SPRINT—A Kidney-Centric Narrative Review: Recent Advances in Hypertension

Author(s):  
Austin H. Hu ◽  
Tara I. Chang

Hypertension is a potent cardiovascular risk factor with deleterious end-organ effects and is especially prevalent among patients with chronic kidney disease. The SPRINT (Systolic Blood Pressure Intervention Trial) enrolled patients at an elevated cardiac risk including patients with mild to moderate chronic kidney disease and found that an intensive systolic blood pressure goal of <120 mm Hg significantly reduced the rates of adverse cardiovascular events and all-cause mortality and nonsignificantly reduced the rates of probable dementia; these results were consistent whether one had chronic kidney disease or not. However, results of intensive blood pressure therapy on chronic kidney disease progression were inconclusive, and there was an increased risk of incident chronic kidney disease and acute kidney injury, but the declines in kidney function appear to be hemodynamically driven and reversible. Overall, an intensive blood pressure target is effective in reducing cardiovascular disease and all-cause mortality and may reduce the risk of probable dementia in patients with mild to moderate chronic kidney disease. More studies are needed to determine its long-term effects on kidney function.

2019 ◽  
Vol 49 (4) ◽  
pp. 297-306 ◽  
Author(s):  
Manuel Rivera ◽  
Leonardo Tamariz ◽  
Maritza Suarez ◽  
Gabriel Contreras

Background: Management of chronic kidney disease (CKD) patients includes efforts directed toward modifying traditional cardiovascular risk factors. Such efforts include optimal management of hypertension together with the initiation of statin therapy. Methods: In this observational study, we determine the modifying effect of statins on the relationship of systolic blood pressure (SBP) goal with mortality and other outcomes in patients with CKD participating in a clinical trial. At baseline, 2,646 CKD patients (estimated glomerular filtration rate < 60 mL/min/1.73 m2) were randomized to an intensive SBP goal < 120 mm Hg or standard SBP goal <140 mm Hg. One thousand two hundred and seventy-three were not on statin, 1,354 were on a statin, and in 19 the use of statin was unknown. The 2 primary outcomes were all-cause mortality and cardiovascular disease (CVD) mortality. Results: The relationships of SBP goal with all-cause mortality (interaction p = 0.009) and cardiovascular (CV) mortality (interaction p = 0.021) were modified by the use of statin after adjusting for age, gender, race, CVD history, smoking, aspirin use, and blood pressure at baseline. In the statin group, targeting SBP to < 120 mm Hg compared to SBP < 140 mm Hg significantly reduced the risk of all-cause mortality (adjusted hazard ratio [aHR] 0.44 [0.28–0.71]; event rates 1.16 vs. 2.5 per 100 patient-years) and CV mortality (aHR 0.29 [0.12–0.74]; event rates 0.28 vs. 0.92 per 100 patient-years) after a median follow-up of 3.26 years. In the non-statin group, the risk of all-cause mortality (aHR 1.07 [0.69–1.66]; event rates 2.01 vs. 1.94 per 100 patient-years) and CV mortality (aHR 1.42 [0.56–3.59]; event rates 0.52 vs. 0.41 per 100 patient-years) were not significantly different in both SBP goal arms. Conclusion: The combination of statin therapy and intensive SBP management leads to improved survival in hypertensive patients with CKD.


Author(s):  
So Mi J Cho ◽  
Hokyou Lee ◽  
Tae-Hyun Yoo ◽  
Jong Hyun Jhee ◽  
Sungha Park ◽  
...  

Abstract Background Although abnormal blood pressure patterns are associated with adverse cardiorenal outcomes, their associations are yet unquantified by nocturnal dipping status. We examined the association of nocturnal blood pressure dipping pattern with albuminuria and kidney function among participants with controlled hypertension without prior advanced kidney disease. Methods Ambulatory blood pressure measurements were collected from 995 middle-aged, cardiology clinic patients with controlled office blood pressure (&lt;140/90 mmHg). The magnitude of dipping was calculated as the difference between daytime and nighttime systolic blood pressure divided by daytime systolic blood pressure. Accordingly, the participants were categorized as extreme-dipper (≥20%), dipper (10-&lt;20%), non-dipper (0-&lt;10%), or reverse-dipper (&lt;0%). We analyzed the cross-sectional associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (&lt;60 ml/min/1.73m 2), adjusting for office/ambulatory blood pressure, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior. Results The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% extreme-dippers, 43.1% dippers, 34.7% non-dippers, and 8.7% reverse-dippers. In reference to dippers, odds ratios [95% confidence interval] for albuminuria were 1.73 [1.04-2.60] in reverse-dippers, 1.67 [1.20-2.32] in non-dippers, and 0.62 [0.38-1.04] in extreme-dippers. Likewise, abnormal dipping profile was associated with decreased kidney function: reverse-dipping, 2.02 [1.06-3.84]; non-dipping, 1.98 [1.07-3.08]; extreme-dipping, 0.69 [0.20-1.17]. The associations persisted participants with more conservatively controlled office blood pressure (&lt;130/80 mmHg). Conclusions Monitoring diurnal and nocturnal blood pressure may identify chronic kidney disease otherwise overlooked based on office blood pressure.


