Genomic supremacy: the harm of conflating genetic ancestry and race.

BACKGROUND: Recent studies have reignited the tinderbox of debate surrounding the use of race and ancestry in medicine. These controversial studies have argued for a strong correlation between genetic ancestry and race, justifying continued use of genetic ancestry measures in studies of disease. These studies contend that increased use of continental ancestry estimates can inform clinical risk assessments and management. Further, recent studies of racial corrections used in clinical algorithms, such as those used to estimate 'normal' lung function, also advocate for use of genetic ancestry in place of race for refining risk algorithms. MAIN BODY: These positions are misleading, harmful, and reflect superficial interpretations of population genetics. In this Perspective, we argue that continental genetic ancestry, often proxied by race, serves as a poor indicator of disease risk, and reinforces racialized inequities. CONCLUSION: Instead, we endorse that racial disparities in disease should be investigated by rigorous measures of structural racism alongside careful measures of genetic factors in relevant disease pathways, rather than relying on genetic ancestry or race as a crude proxy for disease-causing alleles.

Impact of pre-dialysis nephrology care engagement and decision-making on provider and patient action toward permanent vascular access.

BACKGROUND: While catheters are often thought the result of emergency hemodialysis (HD) initiation among patients with little or no pre-dialysis nephrology care, the role of patient level of engagement in care and modality decision-making have not been fully explored. METHODS: This is a retrospective medical record review of adults (age 18-89 years) who received care in academically affiliated private practice, public hospital, or Veterans Administration settings prior to initiating HD with a catheter between 10/1/2011 and 9/30/2012. Primary predictors were level of patient engagement in nephrology care within 6 months of HD initiation and timing of modality decision-making. Primary outcomes were provider action (referral) and any patient action (evaluation by a vascular surgeon, vein mapping or vascular surgery) toward [arteriovenous fistula or graft, (AVF/AVG)] creation. RESULTS: Among 92 incident HD patients, 66% (n = 61) initiated HD via catheter, of whom 34% (n = 21) had ideal engagement in care but 42% (n = 25) had no documented decision. Providers referred 48% (n = 29) of patients for AVF/AVG, of whom 72% (n = 21) took any action. Ideal engagement in care predicted provider action (adjusted OR 13.7 [95% CI 1.08, 175.1], p = 0.04), but no level of engagement in care predicted patient action (p > 0.3). Compared to patients with no documented decision, those with documented decisions within 3, 3-12, or more than 12 months before initiating dialysis were more likely to have provider action toward AVF/AVG (adjusted OR [95% CI]: 9.0 [1.4,55.6], p = 0.2, 37.6 [3.3423.4] p = 0.003, and 4.8 [0.8, 30.6], p = 0.1, respectively); and patient action (adjusted OR [95% CI]: 18.7 [2.3, 149.0], p = 0.006, 20.4 [2.6, 160.0], p = 0.004, and 6.2 [0.9, 44.0], p = 0.07, respectively). CONCLUSIONS: Timing of patient modality decision-making, but not level of engagement in pre-dialysis nephrology care, was predictive of patient and provider action toward AVF/AVG Interventions addressing patients' psychological preparation for dialysis are needed.

Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.

System-Level Barriers and Facilitators for Foregoing or Withdrawing Dialysis: A Qualitative Study of Nephrologists in the United States and England.

BACKGROUND: Despite a growing body of literature suggesting that dialysis does not confer morbidity or mortality benefits for all patients with chronic kidney failure, the initiation and continuation of dialysis therapy in patients with poor prognosis is commonplace. Our goal was to elicit nephrologists' perspectives on factors that affect decision making regarding end-stage renal disease. STUDY DESIGN: Semistructured, individual, qualitative interviews. METHODOLOGY: Participants were purposively sampled based on age, race, sex, geographic location, and practice type. Each was asked about his or her perspectives and experiences related to foregoing and withdrawing dialysis therapy. ANALYTICAL APPROACH: Interviews were audiotaped, transcribed, and analyzed using narrative and thematic analysis. RESULTS: We conducted 59 semistructured interviews with nephrologists from the United States (n=41) and England (n=18). Most participants were 45 years or younger, men, and white. Average time since completing nephrology training was 14.2±11.6 (SD) years. Identified system-level facilitators and barriers for foregoing and withdrawing dialysis therapy stemmed from national and institutional policies and structural factors, how providers practice medicine (the culture of medicine), and beliefs and behaviors of the public (societal culture). In both countries, the predominant barriers described included lack of training in end-of-life conversations and expectations for aggressive care among non-nephrologists and the general public. Primary differences included financial incentives to dialyze in the United States and widespread outpatient conservative management programs in England. LIMITATIONS: Participants' views may not fully capture those of all American or English nephrologists. CONCLUSIONS: Nephrologists in the United States and England identified several system-level factors that both facilitated and interfered with decision making around foregoing and withdrawing dialysis therapy. Efforts to expand facilitators while reducing barriers could lead to care practices more in keeping with patient prognosis.

