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Background: The metabolic syndrome (MetS) is associated with elevated urinary albumin (UA) excretion and C-reactive protein (CRP). However, potential differences in CRP levels on the association between individual components of the MetS and microalbuminuria (MA; 30–300 μg/mL) and/or UA (0–300 μg/mL) by race/ethnicity is unknown. Methods: We analyzed National Health and Nutrition Examination Surveys (NHANES) data, (1999–2010) for adults (≥20 years of age) with the MetS (N = 5700). The Sobel–Goodman mediation test examined the influence of CRP on the association between individual MetS components and both MA and UA by race/ethnicity. We applied machine learning models to predict UA. Results: CRP mediated the association between waist circumference (WC) and MA in Whites and Hispanics but not in Blacks. However, in general, the proportion of the total effect of MetS components on UA, mediated by CRP, was: 11% for high-density lipoprotein cholesterol (HDL-C) and 40% for WC (P

Background: Podocyte foot process effacement is a key histologic finding in proteinuric kidney disease. We previously showed that 3-week old CD2AP-deficient mice have significant proteinuria, glomerular hypertrophy and mesangial expansion. The goal of this study is to use morphometry to establish the temporal sequence of podocyte foot process effacement, glomerular volume expansion and albuminuria in Cd2ap−/− mice by measuring these parameters at the 2-week time point.Methods: Wild-type mice age 14 ± 1 days with the Cd2ap gene (WT, N = 5) and mice deficient for Cd2ap (Cd2ap KO, N = 5) were generated. Kidneys were harvested and fixed in 2.5% glutaraldehyde and processed for examination by light and electron microscopy. An average of 415.2 (range 268–716) grid points were counted for all the glomeruli, and quantification of glomerular volume from each kidney. Urine was collected the day prior to sacrifice for urine albumin-to-creatinine ratio (ACR) measurements.Results: There was no difference in albuminuria [median (range) mg/g] between WT [212.2 (177.6–388.4) mg/g] vs. Cd2ap KO mice [203.3 (164.7–910.2) mg/g], P = 0.89; or glomerular volume 68,307[10,931] vs. 66,844[13,022] μm3, p = 0.92. The volume densities of glomerular components of the podocyte, capillary lumen and mesangium were not different for the two groups, P = 0.14, 0.14 and 0.17 respectively. However, foot process width was increased in Cd2ap KO 1128[286] vs. WT [374 ± 42] nm, P = 0.02.Conclusion: Here we show that while 2-week old WT and Cd2ap KO mice have similar levels of albuminuria, glomerular and mesangial volume, Cd2ap KO mice have more extensive podocyte foot process effacement. The data suggests that podocyte injury is the initiating event leading to mesangial expansion and albuminuria in this model.

Background Chronic kidney disease (CKD) is a leading cause of healthcare morbidity, utilization, and expenditures nationally, and caring for late-stage CKD populations is complex. Improving health system efficiency could mitigate these outcomes and, in the COVID-19 era, reduce risks of viral exposure. Objective As part of a system-wide transformation to improve healthcare value among populations with high healthcare utilization and morbidity, UCLA Health evaluated a new patient-centered approach that we hypothesized would reduce inpatient utilization for CKD patients. Design For 18 months in 2015–2016 and 12 months in 2017, we conducted an interrupted time series regression analysis to evaluate the intervention’s impact on inpatient utilization. We used internal electronic health records and claims data across six payers. Participants A total of 1442 stage 4–5 CKD patients at a large academic medical center. Intervention Between October and December 2016, the organization implemented a Population Health Value CKD intervention for the CKD stages 4–5 population. A multispecialty leadership team risk stratified the population and identified improvement opportunities, redesigned multispecialty care coordination pathways across settings, and developed greater ambulatory infrastructure to support care needs. Main Measures Outcomes included utilization of hospitalizations, emergency department (ED) visits, inpatient bed days, and 30-day all-cause readmissions. Key Results During the 12 months following intervention implementation, the monthly estimated rate of decline for hospitalizations was 5.4% (95% CI: 3.4–7.4%), which was 3.4 percentage points faster than the 18-month pre-intervention decline of 2.0% (95% CI: 1.0–2.2%) per month (p = 0.004). Medicare CKD patients’ monthly ED visit rate of decline was 3.0% (95% CI: 1.2–4.8%) after intervention, which was 2.6 percentage points faster than the pre-intervention decline of 0.4% (95% CI: − 0.8 to 1.6%) per month (p = 0.02). Conclusions By creating care pathways that link primary and specialty care teams across settings with increased ambulatory infrastructure, healthcare systems have potential to reduce inpatient healthcare utilization. Electronic supplementary material The online version of this article (10.1007/s11606-020-06272-5) contains supplementary material, which is available to authorized users.

