Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.

BACKGROUND: Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population. METHODS: We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). Cox proportional models were used to estimate hazard ratios for major bleeding and major or clinically relevant nonmajor bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using nonlinear mixed effects models. RESULTS: Among patients with CrCl 25 to 30 mL/min, apixaban caused less major bleeding (hazard ratio, 0.34 [95% CI, 0.14-0.80]) and major or clinically relevant nonmajor bleeding (hazard ratio, 0.35 [95% CI, 0.17-0.72]) compared with warfarin. Patients with CrCl 25 to 30 mL/min randomized to apixaban demonstrated a trend toward lower rates of major bleeding when compared with those with CrCl >30 mL/min (P interaction=0.08) and major or clinically relevant nonmajor bleeding (P interaction=0.05). Median daily steady-state areas under the curve for apixaban 5 mg twice daily were 5512 ng/(mL·h) and 3406 ng/(mL·h) for patients with CrCl 25 to 30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/(mL·h) for patients with CrCl 25 to 30 mL/min. The area under the curve values for patients with CrCl 25 to 30 mL/min fell within the ranges demonstrated for patients with CrCl >30 mL/min. CONCLUSIONS: Among patients with atrial fibrillation and CrCl 25 to 30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced chronic kidney disease, supporting conventional dosing in patients with CrCl 25 to 30 mL/min. Randomized, controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced chronic kidney disease, including those receiving dialysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.

Spirituality, Coping, and Resilience Among Rural Residents Living with Chronic Kidney Disease.

Spirituality, an established resource within rural America, serves as an important coping mechanism for crises of chronic illness. We examined the effects of spirituality on chronic kidney disease (CKD) maintenance in the rural community of Robeson County, North Carolina. We conducted nine focus group discussions and 16 interviews involving 80 diverse key informants impacted by CKD. As disenfranchised patients, they locally engaged in spirituality which mobilized personal and social resources and elicited support from a transcendent authority. Our participants developed a heuristic and aesthetic understanding of disease, built resilience and self-care skills, and improved overall coping and survival.

The global burden of kidney disease and the sustainable development goals.

Kidney disease has been described as the most neglected chronic disease. Reliable estimates of the global burden of kidney disease require more population-based studies, but specific risks occur across the socioeconomic spectrum from poverty to affluence, from malnutrition to obesity, in agrarian to post-industrial settings, and along the life course from newborns to older people. A range of communicable and noncommunicable diseases result in renal complications and many people who have kidney disease lack access to care. The causes, consequences and costs of kidney diseases have implications for public health policy in all countries. The risks of kidney disease are also influenced by ethnicity, gender, location and lifestyle.  Increasing economic and health disparities, migration, demographic transition, unsafe working conditions and environmental threats, natural disasters and pollution may thwart attempts to reduce the morbidity and mortality from kidney disease. A multisectoral approach is needed to tackle the global burden of kidney disease. The sustainable development goals (SDGs) emphasize the importance of a multisectoral approach to health. We map the actions towards achieving all of the SDGs that have the potential to improve understanding, measurement, prevention and treatment of kidney disease in all age groups. These actions can also foster treatment innovations and reduce the burden of such disease in future generations.

