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Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of

The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results.SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261.From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group.This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control.Medtronic.

The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.To determine whether there is an association between CKD and ICH risk.A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.CKD stages 1 to 5.The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007).In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

The SPYRAL HTN-OFF MED Pivotal trial (https://clinicaltrials.gov/ct2/show/NCT02439749) demonstrated significant reductions in blood pressure (BP) after renal denervation (RDN) compared to sham control in the absence of anti-hypertensive medications. Prior to the 3-month primary endpoint, medications were immediately reinstated for patients who met escape criteria defined as office systolic BP (SBP) ≥ 180 mmHg or other safety concerns. Our objective was to compare the rate of hypertensive urgencies in RDN vs. sham control patients. Patients were enrolled with office SBP ≥ 150 and p = 0.032), as well as for patients with a hypertensive urgency with office SBP ≥ 180 mmHg (p = 0.046). Rate of escape was similar between RDN and sham control for patients without a measured BP exceeding 180 mmHg (p = 0.32). In the SPYRAL HTN-OFF MED Pivotal trial, RDN patients were less likely to experience hypertensive urgencies that required immediate use of anti-hypertensive medications compared to sham control. Graphical abstract

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort with CKD and no self-reported history of cardiovascular disease (CVD). EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOMES: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH:. We described the proportion of participants above the conventional URL for NT-proBNP (125 pg/ml) and hsTnT (14 ng/L) overall, and by eGFR. We then estimated 99(th) percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99(th) percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above conventional URL, respectively. In those with eGFR

Disordered iron and mineral homeostasis are interrelated complications of chronic kidney disease that may influence cardiovascular and kidney outcomes. In a prospective analysis of 3747 participants in the Chronic Renal Insufficiency Cohort Study, we investigated risks of mortality, heart failure, end-stage kidney disease (ESKD), and atherosclerotic cardiovascular disease according to iron status, and tested for mediation by C-terminal fibroblast growth factor 23 (FGF23), hemoglobin and parathyroid hormone. Study participants were agnostically categorized based on quartiles of transferrin saturation and ferritin as: “Iron Replete” (27.1% of participants; referent group for all outcomes analyses), “Iron Deficiency” (11.1%), “Functional Iron Deficiency” (7.6%), “Mixed Iron Deficiency” (iron indices between the Iron Deficiency and Functional Iron Deficiency groups; 6.3%), “High Iron” (9.2%), or “Non-Classified” (the remaining 38.8% of participants). In multivariable-adjusted Cox models, Iron Deficiency independently associated with mortality (hazard ratio 1.28, 95% confidence interval 1.04–1.58) and heart failure (1.34, 1.05–1.72). Mixed Iron Deficiency associated with mortality (1.61, 1.27–2.04) and ESKD (1.33, 1.02–1.73). High Iron associated with mortality (1.54, 1.24–1.91), heart failure (1.58, 1.21–2.05), and ESKD (1.41, 1.13–1.77). Functional Iron Deficiency did not significantly associate with any outcome, and no iron group significantly associated with atherosclerotic cardiovascular disease. Among the candidate facilitators, FGF23 most significantly mediated the risks of mortality and heart failure conferred by Iron Deficiency. Thus, alterations in iron homeostasis associated with adverse cardiovascular and kidney outcomes in patients with chronic kidney disease.

BACKGROUND The purpose of this document is to provide clinicians with guidance, using expert consensus, to help summarize evidence and offer practical recommendations. METHODS Expert Consensus Documents are intended to provide guidance for clinicians in areas in which there are no clinical practice guidelines, especially for new and evolving tests such as arterial stiffness measurements, until any formal guidelines are released. RESULTS This expert consensus document is intended as a source of information for decision-making and to guide clinician–patient discussions in various clinical scenarios. CONCLUSIONS The goal is to help clinicians and patients make a more informed decision together.

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin–angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.

Sham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood.The purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial.Patients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and 180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate 70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance.Scatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was -6.2 mm Hg (95% CI: -9.0 to -3.5 mm Hg) (P 0.001) and for baseline office heart rate 70 beats/min it was -0.1 mm Hg (-3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min.Reduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than 70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL-SPYRAL HTN-OFF MED Study; NCT02439749).