Author(s):  
George Bakris ◽  
Pablo E. Pergola ◽  
Belkis Delgado ◽  
Diyan Genov ◽  
Tamar Doliashvili ◽  
...  

In patients with resistant or poorly controlled hypertension and advanced chronic kidney disease, mineralocorticoid receptor antagonists are recommended; however, hyperkalemia limits their use. BLOCK-CKD was a phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the safety, efficacy, and pharmacokinetics of KBP-5074, a nonsteroidal mineralocorticoid receptor antagonist, for uncontrolled hypertension in patients with stage 3b/4 chronic kidney disease. The study tested the hypothesis that addition of KBP-5074 to standard treatment lowers blood pressure without increased risk of hyperkalemia. Patients (N=162) were randomly assigned 1:1:1 to once-daily oral treatment with placebo, KBP-5074 0.25 mg, or KBP-5074 0.5 mg. The primary end point was systolic blood pressure change from baseline at day 84. Baseline mean (SD) systolic blood pressure was 155.3 (13.55) mm Hg. After 84 days, the placebo-subtracted treatment difference was −7.0 (3.37) mm Hg with KBP-5074 0.25 mg ( P =0.0399) and −10.2 (3.32) mm Hg with KBP-5074 0.5 mg ( P =0.0026). Hyperkalemia incidence, ≥5.6 <6 mmol/L, were similar among groups 5 (8.8%) placebo, 6 (11.8%) 0.25 mg, and 9 (16.7%) 0.5 mg patients. No hyperkalemia ≥6.0 mmol/L was observed. We conclude that KBP-5074 effectively lowers blood pressure with some risk of hyperkalemia in individuals with advanced chronic kidney disease and uncontrolled blood pressure. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03574363.


2020 ◽  
Author(s):  
Pantelis Sarafidis ◽  
Charalampos Loutradis ◽  
Alberto Ortiz ◽  
Luis M Ruilope

Abstract Recent American and European hypertension guidelines are not in agreement regarding blood pressure (BP) targets for persons with chronic kidney disease (CKD). Previous analyses from the African American Study on Kidney Disease (AASK) and Modification of Diet in Renal Disease (MDRD) trials suggested that strict BP control confers nephroprotection for patients with proteinuria, but a mortality benefit was not apparent. In contrast, an analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) subpopulation of CKD patients showed a mortality benefit with the systolic blood pressure (SBP) &lt;120 mmHg versus the SBP &lt;140 target. A recent analysis of the combined MDRD and AASK cohorts supports previous evidence on nephroprotection but also findings from the SPRINT trial on all-cause mortality benefits of intensive versus usual BP control in individuals with CKD.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Charles A German ◽  
Tali Elfassy ◽  
Matthew J Singleton ◽  
Carlos J Rodriguez ◽  
Walter T Ambrosius ◽  
...  

Introduction: Blood pressure trajectories have been associated with cardiovascular disease (CVD) in observational studies. It is unclear whether these associations are independent of average blood pressure over time. Methods: We used data from SPRINT to identify systolic blood pressure (SBP) trajectories among a cohort of 8901 participants by incorporating SBP measures during the first 12 months of the trial post randomization. Trajectories were identified using latent class based modeling. Study outcomes included incident CVD, defined as myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death attributable to CVD, and all-cause mortality. Cox proportional hazards models were used to evaluate associations between SBP trajectories and our outcomes of interest. Results: Four distinct SBP trajectories were identified: ‘low decline’ (40%), ‘high decline’ (6%), ‘low stable’ (48%), and ‘high stable’ (5%) (Figure 1). Relative to the low decline group, the low stable group was associated with a 29% increased risk of CVD (HR: 1.29, 95%CI: 1.06-1.57) and the high stable group was associated with a 76% increased risk of all-cause mortality (HR: 1.76, 95%CI: 1.15-2.68) after baseline multivariable adjustment. Relative to the low stable group, the high stable group was associated with a 54% increased risk of all-cause mortality (HR: 1.54, 95%CI: 1.05-2.28). When adjusting for average blood pressure across the 12 month time period, there were no significant differences in outcomes. Conclusion: We identified 4 SBP trajectories using data from SPRINT and found differences in the risk of CVD and all-cause mortality after baseline adjustment. However, there were no differences in the risk of these outcomes after adjusting for average blood pressure over time. These results suggest that the pattern of blood pressure control may not be relevant as long as the target blood pressure is achieved.