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

Longitudinal data are critical to inform prediction of transition to type 2 diabetes mellitus (T2DM) from prediabetes. This study aimed to ascertain T2DM incidence and risk factors, including chronic kidney disease (CKD), in patients with prediabetes. The CURE-CKD registry of electronic health record data includes >2.6 million patients with and at-risk for CKD (T2DM, hypertension, prediabetes). Adults with prediabetes were identified by established criteria for % A1C, random and fasting glycemia, and administrative codes. T2DM was defined by corresponding established criteria. CKD was defined by estimated glomerular filtration rate 30 mg/g based upon 2 or more measurements >90 days apart, and administrative codes. Cox proportional hazards regression was used to predict T2DM. From 2006 to 2017, there were 678,493 patients with prediabetes and baseline A1C 5.9±0.3% (mean±SD). Incident T2DM occurred in 185,770 (27%) at a mean of 3.6 years. At baseline, 134,240 (20%) had CKD. Adjusted for age, gender, race/ethnicity, and hypertension, hazard ratios for T2DM were greater in patients with CKD (1.44, 95%CI [1.42, 1.47]) and with increases in 1% A1C (4.59 95%CI [4.47, 4.72]). CKD was common in prediabetes and, along with higher A1C, demonstrated the greatest hazards for incident T2DM. Presence of CKD identifies patients with prediabetes who are high-risk for transition to T2DM. Disclosure K.A. Hennessey: None. R.Z. Alicic: None. K.B. Daratha: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.

The magnitude of risk for chronic kidney disease (CKD) in prediabetes is unclear. The study aim was to determine CKD incidence and risk factors in patients with prediabetes from the CURE-CKD registry of electronic health record data from >2.6 million patients with or at-risk for CKD. Adults with prediabetes were identified by established criteria for %A1C, random and fasting blood glycemia, and administrative codes. CKD was defined by estimated glomerular filtration rate (eGFR) 30 mg/g based upon two or more measurements >90 days apart and administrative codes. Cox proportional hazards regression was used to predict incident CKD. From 2006 to 2017, there were 544,253 patients with prediabetes and no CKD. Baseline A1C was 5.9±0.3% (mean±SD) and eGFR was 90.7±16.8 mL/min/1.73 m2. Notable medication use was: NSAIDs n=110,964 (20%), PPIs n=49,916 (9%), and ACEi/ARB n=63,738 (12%). Incident CKD occurred (n=59,583) at a rate of 25.2/1,000 person-years with mean time to CKD of 2.9 years. Older age, female gender, Hispanic/Latinx, Black, Native Hawaiian and Other Pacific Islander race/ethnicity, lower eGFR, PPI and ACEi/ARB use were associated with higher hazards of CKD in prediabetes (Table 1). Incident CKD is common in prediabetes with risk factors similar to those in diabetes. CKD screening and detection with a focus on kidney protection may offer novel opportunities to reduce CKD risk in prediabetes. Disclosure K.A. Hennessey: None. K.B. Daratha: None. R.Z. Alicic: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.

