Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities. Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death. Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10). Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

Using Relative Survival to Estimate the Burden of Kidney Failure.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: Using data from the US 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. EXPOSURE: Kidney failure. OUTCOME: Death. ANALYTICAL APPROACH: 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). RESULTS: The analysis included 31,944 adults with kidney failure with a mean age of 77±7 years. The 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. LIMITATIONS: Relative survival estimates can be improved by narrowing the specificity of the covariates collected (eg, disease severity and ethnicity). CONCLUSIONS: 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. PLAIN-LANGUAGE SUMMARY: Estimates of death due to kidney failure can be misleading because death information from kidney failure is intertwined with death due to aging and other chronic diseases. Life tables are an old method, commonly used by actuaries and demographers to describe the life expectancy of a population. We developed life tables specific to a patient's age, sex, year, race, and comorbidity. Survival is derived from the life tables as the percentage of patients who are still alive in a specified period. By comparing survival of patients with kidney failure to the survival of people from the general population, we estimate that patients with kidney failure have one-third the chance of survival in 5 years compared with people with similar demographics and comorbidity but without kidney failure. The importance of this measure is that it provides a quantifiable estimate of the immense mortality burden of kidney failure.

"Diving in the deep-end and swimming": a mixed methods study using normalization process theory to evaluate a learning collaborative approach for the implementation of palliative care practices in hemodialysis centers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease.

Introduction: Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD. Methods: We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause. Results: In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88). Conclusions: In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes.

Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear. Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI). Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes. Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant. Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant. Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P < .001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%). Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

Serum testosterone concentrations and outcomes in hemodialysis patients enrolled in the EVOLVE trial.

BACKGROUND: Hypogonadism is common in end-stage kidney disease and may contribute to morbidity and mortality. METHODS: Using data from the randomized controlled Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial of cinacalcet, we analyzed the associations of total testosterone, free testosterone and sex hormone-binding globulin (SHBG) serum concentrations with mortality and major cardiovascular events in 1692 men and 1059 women receiving hemodialysis. We also describe the effect of cinacalcet treatment on serum concentrations of testosterone. RESULTS: Among men, lower serum free testosterone [odds ratio (OR) 0.18, 95% confidence interval (CI) 0.04-0.82, P = .026] and higher SHBG (OR 1.05 per 10 nmol/L, 95% CI 1.01-1.10, P = .012), but not total testosterone, were associated with higher risk of death or cardiovascular event. Only SHBG was associated with all-cause mortality (OR 1.07 per 10 nmol/L, 95% CI 1.02-1.12, P = .0073). Among women, neither total nor free testosterone, nor SHBG were associated with outcomes. We found no statistically significant effect of cinacalcet treatment on SHBG, free or total testosterone. CONCLUSIONS: Lower free testosterone and higher SHBG in serum are associated with higher risk of death or cardiovascular event in men undergoing chronic hemodialysis.

National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department.

This cohort study examines the use of an ultrasonography-first strategy for urinary stone disease.

APOL1 G3 Variant Is Associated with Cardiovascular Mortality and Sudden Cardiac Death in Patients Receiving Maintenance Hemodialysis of European Ancestry.

INTRODUCTION: The G1 and G2 variants in the APOL1 gene convey high risk for the progression of chronic kidney disease in African Americans. The G3 variant in APOL1 is more common in patients of European ancestry (EA); outcomes associated with this variant have not been explored previously in EA patients receiving dialysis. METHODS: DNA was collected from approximately half of the patients enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial and genotyped for the G3 variants. We utilized an additive genetic model to test associations of G3 with the EVOLVE adjudicated endpoints of all-cause mortality, cardiovascular mortality, sudden cardiac death (SCD), and heart failure. EA and African ancestry samples were analyzed separately. Validation was done in the Vanderbilt BioVU using ICD codes for cardiovascular events that parallel the adjudicated endpoints in EVOLVE. RESULTS: In EVOLVE, G3 in EA patients was associated with the adjudicated endpoints of cardiovascular mortality and SCD. In a validation cohort from the Vanderbilt BioVU, cardiovascular events and cardiovascular mortality defined by ICD codes showed similar associations in EA participants who had been on dialysis for 2 to <5 years. DISCUSSION/CONCLUSIONS: G3 in APOL1 variant was associated with cardiovascular events and cardiovascular mortality in the EA patients receiving dialysis. This suggests that variations in the APOL1 gene that differ in populations of different ancestry may contribute to cardiovascular disease.

Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Limited implementation of palliative care practices in hemodialysis may contribute to end-of-life care that is intensive and not patient centered. We determined whether a learning collaborative for hemodialysis center providers improved delivery of palliative care best practices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ten US hemodialysis centers participated in a pre-post study targeting seriously ill patients between April 2019 and September 2020. Three practices were prioritized: screening for serious illness, goals of care discussions, and use of a palliative dialysis care pathway. The collaborative educational bundle consisted of learning sessions, communication skills training, and implementation support. The primary outcome was change in the probability of complete advance care planning documentation among seriously ill patients. Health care utilization was a secondary outcome, and implementation outcomes of acceptability, adoption, feasibility, and penetration were assessed using mixed methods. RESULTS: One center dropped out due to the coronavirus disease 2019 pandemic. Among the remaining nine centers, 20% (273 of 1395) of patients were identified as seriously ill preimplementation, and 16% (203 of 1254) were identified as seriously ill postimplementation. From the preimplementation to postimplementation period, the adjusted probability of complete advance care planning documentation among seriously ill patients increased by 34.5 percentage points (95% confidence interval, 4.4 to 68.5). There was no difference in mortality or in utilization of palliative hemodialysis, hospice referral, or hemodialysis discontinuation. Screening for serious illness was widely adopted, and goals of care discussions were adopted with incomplete integration. There was limited adoption of a palliative dialysis care pathway. CONCLUSIONS: A learning collaborative for hemodialysis centers spanning the coronavirus disease 2019 pandemic was associated with adoption of serious illness screening and goals of care discussions as well as improved documentation of advance care planning for seriously ill patients. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pathways Project: Kidney Supportive Care, NCT04125537.

Trends in Coronary Artery Disease Screening before Kidney Transplantation.

Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States. Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant. Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods. Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States.

BACKGROUND AND OBJECTIVES: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine the time from first activation on the transplant list and the time on dialysis to deceased donor transplant, each with KAS era or race and ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial and ethnic groups across KAS eras. RESULTS: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black and Hispanic children and other children of color experienced longer times from activation to transplant compared with White children in both eras; this finding was largely attenuated after multivariable analysis (time ratio, 1.16; 95% confidence interval, 1.01 to 1.32; time ratio, 1.13; 95% confidence interval, 1.00 to 1.28; and time ratio, 1.17; 95% confidence interval, 0.96 to 1.41 post-KAS, respectively). Multivariable analysis also showed that racial and ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era were mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black and Hispanic children experienced longer times with a functioning graft in the post-KAS era. CONCLUSIONS: No racial and ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of the KAS in multivariable analysis, whereas time on dialysis to transplantation and odds of short-term graft loss improved in equity after the implementation of the KAS, without compromising disparities in delayed graft function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_07_CJN06740521.mp3.

Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy?

Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility. METHODS: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist. RESULTS: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score. CONCLUSIONS: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates.

INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions. OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting. METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events. RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m). CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation.

BACKGROUND: Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown. METHODS: We examined all adult SLK and SHK transplants in the United States during 1995-2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1-89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups. RESULTS: Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%-3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55-0.96]). CONCLUSIONS: Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates.

Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-min walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).

SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.

Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist.

RATIONALE & OBJECTIVE: Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments. EXPOSURES: 6MWT and STS test results. OUTCOMES: The primary outcome was time to adverse waitlist outcomes (removal from waitlist or death); secondary outcomes were time to transplantation and time to death. ANALYTICAL APPROACH: We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes. RESULTS: Median 6MWT and STS results were 393 (IQR, 305-455) m and 17 (IQR, 12-21) repetitions, respectively. Clinical characteristics and Estimated Post-Transplant Survival scores accounted for only 14% to 21% of the variance in 6MWT/STS results. Physical performance test results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% CI, 1.30-1.56] per 50-m lower 6MWT test result and 1.53 [95% CI, 1.33-1.75] per 5-repetition lower STS test result) and with transplantation (adjusted sHR of 0.80 [95% CI, 0.72-0.88] per 50-m lower 6MWT test result and 0.80 [95% CI, 0.71-0.89] per 5-repetition lower STS test result). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test P<0.001). LIMITATIONS: Single-center observational study. Other measures of global health status (eg, Fried Frailty Index or Short Physical Performance Battery) were not examined. CONCLUSIONS: Among waitlisted kidney transplant candidates with high kidney allocation scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study.

Resistant hypertension is associated with higher rates of cardiovascular disease, kidney disease, and death than primary hypertension. Although clinical practice guidelines recommend screening for primary aldosteronism among persons with resistant hypertension, rates of screening are unknown. We identified 145 670 persons with hypertension and excluded persons with congestive heart failure or advanced chronic kidney disease. Among this cohort, we studied 4660 persons ages 18 to <90 from the years 2008 to 2014 with resistant hypertension and available laboratory tests within the following 24 months. The screening rate for primary aldosteronism in persons with resistant hypertension was 2.1%. Screened persons were younger (55.9±13.3 versus 65.5±11.6 years; P<0.0001) and had higher systolic (145.1±24.3 versus 139.6±20.5 mm Hg; P=0.04) and diastolic blood pressure (81.8±13.6 versus 74.4±13.8 mm Hg; P<0.0001), lower rates of coronary artery disease (5.2% versus 14.2%; P=0.01), and lower serum potassium concentrations (3.9±0.6 versus 4.1±0.5 mmol/L; P=0.04) than unscreened persons. Screened persons had significantly higher rates of prescription for calcium channel blockers, mixed α/ß-adrenergic receptor antagonists, sympatholytics, and vasodilators, and lower rates of prescription for loop, thiazide, and thiazide-type diuretics. The prescription of mineralocorticoid receptor antagonists or other potassium-sparing diuretics was not significantly different between groups (P=0.20). In conclusion, only 2.1% of eligible persons received a screening test within 2 years of meeting criteria for resistant hypertension. Low rates of screening were not due to the prescription of antihypertensive medications that may potentially interfere with interpretation of the screening test. Efforts to highlight guideline-recommended screening and targeted therapy are warranted.