Comparative Effectiveness of Alternative Treatment Approaches to Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: An Observational Trial Emulation.

RATIONALE & OBJECTIVE: Optimal approaches to treat secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis (HD) have yet to be established in randomized controlled trials (RCTs). STUDY DESIGN: Two observational clinical trial emulations. SETTING & PARTICIPANTS: Both emulations included adults receiving in-center HD from a national dialysis organization. The patients who had SHPT in the period between 2009 and 2014, were insured for≥180 days by Medicare as primary payer, and did not have contraindications or poor health status limiting theoretical trial participation. EXPOSURE: The parathyroid hormone (PTH) Target Trial emulation included patients with new-onset SHPT (first PTH 300-600pg/mL), with 2 arms defined as up-titration of either vitamin D sterols or cinacalcet within 30 days (lower target) or no up-titration (higher target). The Agent Trial emulation included patients with a PTH≥300 pg/mL while on≥6µg weekly of vitamin D sterol (paricalcitol equivalent dose) and no prior history of cinacalcet. The 2 arms were defined by the first dose or agent change within 30 days (vitamin D-favoring [vitamin-D was up-titrated] vs cinacalcet-favoring [cinacalcet was added] vs nondefined [neither applies]). Multiple trials per patient were allowed in trial 2. OUTCOME: The primary outcome was all-cause death over 24 months; secondary outcomes included cardiovascular (CV) hospitalization or the composite of CV hospitalization or death. ANALYTICAL APPROACH: Pooled logistic regression. RESULTS: There were 1,152 patients in the PTH Target Trial (635 lower target and 517 higher target). There were 2,726 unique patients with 6,727 patient trials in the Agent Trial (6,268 vitamin D-favoring trials and 459 cinacalcet-favoring trials). The lower PTH target approach was associated with reduced adjusted hazard of death (HR, 0.71 [95% CI, 0.52-0.93]), CV hospitalization (HR, 0.78 [95% CI, 0.63-0.98]), and their composite (HR, 0.74 [95% CI, 0.61-0.89]). The cinacalcet-favoring approach demonstrated lower adjusted hazard of death compared to the vitamin D-favoring approach (HR, 0.79 [95% CI, 0.62-0.99]), but not of CV hospitalization or the composite outcome. LIMITATIONS: Potential for residual confounding; low use of cinacalcet with low power. CONCLUSIONS: SHPT management that is focused on lower PTH targets may lower mortality and CV disease in patients receiving HD. These findings should be confirmed in a pragmatic randomized trial. PLAIN-LANGUAGE SUMMARY: Optimal approaches to treat secondary hyperparathyroidism (SHPT) have not been established in randomized controlled trials. Data from a national dialysis organization was used to identify patients with SHPT in whom escalated treatment may be indicated. The approach to treatment was defined based on observed upward titration of SHPT-controlling medications: earlier titration (lower target) versus delayed titration (higher target); and the choice of medication (cinacalcet vs vitamin D sterols). In the first trial emulation, we estimated a 29% lower rate of death and 26% lower rate of cardiovascular disease or death for patients managed with a lower versus higher target approach. Cinacalcet versus vitamin D-favoring approaches were not consistently associated with outcomes in the second trial emulation. This observational study suggests the need for additional clinical trials of SHPT treatment intensity.

Association of Coprescribing of Gabapentinoid and Other Psychoactive Medications With Altered Mental Status and Falls in Adults Receiving Dialysis.