Hospitalizations and Nursing Facility Stays During the Transition from CKD to ESRD on Dialysis: An Observational Study.

BACKGROUND: There is little information on hospital and nursing facility stays during the transition from pre-dialysis kidney disease to end-stage renal disease treated with dialysis. OBJECTIVES: To examine hospital and nursing facility stays in the years pre- and post-dialysis initiation, and to develop a novel method for visualizing these data. DESIGN: Observational study of patients in the US Renal Data System initiating dialysis from October 2011 to October 2012. PARTICIPANTS: Patients aged ≥67 years with Medicare Part A/B coverage for 1 year pre-dialysis initiation. MAIN MEASURES: Proportion of patients with ≥1 facility day, and among these, the mean number of days and the mean proportion of time spent in a facility in the first year post-dialysis initiation. We created "heat maps" to represent data visually. KEY RESULTS: Among 28,049 patients, > 60% initiated dialysis in the hospital. Patients with at least 1 facility day spent 37-42 days in a facility in the year pre-dialysis initiation and 59-67 facility days in the year post-dialysis initiation. The duration of facility stay varied by age: patients aged 67-70 years spent 60 (95% CI 57-62) days or 25.8% of the first year post-dialysis initiation in a facility, while patients aged >80 years spent 67 (CI 65-69) days or 36.8% of the first year post-dialysis initiation in a facility. Patterns varied depending on the presence or absence of certain comorbid conditions, with dementia having a particularly large effect: patients with dementia spent approximately 50% of the first year post-dialysis initiation in a facility, regardless of age. CONCLUSIONS: Older patients, particularly octogenarians and patients with dementia or other comorbidities, spend a large proportion of time in a facility during the first year after dialysis initiation. Our heat maps provide a novel and concise visual representation of a large amount of quantitative data regarding expected outcomes after initiation of dialysis.

The association of periodontal disease with kidney function decline: a longitudinal retrospective analysis of the MrOS dental study.

BACKGROUND: Identifying modifiable risk factors for chronic kidney disease (CKD) is essential for reducing its burden. Periodontal disease is common, modifiable and has been implicated as a novel potential CKD risk factor, but evidence of its association with kidney function decline over time is limited. METHODS: In a longitudinal retrospective cohort of 761 elderly men with preserved kidney function [estimated glomerular filtration rate > 60 mL/min/1.73 m(2) using a calibrated creatinine and cystatin C (eGFRcr-cys) equation] at baseline, we performed multivariable Poisson's regression to examine the association of severe periodontal disease with incident CKD, defined as incident eGFRcr-cys <60 mL/min/1.73 m(2) and rapid (>5% annualized) eGFRcr-cys decline. Severe periodontal disease was defined in two ways: (i) ≥5 mm proximal attachment loss in 30% of teeth examined (European Workshop in Periodontology Group C, European Workshop); and (ii) 2+ interproximal sites with attachment loss ≥6 mm and 1+ interproximal sites with probing depth ≥5 mm (Centers for Disease Control/American Academy of Periodontology, CDC/AAP). RESULTS: At baseline, the mean age was 73.4 (SD 4.8) years, the median eGFRcr-cys was 82.4 mL/min/1.73 m(2), and 35.5 and 25.4% of participants had severe periodontal disease by European Workshop and CDC/AAP criteria, respectively. After a mean follow-up of 4.9 years (SD 0.3), 56 (7.4%) participants had incident CKD. Severe periodontal disease was associated with a 2-fold greater rate of incident CKD [incidence rate ratio (IRR) 2.01 (1.21-3.44), P = 0.007] after adjusting for confounders compared with not severe periodontal disease by European Workshop criteria but did not reach statistical significance by CDC/AAP criteria [IRR 1.10 (0.63-1.91), P = 0.9]. CONCLUSIONS: Severe periodontal disease may be associated with incident clinically significant kidney function decline among a cohort of elderly men.

Mortality and illicit drug dependence among hemodialysis patients in the United States: a retrospective cohort analysis.