Background and objectives Atrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population. Design, setting, participants, & measurements We studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated C-index; calibration was evaluated graphically and with the Gronnesby and Borgan test. Results Mean (SD) age of participants was 57 (11) years, 55% were men, 38% were Black, and mean (SD) eGFR was 45 (15) ml/min per 1.73 m2; 259 incident AF events occurred during a median of 8 years of follow-up. The CHARGE-AF prediction equation using original and re-estimated coefficients had C-indices of 0.67 (95% confidence interval, 0.64 to 0.71) and 0.67 (95% confidence interval, 0.64 to 0.70), respectively. A likelihood-based boosting model using clinical variables only had a C-index of 0.67 (95% confidence interval, 0.64 to 0.70); adding N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or both biomarkers improved the C-index by 0.04, 0.01, and 0.04, respectively. In addition to N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, the final model included age, non-Hispanic Black race/ethnicity, Hispanic race/ethnicity, cardiovascular disease, chronic obstructive pulmonary disease, myocardial infarction, peripheral vascular disease, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, calcium channel blockers, diuretics, height, and weight. Conclusions Using machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.

Background: Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses. Methods: Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5676 participants of the FHS (Framingham Heart Study) without diabetes. We used Cox proportional hazards regression to evaluate the association of CF-PWV and pulse pressure with incident diabetes. We subsequently performed 2-sample Mendelian randomization analyses evaluating the associations of genetically predicted brachial pulse pressure with type 2 diabetes in the UKBB (United Kingdom Biobank). Results: In FHS, individuals with higher CF-PWV were older, more often male, and had higher body mass index and mean arterial pressure compared to those with lower CF-PWV. After a median follow-up of 7 years, CF-PWV and central pulse pressure were associated with an increased risk of new-onset diabetes (per SD increase, multivariable-adjusted CF-PWV hazard ratio, 1.36 [95% CI, 1.03–1.76]; P =0.030; central pulse pressure multivariable-adjusted CF-PWV hazard ratio, 1.26 [95% CI, 1.08–1.48]; P =0.004). In United Kingdom Biobank, genetically predicted brachial pulse pressure was associated with type 2 diabetes, independent of mean arterial pressure (adjusted odds ratio, 1.16 [95% CI, 1.00–1.35]; P =0.049). Conclusions: Using prospective cohort data coupled with Mendelian randomization analyses, we found evidence supporting that greater LAS is associated with increased risk of developing diabetes. LAS may play an important role in glucose homeostasis and may serve as a useful marker of future diabetes risk.

Elevated blood pressure ranks among the most important modifiable risk factors for premature death, and disability from hypertension mediated organ damage in the world. Many studies attest to the value of lifestyle adjustments and pharmacologic therapy in improving outcomes in patients with hypertension. Since blood pressure is a dynamic vitals sign, variability in visit-to-visit measurements is expected. While guidelines recommend a goal blood pressure, increasing attention is centered on how often a patient's blood pressure is found to be not only below the recommended goal value, but also how much of the time the blood pressure is below what is considered a safe lower goal threshold for blood pressure. In this Perspective we review a relatively new technique in addressing adequacy of blood pressure treatment, the time in therapeutic range, and provide examples supporting the clinical relevance of this novel metric.

Elevated morning and nighttime blood pressures (BP) are associated with increased risk of cardiovascular events such as stroke and myocardial infarction. We compared the long-term changes in morning and nighttime BP in patients with uncontrolled hypertension (office systolic BP between 150 and N = 23 RDN group; N = 23 sham group), the 24 h ambulatory SBP as well as morning (7:00–9:00AM) and nighttime (1:00–6:00AM) ambulatory SBP were significantly lower for the RDN group compared to sham control (24 h SBP: −20.2 vs. −10.2, p = 0.0087; morning SBP: −23.9 vs. −8.0 mmHg, p = 0.029; nighttime SBP: −20.8 vs. −7.2 mmHg, p = 0.0011). At 36 months, 24 h SBP was controlled to P = 0.021 and in 80% of the RDN patients at night compared to 39% in the sham group; P = 0.019. Major adverse events through 36 months were rare in both groups, and there were no renal artery re-interventions or vascular complications. Morning and nighttime SBP were significantly lower in patients prescribed at least 3 antihypertensive medications at 36 months in the SPYRAL HTN-ON MED trial for RDN compared with sham control. The results suggest RDN has significant benefit when the risk of cardiovascular events is highest.