2019 ◽  
Vol 27 (9) ◽  
pp. 978-987 ◽  
Author(s):  
Kristofer Hedman ◽  
Nicholas Cauwenberghs ◽  
Jeffrey W Christle ◽  
Tatiana Kuznetsova ◽  
Francois Haddad ◽  
...  

Aims The association between peak systolic blood pressure (SBP) during exercise testing and outcome remains controversial, possibly due to the confounding effect of external workload (metabolic equivalents of task (METs)) on peak SBP as well as on survival. Indexing the increase in SBP to the increase in workload (SBP/MET-slope) could provide a more clinically relevant measure of the SBP response to exercise. We aimed to characterize the SBP/MET-slope in a large cohort referred for clinical exercise testing and to determine its relation to all-cause mortality. Methods and results Survival status for male Veterans who underwent a maximal treadmill exercise test between the years 1987 and 2007 were retrieved in 2018. We defined a subgroup of non-smoking 10-year survivors with fewer risk factors as a lower-risk reference group. Survival analyses for all-cause mortality were performed using Kaplan–Meier curves and Cox proportional hazard ratios (HRs (95% confidence interval)) adjusted for baseline age, test year, cardiovascular risk factors, medications and comorbidities. A total of 7542 subjects were followed over 18.4 (interquartile range 16.3) years. In lower-risk subjects ( n = 709), the median (95th percentile) of the SBP/MET-slope was 4.9 (10.0) mmHg/MET. Lower peak SBP (<210 mmHg) and higher SBP/MET-slope (>10 mmHg/MET) were both associated with 20% higher mortality (adjusted HRs 1.20 (1.08–1.32) and 1.20 (1.10–1.31), respectively). In subjects with high fitness, a SBP/MET-slope > 6.2 mmHg/MET was associated with a 27% higher risk of mortality (adjusted HR 1.27 (1.12–1.45)). Conclusion In contrast to peak SBP, having a higher SBP/MET-slope was associated with increased risk of mortality. This simple, novel metric can be considered in clinical exercise testing reports.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Wondimeneh Shibabaw Shiferaw ◽  
Tadesse Yirga Akalu ◽  
Yared Asmare Aynalem

Background. Though different primary studies have reported the burden of chronic kidney disease among diabetes patients, their results have demonstrated substantial variation regarding its prevalence in Ethiopia. Therefore, this study aimed to estimate the pooled prevalence of chronic kidney disease and its associated factors among diabetes patients in Ethiopia. Method. PubMed, African Journals Online, Google Scholar, Scopus, and Wiley Online Library were searched to identify relevant studies. The I2 statistic was used to check heterogeneity across the included studies. A random-effects model was applied to estimate the pooled effect size across studies. A funnel plot and Egger’s regression test were used to determine the presence of publication bias. All statistical analyses were performed using STATA™ version 14 software. Result. In this meta-analysis, a total of 12 studies with 4,075 study participants were included. The estimated prevalence of CKD among diabetes patients was found to be 35.52% (95% CI: 25.9–45.45, I2 = 96.3%) for CKD stages 1 to 5 and 14.5% (95% CI: 10.5–18.49, I2 = 91.1%) for CKD stages 3 to 5. Age greater than 60 years (OR = 2.99; 95% CI: 1.56–5.73), female sex (OR = 1.68; 95% CI: 1.04–2.69), duration of diabetes >10 years (OR = 2.76; 95% CI: 1.38–5.51), body mass index >30 kg/m2 (OR = 2.06; 95% CI: 1.41–3.00), type 2 diabetes (OR = 2.54; 95% CI: 1.73–3.73), poor glycemic control (OR = 2.01; 95% CI: 1.34–3.02), fasting blood glucose >150 mg/dl (OR = 2.58; 95% CI: 1.79–3.72), high density lipoprotein >40 mg/dl (OR = 0.48; 95% CI: 0.30–0.85–25), systolic blood pressure>140 mmHg (OR = 3.26; 95% CI: 2.24–4.74), and diabetic retinopathy (OR = 4.54; CI: 1.08–25) were significantly associated with CKD. Conclusion. This study revealed that the prevalence of chronic kidney disease remains high among diabetes patients in Ethiopia. This study found that a long duration of diabetes, age>60 years, diabetic retinopathy, female sex, family history of kidney disease, poor glycemic control, systolic blood pressure, overweight, and high level of high-density lipoprotein were associated with chronic kidney disease among diabetic patients. Therefore, situation-based interventions and context-specific preventive strategies should be developed to reduce the prevalence and risk factors of chronic kidney disease among diabetes patients.


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