La maladie rénale est décrite comme la maladie chronique la plus négligée. Si d'autres études en population sont nécessaires pour établir des estimations fiables de la charge mondiale de la maladie rénale, les risques spécifiques sont présents dans l'ensemble du spectre socioéconomique, à la fois en situation de pauvreté et de richesse, de malnutrition et d'obésité, dans des environnements agricoles et postindustriels, et à tous les âges, aussi bien chez les nouveau-nés que chez les personnes âgées. Diverses maladies transmissibles et non transmissibles entraînent des complications rénales et de nombreuses personnes atteintes de maladie rénale n'ont pas accès aux soins. Les causes, les conséquences et les coûts de la maladie rénale ont une incidence sur la politique de santé publique dans tous les pays. Le risque de développer une maladie rénale est également influencé par l'origine ethnique, le sexe, le lieu et le mode de vie. L'accroissement des disparités économiques et sanitaires, les migrations, la transition démographique, les conditions de travail dangereuses, les menaces environnementales, les catastrophes naturelles et la pollution sont susceptibles de faire échouer les tentatives de réduction de la morbidité et de la mortalité liées à la maladie rénale. Une approche multisectorielle est nécessaire pour faire face à la charge mondiale de la maladie rénale. Les objectifs de développement durable (ODD) soulignent l'importance d'une approche multisectorielle en matière de santé. Nous établissons une cartographie des actions à entreprendre pour atteindre tous les ODD qui sont susceptibles d'améliorer la connaissance, la mesure, la prévention et le traitement de la maladie rénale dans toutes les tranches d'âge. Ces actions peuvent également favoriser les innovations thérapeutiques et réduire la charge de cette affection pour les générations futures.

La insuficiencia renal se ha descrito como la enfermedad crónica más olvidada. Serían necesarios más estudios basados en la población para obtener estimaciones fiables de la carga mundial de la insuficiencia renal, pero existen riesgos específicos en todo el espectro socioeconómico desde la pobreza hasta la prosperidad, desde la desnutrición hasta la obesidad, en contextos agrarios y postindustriales, y a lo largo de la vida desde recién nacidos hasta la tercera edad. Una variedad de enfermedades contagiosas y no contagiosas producen complicaciones renales y muchas personas que padecen una insuficiencia renal no tienen acceso a la atención. Las causas, las consecuencias y los costes de las insuficiencias renales tienen implicaciones para la política de salud pública en todos los países. Los riesgos de la insuficiencia renal también están influenciados por la raza, el sexo, la ubicación y el estilo de vida.  El aumento de las disparidades económicas y de salud, la migración, la transición demográfica, las condiciones de trabajo inseguras y las amenazas ambientales, los desastres naturales y la contaminación pueden frustrar los intentos de reducir la morbilidad y la mortalidad por insuficiencia renal. Se necesita un enfoque multisectorial para abordar la carga mundial de la insuficiencia renal. Los Objetivos de Desarrollo Sostenible (ODS) hacen hincapié en la importancia de un enfoque multisectorial de la salud. Planificamos las acciones para alcanzar todos los ODS con el potencial de mejorar la comprensión, la medición, la prevención y el tratamiento de la insuficiencia renal en todos los grupos de edad. Estas acciones también pueden fomentar innovaciones en el tratamiento y reducir la carga de dicha enfermedad en las generaciones futuras.

Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review.

BACKGROUND: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. PURPOSE: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. DATA SOURCES: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. STUDY SELECTION: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. DATA EXTRACTION: 2 reviewers abstracted data and independently rated study quality and strength of evidence. DATA SYNTHESIS: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. LIMITATIONS: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. CONCLUSION: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).

Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.

Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.

Chronic kidney disease in low- and middle-income countries.

Most of the global burden of chronic kidney disease (CKD) is occurring in low- and middle-income countries (LMICs). As a result of rapid urbanization in LMICs, a growing number of populations are exposed to numerous environmental toxins, high infectious disease burdens and increasing rates of noncommunicable diseases. For CKD, this portends a high prevalence related to numerous etiologies, and it presents unique challenges. A better understanding of the epidemiology of CKD in LMICs is urgently needed, but this must be coupled with strong public advocacy and broad, collaborative public health efforts that address environmental, communicable, and non-communicable risk factors.

Clinical nephrology research in low-resource settings: opportunities, priorities, and challenges for young investigators.