Background and Aims Glomerular filtrate rate (GFR) is a key index of kidney function, and directly measured GFR (mGFR) is the gold standard, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR with high accuracy. However, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. This study aimed to systematically assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care. Method Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for studies comparing mGFR with simultaneous eGFR using CKD-EPI calculated from standardized serum creatinine and cystatin C. We pooled data on bias (difference between mGFR and eGFR), accuracy (P30; proportion of eGFR within 30% of mGFR), and correlation coefficient (R; between mGFR and eGFR), using random-effects models. Results A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included (Figure 1). The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88∼7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05∼2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR ( Conclusion CKD-EPIcrea/cys and CKD-EPIcys equations gave less bias and more accurate estimates of mGFR than CKD-EPIcrea equation. Our findings validated and strengthened the use of cystatin C alone or in combination with creatinine in CKD-EPI equations. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.

End-stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non-Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre-ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.

Background: The directly measured glomerular filtrate rate (mGFR) is the gold standard for kidney function, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR, however, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. We performed this meta-analysis to assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care. Methods: Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for related studies. Results: A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included. The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88~7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05~2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR ( Conclusions: CKD-EPIcrea/cys and CKD-EPIcys gave less bias and more accurate estimates of mGFR than CKD-EPIcrea. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.

Key Points Question What are the clinical characteristics of and major risk factors for chronic kidney disease among patients in 2 large US health care systems? Findings In this cohort study of the Center for Kidney Research, Education, and Hope (CURE-CKD) registry, more than 2.6 million adults and children had chronic kidney disease or were at risk. Albuminuria or proteinuria was tested in approximately one-eighth of adults with chronic kidney disease, renin-angiotensin system inhibitors were prescribed to one-fifth, and nonsteroidal anti-inflammatory agents or proton pump inhibitors were prescribed to more than one-third. Meaning Despite common occurrence of chronic kidney disease, rates of identification and use of kidney protective agents were low, while use of potential nephrotoxins was widespread., This cohort study examines the clinical features of, prevalence of, major risk factors for, and care for chronic kidney disease among adults and children treated in 2 large US health care systems., Importance Chronic kidney disease (CKD) is serious and common, yet recognition and public health responses are limited. Objective To describe clinical features of, prevalence of, major risk factors for, and care for CKD among patients treated in 2 large US health care systems. Design, Setting, and Participants This cohort study collected data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) registry, an electronic health record–based registry jointly curated and sponsored by Providence St Joseph Health and the University of California, Los Angeles. Patients were adults and children with CKD (excluding end-stage kidney disease) and adults at risk of CKD (ie, with diabetes, hypertension, or prediabetes) identified by laboratory values, vital signs, prescriptions, and administrative codes. Data were collected from January 2006 through December 2017, with analyses performed from March 2019 through November 2019. Exposures Diabetes, hypertension, and prediabetes. Main Outcomes and Measures Clinical and demographic characteristics, prevalence, and prescribed medications. Results Of 2 625 963 adults and children in the sample, 606 064 adults (23.1%) with CKD had a median (interquartile range [IQR]) age of 70 (59-81) years, with 338 785 women (55.9%) and 434 474 non-Latino white individuals (71.7%). A total of 12 591 children (0.4%) with CKD had a median (IQR) age of 6 (1-13) years, with 7079 girls (56.2%) and 6653 non-Latino white children (52.8%). Median (IQR) estimated glomerular filtration rate was 53 (41-61) mL/min/1.73 m2 among adults and 70 (50-95) mL/min/1.73 m2 in children. Prevalence rates for CKD in adults were 4.8% overall (606 064 of 12 669 700) with 1.6% (93 644 of 6 011 129) during 2006 to 2009, 5.7% (393 455 of 6 903 084) during 2010 to 2013, and 8.4% (683 574 of 8 179 860) during 2014 to 2017 (P

