Article Information

Mohammad Tinawi^*

Adjunct Clinical Assistant Professor of Medicine, Indiana University School of Medicine Northwest-Gary, Nephrology Specialists, IN, USA

*Corresponding author: Mohammad Tinawi, Nephrology Specialists, P.C., 8840 Calumet Ave, Suite 101, Munster, IN 46321, USA

Received: 14 September 2021; Accepted: 19 January 2022; Published: 21 January 2022

Citation: Mohammad Tinawi. Current Trends in Hypertension: Takeaways from the 2021 KDIGO Guidelines for the Management of Blood Pressure in Chronic Kidney Disease. Cardiology and Cardiovascular Medicine 6 (2022): 07-12.

Abstract

Keywords

Hypertension, CKD, KDIGO guide-lines, SPRINT

Article Details

1. Introduction

1.1 The Systolic Blood Pressure Intervention Trial (SPRINT)

SPRINT was published in 2015 [1, 2]. It is a landmark study in hypertension. SPRINT enrolled 9361 subjects. It was a randomized, multicenter, and controlled trial. The enrollees were 50 years or older with systolic blood pressure (SBP) above 130 mm Hg and one of the following conditions: CKD (estimated glomerular filtration rate [eGFR] 20-59 ml/min/1.73 m²), history of cardiovascular disease (CVD), intermediate to high risk for CVD other than cere-brovascular accident (CVA), or age over 75 years. The standard treatment target was SBP< 140 mm Hg, while the intensive treatment target was SBP < 120 mm Hg. In the group randomized to the lower SBP goal of (< 120 mm Hg), the primary combined cardiovascular endpoints decreased by 25%, while mortality was reduced by 27%.

CKD defined as eGFR 20-59 ml/min/1.73 m² was present in 28% of SPRINT subjects. Based on SPRINT inclusion and exclusion criteria, none of the subjects had polycystic kidney disease or proteinuria ≥ 1 g/day. In the SPRINT-CKD cohort, there was no difference between the standard and intensive treat-ment groups with regard to serious adverse events or end-stage renal disease (ESRD). The intensive treat-ment group had a lower mortality rate [3]. The higher risk of ≥ 30% decline in eGFR in the intensive treatment group was credited to the hemodynamic effect of intensive blood pressure (BP) lowering. The decline was ameliorated after the initial 6 months of intensive BP therapy.

1.2 Rating of recommendations

The strength of each recommendation in the guide-lines is indicated as Level 1 (strong, the authors recommend), or Level 2 (weak, the authors suggest), and the quality of the supporting evidence is shown as A (high), B (moderate), C (low), or D (very low) [4].

1.3 Chronic kidney disease (CKD) categories

Based on GFR in ml/min/1.73 m², CKD is divided into five categories or stages: G1 (GFR  ≥ 90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), and G5 (<15) [5].

1.4 Persistent albuminuria categories

A1 (<30 mg albumin /g creatinine, or < 3 mg album-in/mmol creatinine), A2 (30-300 mg/g, or 3-30 mg/ mmol), and A3 (>300 mg/g, or >30 mg/mmol) [5].

2. Summary of Guidelines

2.1 Blood pressure measurement

Standardized office BP measurement rather than routine BP measurement is recommended for high BP management in adults. An Oscillometric BP device may be preferable to a manual one. The former may be used in atrial fibrillation patients. An automated office BP device whether attended or unattended is preferred. All the above recomm-endations are rated (1B). Ambulatory (ABPM) and home BP (HBPM) monitoring are complementary to standardized office BP measurement (2B) [6]. HBPM should not solely guide BP management. It is worth mentioning that SPRINT utilized a fully automated oscillometric BP device. BP readings were attended by staff at some but not all of the study centers [1]. This automated approach was implemented to reduce errors in BP measurements and possibly reduce white coat effect. Ambulatory self BP monitoring should only be done via a certified device. The American Medical Association published a list of validated devices in the United States after conducting an independent review process. It can be found online at: https://www.validatebp.org.

Standardized office BP measurement should be done in a quiet room, the patient is seated, and the back is supported while the feet are flat on the floor [6]. The arm is bare and resting at the same level of the device. No talking by the patient or the observer is allowed. The patient should not have smoked, consumed caffeine, or exercised for 30 minutes. The patient should relax with an empty bladder for at least five minutes prior to BP measurement. Cuff size should be appropriate for the arm, and the device should be calibrated periodically. It is important to know that BP measurements using a standardized office BP measurement protocol may yield different results compared to routine office BP measurements. The relationship between the two measurements is variable and a correction factor to convert one to the other does not exist.