RATIONALE & OBJECTIVE: Prescribing psychoactive medications for patients with kidney disease is common, but for patients receiving dialysis, some medications may be inappropriate. We evaluated the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (PPIMs) (e.g., sedatives, opioids) with altered mental status (AMS) and falls, and whether the associations are modified by frailty. STUDY DESIGN: Observational cohort study. SETTING: & Participants: Adults receiving dialysis represented in the United States Renal Data System who had an active gabapentinoid prescription and no other PPIM prescriptions in the prior 6 months. EXPOSURE: PPIM coprescribing, or the presence of overlapping prescriptions of a gabapentinoid and ≥1 additional PPIM. OUTCOMES: Acute care visits for AMS and injurious falls. ANALYTICAL APPROACH: Prentice-Williams-Petersen Gap Time models estimated the association between PPIM coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty (assessed by a validated frailty index (FI)). Each model tested for interaction between PPIM coprescribing and frailty. RESULTS: Overall, PPIM coprescribing was associated with increased hazard of AMS (HR: 1.66 [95% CI 1.44, 1.92]) and falls (HR: 1.55 [95% CI 1.36, 1.77]). Frailty significantly modified the effect of PPIM coprescribing on the hazard of AMS (interaction p=0.01), but not falls. Among individuals with low frailty (FI=0.15), the hazard ratio for AMS with PPIM co-prescribing was 2.14 (95% CI: 1.69, 2.71); while for individuals with severe frailty (FI=0.34), the hazard ratio for AMS with PPIM coprescribing was 1.64 (95% CI: 1.42, 1.89). Individuals with PPIM coprescribing and severe frailty (FI =0.34) had the highest hazard of AMS [HR 4.04 (95% CI: 3.20, 5.10)] and falls [HR 2.77 (95% CI: 2.27, 3.38)] compared to non-frail individuals without PPIM coprescribing. LIMITATIONS: Outcome ascertainment bias; residual confounding. CONCLUSIONS: Compared to gabapentinoid prescriptions alone, PPIM coprescribing was associated with an increased risk of AMS and falls. Clinicians should consider these risks when coprescribing PPIMs to patients receiving dialysis.

Clinical Outcomes Among High-Risk Primary Care Patients With Diabetic Kidney Disease: Methodological Challenges and Results From the STOP-DKD Study.

BACKGROUND/OBJECTIVE: Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression. METHODS: We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control. RESULTS: We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m 2 , 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m 2 for the control and intervention groups, respectively, with no significant between-group difference ( P =0.75). CONCLUSIONS: We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.

A comparison of deprivation indices and application to transplant populations.

The choice of deprivation index can influence conclusions drawn regarding the extent of deprivation within a community and the identification of the most deprived communities in the United States. This study aimed to determine the degree of correlation among deprivation indices commonly used to characterize transplant populations. We used a retrospective cohort consisting of adults listed for liver or kidney transplants between 2008 and 2018 to compare 4 deprivation indices: neighborhood deprivation index, social deprivation index (SDI), area deprivation index, and social vulnerability index. Pairwise correlation between deprivation indices by transplant referral regions was measured using Spearman correlations of population-weighted medians and upper quartiles. In total, 52 individual variables were used among the 4 deprivation indices with 25% overlap. For both organs, the correlation between the population-weighted 75th percentile of the deprivation indices by transplant referral region was highest between SDI and social vulnerability index (liver and kidney, 0.93) and lowest between area deprivation index and SDI (liver, 0.19 and kidney, 0.15). The choice of deprivation index affects the applicability of research findings across studies examining the relationship between social risk and clinical outcomes. Appropriate application of these measures to transplant populations requires careful index selection based on the intended use and included variable relevance.

Goal-Concordance in Children with Complex Chronic Conditions.

OBJECTIVES: To characterize delivery of goal-concordant end-of-life (EOL) care among children with complex chronic conditions and to determine factors associated with goal-concordance. STUDY DESIGN: This was a retrospective review of goals of care discussions for 272 children with at least 1 complex chronic condition who died at a tertiary care hospital between January 1, 2014, and December 31, 2017. Goals of care and code status were assessed before and within the last 72 hours of life. Goals of care discussions were coded as full interventions; considering withdrawal of interventions (palliation); planned transition to palliation; or actively transitioning/transitioned to palliation. RESULTS: In total, 158 children had documented goals of care discussions before and within the last 72 hours of life, 18 had goals of care discussions only >72 hours before death, 54 only in the last 72 hours of life, and 42 had no documented goals of care. For children with goals of care, EOL care was goal-concordant for 82.2%, discordant in 7%, and unclear in 10.8%. Black children had a greater than 8-fold greater odds of discordant care compared with White children (OR 8.34, P = .007). Comparison of goals of care and code status before and within the last 72 hours of life revealed trends toward nonescalation of care. Specifically, rates of active palliation increased from 11.7% to 63.0%, and code status shifted from 32.6% do not resuscitate to 65.2% (P < .001). CONCLUSIONS: In this cohort, a majority of children had documented goals of care discussions and received goal-concordant EOL care. However, Black children had greater odds of receiving goal-discordant care. Goals of care and code status shifted toward palliation during the last 72 hours of life.

