Abstract

Deprescribing antihypertensives is of growing interest in geriatric medicine, yet the impact on functional status is unknown. We emulated a target trial of deprescribing antihypertensive medications compared with continued use on functional status measured by activities of daily living (ADL) in a long-term care population.We included 12,238 Veteran Affairs long-term care residents age 65+ who had a stay ≥ 12 weeks between 2006 and 2019. After 4+ weeks of stable antihypertensive medication use, residents were classified as either deprescribed antihypertensives (reduced ≥ 1 medication or ≥ 30% dose) or continued users. Residents were followed up for 2 years, or censored at discharge, admission to hospice, protocol deviation (per-protocol analysis only), or Sept 30, 2019. The outcome was ADL dependencies (scored 0-28; higher score = worse functionality), assessed approximately every 3 months. Our primary approach was to estimate per-protocol effects using linear mixed-effects regressions with inverse probability of treatment and censoring weighting, overall and stratified by dementia status. We estimated intention-to-treat effects as a secondary analysis.In long-term care residents, ADL scores worsened by a mean of 0.29 points (95%CI = 0.27, 0.31) per 3 months and antihypertensive deprescribing did not impact this worsening (difference between groups -0.04 points every 3 months, 95%CI = -0.15, 0.06). In the non-dementia subgroup, ADL worsened by 0.15 points (95%CI = 0.11, 0.19) every 3 months. However, residents who were deprescribed showed a slightly improved ADL score over time while the continued users showed ADL decline (difference between groups -0.23 points every 3 months, 95%CI = -0.43, -0.03). Deprescribing was not associated with ADL change in the dementia subgroup. The intention-to-treat results were not meaningfully different.Antihypertensive deprescribing did not have a deleterious effect on functional status in long-term care residents with or without dementia. This may be reassuring to residents and clinicians who are considering antihypertensive medication reduction or discontinuation in long-term care settings.

View details for DOI 10.1111/jgs.19342

View details for PubMedID 39750005

Abstract

It is unclear whether the effects of intensive vs standard blood pressure (BP) targets seen in clinical trials generalize to patients with chronic kidney disease (CKD) encountered in everyday practice due to differences in the distribution of cardiovascular risk factors and coexisting conditions.To evaluate whether the beneficial and adverse effects of intensive vs standard BP control observed in the Systolic Blood Pressure Intervention Trial (SPRINT) are transportable to a target population of adults with CKD in clinical practice.This comparative effectiveness study identified 2 populations with CKD who met the eligibility criteria for SPRINT between January 1 and December 31, 2019, in the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC). Baseline covariate, treatment, and outcome data from SPRINT were combined with covariate data from these populations to estimate the treatment effects in the target population, applying models that estimated outcomes using distributions in the trial. Analysis was performed between May 2023 and October 2024.The main outcomes were major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.A total of 85 938 patients (mean [SD] age, 75.7 [10.0] years; 81 628 [95.0%] male) from the VHA and 13 983 patients (mean [SD] age, 77.4 [9.6] years; 5371 [38.4%] male) from KPSC were included. Compared with 9361 SPRINT participants (mean [SD] age, 67.9 [9.4] years; 6029 [64.4%] male), these patients were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins. The associations of intensive vs standard BP control with major cardiovascular events, all-cause death, and adverse events were transportable from the trial to the VHA and KPSC populations; however, the trial's effects on cognitive and CKD outcomes were not transportable in 1 or both clinical populations. Intensive vs standard BP treatment was associated with lower absolute risks for major cardiovascular events at 4 years by 5.1% (95% CI, -9.8% to 3.2%) in the VHA population and 3.0% (95% CI, -6.3% to 0.3%) in the KPSC population and higher risks for adverse events by 1.3% (95% CI, -5.5% to 7.7%) in the VHA population and 3.1% (95% CI, -1.5% to 8.3%) in the KPSC population.In this comparative effectiveness study, the reduction in fatal and nonfatal cardiovascular end points and the increase in adverse events observed in SPRINT were largely transportable to trial-eligible CKD populations from clinical practice, suggesting benefits of implementing intensive BP targets.