The increased recognition of the growing, worldwide burden of kidney disease has led to calls for prioritizing nephrology research in a global context. However, many challenges exist for young investigators interested in studying kidney disease in low-resource global settings. A lack of clear research priorities, limited funding options, poor infrastructure, difficulty forming partnerships, and unestablished paths for career advancement are a few examples. To discuss these issues, we held a moderated panel discussion in March 2015 as part of the 10th Conference on Kidney Disease in Disadvantaged Populations in Cape Town, South Africa. A group of senior investigators discussed research priorities for studying kidney disease in a global context, collaborations for clinical research, and strategies for dealing with the unique challenges faced by young investigators working in this field.

Neighborhood clustering of non-communicable diseases: results from a community-based study in Northern Tanzania.

BACKGROUND: In order to begin to address the burden of non-communicable diseases (NCDs) in sub-Saharan Africa, high quality community-based epidemiological studies from the region are urgently needed. Cluster-designed sampling methods may be most efficient, but designing such studies requires assumptions about the clustering of the outcomes of interest. Currently, few studies from Sub-Saharan Africa have been published that describe the clustering of NCDs. Therefore, we report the neighborhood clustering of several NCDs from a community-based study in Northern Tanzania. METHODS: We conducted a cluster-designed cross-sectional household survey between January and June 2014. We used a three-stage cluster probability sampling method to select thirty-seven sampling areas from twenty-nine neighborhood clusters, stratified by urban and rural. Households were then randomly selected from each of the sampling areas, and eligible participants were tested for chronic kidney disease (CKD), glucose impairment including diabetes, hypertension, and obesity as part of the CKD-AFRiKA study. We used linear mixed models to explore clustering across each of the samplings units, and we estimated absolute-agreement intra-cluster correlation (ICC) coefficients (ρ) for the neighborhood clusters. RESULTS: We enrolled 481 participants from 346 urban and rural households. Neighborhood cluster sizes ranged from 6 to 49 participants (median: 13.0; 25th-75th percentiles: 9-21). Clustering varied across neighborhoods and differed by urban or rural setting. Among NCDs, hypertension (ρ = 0.075) exhibited the strongest clustering within neighborhoods followed by CKD (ρ = 0.440), obesity (ρ = 0.040), and glucose impairment (ρ = 0.039). CONCLUSION: The neighborhood clustering was substantial enough to contribute to a design effect for NCD outcomes including hypertension, CKD, obesity, and glucose impairment, and it may also highlight NCD risk factors that vary by setting. These results may help inform the design of future community-based studies or randomized controlled trials examining NCDs in the region particularly those that use cluster-sampling methods.

Traditional medicine practices among community members with diabetes mellitus in Northern Tanzania: an ethnomedical survey.

BACKGROUND: Diabetes is a growing burden in sub-Saharan Africa where traditional medicines (TMs) remain a primary form of healthcare in many settings. In Tanzania, TMs are frequently used to treat non-communicable diseases, yet little is known about TM practices for non-communicable diseases like diabetes. METHODS: Between December 2013 and June 2014, we assessed TM practices, including types, frequencies, reasons, and modes, among randomly selected community members. To further characterize TMs relevant for the local treatment of diabetes, we also conducted focus groups and semi-structured interviews with key informants. RESULTS: We enrolled 481 adults of whom 45 (9.4 %) had diabetes. The prevalence of TM use among individuals with diabetes was 77.1 % (95 % CI 58.5-89.0 %), and the prevalence of using TMs and biomedicines concurrently was 37.6 % (95 % CI 20.5-58.4 %). Many were using TMs specifically to treat diabetes (40.3 %; 95 % CI 20.5-63.9), and individuals with diabetes reported seeking healthcare from traditional healers, elders, family, friends, and herbal vendors. We identified several plant-based TMs used toward diabetes care: Moringa oleifera, Cymbopogon citrullus, Hagenia abyssinica, Aloe vera, Clausena anisata, Cajanus cajan, Artimisia afra, and Persea americana. CONCLUSIONS: TMs were commonly used for diabetes care in northern Tanzania. Individuals with diabetes sought healthcare advice from many sources, and several individuals used TMs and biomedicines together. The TMs commonly used by individuals with diabetes in northern Tanzania have a wide range of effects, and understanding them will more effectively shape biomedical practitices and public health policies that are patient-centered and sensitive to TM preferences.