Background Chronic kidney disease (CKD) is a global public health problem, exhibiting sharp increases in incidence, prevalence, and attributable morbidity and mortality. There is a critical need to better understand the demographics, clinical characteristics, and key risk factors for CKD; and to develop platforms for testing novel interventions to improve modifiable risk factors, particularly for the CKD patients with a rapid decline in kidney function. Methods We describe a novel collaboration between two large healthcare systems (Providence St. Joseph Health and University of California, Los Angeles Health) supported by leadership from both institutions, which was created to develop harmonized cohorts of patients with CKD or those at increased risk for CKD (hypertension/HTN, diabetes/DM, pre-diabetes) from electronic health record data. Results The combined repository of candidate records included more than 3.3 million patients with at least a single qualifying measure for CKD and/or at-risk for CKD. The CURE-CKD registry includes over 2.6 million patients with and/or at-risk for CKD identified by stricter guide-line based criteria using a combination of administrative encounter codes, physical examinations, laboratory values and medication use. Notably, data based on race/ethnicity and geography in part, will enable robust analyses to study traditionally disadvantaged or marginalized patients not typically included in clinical trials. Discussion CURE-CKD project is a unique multidisciplinary collaboration between nephrologists, endocrinologists, primary care physicians with health services research skills, health economists, and those with expertise in statistics, bio-informatics and machine learning. The CURE-CKD registry uses curated observations from real-world settings across two large healthcare systems and has great potential to provide important contributions for healthcare and for improving clinical outcomes in patients with and at-risk for CKD.

PURPOSE OF REVIEW: We summarize the evidence for and against a target systolic blood pressure (SBP)

Author(s): Harding, Kimberly; Mersha, Tesfaye B; Pham, Phuong-Thu; Waterman, Amy D; Webb, Fern A; Vassalotti, Joseph A; Nicholas, Susanne B | Abstract: BackgroundThe persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system.SummaryThere are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

Author(s): Tuttle, Katherine; Alicic, Radica Z; Duru, O Kenrik; Jones, Cami R; Daratha, Kenn B; Nicholas, Susanne B; McPherson, Sterling M; Neumiller, Joshua J; Bell, Douglas S; Mangione, Carol M; Norris, Keith C

OBJECTIVE African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA. RESEARCH DESIGN AND METHODS We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data. RESULTS During 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile ( CONCLUSIONS Inflammation, as measured by hs-CRP levels, may be associated with incident DN in AA. Further studies are warranted to replicate and elucidate the basis for this association.

Renal artery dissections (RADs) are lesions that disrupt vessels that primarily occur in patients with a known history of hypertension and caused by stenosis or enlargement of the renal artery typically due to underlying connective tissue disorders. However, RADs may occur spontaneously from trauma and no previous history of hypertension. Here, we report a rare case of bilateral isolated spontaneous RADs that characteristically occurs in healthy males. A 52-year-old male presented with left lower quadrant abdominal pain and renal insufficiency. Two years prior, he had experienced a similar episode of pain on the contralateral side, which was due to an infarct of the right kidney. On this admission, a computed tomography angiogram confirmed a new infarct of the left kidney, with dissection of a branch of the renal artery supplying the upper lobe. Work-up for cardiovascular, hematologic, radiographic or connective tissue causes was negative. We postulate that both RADs were potentially associated with the rapid twisting and turning of the abdominal area on a daily basis required for his occupation as an air traffic controller. The patient was treated with a renin angiotensin system inhibitor. After one year, both RADs had significantly improved and his renal function increased by ~23%. Isolated RAD may be associated with consistent or long-term activities that require rapid twisting and turning of the abdominal area. If left untreated, this may result in malignant hypertension, bilateral dissections, or renal ischemia. To avoid misdiagnosis; we provide a comprehensive review of the typical presentation and necessary assessment and management.