Exploration of model misspecification in latent class methods for longitudinal data: Correlation structure matters.

Modeling longitudinal trajectories and identifying latent classes of trajectories is of great interest in biomedical research, and software to identify latent classes of such is readily available for latent class trajectory analysis (LCTA), growth mixture modeling (GMM) and covariance pattern mixture models (CPMM). In biomedical applications, the level of within-person correlation is often non-negligible, which can impact the model choice and interpretation. LCTA does not incorporate this correlation. GMM does so through random effects, while CPMM specifies a model for within-class marginal covariance matrix. Previous work has investigated the impact of constraining covariance structures, both within and across classes, in GMMs-an approach often used to solve convergence problems. Using simulation, we focused specifically on how misspecification of the temporal correlation structure and strength, but correct variances, impacts class enumeration and parameter estimation under LCTA and CPMM. We found (1) even in the presence of weak correlation, LCTA often does not reproduce original classes, (2) CPMM performs well in class enumeration when the correct correlation structure is selected, and (3) regardless of misspecification of the correlation structure, both LCTA and CPMM give unbiased estimates of the class trajectory parameters when the within-individual correlation is weak and the number of classes is correctly specified. However, the bias increases markedly when the correlation is moderate for LCTA and when the incorrect correlation structure is used for CPMM. This work highlights the importance of correlation alone in obtaining appropriate model interpretations and provides insight into model choice.

Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study, a randomized comparative effectiveness trial.

Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans' potential living kidney donors. African Americans (N = 300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants' mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n = 39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51-2.30] for TALK SWI and 0.92 [0.42-2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p = 91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks. METHODS: Using data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/nonfatal myocardial infarction and stroke (including within prespecified subgroups of younger age [<50 years] and waitlisting status); secondary outcomes included all-cause mortality and the composite of all-cause mortality, nonfatal myocardial infarction, or stroke. RESULTS: Of 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]). Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01). CONCLUSIONS: Our large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study.

RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. STUDY DESIGN: Randomized order, cross-over study with controlled feeding. SETTING & PARTICIPANTS: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. INTERVENTION: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. OUTCOMES: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. RESULTS: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. LIMITATIONS: Small sample size and short feeding duration. CONCLUSIONS: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02427594.

Risks associated with continuation of potentially inappropriate antihypertensive medications in older adults receiving hemodialysis.

BACKGROUND AND OBJECTIVES: After dialysis initiation, older adults may experience orthostatic or post-dialysis hypotension. Some orthostasis-causing antihypertensives (i.e., central alpha agonists and alpha blockers), are considered potentially inappropriate medications (PIMs) for older adults because they carry more risk than benefit. We sought to (1) describe antihypertensive PIM prescribing patterns before and after dialysis initiation and (2) ascertain the potential risk of adverse outcomes when these medications are continued after dialysis initiation. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Using United States Renal Data System data, we evaluated monthly prevalence of antihypertensive PIM claims in the period before and after dialysis initiation among older adults aged ≥66 years initiating in-center hemodialysis in the US between 2013 and 2014. Patients with an antihypertensive PIM prescription at hemodialysis initiation and who survived for 120 days were classified as 'continuers' or 'discontinuers' based on presence or absence of a refill within the 120 days after initiation. We compared rates of hospitalization and risk of death across these groups from day 121 through 24 months after dialysis initiation. RESULTS: Our study included 30,760 total patients, of whom 5981 (19%) patients had an antihypertensive PIM claim at dialysis initiation and survived ≥120 days. Most [65% (n = 3920)] were continuers. Those who continued (versus discontinued) were more likely to be black race (26% versus 21%), have dual Medicare-Medicaid coverage (31% versus 27%), have more medications on average (12 versus 9) and have no functional limitations (84% versus 80%). Continuers experienced fewer all-cause hospitalizations and deaths, but neither were statistically significant after adjustment (Hospitalization: RR 0.93, 95% CI 0.86, 1.00; Death: HR 0.89, 95% CI: 0.78-1.02). CONCLUSIONS: Nearly one in five older adults had an antihypertensive PIM at dialysis initiation. Among those who survived ≥120 days, continuation of an antihypertensive PIM was not associated with increased risk of all-cause hospitalization or mortality.