View details for DOI 10.1001/jamanetworkopen.2024.53458

View details for PubMedID 39777440

View details for PubMedCentralID PMC11707627

Abstract

Surgical quality improvement efforts have largely focused on 30-day outcomes, such as readmissions and complications. Surgery may have a sustained impact on the health and quality of life of patients considered frail, yet data are lacking on the long-term health care utilization of patients with frailty following surgery.To examine the independent association of preoperative frailty on long-term health care utilization (up to 24 months) following surgery.This retrospective, observational cohort study included patients undergoing elective general and vascular surgery performed in the Veterans Affairs (VA) Surgical Quality Improvement Program with study entry from October 1, 2013, to September 30, 2018. Patients were followed up for 24 months. Patients with nursing home visits prior to surgery, emergent cases, and in-hospital deaths were excluded. Data analysis was conducted from September 2022 to May 2024.Preoperative frailty as assessed by the Risk Analysis Index (RAI-A) score: robust, less than 20; normal, 20 to 29; frail, 30 to 39; and very frail, 40 or more.The primary outcome was health care utilization through 24 months, defined as inpatient admissions, outpatient visits, emergency department (ED) visits, and nursing home or rehabilitation services collected via Corporate Data Warehouse and Centers for Medicare & Medicaid Services data. χ2 Tests and analysis of variance were used to assess preoperative frailty status, and a Cox proportional hazards model was used to calculate the adjusted association of preoperative frailty on each postdischarge health care utilization outcome.This study identified 183 343 elective general (80.5%) and vascular (19.5%) procedures (mean [SD] age, 62 [12.7] years; 12 915 females [7.0%]; 28 671 Black patients [16.0]; 138 323 White patients [77.3%]; 94 451 Medicare enrollees [51.5%]) with mean (SD) RAI-A score of 22.2 (7.0). After adjustment for baseline characteristics and preoperative use of health care services, frailty was associated with higher inpatient admissions (frail: hazard ratio [HR], 1.75; 95% CI, 1.70-1.79; very frail: HR, 2.33; 95% CI, 2.25-2.42), ED visits (frail: HR, 1.39; 95% CI, 1.36-1.41; very frail: HR, 1.70; 95% CI, 1.65-1.75), and nursing home or rehabilitation encounters (frail: HR, 4.97; 95% CI, 4.36-5.67; very frail: HR, 7.44; 95% CI, 6.34-8.73). For patients considered frail and very frail, health care utilization was higher after surgery and remained significant through 24 months for all outcomes (using piecewise Cox proportional hazards modeling).In this study, frailty was a significant risk factor for high long-term health care utilization after surgery. This may have quality of life implications for patients and policy implications for health care systems and payers.

View details for DOI 10.1001/jamasurg.2024.5711

View details for PubMedID 39714891

Abstract

Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown.To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management.Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023.Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management.New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL).The study team identified 40 231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium.In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.

View details for DOI 10.1001/jamasurg.2024.3509

View details for PubMedID 39230896

Abstract

Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was -0.7 (-2.1, 1.1) and -0.1 (-1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.

View details for DOI 10.3390/antiox13080983

View details for PubMedID 39199229

View details for PubMedCentralID PMC11352164

Abstract

Accurate mortality prediction can guide clinical care for older adults with chronic kidney disease (CKD). Yet existing tools do not incorporate physical function, an independent predictor of death in older adults. We determined whether incorporating physical function measurements improve mortality prediction among older adults with CKD.We included Chronic Renal Insufficiency Cohort participants who were ≥65 years old, had estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2, not receiving kidney failure replacement therapy (KFRT), and had least one gait speed assessment. Gait speed was measured at usual pace (≥0.84, 0.83-0.65, 0.64-0.47, ≤0.46 meters/second, or unable), and frailty was assessed using Physical Frailty Phenotype criteria (range 0 to 5 points, also known as Fried criteria). We modeled time to all-cause death over five years using Cox proportional hazard models, treating KFRT as censored and non-censored events in separate analyses. C-statistics assessed model discrimination.Among 2,338 persons, mean age was 70±4 years; 43% were female and 43% were Black. Mean eGFR was 42±13 mL/min/1.73m2 and median urine albumin-to-creatinine ratio was 33 mg/g [Q1 9, Q3 206]. Over a median follow-period of 5 years, 392 died and 164 developed KFRT. In censored analyses, adding gait speed or frailty improved mortality risk prediction. The C-statistic changed from 0.69 to 0.72 with gait speed scores, and from 0.70 to 0.73 with frailty scores. The performance of models with gait speed or frailty was similar in non-censored analyses.Among older adults with CKD, adding measures of physical function modestly improves mortality prediction.