Traditional medicine practices among community members with chronic kidney disease in northern Tanzania: an ethnomedical survey.

BACKGROUND: In sub-Saharan Africa, chronic kidney disease (CKD) is being recognized as a non-communicable disease (NCD) with high morbidity and mortality. In countries like Tanzania, people access many sources, including traditional medicines, to meet their healthcare needs for NCDs, but little is known about traditional medicine practices among people with CKD. Therefore, we sought to characterize these practices among community members with CKD in northern Tanzania. METHODS: Between December 2013 and June 2014, we administered a previously-developed survey to a random sample of adult community-members from the Kilimanjaro Region; the survey was designed to measure traditional medicine practices such as types, frequencies, reasons, and modes. Participants were also tested for CKD, diabetes, hypertension, and HIV as part of the CKD-AFRiKA study. To identify traditional medicines used in the local treatment of kidney disease, we reviewed the qualitative sessions which had previously been conducted with key informants. RESULTS: We enrolled 481 adults of whom 57 (11.9 %) had CKD. The prevalence of traditional medicine use among adults with CKD was 70.3 % (95 % CI 50.0-84.9 %), and among those at risk for CKD (n = 147; 30.6 %), it was 49.0 % (95 % CI 33.1-65.0 %). Among adults with CKD, the prevalence of concurrent use of traditional medicine and biomedicine was 33.2 % (11.4-65.6 %). Symptomatic ailments (66.7 %; 95 % CI 17.3-54.3), malaria/febrile illnesses (64.0 %; 95 % CI 44.1-79.9), and chronic diseases (49.6 %; 95 % CI 28.6-70.6) were the most prevalent uses for traditional medicines. We identified five plant-based traditional medicines used for the treatment of kidney disease: Aloe vera, Commifora africana, Cymbopogon citrullus, Persea americana, and Zanthoxylum chalybeum. CONCLUSIONS: The prevalence of traditional medicine use is high among adults with and at risk for CKD in northern Tanzania where they use them for a variety of conditions including other NCDs. Additionally, many of these same people access biomedicine and traditional medicines concurrently. The traditional medicines used for the local treatment of kidney disease have a variety of activities, and people with CKD may be particularly vulnerable to adverse effects. Recognizing these traditional medicine practices will be important in shaping CKD treatment programs and public health policies aimed at addressing CKD.

The landscape of clinical trials in nephrology: a systematic review of Clinicaltrials.gov.

BACKGROUND: Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need. STUDY DESIGN: Systematic review. SETTING & POPULATION: Studies registered with ClinicalTrials.gov. SELECTION CRITERIA FOR STUDIES: Interventional (ie, nonobservational) studies (both randomized and nonrandomized) registered between October 2007 and September 2010 were included for analysis. Studies were reviewed independently by physicians and classified by clinical specialty. PREDICTOR: Nephrology versus cardiology versus other trials. OUTCOMES: Select clinical trial characteristics. RESULTS: Of 40,970 trials overall, 1,054 (2.6%) were classified as nephrology. Most nephrology trials were for treatment (75.4%) or prevention (15.7%), with very few diagnostic, screening, or health services research studies. Most nephrology trials were randomized (72.3%). Study designs included 24.9% with a single study group, 64.0% that included parallel groups, and 9.4% that were crossover trials. Nephrology trials, compared with 2,264 cardiology trials (5.5% overall), were more likely to be smaller (64.5% vs 48.0% enrolling≤100 patients), phases 1-2 (29.0% vs 19.7%), and unblinded (66.2% vs 53.3%; P<0.05 for all). Nephrology trials also were more likely than cardiology trials to include a drug intervention (72.4% vs 41.9%) and less likely to report having a data monitoring committee (40.3% vs 48.5%; P<0.05 for all). Finally, there were few trials funded by the National Institutes of Health (NIH; 3.3%, nephrology; 4.2%, cardiology). LIMITATIONS: Does not include all trials performed worldwide, and frequent categorization of funding source as university may underestimate NIH support. CONCLUSIONS: Critical differences remain between clinical trials in nephrology and other specialties. Improving care for patients with kidney disease will require a concerted effort to increase the scope, quality, and quantity of clinical trials within nephrology.