Psychosocial determinants of cardiovascular events among black Americans with chronic kidney disease or associated risk factors in the Jackson heart study.

BACKGROUND: Individuals with chronic kidney disease (CKD), hypertension (HTN), or diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD). The extent to which psychosocial factors are associated with increased CVD risk within these individuals is unclear. Black individuals experience a high degree of psychosocial stressors due to socioeconomic factors, environment, racism, and discrimination. We examined the association between psychosocial factors and risk of CVD events among Black men and women with CKD and CKD risk factors in the Jackson Heart Study. METHODS AND RESULTS: We identified 1919 participants with prevalent CKD or CKD risk factors at baseline. We used rotated principal component analysis - a form of unsupervised machine learning that may identify constructs not intuitively identified by a person - to describe five groups of psychosocial components (including negative moods, religiosity, discrimination, negative outlooks, and negative coping resources) based on a battery of questionnaires. Multiple imputation by chained equation (MICE) was used to impute missing covariate data. Cox models were used to quantify the association between psychosocial components and incident CVD, defined as a fatal coronary heart disease event, myocardial infarction, cardiac procedure (angiography or revascularization procedure), or stroke. Of the 929 participants in the analysis, 67% were female, 28% were current/former smokers with mean age of 56 years and mean BMI of 33 kg/m2. Over a median follow-up of 8 years, 6% had an incident CVD event. In multivariable models, each standard deviation (SD) increase in the religiosity component was associated with an increased hazard for CVD event (hazard ratio [HR] = 1.52, 95% CI: 1.09-2.13). CONCLUSIONS: Religiosity was associated with CVD among participants with prevalent CKD or CKD risk factors. Studies to better understand the mechanisms of this relationship are needed.

Racial Differences in the Effectiveness of a Multifactorial Telehealth Intervention to Slow Diabetic Kidney Disease.

BACKGROUND: African Americans are significantly more likely than non-African Americans to have diabetes, chronic kidney disease, and uncontrolled hypertension, increasing their risk for kidney function decline. OBJECTIVE: The objective of this study was to compare how African Americans and non-African Americans with diabetes responded to a multifactorial telehealth intervention designed to slow kidney function decline. RESEARCH DESIGN: Secondary analysis of a randomized trial. Primary care patients (N=281, 56% African American) were allocated to either: (1) a multifactorial, pharmacist-delivered phone-based telehealth intervention focused on behavioral and medication management of diabetic kidney disease; or (2) an education control. MEASURES: The primary study outcome was change in estimated glomerular filtration rate (eGFR). Linear mixed models were used to explore the moderating effect of race on the relationship between study arm and eGFR decline over time; the mean annual rate of eGFR decline was estimated by race and study arm. RESULTS: Findings demonstrated a differential intervention effect on kidney function over time by race (Pinteraction=0.005). Among African Americans, the intervention arm had significantly greater preservation of eGFR over time than the control arm (difference in the annual rate of eGFR decline=1.5 mL/min/1.73 m; 95% confidence interval: 0.04, 3.02). For non-African Americans, the intervention arm had a faster decline in eGFR over time than the control arm (difference in the annual rate of eGFR decline=-1.7 mL/min/1.73 m; 95% confidence interval: -3.3, -0.02). CONCLUSION: A multifactorial, pharmacist-delivered telehealth intervention for diabetic kidney disease may be more effective for slowing eGFR decline among African Americans than non-African Americans.

Hypertension Self-management in Socially Disadvantaged African Americans: the Achieving Blood Pressure Control Together (ACT) Randomized Comparative Effectiveness Trial.