Rationale & Objective Circulating cardiac biomarkers may signal potential mechanistic pathways involved in heart failure (HF) and atrial fibrillation (AF). Single measures of circulating cardiac biomarkers are strongly associated with incident HF and AF in chronic kidney disease (CKD). We tested the associations of longitudinal changes in the N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor 15 (GDF-15), and soluble ST-2 (sST-2) with incident HF and AF in patients with CKD. Study Design Observational, case-cohort study design. Setting & Participants Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort study. Exposures Biomarkers were measured at baseline and 2 years later among those without kidney failure. We created 3 categories of absolute change in each biomarker: the lowest quartile, the middle 2 quartiles, and the top quartile. Outcomes The primary outcomes were incident HF and AF. Analytical Approach Cox proportional hazards regression models were used to test the associations of the change categories of each cardiac biomarker with each outcome (with the middle 2 quartiles of change as the referent group), adjusting for potential confounders and baseline concentrations of each biomarker. Results The incident HF analysis included 789 participants (which included 138 incident HF cases), and the incident AF analysis included 774 participants (123 incident AF cases). In multivariable models, the top quartile of NT-proBNP change (>232 pg/mL over 2 years) was associated with increased risk of incident HF (HR, 1.79 [95% CI, 1.06-3.04]) and AF (HR, 2.32 [95% CI, 1.37-3.93]) compared with the referent group. Participants in the top quartile of sST2 change (>3.37 ng/mL over 2 years) had significantly greater risk of incident HF (HR, 1.89 [95% CI, 1.13-3.16]), whereas those in the bottom quartile (≤−3.78 ng/mL over 2 years) had greater risk of incident AF (HR, 2.43 [95% CI, 1.39-4.22]) compared with the 2 middle quartiles. There was no association of changes in hsTnT, galectin-3, or GDF-15 with incident HF or AF. Limitations Observational study. Conclusions In CKD, increases in NT-proBNP were significantly associated with greater risk of incident HF and AF, and increases in sST2 were associated with HF. Further studies should investigate whether these markers of subclinical cardiovascular disease can be modified to reduce the risk of cardiovascular disease in CKD.

Introduction Management of chronic kidney disease (CKD) entails high medical complexity and often results in high hospitalization burden. There are limited data on the associations of longitudinal hospital utilization patterns with adverse clinical outcomes in individuals with CKD. Methods We derived cumulative all-cause hospitalization trajectory groups using latent class trajectory analysis in 3012 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study who were alive and did not reach end-stage kidney disease (ESKD) within 4 years of study entry. Cox proportional hazards models tested the associations between hospitalization trajectory groups and risks of ESKD and death prior to the onset of ESKD (ESKD-censored death). Results Within 4 years of study entry, there were 5658 hospitalizations among 3012 participants. We identified 3 distinct subgroups of individuals with CKD based on cumulative all-cause hospitalization trajectories over 4 years: low-utilizer (n = 1066), intermediate-utilizer (n = 1802), and high-utilizer (n = 144). High-utilizers represented a patient population of lower socioeconomic status who had a greater prevalence of comorbid conditions and lower kidney function compared with intermediate- and low-utilizers. After the 4-year ascertainment period to form the trajectory subgroups, there were 544 ESKD events and 437 ESKD-censored deaths during a median follow-up time of 5.1 years. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.49-fold (95% confidence interval [CI] 1.22–1.84) and 1.75-fold (95% CI 1.20–2.56) higher risk of ESKD in adjusted analyses, respectively. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.48-fold (95% CI 1.17–1.87) and 2.58-fold (95% CI 1.74–3.83) higher risk of ESKD-censored death in adjusted analyses, respectively. Conclusions Trajectories of cumulative all-cause hospitalization identify subgroups of individuals with CKD who are at high risk of ESKD and death., Graphical abstract