Hypertension in an Emergency Department Population in Moshi, Tanzania; A Qualitative Study of Barriers to Hypertension Control.

BACKGROUND: Sub-Saharan Africa has a high prevalence of hypertension with a low rate of awareness, treatment adherence, and control. The emergency department (ED) may represent a unique opportunity to improve hypertension screening, awareness, and linkage to care. We conducted a qualitative study among hypertensive patients presenting to the ED and their healthcare providers to determine barriers to hypertension care and control. METHODS: In northern Tanzania, between November and December 2017, we conducted three focus group discussions among patients with hypertension presenting to the emergency department and three in-depth interviews among emergency department physicians. In our study, hypertension was defined as a single blood pressure of ≥160/100 mm Hg or a two-time average of ≥140/90 mm Hg. Barriers to care were identified by thematic analysis applying an inductive approach within the framework method. RESULTS: We enrolled 24 total patients into three focus groups and performed three in-depth interviews with individual providers. Thematic analysis identified two major domains: 1) patient knowledge, attitudes, and practices, and 2) structural barriers to hypertension care. Four major themes emerged within the knowledge, attitudes, and practices domain, including disease chronicity, provider communication, family support, and fear-based attitudes. Within the structural domain, several themes emerged that identified barriers that impeded hypertension follow-up care and self-management, including cost, access to care, and transportation and wait time. CONCLUSION: Patients and physicians identified multiple barriers and facilitators to hypertension care. These perspectives may be helpful to design emergency department-based interventions that target blood pressure control and linkage to outpatient care.

Practices and Perspectives of Traditional Bone Setters in Northern Tanzania.

Background: Traditional health practitioners remain a critical source of care in Tanzania, more than 50% of Tanzanians frequently using their services. With a severe shortage of orthopaedic surgeons (1:3.3 million Tanzanians) traditional bone setters (TBSs) could potentially expand access to musculoskeletal care and improve outcomes for morbidity as a result of trauma. Objective: We sought to identify the advantages and disadvantages of traditional bone setting in Tanzania and to assess potential for collaboration between TBSs and allopathic orthopaedic surgeons. Methods: Between June and July 2017 we interviewed six TBSs identified as key informants in the regions of Kilimanjaro, Arusha, and Manyara. We conducted semi-structured interviews about practices and perspectives on allopathic healthcare, and analyzed the data using a deductive framework method. Findings: The TBSs reported that their patients were primarily recruited from their local communities via word-of-mouth communication networks. Payment methods for services included bundling costs, livestock barter, and sliding scale pricing. Potentially unsafe practices included lack of radiographic imaging to confirm reduction; cutting and puncturing of skin with unsterile tools; and rebreaking healed fractures. The TBSs described past experience collaborating with allopathic healthcare providers, referring patients to hospitals, and utilizing allopathic techniques in their practice. All expressed enthusiasm in future collaboration with allopathic hospitals. Conclusions: TBSs confer the advantages of word-of-mouth communication networks and greater financial and geographic accessibility. However, some of their practices raise concerns relating to infection, fracture malunion or nonunion, and iatrogenic trauma from manipulating previously healed fractures. A formal collaboration between TBSs and orthopaedic surgeons, based on respect and regular communication, could alleviate concerns through the development of care protocols and increase access to optimal orthopaedic care through a standardized triage and follow-up system.

Life Course Socioeconomic Status, Allostatic Load, and Kidney Health in Black Americans.