BACKGROUND AND OBJECTIVES: Incidence of ESKD is three times higher in black Americans than in whites, and CKD prevalence continues to rise among black Americans. Community-based kidney disease screening may increase early identification and awareness of black Americans at risk, but it is challenging to implement. This study aimed to identify participants’ perspectives of community kidney disease screening. The Health Belief Model provides a theoretic framework for conceptualization of these perspectives and optimization of community kidney disease screening activities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Researchers in collaboration with the Tennessee Kidney Foundation conducted three focus groups of adults in black American churches in Nashville, Tennessee. Questions examined views on CKD information, access to care, and priorities of kidney disease health. Content analysis was used. Guided by the Health Belief Model, a priori themes were generated, and additional themes were derived from the data using an inductive approach. RESULTS: Thirty-two black Americans completed the study in 2014. Participants were mostly women (79%) with a mean age of 56 years old (range, 24–78). Two major categories of barriers to kidney disease screening were identified: (1) participant factors, including limited kidney disease knowledge, spiritual/religious beliefs, emotions, and culture of the individual; and (2) logistic factors, including lack of convenience and incentives and poor advertisement. Potential facilitators of CKD screening included provision of CKD education, convenience of screening activities, and use of culturally sensitive and enhanced communication strategies. Program recommendations included partnering with trusted community members, selecting convenient locations, tailored advertising, and provision of compensation. CONCLUSIONS: Findings of this study suggest that provider-delivered culturally sensitive education and stakeholder engagement are critical to increase trust, decrease fear, and maximize participation and early identification of kidney disease among black Americans considering community screening.

Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin.

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

The goal of the OSIRIS-REx mission is to return a sample of asteroid material from Near-Earth Asteroid (101955) Bennu. The role of the navigation and flight dynamics team is critical for the spacecraft to execute a precisely planned sampling maneuver over a specifically-selected landing site. In particular, the orientation of Bennu needs to be recovered with good accuracy during orbital operations to contribute as small an error as possible to the landing error budget. Although Bennu is well characterized from Earth-based radar observations, its orientation dynamics are not sufficiently known to exclude the presence of a small wobble. To better understand this contingency and evaluate how well the orientation can be recovered in the presence of a large 1$^{\circ}$ wobble, we conduct a comprehensive simulation with the NASA GSFC GEODYN orbit determination and geodetic parameter estimation software. We describe the dynamic orientation modeling implemented in GEODYN in support of OSIRIS-REx operations, and show how both altimetry and imagery data can be used as either undifferenced (landmark, direct altimetry) or differenced (image crossover, altimetry crossover) measurements. We find that these two different types of data contribute differently to the recovery of instrument pointing or planetary orientation. When upweighted, the absolute measurements help reduce the geolocation errors, despite poorer astrometric (inertial) performance. We find that with no wobble present, all the geolocation requirements are met. While the presence of a large wobble is detrimental, the recovery is still reliable thanks to the combined use of altimetry and imagery data., 35 pages, 7 figures, 7 tables. Accepted for publication in Journal of Geodesy

OBJECTIVE African Americans (AAs) and Hispanics have higher diabetes and end-stage renal disease but similar or lower early chronic kidney disease (CKD) compared with whites. Inflammation plays a critical role in the pathogenesis of diabetes-related CKD. We postulated that in contrast to the general population, AAs and Hispanics have a higher prevalence of early diabetic CKD and systemic inflammatory markers compared with whites. RESEARCH DESIGN AND METHODS We analyzed the National Health and Nutrition Examination Survey 1999–2008 of 2,310 diabetic patients aged ≥20 years with fasting plasma glucose (FPG) ≥126 mg/dL. We performed multiple linear regression among patients with early CKD (urinary albumin excretion [UAE] ≥30 μg/mL and estimated glomerular filtration rate ≥60 mL/min/1.73 m2) to test the relationship between UAE and C-reactive protein (CRP) by race/ethnicity, adjusting for demographics, diabetes duration, FPG, hemoglobin A1c, uric acid, white blood cell count, medication use, cardiovascular disease, and related parameters. RESULTS In patients with diabetes, the prevalence of early CKD was greater among Hispanics and AAs than whites (P < 0.0001). AAs had higher adjusted odds ratio (AOR) for CRP ≥0.2 mg/dL (AOR 1.81 [95% CI 1.19–2.78]), and Hispanics had higher AOR for UAE ≥30 μg/mL (AOR 1.65 [1.07–2.54]). In a regression model adjusted for confounding variables, there was a significant association between UAE and CRP in the mid-CRP tertile (CRP 0.20–0.56 mg/dL, P = 0.001) and highest CRP tertile (CRP ≥0.57 mg/dL, P = 0.01) for Hispanics, but only in the mid-CRP tertile (P = 0.04) for AAs, compared with whites. CONCLUSIONS AAs and Hispanics with diabetes have a higher prevalence of early CKD compared with whites, which is significantly associated with UAE and/or CRP.