Rationale & Objective: There are limited data about the prevalence and prognostic significance of orthostatic hypo- and hypertension in patients with chronic kidney disease. The objective of this study is to determine the prevalence of orthostatic hypo- and hypertension in a cohort of patients with chronic kidney disease and examine their association with clinical outcomes. Study Design: Prospective cohort study: Chronic Renal Insufficiency Cohort (CRIC) Study. Setting & Population: 7 clinical centers, participants with chronic kidney disease. Exposures: Orthostatic hypotension (decline in systolic blood pressure [BP] > 20 mm Hg) and orthostatic hypertension (increase in systolic BP > 20 mm Hg) from seated to standing position. Outcomes: Cardiovascular and kidney outcomes and mortality. Analytical Approach: Logistic regression was used to determine factors associated with orthostatic hypo- and hypertension; Cox regression was used to examine associations with clinical outcomes. Results: Mean age of study population (n = 3,873) was 58.1 ± 11.0 years. There was a wide distribution of change in systolic BP from seated to standing (from −73.3 to +60.0 mm Hg); 180 participants (4.6%) had orthostatic hypotension and 81 (2.1%) had orthostatic hypertension. Diabetes, reduced body mass index, and β-blocker use were independently associated with orthostatic hypotension. Black race and higher body mass index were independently associated with orthostatic hypertension. After a median follow-up of 7.9 years, orthostatic hypotension was independently associated with high risk for cardiovascular (HR, 1.12; 95% CI, 1.03-1.21) but not kidney outcomes or mortality. Orthostatic hypertension was independently associated with high risk for kidney (HR, 1.51; 96% CI, 1.14-1.97) but not cardiovascular outcomes or mortality. Limitations: Orthostatic change in BP was ascertained at a single visit. Conclusions: Orthostatic hypotension was independently associated with higher risk for cardiovascular outcomes, whereas orthostatic hypertension was associated with higher risk for kidney outcomes. These findings highlight the importance of orthostatic BP measurement in practice and the need for future investigation to understand the mechanisms and potential interventions to minimize the risk associated with orthostatic changes in BP.

Renal denervation has emerged as a safe and effective therapy to lower blood pressure in hypertensive patients. In addition to the main renal arteries, branch vessels are also denervated in more contemporary studies. Accurate and reliable imaging in renal denervation patients is critical for long-term safety surveillance due to the small risk of renal artery stenosis that may occur after the procedure. This review summarizes three common non-invasive imaging modalities: Doppler ultrasound (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). DUS is the most widely used owing to cost considerations, ease of use, and the fact that it is less invasive, avoids ionizing radiation exposure, and requires no contrast media use. Renal angiography is used to determine if renal artery stenosis is present when non-invasive imaging suggests renal artery stenosis. We compiled data from prior renal denervation studies as well as the more recent SPYRAL-HTN OFF MED Study and show that DUS demonstrates both high sensitivity and specificity for detecting renal stenosis de novo and in longitudinal assessment of renal artery patency after interventions. In the context of clinical trials DUS has been shown, together with the use of the baseline angiogram, to be effective in identifying stenosis in branch and accessory arteries and merits consideration as the main screening imaging modality to detect clinically significant renal artery stenosis after renal denervation and this is consistent with guidelines from the recent European Consensus Statement on Renal Denervation.