BACKGROUND: Illicit drug use is common and known to cause and exacerbate a wide spectrum of kidney disease, often leading to end-stage renal disease (ESRD), but little is known about its prevalence or associated mortality among incident hemodialysis patients. METHODS: This study is a retrospective cohort analysis using data obtained from the United States Renal Data System. We assembled a cohort of 511,821 incident hemodialysis patients age 20 years and older who initiated hemodialysis between January 1, 2006 and December 31, 2010. Illicit drug dependence was defined by comorbidity on the ESRD Medical Evidence Report (Form CMS-2728). We performed survival analysis to examine the association of drug dependence with overall mortality and mortality due to diagnoses that can be associated with intravenous drug use (drug-sensitive diagnoses) in the first year after initiating hemodialysis. RESULTS: Drug dependence was recorded for 1.5 % (n = 7,461). Drug dependence was independently associated with a 1.3-fold and 2.5-fold higher hazard of overall mortality and mortality due to a potentially drug-sensitive diagnosis [adjusted hazard ratio (AHR) 1.34 (1.27-1.41) and 2.54 (2.05-3.14), p < 0.001, respectively]. This association varied significantly by age (pinteraction < 0.001), with a 9-fold higher hazard of mortality due to a potentially drug-sensitive diagnosis among the youngest patients with drug dependence [AHR 9.21 (5.15-16.44), p < 0.001]. CONCLUSION: Illicit drug dependence is a burden within the ESRD program and is strongly associated with premature mortality, particularly among younger patients. Targeted intervention is needed to help reduce this burden.

Specialist and primary care physicians' views on barriers to adequate preparation of patients for renal replacement therapy: a qualitative study.

BACKGROUND: Early preparation for renal replacement therapy (RRT) is recommended for patients with advanced chronic kidney disease (CKD), yet many patients initiate RRT urgently and/or are inadequately prepared. METHODS: We conducted audio-recorded, qualitative, directed telephone interviews of nephrology health care providers (n = 10, nephrologists, physician assistants, and nurses) and primary care physicians (PCPs, n = 4) to identify modifiable challenges to optimal RRT preparation to inform future interventions. We recruited providers from public safety-net hospital-based and community-based nephrology and primary care practices. We asked providers open-ended questions to assess their perceived challenges and their views on the role of PCPs and nephrologist-PCP collaboration in patients' RRT preparation. Two independent and trained abstractors coded transcribed audio-recorded interviews and identified major themes. RESULTS: Nephrology providers identified several factors contributing to patients' suboptimal RRT preparation, including health system resources (e.g., limited time for preparation, referral process delays, and poorly integrated nephrology and primary care), provider skills (e.g., their difficulty explaining CKD to patients), and patient attitudes and cultural differences (e.g., their poor understanding and acceptance of their CKD and its treatment options, their low perceived urgency for RRT preparation; their negative perceptions about RRT, lack of trust, or language differences). PCPs desired more involvement in preparation to ensure RRT transitions could be as "smooth as possible", including providing patients with emotional support, helping patients weigh RRT options, and affirming nephrologist recommendations. Both nephrology providers and PCPs desired improved collaboration, including better information exchange and delineation of roles during the RRT preparation process. CONCLUSIONS: Nephrology and primary care providers identified health system resources, provider skills, and patient attitudes and cultural differences as challenges to patients' optimal RRT preparation. Interventions to improve these factors may improve patients' preparation and initiation of optimal RRTs.

Body mass index and early kidney function decline in young adults: a longitudinal analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) study.

BACKGROUND: Identifying potentially modifiable risk factors is critically important for reducing the burden of chronic kidney disease. We sought to examine the association of body mass index (BMI) with kidney function decline in a cohort of young adults with preserved glomerular filtration at baseline. STUDY DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: 2,839 black and white young adults with cystatin C-based estimated glomerular filtration rate (eGFRcys)>90mL/min/1.73m(2) taking part in the year-10 examination (in 1995-1996) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. PREDICTOR: BMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2). OUTCOMES: Trajectory of kidney function decline, rapid decline (>3% per year), and incident eGFRcys <60mL/min/1.73m(2) over 10 years of follow-up. MEASUREMENTS: GFRcys estimated from the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years 10, 15, and 20. RESULTS: At year 10, participants had a mean age of 35.1 years, median eGFRcys of 114mL/min/1.73m(2), and 24.5% had BMI≥30.0kg/m(2). After age 30 years, average eGFRcys was progressively lower with each increment in BMI after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and physical activity. Higher BMI category was associated with successively higher odds of rapid decline (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), adjusted ORs were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67-3.94], respectively). 18 participants (0.6%) had incident eGFRcys<60mL/min/1.73m(2). In unadjusted analysis, higher BMI category was associated with incident eGFRcys<60mL/min/1.73m(2) (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and 5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer significant. LIMITATIONS: Inability to describe kidney function before differences by BMI category were already evident. Absence of data for measured GFR or GFR estimated from serum creatinine level. CONCLUSIONS: Higher BMI categories are associated with greater declines in kidney function in a cohort of young adults with preserved GFR at baseline. Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline.