View details for DOI 10.2215/CJN.0000000000000515

View details for PubMedID 39115956

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory.CHIP was associated with lower risks of impairment in attention and executive function among CKD patients.Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

View details for DOI 10.1002/alz.14182

View details for PubMedID 39115897

Abstract

The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure.Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020.Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30).Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

View details for DOI 10.1681/ASN.0000000000000459

View details for PubMedID 39078712

Abstract

Little is known about how well trial participants with chronic kidney disease (CKD) represent real-world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real-world adults with CKD.Using a cross-sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline-recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%-24.0%] in the Veterans Affairs and 20.8% [20.5%-21.1%] in Kaiser Permanente of Southern California were trial-eligible. Among trial-ineligible patients, >50% met >1 exclusion criteria.Major BP target trials were representative of fewer than 1 in 4 real-world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

View details for DOI 10.1161/JAHA.123.031742

View details for PubMedID 38533947

View details for DOI 10.1001/jamanetworkopen.2023.52415

View details for PubMedID 38289607

Abstract

Normalization Process Theory (NPT) is an implementation theory that can be used to explain how and why implementation strategies work or not in particular circumstances. We used it to understand the mechanisms that lead to the adoption and routinization of palliative care within hemodialysis centers.We employed a longitudinal, mixed methods approach to comprehensively evaluate the implementation of palliative care practices among ten hemodialysis centers participating in an Institute for Healthcare Improvement Breakthrough- Series learning collaborative. Qualitative methods included longitudinal observations of collaborative activities, and interviews with implementers at the end of the study. We used an inductive and deductive approach to thematic analysis informed by NPT constructs (coherence, cognitive participation, collective action, reflexive monitoring) and implementation outcomes. The NoMAD survey, which measures NPT constructs, was completed by implementers at each hemodialysis center during early and late implementation.The four mechanisms posited in NPT had a dynamic and layered relationship during the implementation process. Collaborative participants participated because they believed in the value and legitimacy of palliative care for patients receiving hemodialysis and thus had high levels of cognitive participation at the start. Didactic Learning Sessions were important for building practice coherence, and sense-making was solidified through testing new skills in practice and first-hand observation during coaching visits by an expert. Collective action was hampered by limited time among team members and practical issues such as arranging meetings with patients. Reflexive monitoring of the positive benefit to patient and family experiences was key in shifting mindsets from disease-centric towards a patient-centered model of care. NoMAD survey scores showed modest improvement over time, with collective action having the lowest scores.NPT was a useful framework for understanding the implementation of palliative care practices within hemodialysis centers. We found a nonlinear relationship among the mechanisms which is reflected in our model of implementation of palliative care practices through a learning collaborative. These findings suggest that the implementation of complex practices such as palliative care may be more successful through iterative learning and practice opportunities as the mechanisms for change are layered and mutually reinforcing.ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

View details for DOI 10.1186/s12913-023-10360-7

View details for PubMedID 38082293

View details for PubMedCentralID PMC10712060

Abstract

Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes.We divided the ACCORD trial population into quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 (95% CI 58.1, 176.4)v. 48.4 (25.3, 69.6) days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of -56.7 (-100.2, -17.5) v. -23.6 (-42.2, -6.6)days).We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

View details for DOI 10.1681/ASN.0000000000000272

View details for PubMedID 38073026

View details for DOI 10.7326/L23-0280

View details for PubMedID 37983791

Abstract

Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD.We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio ≥30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications.The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were male. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received ≥3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased.Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications.

View details for DOI 10.1161/HYPERTENSIONAHA.123.21523

View details for PubMedID 37706307

View details for DOI 10.2215/CJN.0000000000000323

View details for PubMedID 37707829

Abstract

Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods.Longitudinal cohort study.Using data from the United States Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure.Kidney failure.Death.We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity).The analysis included 31,944 adults with kidney failure with a mean age of 77 +/- 7 years. 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively.Relative survival estimates can be improved by narrowing the specificity of the covariates collected, (e.g. disease severity and ethnicity).Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults.