BACKGROUND AND OBJECTIVES: Low socioeconomic status confers unfavorable health, but the degree and mechanisms by which life course socioeconomic status affects kidney health is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined the association between cumulative lifetime socioeconomic status and CKD in black Americans in the Jackson Heart Study. We used conditional process analysis to evaluate allostatic load as a potential mediator of this relation. Cumulative lifetime socioeconomic status was an age-standardized z-score, which has 1-SD units by definition, and derived from self-reported childhood socioeconomic status, education, and income at baseline. Allostatic load encompassed 11 baseline biomarkers subsuming neuroendocrine, metabolic, autonomic, and immune physiologic systems. CKD outcomes included prevalent CKD at baseline and eGFR decline and incident CKD over follow-up. RESULTS: Among 3421 participants at baseline (mean age 55 years [SD 13]; 63% female), cumulative lifetime socioeconomic status ranged from -3.3 to 2.3, and 673 (20%) had prevalent CKD. After multivariable adjustment, lower cumulative lifetime socioeconomic status was associated with greater prevalence of CKD both directly (odds ratio [OR], 1.18; 95% confidence interval [95% CI], 1.04 to 1.33 per 1 SD and OR, 1.45; 95% CI, 1.15 to 1.83 in lowest versus highest tertile) and via higher allostatic load (OR, 1.09; 95% CI, 1.06 to 1.12 per 1 SD and OR, 1.17; 95% CI, 1.11 to 1.24 in lowest versus highest tertile). After a median follow-up of 8 years (interquartile range, 7-8 years), mean annual eGFR decline was 1 ml/min per 1.73 m2 (SD 2), and 254 out of 2043 (12%) participants developed incident CKD. Lower cumulative lifetime socioeconomic status was only indirectly associated with greater CKD incidence (OR, 1.04; 95% CI, 1.01 to 1.07 per 1 SD and OR, 1.08; 95% CI, 1.02 to 1.14 in lowest versus highest tertile) and modestly faster annual eGFR decline, in milliliters per minute (OR, 0.01; 95% CI, 0.00 to 0.02 per 1 SD and OR, 0.02; 95% CI, 0.00 to 0.04 in lowest versus highest tertile), via higher baseline allostatic load. CONCLUSIONS: Lower cumulative lifetime socioeconomic status was substantially associated with CKD prevalence but modestly with CKD incidence and eGFR decline via baseline allostatic load.

The burden of hypertension in the emergency department and linkage to care: A prospective cohort study in Tanzania.

OBJECTIVES: Globally, hypertension affects one billion people and disproportionately burdens low-and middle-income countries. Despite the high disease burden in sub-Saharan Africa, optimal care models for diagnosing and treating hypertension have not been established. Emergency departments (EDs) are frequently the first biomedical healthcare contact for many people in the region. ED encounters may offer a unique opportunity for identifying high risk patients and linking them to care. METHODS: Between July 2017 and March 2018, we conducted a prospective cohort study among patients presenting to a tertiary care ED in northern Tanzania. We recruited adult patients with a triage blood pressure ≥ 140/90 mmHg in order to screen for hypertension. We explored knowledge, attitudes and practices for hypertension using a questionnaire, and assessed factors associated with successful follow-up. Hypertension was defined as a single blood pressure measurement ≥ 160/100 mmHg or a three-time average of ≥ 140/90 mmHg. Uncontrolled hypertension was defined as a three-time average measurement of ≥ 160/100 mmHg. Successful follow-up was defined as seeing an outpatient provider within one month of the ED visit. RESULTS: We enrolled 598 adults (mean age 59.6 years), of whom 539 (90.1%) completed the study. The majority (78.6%) of participants were aware of having hypertension. Many (223; 37.2%) had uncontrolled hypertension. Overall, only 236 (43.8%) of participants successfully followed-up within one month. Successful follow-up was associated with a greater understanding that hypertension requires lifelong treatment (RR 1.11; 95% CI 1.03,1.21) and inversely associated with greater anxiety about the future (RR 0.80; 95% CI 0.64,0.99). CONCLUSION: In a northern Tanzanian tertiary care ED, the burden of hypertension is high, with few patients receiving optimal outpatient care follow-up. Multi-disciplinary strategies are needed to improve linkage to care for high-risk patients from ED settings.