BACKGROUND: Effective hypertension self-management interventions are needed for socially disadvantaged African Americans, who have poorer blood pressure (BP) control compared to others. OBJECTIVE: We studied the incremental effectiveness of contextually adapted hypertension self-management interventions among socially disadvantaged African Americans. DESIGN: Randomized comparative effectiveness trial. PARTICIPANTS: One hundred fifty-nine African Americans at an urban primary care clinic. INTERVENTIONS: Participants were randomly assigned to receive (1) a community health worker ("CHW") intervention, including the provision of a home BP monitor; (2) the CHW plus additional training in shared decision-making skills ("DoMyPART"); or (3) the CHW plus additional training in self-management problem-solving ("Problem Solving"). MAIN MEASURES: We assessed group differences in BP control (systolic BP (SBP) < 140 mm Hg and diastolic BP (DBP) < 90 mmHg), over 12 months using generalized linear mixed models. We also assessed changes in SBP and DBP and participants' BP self-monitoring frequency, clinic visit patient-centeredness (i.e., extent of patient-physician discussions focused on patient emotional and psychosocial concerns), hypertension self-management behaviors, and self-efficacy. KEY RESULTS: BP control improved in all groups from baseline (36%) to 12 months (52%) with significant declines in SBP (estimated mean [95% CI] - 9.1 [- 15.1, - 3.1], - 7.4 [- 13.4, - 1.4], and - 11.3 [- 17.2, - 5.3] mmHg) and DBP (- 4.8 [- 8.3, - 1.3], - 4.0 [- 7.5, - 0.5], and - 5.4 [- 8.8, - 1.9] mmHg) for CHW, DoMyPART, and Problem Solving, respectively). There were no group differences in BP outcomes, BP self-monitor use, or clinic visit patient-centeredness. The Problem Solving group had higher odds of high hypertension self-care behaviors (OR [95% CI] 18.7 [4.0, 87.3]) and self-efficacy scores (OR [95% CI] 4.7 [1.5, 14.9]) at 12 months compared to baseline, while other groups did not. Compared to DoMyPART, the Problem Solving group had higher odds of high hypertension self-care behaviors (OR [95% CI] 5.7 [1.3, 25.5]) at 12 months. CONCLUSION: A context-adapted CHW intervention was correlated with improvements in BP control among socially disadvantaged African Americans. However, it is not clear whether improvements were the result of this intervention. Neither the addition of shared decision-making nor problem-solving self-management training to the CHW intervention further improved BP control. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01902719.

Associations of perceived information adequacy and knowledge with pursuit of live donor kidney transplants and living donor inquiries among African American transplant candidates.

We studied associations between perceived adequacy of live donor kidney transplant (LDKT) information or knowledge with pursuit of LDKT or receipt of live donor inquiries among 300 African American kidney transplant candidates. Participants reported via questionnaire how informed or knowledgeable they felt regarding LDKT. Participants also reported their pursuit of LDKT, categorized as "low" (no discussion with family or friends about LDKT and no identified donor), "intermediate" (discussed LDKT with family but no identified donor) or "high" (discussed LDKT with family and identified a potential donor). We reviewed participants' electronic health records to identify potential donors' transplant center inquiries on participants' behalves. A minority of participants reported they felt "very" or "extremely" well informed about LDKT (39%) or had "a great deal" of LDKT knowledge (38%). Participants perceiving themselves as "very" or "extremely" (vs "not" or "slightly") well informed about LDKT had statistically significantly greater odds of intermediate or high (vs low) pursuit of LDKT (odds ratio [95% confidence interval] 2.71 [1.02-7.17]). Perceived LDKT knowledge was not associated with pursuit of LDKT. Neither perceived information adequacy nor knowledge was associated with living donor inquiries. Efforts to better understand the role of education in the pursuit of LDKT among African American transplant candidates are needed.

Predictors of Net Acid Excretion in the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements. PREDICTORS: A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition. OUTCOME: 24-hour urine NAE. ANALYTICAL APPROACH: NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH < 4 (n = 1) or ≥7.4 (n = 19) or extreme outliers of NAE values (n = 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R2 from a domain-specific model. RESULTS: Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. By domains, more variance was explained by demographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level. LIMITATIONS: Cross-sectional; use of stored biological samples. CONCLUSIONS: NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications.

Smoking Status and Survival Among a National Cohort of Lung and Colorectal Cancer Patients.