Effect of food insecurity on chronic kidney disease in lower-income Americans.

BACKGROUND: The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population. METHODS: We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression. RESULTS: In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. CONCLUSION: Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.

Health status as a potential mediator of the association between hemodialysis vascular access and mortality.

BACKGROUND: It is unknown whether the selection of healthier patients for arteriovenous fistula (AVF) placement explains higher observed catheter-associated mortality among elderly hemodialysis patients. METHODS: From the United States Renal Data System 2005-2007, we used proportional hazard models to examine 117 277 incident hemodialysis patients aged 67-90 years for the association of initial vascular access type and 5-year mortality after accounting for health status. Health status was defined as functional status at dialysis initiation and number of hospital days within 2 years prior to dialysis initiation. RESULTS: Patients with catheter alone had more limited functional status (25.5 versus 10.8% of those with AVF) and 3-fold more prior hospital days than those with AVF (mean 18.0 versus 5.4). In the unadjusted model, the likelihood of death was higher for arteriovenous grafts (AVG) {Hazard ratio (HR) 1.20 [95% CI (1.16-1.25)], catheter plus AVF [HR 1.34 (1.31-1.38)], catheter plus AVG [HR 1.46 (1.40-1.52)] and catheter only [HR 1.95 (1.90-1.99)]}, compared with AVF (P < 0.001). The association attenuated -23.7% (95% CI -22.0, -25.5) overall (AVF versus all other access types) after adjusting for the usual covariates (including sociodemographics, comorbidities and pre-dialysis nephrology care) {AVG [HR 1.21 (1.17-1.26)], catheter plus AVF [HR 1.27 (1.24-1.30)], catheter plus AVG [HR 1.38 (1.32-1.43)] and catheter only [HR 1.69 (1.66-1.73)], P < 0.001}. Additional adjustment for health status further attenuated the association by another -19.7% (-18.2, -21.3) overall but remained statistically significant . CONCLUSIONS: The observed attenuation in mortality differences previously attributed to access type alone suggests the existence of selection bias. Nevertheless, the persistence of an apparent survival advantage after adjustment for health status suggests that AVF should still be the access of choice for elderly individuals beginning hemodialysis until more definitive data eliminating selection bias become available.

Estimated kidney function based on serum cystatin C and risk of subsequent coronary artery calcium in young and middle-aged adults with preserved kidney function: results from the CARDIA study.

Whether kidney dysfunction is associated with coronary artery calcium (CAC) in young and middle-aged adults who have a cystatin C-derived estimated glomerular filtration rate (eGFRcys) greater than 60 mL/min/1.73 m(2) is unknown. In the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (recruited in 1985 and 1986 in Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California), we examined 1) the association of eGFRcys at years 10 and 15 and detectable CAC over the subsequent 5 years and 2) the association of change in eGFRcys and subsequent CAC, comparing those with stable eGFRcys to those whose eGFRcys increased (>3% annually over 5 years), declined moderately (3%-5%), or declined rapidly (>5%). Generalized estimating equation Poisson models were used, with adjustment for age, sex, race, educational level, income, family history of coronary artery disease, diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and tobacco use. Among 3,070 participants (mean age 35.6 (standard deviation, 4.1) years and mean eGFRcys 106.7 (standard deviation, 18.5) mL/min/1.73 m(2)), 529 had detectable CAC. Baseline eGFRcys was not associated with CAC. Moderate eGFRcys decline was associated with a 33% greater relative risk of subsequent CAC (95% confidence interval: 5, 68; P = 0.02), whereas rapid decline was associated with a 51% higher relative risk (95% confidence interval: 10, 208; P = 0.01) in adjusted models. In conclusion, among young and middle-aged adults with eGFRcys greater than 60 mL/min/1.73 m(2), annual decline in eGFRcys is an independent risk factor for subsequent CAC.