2.2 Lifestyle interventions for non-dialysis CKD patients

The guidelines recommend sodium intake <2 g per day (<90 mEq or 90 mmol/day), or <5 g of sodium chloride (NaCl) per day (2C) [6]. Utilization of diets that are high in potassium such as [The Dietary Approaches to Stop Hypertension (DASH)] or pota-ssium-containing salt substitutes is not appropriate for CKD patients prone to hyperkalemia such as those with diabetic kidney disease and hyporen-inemic hypoaldosteronism. Depending on the fitness level and cardiovascular tolerance of the patient, a moderately intense physical activity of a minimum of 150 minutes per week is recommended (2C).

2.3 Blood pressure targets

The 2012 guidelines recommended a target BP (<130-140/80-90) mm Hg depending on the specific CKD population [7]. The updated 2021 guidelines recommend a target systolic blood pressure SBP of <120 mm Hg using standardized office BP measure-ment (2B) [4]. This target reduces major cardiovas-cular events and all-cause mortality in CKD patients. It is unclear whether it impacts kidney disease progression. This lower target is based on the results of SPRINT [3]. The benefits of this intensive BP lowering (SBP <120 mm Hg) is less certain in diabetics with CKD, patients with stage 5 CKD, and those with A3 albuminuria (>300 mg/g, or >30 mg/mmol). This conclusion is based on the results of previous clinical trials including ACCORD, MDRD, AASK, and REIN-2 [8-11]. A higher target may be considered in patients with postural hypotension or limited longevity.

2.4 Choice of antihypertensive drugs

Inhibitors of the renin-angiotensin-system (RASi) including (angiotensin converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB]) are recommended for non-diabetics with high BP, CKD (G1, G2, G3, and G4) and A3 albuminuria (>300 mg/g, or >30 mg/mmol) [1B] and suggested in case of A2 albuminuria (30-300 mg/g, or 3-30 mg/mmol) [1C] [11]. The same recommendation applies to diabetics with A2 or A3 albuminuria with a (1B) rating [12, 13]. Several practical points are empha-sized by the authors of the guidelines regarding the choice of antihypertensive drugs. RASi may be used for managing hypertensive CKD patients without albuminuria. This applies to both diabetic and non-diabetic patients. Since clinical trials with RASi utilized the highest tolerated approved doses, the same approach should be used to maximize the benefit of these medications. BP and a chemistry panel including creatinine and potassium should be checked within 2-4 weeks of treatment initiation of RASi. There is no indication to discontinue treatment with RASi unless creatinine rises by more than 30% within 4 weeks of treatment initiation or dose escala-tion. Measures to mitigate hyperkalemia should be implemented (low potassium diet, potassium binders), rather than dose reduction or discontin-uation [14, 15]. A retrospective review of a large database of electronic health records involving over 200,000 patients, showed that RASi discontinuation or dose reduction is associated with increased mortality [16]. On the other hand, RASi disconti-nuation or dose reduction maybe considered in hyper-kalemia unresponsive to medical treatment, sympt-omatic hypotension, or patients with stage 5 CKD (G5, GFR < 15 ml/min/1.73 m²) to reduce uremic symptoms. Mineralocorticoid receptor antagonists such as spironolactone are effective in CKD patients with resistant hypertension; however, hyperkalemia and a reversible decline in renal function are limiting factors especially in patients with advanced CKD [17].

2.5 Dual therapy with RASi

The use of any combination of ACEi, ARB, and direct renin inhibitors is not recommended in patients with CKD, with or without diabetes (1B) [18].

2.6 Kidney transplant recipients

BP target in adult kidney transplant recipients is <130 mm Hg systolic and <80 mm Hg diastolic. This is the same recommendation from the previous 2012 guidelines [7]. There are no published randomized clinical trials concerning different BP targets and subsequent clinical outcomes in kidney transplant recipients. In this population, dihydropyridine cal-cium channel blockers (CCB) or ARB are first-line antihypertensive agents (1C) [19, 20].

2.7 Children with CKD

Ambulatory BP monitoring (ABPM)  should be done in children with CKD to determine 24-hour mean arterial pressure (MAP). MAP should be lowered to ≤ 50^th percentile for height, age, and sex of the child (2C) [21]. ABPM is suggested annually for BP monitoring in children with CKD. Otherwise, regular monitoring with standardized auscultatory office BP monitoring is done every 3-6 months. If ABPM is not available, standardized manual auscultatory office BP should be lowered to achieve SBP <90^th percentile for height, age, and sex of the child. ACEi or ARB are first-line therapy, but they should be avoided in pregnancy.

3. Conclusion

The new 2021 KDIGO guidelines on the mana-gement of blood pressure in chronic kidney disease (CKD) patients update the 2012 guidelines. They recommend a target systolic blood pressure SBP of <120 mm Hg and emphasize the importance of using standardized office BP measurement. RASi are recommended as first line agents. Any combination of ACEi, ARB, and direct renin inhibitors should be avoided. Pending further data, adult kidney transplant receipts should be treated to a BP target of (<130/<80) mm Hg.

Conflict of Interest

None

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