INTRODUCTION: The purpose of this study was to explore the association of smoking status and clinically relevant duration of smoking cessation with long-term survival after lung cancer (LC) or colorectal cancer (CRC) diagnosis. We compared survival of patients with LC and CRC who were never-smokers, long-term, medium-term, and short-term quitters, and current smokers around diagnosis. METHODS: We studied 5575 patients in Cancer Care Outcomes Research and Surveillance (CanCORS), a national, prospective observational cohort study, who provided smoking status information approximately 5 months after LC or CRC diagnosis. Smoking status was categorized as: never-smoker, quit >5 years prior to diagnosis, quit between 1-5 years prior to diagnosis, quit less than 1 year before diagnosis, and current smoker. We examined the relationship between smoking status around diagnosis with mortality using Cox regression models. RESULTS: Among participants with LC, never-smokers had lower mortality risk compared with current smokers (HR 0.71, 95% CI 0.57 to 0.89). Among participants with CRC, never-smokers had a lower mortality risk as compared to current smokers (HR 0.79, 95% CI 0.64 to 0.99). CONCLUSIONS: Among both LC and CRC patients, current smokers at diagnosis have higher mortality than never-smokers. This effect should be further studied in the context of tumor biology. However, smoking cessation around the time of diagnosis did not affect survival in this sample. IMPLICATIONS: The results from our analysis of patients in the CanCORS consortium, a large, geographically diverse cohort, show that both LC and CRC patients who were actively smoking at diagnosis have worse survival as compared to never-smokers. While current smoking is detrimental to survival, cessation upon diagnosis may not mitigate this risk.

Association of functional and structural social support with chronic kidney disease among African Americans: the Jackson Heart Study.

BACKGROUND: There is limited evidence on the relationship between social support and renal outcomes in African Americans. We sought to determine the association of social support with prevalent chronic kidney disease (CKD) and kidney function decline in an African American cohort. We also examined whether age modifies the association between social support and kidney function decline. METHODS: We identified Jackson Heart Study (JHS) participants with baseline (Exam in 2000-2004) functional and structural social support data via the Interpersonal Support Evaluation List (ISEL) and social network size questions, respectively. With ISEL as our primary exposure variable, we performed multivariable regression models to evaluate the association between social support and prevalent CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin-creatinine ratio (ACR) ≥30 mg/g], eGFR decline, and rapid renal function decline (RRFD) (> 30% decrease in eGFR over approximately 10 years). All models were adjusted for baseline sociodemographics, diabetes, hypertension, smoking status, and body mass index; models for eGFR decline and RRFD were additionally adjusted for eGFR and ACR. In models for eGFR decline, we assessed for interaction between age and social support. For secondary analyses, we replaced ISEL with its individual domains (appraisal, belonging, self-esteem, and tangible) and social network size in separate models as exposure variables. RESULTS: Of 5301 JHS participants, 4015 (76%) completed the ISEL at baseline. 843 (21%) had low functional social support (ISEL score < 32). Participants with low (vs. higher) functional social support were more likely to have lower income (47% vs. 28%), be current or former tobacco users (39% vs. 30%), have diabetes (25% vs. 21%) or CKD (14% vs. 12%). After multivariable adjustment, neither ISEL or social network size were independently associated with prevalent CKD, eGFR decline, or RRFD. Of the ISEL domains, only higher self-esteem was associated with lower odds of prevalent CKD [OR 0.94 (95% CI 0.89-0.99)]. The associations between social support measures and eGFR decline were not modified by age. CONCLUSIONS: In this African-American cohort, social support was not associated with prevalent CKD or kidney function decline. Further inquiry of self-esteem's role in CKD self-management and renal outcomes is warranted.

Addressing Diabetes and Poorly Controlled Hypertension: Pragmatic mHealth Self-Management Intervention.