RATIONALE & OBJECTIVE: Current dietary guidelines recommend that chronic kidney disease (CKD) patients restrict individual nutrients, such as sodium, potassium, phosphorus and protein. This approach can be difficult for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of four healthy dietary patterns with risk of CKD progression and all-cause mortality among people with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,403 participants aged 21–74 years with an estimated glomerular filtration rate (eGFR) of 20–70 mL/min/1.73 m(2) and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) study. EXPOSURES: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires. OUTCOMES: 1) CKD progression defined as ≥50% eGFR decline, kidney transplantation, or dialysis and 2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: There were 855 cases of CKD progression and 773 deaths over a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of AHEI-2010, aMed, and DASH had lower adjusted risk of CKD progression with the strongest results for aMed (HR: 0.75, 95% CI: 0.62–0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk of all-cause mortality for each index (24–31% lower risk). LIMITATIONS: Self-reported dietary intake. CONCLUSIONS: Greater adherence to several healthy dietary patterns is associated with a lower risk of CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD. INDEX WORDS: dietary patterns, nutrition, kidney disease, renal, mortality

Large artery stiffness (LAS) has proven to be an independent risk factor for cardiovascular disease and mortality. Nevertheless, the position of current hypertension guidelines regarding the usefulness of assessing LAS differs across different continents. In general, European Guidelines recognize pulse wave velocity (PWV) as a marker of target organ damage but do not recommend its systematic use in general population. Asian guidelines consider PWV as a recommended test at diagnosis of hypertension, in contrast to North American guidelines that do not state any position about its usefulness. However, PWV predicts cardiovascular events, and several studies have shown that it improves risk classification adjusting for established risk factors especially for intermediate-risk patients. Finally, some advances have been made related to treatments affecting LAS. Dietary interventions such as sodium restriction and exercise-based interventions have a modest effect in reducing LAS. Pharmacological interventions, such as statins, or more recent advances with mineralocorticoid blocker seem to have a beneficial effect. Last, controversial effects of renal denervation on LAS have been found. Our goal here is to update the reader on LAS on these areas since the 2015 American Heart Association Scientific Statement.

Rationale & objectiveObservational studies have reported a U-shaped association between blood pressure (BP) before a hemodialysis session and death. In contrast, because a linear association between out-of-dialysis-unit BP and death has been reported, home BP may be a better target for treatment. To test the feasibility of this approach, we conducted a pilot trial of treating home versus predialysis BP in hemodialysis patients.Study designA 4-month, parallel, randomized, controlled trial.Settings & participants50 prevalent hemodialysis patients in San Francisco and Seattle. Participants were randomly assigned using 1:1 block randomization, stratified by site.InterventionsTo target home systolic BP (SBP)of 100-200mm Hg; 0.2% vs 0%) or low (defined as

Background: The Revised Illness Perception Questionnaire (IPQ-R) measures individuals’ unique perceptions of their illness. While psychometric properties of the IPQ-R have been demonstrated in many disease populations, its content validity has not been extensively studied in non-dialysis chronic kidney disease (CKD). Unique features of CKD (e.g., few symptoms in early stages) may impact the measurement of illness perceptions. The purpose of this study was to explore the IPQ-R content validity in a sample of CKD patients. Methods: Thirty-one participants completed the IPQ-R and were interviewed regarding their subscale scores (timeline, consequences, personal control, treatment control, coherence, cyclical, and emotions). Participants’ agreement with their scores was tallied and assessed qualitatively for themes related to the content validity of the measure. Results: Individual participant agreement with their subscale scores averaged 79% (range: 29–100%). Subscale agreement varied: timeline (100%), consequences, coherence, and emotion (83% each), cyclical (75%), personal control (65%), and treatment control (64%). A qualitative exploration of disagreement responses revealed concerns with the relevance and comprehensibility of personal control and treatment control. Conclusions: Some IPQ-R subscales may pose content validity concerns in the non-dialysis CKD population. Item modification for comprehensibility (personal control) and relevance (treatment control) should be considered. Future studies should explore the impact of a patient’s symptom experience on IPQ-R validity, especially in populations like CKD with a higher proportion of asymptomatic patients.

Background: Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN. Methods: From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group. Results: There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value ( P P Conclusions: These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.

