Guideline-Driven Management of Hypertension: An Evidence-Based Update.

Several important findings bearing on the prevention, detection, and management of hypertension have been reported since publication of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. This review summarizes and places in context the results of relevant observational studies, randomized clinical trials, and meta-analyses published between January 2018 and March 2021. Topics covered include blood pressure measurement, patient evaluation for secondary hypertension, cardiovascular disease risk assessment and blood pressure threshold for drug therapy, lifestyle and pharmacological management, treatment target blood pressure goal, management of hypertension in older adults, diabetes, chronic kidney disease, resistant hypertension, and optimization of care using patient, provider, and health system approaches. Presenting new information in each of these areas has the potential to increase hypertension awareness, treatment, and control which remain essential for the prevention of cardiovascular disease and mortality in the future.

Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy.

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.

Renal function outcomes and kidney biopsy features of living kidney donors with hypertension.

BACKGROUND: The medium- to long-term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines. METHODS: We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension. RESULTS: After adjusting for years of follow-up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m2 at a median follow-up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00-2.36; p = .051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers. CONCLUSIONS: In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long-term risk for proteinuria, and particularly for these donors, longer follow-up is warranted.

Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient.

BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

Comparison of high glomerular filtration rate thresholds for identifying hyperfiltration.

BACKGROUND: High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration. METHODS: We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine-based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed. RESULTS: We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134 mL/min/1.73 m2 and for eGFR was 118 mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198 mL/min - 0.943×Age, for corrected mGFR it was 164 mL/min/1.73 m2 - 0.730×Age and for eGFR it was 146 mL/min/1.73 m2 - 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender-based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender. CONCLUSIONS: High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number.

Potential US Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults provides recommendations for the definition of hypertension, systolic and diastolic blood pressure (BP) thresholds for initiation of antihypertensive medication, and BP target goals. OBJECTIVES: This study sought to determine the prevalence of hypertension, implications of recommendations for antihypertensive medication, and prevalence of BP above the treatment goal among US adults using criteria from the 2017 ACC/AHA guideline and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). METHODS: The authors analyzed data from the 2011 to 2014 National Health and Nutrition Examination Survey (N = 9 623). BP was measured 3 times following a standardized protocol and averaged. Results were weighted to produce US population estimates. RESULTS: According to the 2017 ACC/AHA and JNC7 guidelines, the crude prevalence of hypertension among US adults was 45.6% (95% confidence interval [CI]: 43.6% to 47.6%) and 31.9% (95% CI: 30.1% to 33.7%), respectively, and antihypertensive medication was recommended for 36.2% (95% CI: 34.2% to 38.2%) and 34.3% (95% CI: 32.5% to 36.2%) of US adults, respectively. Nonpharmacological intervention is advised for the 9.4% of US adults with hypertension who are not recommended for antihypertensive medication according to the 2017 ACC/AHA guideline. Among US adults taking antihypertensive medication, 53.4% (95% CI: 49.9% to 56.8%) and 39.0% (95% CI: 36.4% to 41.6%) had BP above the treatment goal according to the 2017 ACC/AHA and JNC7 guidelines, respectively. CONCLUSIONS: Compared with the JNC7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in the prevalence of hypertension, a small increase in the percentage of US adults recommended for antihypertensive medication, and more intensive BP lowering for many adults taking antihypertensive medication.

Larger nephron size, low nephron number, and nephrosclerosis on biopsy as predictors of kidney function after donating a kidney.

It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4 months after donation, with measured GFR <60 mL/min/1.73 m2 in 34%, urine albumin >5 mg/24 h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60 mL/min/1.73 m2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5 mg/24 h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60 mL/min/1.73 m2 , modest increases in urine albumin, and hypertension shortly after kidney donation.

Hypertension guideline update: A new guideline for a new era.

In the United States, hypertension affects about one-third of adults and contributes to one out of every seven deaths. Evidence-based treatment is associated with reductions in incidence of stroke, myocardial infarction, and heart failure as well as associated disability and death. This article reviews the ACC/AHA Task Force on Clinical Practice Guidelines' 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Key changes include reclassification of BP stages and lowering of hypertension treatment goals.