BACKGROUND: Patients with diabetes and poorly controlled hypertension are at increased risk for adverse renal and cardiovascular outcomes. Identifying these patients early and addressing modifiable risk factors is central to delaying renal complications such as diabetic kidney disease. Mobile health (mHealth), a relatively inexpensive and easily scalable technology, can facilitate patient-centered care and promote engagement in self-management, particularly for patients of lower socioeconomic status. Thus, mHealth may be a cost-effective way to deliver self-management education and support. OBJECTIVE: This feasibility study aimed to build a population management program by identifying patients with diabetes and poorly controlled hypertension who were at risk for adverse renal outcomes and evaluate a multifactorial intervention to address medication self-management. We recruited patients from a federally qualified health center (FQHC) in an underserved, diverse county in the southeastern United States. METHODS: Patients were identified via electronic health record. Inclusion criteria were age between 18 and 75 years, diagnosis of type 2 diabetes, poorly controlled hypertension over the last 12 months (mean clinic systolic blood pressure [SBP] ≥140 mm Hg and/or diastolic blood pressure [DBP] ≥90 mm Hg), access to a mobile phone, and ability to receive text messages and emails. The intervention consisted of monthly telephone calls for 6 months by a case manager and weekly, one-way informational text messages. Engagement was defined as the number of phone calls completed during the intervention; individuals who completed 4 or more calls were considered engaged. The primary outcome was change in SBP at the conclusion of the intervention. RESULTS: Of the 141 patients enrolled, 84.0% (118/141) of patients completed 1 or more phone calls and had follow-up SBP measurements for analysis. These patients were on average 56.9 years of age, predominately female (73/118, 61.9%), and nonwhite by self-report (103/118, 87.3%). The proportion of participants with poor baseline SBP control (50/118, 42.4%) did not change significantly at study completion (53/118, 44.9%) (P=.64). Participants who completed 4 or more phone calls (98/118, 83.1%) did not experience a statistically significant decrease in SBP when compared to those who completed fewer calls. CONCLUSION: We did not reduce uncontrolled hypertension even among the more highly engaged. However, 83% of a predominately minority and low-income population completed at least 67% of the multimodal mHealth intervention. Findings suggest that combining an automated electronic health record system to identify at-risk patients with a tailored mHealth protocol can provide education to this population. While this intervention was insufficient to effect behavioral change resulting in better hypertension control, it does suggest that this FQHC population will engage in low-cost population health applications with a potentially promising impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT02418091; https://clinicaltrials.gov/ct2/show/NCT02418091 (Archived by WebCite at http://www.webcitation.org/76RBvacVU).

Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

Background: African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods: We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study. We quantified obesity as body mass index (BMI), sex-normalized waist circumference and visceral adipose volume measured by abdominal computed tomography at an interim study visit. Interactions were hypothesized with (i) metabolic risk factors (dietary quality and physical activity, both quantified by concordance with American Heart Association guidelines) and (ii) factors exacerbating or mitigating hyperfiltration (dietary protein intake, APOL1 risk status and use of renin-angiotensin system blocking medications). Using multivariable regression, we evaluated associations between obesity measures and incident CKD over the follow-up period, as well as interactions with metabolic and hyperfiltration factors. Results: Assessed after a median of 8 years (range 6-11 years), baseline BMI and waist circumference were not associated with incident CKD. Higher visceral adipose volume was independently associated with incident CKD (P = 0.008) in a nonlinear fashion, but this effect was limited to those with lower dietary quality (P = 0.001; P-interaction = 0.04). In additional interaction models, higher waist circumference was associated with greater risk of incident CKD among those with the low-risk APOL1 genotype (P = 0.04) but not those with a high-risk genotype (P-interaction = 0.02). Other proposed factors did not modify obesity-CKD associations. Conclusions. Higher risks associated with metabolically active visceral adipose volume and interactions with dietary quality suggest that metabolic factors may be key determinants of obesity-associated CKD risk. Interactions between obesity and APOL1 genotype should be considered in studies of African Americans.

Trends in African Americans' Attitudes and Behaviors About Living Donor Kidney Transplantation.

BACKGROUND: Due to marginal efforts to increase living donor kidney transplantation, it is unclear whether interventions to improve African Americans' interest and pursuit of living donation should be tailored to address patients' exposure to or familiarity with dialysis or transplant settings. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional secondary analysis of baseline data from 3 separate randomized clinical trials among African Americans with varying degrees of experience with dialysis or transplantation (predialysis, on dialysis but not on transplant list, and on transplant wait-list) settings. METHODS: Interest in living donation was described using a 0 to 10 scale and pursuit of living donor kidney transplantation by achievement of at least 1 pursuant behavior. In multivariable logistic regression analyses, we assessed the association of knowledge, health literacy, and trust in health care with interest in or pursuit of living donation. RESULTS: Interest among the 3 study cohorts was high (predialysis, 62.9%; dialysis, 67.4%; and transplant wait-list, 74.2%). The dialysis and transplant wait-list study cohorts pursued living donation more readily than those not on dialysis (73%, 92%, and 45%, respectively). Interest and pursuit were not statistically significantly associated with knowledge, health literacy, or the 3 factors reflecting medical mistrust. CONCLUSION: Interest and pursuit of living donation were greater among study participants with greater exposure to dialysis or transplant settings. Efforts to promote patients' early interest and pursuit of living donor transplants may consider novel strategies to educate patients with less experience about the benefits of living donor kidney transplantation.