STUDY OBJECTIVES: Positive airway pressure (PAP) treatment of obstructive sleep apnea reduces blood pressure (BP). Retrospective data suggest that African Americans (AA), a group at high-risk for hypertensive organ dysfunction, may have a greater BP response to PAP therapy than European Americans (EA). We examined the difference in 24-hour BP response to 3 months of PAP treatment between AA and EA. METHODS: Participants (n = 259, 161 AA and 98 EA) with apnea-hypopnea index ≥ 15 events/h from 2 prospective cohorts were included. t-Tests and multiple linear regression were used to examine BP outcomes in AA vs EA, adjusting for PAP adherence, socioeconomic status, and baseline characteristics. RESULTS: Participants were middle aged (mean ± SD, 53.8 ± 9.3 years), 86% (227) men, apnea-hypopnea index 35.6 ± 19.2 events/h, and PAP adherence of 3.36 ± 2.24 h/day. The reductions in 24-hour systolic and diastolic BP (mm Hg) were not different in AA vs EA (systolic = −1.13 ± 12.1 vs −0.61 ± 12.8, P = .80 and diastolic = −0.74 ± 7.9 vs −0.80 ± 7.4, P = .96), and race was not a predictor of 24-hour systolic or diastolic BP reduction (P = .75 and 0.54). Socioeconomic status and PAP adherence demonstrated a significant interaction; low socioeconomic status was associated with an increase in 24-hour systolic BP (β = 19.3, P = .03) in the absence of PAP use but a greater reduction in 24-hour systolic BP with higher PAP adherence (β = −3.96, P = .03). CONCLUSIONS: Twenty-four hour BP response to PAP treatment is similar in AA and EA. Adherence to PAP treatment is more effective in improving 24-hour systolic BP in those with low SES. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Race and CPAP Effectiveness (RACE); URL: https://clinicaltrials.gov/ct2/show/NCT01960465; Identifier: NCT01960465 and Registry: ClinicalTrials.gov; Name: The Effects of Treating Obese and Lean Patients with Sleep Apnea (PISA); URL: https://clinicaltrials.gov/ct2/show/NCT01578031; Identifier: NCT01578031. CITATION: Imayama I, Gupta A, Yen PS, et al. Socioeconomic status impacts blood pressure response to positive airway pressure treatment. J Clin Sleep Med. 2022;18(5):1287–1295.

Having a usual source of care increases use of preventive services and is associated with improved survival in the general population. We evaluated this association in adults with chronic kidney disease (CKD).Prospective, observational cohort study.Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.Usual source of care was self-reported as: 1) clinic, 2) emergency department (ED)/urgent care, 3) other.Primary outcomes included incident end-stage kidney disease (ESKD), atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, hospitalization events, and all-cause death.Multivariable regression analyses to evaluate the association between usual source of care (ED/urgent care vs clinic) and primary outcomes.Among 3,140 participants, mean age was 65 years, 44% female, 45% non-Hispanic White, 43% non-Hispanic Black, and 9% Hispanic, mean estimated glomerular filtration rate 50 mL/min/1.73 mCannot be generalized to all patients with CKD. Causal relationships cannot be established.In this large, diverse cohort of adults with moderate-to-severe CKD, those identifying ED/urgent care as usual source of care were at increased risk for death and hospitalizations. These findings highlight the need to develop strategies to improve health care access for this high-risk population.

Introduction Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD. Methods Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor−15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use. Results After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73−2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46−1.78]); and sST-2 (HR = 1.26, CI = 1.16−1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36−0.86) and sST2 (HR = 0.55, 95% CI = 0.36−0.86]) over 2 years were associated with lower risk of all-cause mortality. Conclusion In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality., Graphical abstract