Assessment and management of hypertension in transplant patients.

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.

Gender differences in use of prescription narcotic medications among living kidney donors.

Prescription narcotic use among living kidney donors is not well described. Using a unique database that integrates national registry identifiers for living kidney donors (1987-2007) in the United States with billing claims from a private health insurer (2000-2007), we identified pharmacy fills for prescription narcotic medications in periods 1-4 and >4 yr post-donation and estimated relative likelihoods of post-donation narcotic use by Cox regression. We also compared narcotic fill rates and medication possession ratios (MPRs, defined as (days of medication supplied)/(days observed)), between donors and age- and sex-matched non-donors. Overall, rates of narcotic medication fills were 32.3 and 32.4 per 100 person-years in periods 1-4 and >4 yr post-donation. After age and race adjustment, women were approximately twice as likely as men to fill a narcotic prescription in years 1-4 (adjusted hazard ratio, aHR, 2.28; 95% confidence interval, CI, 1.86-2.79) and >4 yr (aHR 1.70; 95% CI 1.50-1.93). MPRs in donors were low (<2.5% days exposed), and lower than among age- and sex-matched non-donors. Prescription narcotic medication use is more common among women than men in the intermediate term after live kidney donation. Overall, total narcotic exposure is low, and lower than among non-donors from the general population.

Individualizing antihypertensive combination therapies: clinical and hemodynamic considerations.

While there are strong trial data to guide the selection of initial hypertension treatment choice and limited data to support second agent choice, beyond the first two agents, subsequent steps are empiric. As medications are added, the resulting polypharmacy may be complex, inefficient and poorly tolerated, resulting in low treatment adherence rates. The selection of antihypertensive drug therapy based on hemodynamic mechanisms is not new but became practical with the availability of noninvasive hemodynamic parameters using impedance cardiography. Individualized therapy based on hormonal or hemodynamic measurements can effectively control hypertension as shown in several small clinical trials. Hemodynamic measurements are obtained quickly, painlessly and can be used in a serial fashion to guide treatment adjustments. Current limitations relate to availability of the measurement device and personnel trained in its use, reimbursement for the measurements, expertise in interpretation of the measurements and systems to adjust medication and repeat measurements in a serial fashion until targets are attained. The potential utility of this approach increases with greater complexity of the medication regimen. Further studies are indicated and may advance options for individualized treatment of hypertensive patients.

2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement From the American Heart Association.

Over the past 3 decades, a substantial body of high-quality evidence has guided the diagnosis and management of elevated blood pressure (BP) in the outpatient setting. In contrast, there is a lack of comparable evidence for guiding the management of elevated BP in the acute care setting, resulting in significant practice variation. Throughout this scientific statement, we use the terms acute care and inpatient to refer to care received in the emergency department and after admission to the hospital. Elevated inpatient BP is common and can manifest either as asymptomatic or with signs of new or worsening target-organ damage, a condition referred to as hypertensive emergency. Hypertensive emergency involves acute target-organ damage and should be treated swiftly, usually with intravenous antihypertensive medications, in a closely monitored setting. However, the risk-benefit ratio of initiating or intensifying antihypertensive medications for asymptomatic elevated inpatient BP is less clear. Despite this ambiguity, clinicians prescribe oral or intravenous antihypertensive medications in approximately one-third of cases of asymptomatic elevated inpatient BP. Recent observational studies have suggested potential harms associated with treating asymptomatic elevated inpatient BP, which brings current practice into question. Despite the ubiquity of elevated inpatient BPs, few position papers, guidelines, or consensus statements have focused on improving BP management in the acute care setting. Therefore, this scientific statement aims to synthesize the available evidence, provide suggestions for best practice based on the available evidence, identify evidence-based gaps in managing elevated inpatient BP (asymptomatic and hypertensive emergency), and highlight areas requiring further research.