View details for DOI 10.1053/j.ajkd.2023.05.015

View details for PubMedID 37678740

View details for Web of Science ID 001043057201156

View details for DOI 10.1016/j.jpainsymman.2023.05.019

View details for PubMedID 37355055

Abstract

Objective: Clear criteria to individualize glycemic targets are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients who disproportionately benefit from intensive glycemic control on kidney microvascular outcomes.Research design and methods: We divided the ACCORD trial population in quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.Results: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure benefitted the most from intensive glycemic control on kidney microvascular outcomes (7-year RMST difference of 115 v. 48 days in the entire trial population) However, this same patient group also experienced shorter times to death (7-year RMST difference of -57 v. -24 days).Conclusions: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced benefits of treatment on kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

View details for DOI 10.1101/2023.06.14.23291396

View details for PubMedID 37398349

Abstract

Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease.Longitudinal Cohort study.3,768 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study.Baseline SBP and DBP were examined as exposure variables, using continuous (linear, per 10-mm Hg higher), categorical (SBP <120 (reference), 120 to 140, >140 mm Hg; DBP <70 (reference), 70 to 80, >80 mm Hg) and non-linear terms (splines).Incident cognitive impairment defined as a decline in modified mini-mental state exam (3MS) score to greater than 1 standard deviation (SD) below the cohort mean.Cox proportional hazard models adjusted for demographics as well as kidney disease and cardiovascular disease risk factors.The mean (SD) age of participants was 58 (11) years, eGFR was 44 mL/min/1.73m2 (15) and the median (IQR) follow-up time was 11 (7, 13) years. In 3,048 participants without cognitive impairment at baseline and with at least one follow-up 3MS test, higher baseline SBP was significantly associated with incident cognitive impairment only in the eGFR >45 mL/min/1.73m2 subgroup [adjusted hazard ratio (AHR) 1.13, 95% CI 1.05-1.22 per 10-mm Hg higher SBP]. Spline analyses, aimed at exploring non-linearity, showed that the relationship between baseline SBP and incident cognitive impairment was J-shaped and significant only in the eGFR >45 mL/min/1.73m2 subgroup (p=0.02). Baseline DBP was not associated with incident cognitive impairment in any analyses.3MS test as the primary measure of cognitive function.Among patients with chronic kidney disease, higher baseline SBP was associated with higher risk of incident cognitive impairment specifically in those individuals with eGFR >45 ml/min/1.73m2.

View details for DOI 10.1053/j.ajkd.2023.03.012

View details for PubMedID 37245689

Abstract

The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure.Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics.Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013).Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

View details for DOI 10.3174/ajnr.A7852

View details for PubMedID 37105682

Abstract

BACKGROUND: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73 m2. Limited data address the effect of parathyroidectomy on long-term kidney function.OBJECTIVE: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management.DESIGN: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting.SETTING: Veterans Health Administration.PATIENTS: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019.MEASUREMENTS: Sustained decline of at least 50% from pretreatment eGFR.RESULTS: Among 43697 patients with PHPT (mean age, 66.8years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9years. The weighted cumulative incidence of eGFR decline was 5.1% at 5years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60years or older (HR, 1.08 [CI, 0.87 to 1.34]).LIMITATION: Analyses were done in a predominantly male cohort using observational data.CONCLUSION: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions.PRIMARY FUNDING SOURCE: National Institute on Aging.

