92 patients (2.33%) who experienced at least 30% reduction in eGFR (compared with 1.15% in the standard group; HR = 2.03; 95% CI, 1.42-2.91; P < .01); this difference did not persist beyond 6 months post-randomization, however. Incident proteinuria was not different between the two participant groups, though urinary albumin-to-creatinine ratios were consistently lower with intensive BP treatment, particularly in the first 2 years of follow-up.
Debate around the strength of evidence, generalizability, and safety of lowering BP to intensive targets — as suggested by SPRINT — continues, as evidenced by a 2022 review published in Hypertension. The authors cited each of these concerns in considering the advisability and practicality of the KDIGO-recommended systolic target of less than 120 mm Hg in clinical practice, particularly since conditions like diabetes and polycystic kidney disease (causing about 5% of all kidney failure cases) were intentionally not included in the SPRINT design. Appropriateness is also predicated on being able to regularly obtain standardized measurement of BPs in office settings, further impacting feasibility. Additional clinical studies including implementation research would be of benefit. In the meantime, KDIGO web resources include a “point-counterpoint” resource that addresses the differing viewpoints on controversies raised in the 2021 KDIGO revision.
KDIGO practice points
The 2021 KDIGO Guideline includes a new feature of so-called “Practice Points” that are intended to supplement-graded recommendations with detailed guidance in the form of tables, figures or algorithms. Their purpose is to acknowledge areas where evidence is limited but nonetheless warrant elaboration based on clinical judgment and experience of the expert Work Group. A few examples are described in Table 3 and can be used to individualize patient care considering patient preferences and resources, and with a lens to practical implementation and clinical problem-solving.
- References:
- BMJ Best Practice. bestpractice.bmj.com/info/us/toolkit/learn-ebm/what-is-grade/. Accessed Jan. 27, 2023.
- CDC. Chronic Kidney Disease in the United States, 2021. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2021.
- CDC. Chronic Kidney Disease Surveillance System—United States. www.cdc.gov/ckd. Updated Dec. 1, 2022. Accessed Jan. 27, 2023.
- Cheung AK, et al. J Am Soc Nephrol. 2017;doi:10.1681/ASN.2017020148.
- Cheung AK, et al. Kidney Int. 2019; doi:10.1016/j.kint.2018.12.025.
- Dasgupta I, et al. Hypertension. 2022;doi:10.1161/HYPERTENSIONAHA.121.18434.
- Ferdinand KC, et al. Am J Prev Cardiol. 2020;doi:10.1016/j.ajpc.2020.100038.
- Kidney Disease: Improving Global Outcomes. kdigo.org/guidelines. Accessed Jan. 27, 2023.
- Kidney Disease: Improving Global Outcomes. kdigo.org/wp-content/uploads/2021/03/KDIGO-BP-Guideline-Point-Counterpoint_2-Page-Version.pdf. Accessed Jan. 27, 2023.
- Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. Kidney Int. 2021;doi: 10.1016/j.kint.2020.11.003.
- Manning DM, et al. Circulation. 1983; doi:10.1161/01.cir.68.4.763.
- Muntner P, et al. Hypertension. 2019; doi:10.1161/HYP.0000000000000087.
- National Institute for Healthcare Excellence. Hypertension in adults: diagnosis and management. www.nice.org.uk/guidance/ng136. Updated March 18, 2022. Accessed Jan. 27, 2023.
- Ogedegbe G, et al. Cardiol Clin. 2010;doi:10.1016/j.ccl.2010.07.006.
- The SPRINT Research Group. N Engl J Med. 2015;doi:10.1056/NEJMoa1511939.
- Unger T, et al. Hypertension. 2020;doi:10.1161/HYPERTENSIONAHA.120.15026.
- United States Renal Data System. 2021 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; 2021.
- Whelton PK, et al. Hypertension. 2018; doi:10.1161/HYP.0000000000000066.
- Williams B, et al. Eur Heart J. 2018;doi:10.1093/eurheartj/ehy339.
- For more information:
- Maria C. (Pruchnicki) Coyle, PharmD, FCCP, BCPS, BCACP, CLS, is associate clinical professor at The Ohio State University College of Pharmacy and Specialty Practice Pharmacist, Ambulatory Care, at The Ohio State University Wexner Medical Center.
- Kelly Bartsch, PharmD, BCPS, CLS, is specialty practice pharmacist, Ambulatory Care, at The Ohio State University Wexner Medical Center.
- Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS (AQ Cardiology), is the Cardiology Today Pharmacology Consult column editor. She is professor and chair of the department of pharmacy services in the School of Pharmacy and Pharmaceutical Sciences at Binghamton University. Spinler can be reached at sspinler@binghamton.edu.
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