Evaluation of Allostatic Load as a Mediator of Sleep and Kidney Outcomes in Black Americans.

INTRODUCTION: Poor sleep associates with adverse chronic kidney disease (CKD) outcomes yet the biological mechanisms underlying this relation remain unclear. One proposed mechanism is via allostatic load, a cumulative biologic measure of stress. METHODS: Using data from 5177 Jackson Heart Study participants with sleep measures available, we examined the association of self-reported sleep duration: very short, short, recommended, and long (≤5, 6, 7-8, or ≥9 hours per 24 hours, respectively) and sleep quality (high, moderate, low) with prevalent baseline CKD, and estimated glomerular filtration rate (eGFR) decline and incident CKD at follow-up. CKD was defined as eGFR <60 ml/min per 1.73 m2 or urine albumin-to-creatinine ratio ≥30 mg/g. Models were adjusted for demographics, comorbidities, and kidney function. We further evaluated allostatic load (quantified at baseline using 11 biomarkers from neuroendocrine, metabolic, autonomic, and immune domains) as a mediator of these relations using a process analysis approach. RESULTS: Participants with very short sleep duration (vs. 7-8 hours) had greater odds of prevalent CKD (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.03-1.66). Very short, short, or long sleep duration (vs. 7-8 hours) was not associated with kidney outcomes over a median follow-up of 8 years. Low sleep quality (vs. high) associated with greater odds of prevalent CKD (OR 1.26, 95% CI 1.00-1.60) and 0.18 ml/min per 1.73 m2 (95% CI 0.00-0.36) faster eGFR decline per year. Allostatic load did not mediate the associations of sleep duration or sleep quality with kidney outcomes. CONCLUSIONS: Very short sleep duration and low sleep quality were associated with adverse kidney outcomes in this all-black cohort, but allostatic load did not appear to mediate these associations.

Chronic kidney disease care models in low- and middle-income countries: a systematic review.

INTRODUCTION: The number of persons with chronic kidney disease (CKD) living in low- and middle-income countries (LMIC) is increasing rapidly; yet systems built to care for them have received little attention. In order to inform the development of scalable CKD care models, we conducted a systematic review to characterise existing CKD care models in LMICs. METHODS: We searched PubMed, Embase and WHO Global Health Library databases for published reports of CKD care models from LMICs between January 2000 and 31 October 2017. We used a combination of database-specific medical subject headings and keywords for care models, CKD and LMICs as defined by the World Bank. RESULTS: Of 3367 retrieved articles, we reviewed the full text of 104 and identified 17 articles describing 16 programmes from 10 countries for inclusion. National efforts (n=4) focused on the prevention of end-stage renal disease through enhanced screening, public awareness campaigns and education for primary care providers. Of the 12 clinical care models, nine focused on persons with CKD and the remaining on persons at risk for CKD; a majority in the first category implemented a multidisciplinary clinic with allied health professionals or primary care providers (rather than nephrologists) in lead roles. Four clinical care models used a randomised control design allowing for assessment of programme effectiveness, but only one was assessed as having low risk for bias; all four showed significant attenuation of kidney function decline in the intervention arms. CONCLUSIONS: Overall, very few rigorous CKD care models have been reported from LMICs. While preliminary data indicate that national efforts or clinical CKD care models bolstering primary care are successful in slowing kidney function decline, limited data on regional causes of CKD to inform national campaigns, and on effectiveness and affordability of local programmes represent important challenges to scalability.

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health: A Scoping Review.

BACKGROUND AND OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys. RESULTS: We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (n=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (n=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (n=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling. CONCLUSIONS: A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.