View details for DOI 10.7326/M22-2222

View details for PubMedID 37037034

Abstract

Patients receiving maintenance dialysis experience intensive patterns of end-of-life care that might not be consistent with their values.To evaluate the association of patients' health care values with engagement in advance care planning and end-of-life care.Survey study of patients who received maintenance dialysis between 2015 and 2018 at dialysis centers in the greater metropolitan areas of Seattle, Washington, and Nashville, Tennessee, with longitudinal follow-up of decedents. Logistic regression models were used to estimate probabilities. Data analysis was conducted between May and October 2022.A survey question about the value that the participant would place on longevity-focused vs comfort-focused care if they were to become seriously ill.Self-reported engagement in advance care planning and care received near the end of life through 2020 using linked kidney registry data and Medicare claims.Of 933 patients (mean [SD] age, 62.6 [14.0] years; 525 male patients [56.3%]; 254 [27.2%] identified as Black) who responded to the question about values and could be linked to registry data (65.2% response rate [933 of 1431 eligible patients]), 452 (48.4%) indicated that they would value comfort-focused care, 179 (19.2%) that they would value longevity-focused care, and 302 (32.4%) that they were unsure about the intensity of care they would value. Many had not completed an advance directive (estimated probability, 47.5% [95% CI, 42.9%-52.1%] of those who would value comfort-focused care vs 28.1% [95% CI, 24.0%-32.3%] of those who would value longevity-focused care or were unsure; P < .001), had not discussed hospice (estimated probability, 28.6% [95% CI, 24.6%-32.9%] comfort focused vs 18.2% [95% CI, 14.7%-21.7%] longevity focused or unsure; P < .001), or had not discussed stopping dialysis (estimated probability, 33.3% [95% CI, 29.0%-37.7%] comfort focused vs 21.9% [95% CI, 18.2%-25.8%] longevity focused or unsure; P < .001). Most respondents wanted to receive cardiopulmonary resuscitation (estimated probability, 78.0% [95% CI, 74.2%-81.7%] comfort focused vs 93.9% [95% CI, 91.4%-96.1%] longevity focused or unsure; P < .001) and mechanical ventilation (estimated probability, 52.0% [95% CI, 47.4%-56.6%] comfort focused vs 77.9% [95% CI, 74.0%-81.7%] longevity focused or unsure; P < .001). Among decedents, the percentages of participants who received an intensive procedure during the final month of life (estimated probability, 23.5% [95% CI, 16.5%-31.0%] comfort focused vs 26.1% [95% CI, 18.0%-34.5%] longevity focused or unsure; P = .64), discontinued dialysis (estimated probability, 38.3% [95% CI, 32.0%-44.8%] comfort focused vs 30.2% [95% CI, 23.0%-37.8%] longevity focused or unsure; P = .09), and enrolled in hospice (estimated probability, 32.2% [95% CI, 25.7%-38.7%] comfort focused vs 23.3% [95% CI, 16.4%-30.5%] longevity focused or unsure; P = .07) were not statistically different.This survey study found that there appeared to be a disconnect between patients' expressed values, which were largely comfort focused, and their engagement in advance care planning and end-of-life care, which reflected a focus on longevity. These findings suggest important opportunities to improve the quality of care for patients receiving dialysis.

View details for DOI 10.1001/jamainternmed.2023.0265

View details for PubMedID 36972031

View details for PubMedCentralID PMC10043804

Abstract

INTRODUCTION: Among people receiving maintenance dialysis, little is known about racial disparities in the occurrence of prognostic discussions, beliefs about future health, and completion of advance care planning (ACP) documents. We examined whether Black patients receiving maintenance dialysis differ from White patients in prognostic discussions, beliefs about future health, and completion of ACP-related documents.METHODS: We surveyed adult patients receiving maintenance dialysis from seven dialysis units in Cleveland, Ohio, and hospitalized patients at a tertiary care hospital in Cleveland. Of the 450 patients who were asked to participate in the study, 423 (94%) agreed. We restricted the current secondary analyses to include only Black (n=285) and White (n=114) patients. The survey assessed patients' knowledge of their kidney disease, attitudes toward chronic kidney disease (CKD) treatment, preferences for end-of-life (EoL) care, the patient-reported occurrence of prognostic discussions, experiences with kidney therapy decision making, sentiments of dialysis regret, beliefs about health over the next 12 months, and advance care planning. We used stepwise logistic regression to determine if race was associated with the occurrence of prognostic discussions, beliefs about future health, and completion of an ACP-related document, while controlling for potential confounders.RESULTS: We found no significant difference in the frequency of prognostic discussions between Black (11.9%) versus White patients (7%) (P=0.15). However, Black patients (19%) had lower odds of believing that their health would worsen over the next 12 months (OR 0.22, CI 0.12, 0.44) and reporting completion of any ACP-related document (OR 0.5, CI 0.32, 0.81) compared to White patients CONCLUSIONS: Racial differences exist in beliefs about future health and completion of ACP-related documents. Systemic efforts to investigate differences in health beliefs and address racial disparities in the completion of ACP-related documents are needed.

View details for DOI 10.1016/j.jpainsymman.2022.12.002

View details for PubMedID 36521766