Background Whether ambulatory BP monitoring is of value in evaluating risk for outcomes in patients with CKD is not clear. Methods We followed 1502 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study for a mean of 6.72 years. We evaluated, as exposures, ambulatory BP monitoring profiles (masked uncontrolled hypertension, white-coat effect, sustained hypertension, and controlled BP), mean ambulatory BP monitoring and clinic BPs, and diurnal variation in BP-reverse dipper (higher at nighttime), nondipper, and dipper (lower at nighttime). Outcomes included cardiovascular disease (a composite of myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease), kidney disease (a composite of ESKD or halving of the eGFR), and mortality. Results Compared with having controlled BP, the presence of masked uncontrolled hypertension independently associated with higher risk of the cardiovascular outcome and the kidney outcome, but not with all-cause mortality. Higher mean 24-hour systolic BP associated with higher risk of cardiovascular outcome, kidney outcome, and mortality, independent of clinic BP. Participants with the reverse-dipper profile of diurnal BP variation were at higher risk of the kidney outcome. Conclusions In this cohort of participants with CKD, BP metrics derived from ambulatory BP monitoring are associated with cardiovascular outcomes, kidney outcomes, and mortality, independent of clinic BP. Masked uncontrolled hypertension and mean 24-hour BP associated with high risk of cardiovascular disease and progression of kidney disease. Alterations of diurnal variation in BP are associated with high risk of progression of kidney disease, stroke, and peripheral arterial disease. These data support the wider use of ambulatory BP monitoring in the evaluation of hypertension in patients with CKD. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2020_09_24_JASN2020030236.mp3.

Rationale & Objective: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list. Study Design: Prospective cohort study. Setting & Population: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up. Exposures: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory. Outcomes: Time to kidney transplant wait-listing and time to pre-emptive wait-listing. Analytic Approach: Time-to-event analysis using Cox proportional hazards regression. Results: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P

Catheter-based renal denervation (RDN) reduces blood pressure (BP) throughout the 24-h period, as reported in several randomized sham-controlled trials. Reduction of BP in the early morning hours is especially important due to increased cardiovascular risks during that time. In this report, we examine the impact of RDN on systolic BP (SBP) and diastolic BP (DBP) during the critical morning surge period in a post-hoc analysis of patients in the SPYRAL HTN-ON MED trial. Ambulatory BP measurements were collected at baseline and 6 months for treatment and control patient groups over 24-h periods. Average morning BP surge is the difference between average morning BP and average nighttime BP, and the morning surge slope reflects the rate of change of BP from nighttime to morning. Mean morning DBP surge slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6 mmHg/h; p = 0.029). In the RDN group, morning DBP surge slopes were significantly lower at 6 months compared to baseline (1.1 vs. 4.1 mmHg/h; p = 0.006). Similar patterns were observed for mean morning SBP surge slope but did not reach statistical significance. This decrease in the morning DBP surge slope, an index of the sympathetically-mediated morning BP surge, thus indicates a drop in late morning BP relative to early morning/nocturnal BP in the RDN group. Thus, RDN appears effective in attenuating the slope of morning surge in DBP that might indicate possible benefits in a high-risk hypertensive population. https://www.clinicaltrials.gov (NCT02439775), registered May 12, 2015.

BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements

Rationale & Objective Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses. Study Design Case-cohort study. Setting & Participants To evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort. Exposure Serial FGF-23 measurements and FGF-23 trajectory group membership. Outcomes Incident KRT. Analytical Approach To handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure. Results In our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log–transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group. Limitations Residual confounding and lack of intact FGF-23 values. Conclusions Increasing FGF-23 levels are independently associated with increased risk for incident KRT.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Aims We aimed to estimate the rate of renal artery adverse events following renal denervation with the most commonly applied radiofrequency catheter system based on a comprehensive review of published reports. Methods and results We reviewed 50 published renal denervation (RDN) trials reporting on procedural safety including 5,769 subjects with 10,249 patient-years of follow-up. Twenty-six patients with renal artery stenosis or dissection (0.45%) were identified of whom 24 (0.41%) required renal artery stenting. The primary meta-analysis of all reports indicated a 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.12 to 0.29% per year). Additional sensitivity analyses yielded consistent pooled estimates (range: 0.17 to 0.42% per year). Median time from RDN procedure to all renal intervention was 5.5 months (range: 0 to 33 months); 79% of all events occurred within one year of the procedure. A separate review of 14 clinical trials reporting on prospective follow-up imaging using either magnetic resonance imaging, computed tomography or angiography following RDN in 511 total subjects identified just 1 new significant stenosis (0.20%) after a median of 11 months post procedure (one to 36 months). Conclusions Renal artery reintervention following renal denervation with the most commonly applied RF renal denervation system (Symplicity) is rare. Most events were identified within one year.