We examine the impact of using seasonal and long-period time-variable gravity field (TVG) models on GPS orbit determination, through simulations from 1994 to 2012. The models of time-variable gravity that we test include the GRGS release RL02 GRACE-derived 10-day gravity field models up to degree and order 20 (grgs20x20), a 4 A— 4 series of weekly coefficients using GGM03S as a base derived from SLR and DORIS tracking to 11 satellites (tvg4x4), and a harmonic fit to the above 4 A— 4 SLR---DORIS time series (goco2s_fit2). These detailed models are compared to GPS orbit simulations using a reference model (stdtvg) based on the International Earth Rotation Service (IERS) and International GNSS Service (IGS) repro1 standards. We find that the new TVG modeling produces significant along, cross-track orbit differences as well as annual, semi-annual, draconitic and long-period effects in the Helmert translation parameters (Tx, Ty, Tz) of the GPS orbits with magnitudes of several mm. We show that the simplistic TVG modeling approach used by all of the IGS Analysis Centers, which is based on the models provided by the IERS standards, becomes progressively less adequate following 2006 when compared to the seasonal and long-period TVG models.

Chronic kidney disease (CKD) is a national public health problem. Although the prevalence of early stages of CKD is similar across different racial/ethnic and socioeconomic groups, the prevalence of end-stage renal disease is greater for minorities than their non-Hispanic white peers. Paradoxically, once on dialysis, minorities experience survival rates that exceed their non-Hispanic white peers. Advancing our understanding of the unique interplay of biological, genetic, environmental, sociocultural, and health care system level factors may prompt reorientation of our approach to health promotion and disease prevention. The potential of this new approach is to create previously unimagined gains to improve patient outcomes and reduce health inequities for patients with CKD. © 2013 Elsevier Inc.

Background: Chronic kidney disease is a progressive disease, which terminates in end-stage renal diseases (ESRD) that requires either dialysis or kidney transplantation for the patient to survive. There is an alarming trend in the disparities of ESRD in African Americans (AAs). Currently, AAs represent more than 30% of incident ESRD cases, yet they constitute 15% of the overall US population. Despite the reductions in mortality, increases in access to patient-centered home dialysis and preemptive kidney transplantation for the overall US ESRD population over the last decade, disparities in the care of AAs with ESRD remain largely unaffected. Summary: This review discusses patient-, community-, and practitioner-related factors that contribute to disparities in ESRD care for AAs. In particular, the review addresses issues related to end-of-life support, the importance of Apolipoprotein-1 gene variants, and the advent of pharmacogenomics toward achieving precision care. The need for accessible clinical intelligence for the ESRD population is discussed. Several interventions and a call to action to address the disparities are presented. Key Messages: Significant disparities in ESRD care exist for AAs. Strategies to enhance patient engagement, education, accountable partnerships, and clinical intelligence may reduce these disparities.

The current paradigm for the treatment of chronic hepatitis C virus (HCV) infection involves combinations of agents that act directly on steps of the HCV life cycle. Here we report the preclinical characteristics of ITMN-8187, a nonmacrocyclic inhibitor of the NS3/4A HCV protease. X-ray crystallographic studies of ITMN-8187 and simeprevir binding to NS3/4A protease demonstrated good agreement between structures. Low nanomolar biochemical potency was maintained against NS3/4A derived from HCV genotypes 1, 2b, 4, 5, and 6. In cell-based potency assays, half-maximal reduction of genotype 1a and 1b HCV replicon RNA was afforded by 11 and 4 nM doses of ITMN-8187, respectively. Combinations of ITMN-8187 with other directly acting antiviral agents in vitro displayed additive antiviral efficacy. A 30-mg/kg of body weight dose of ITMN-8187 administered for 4 days yielded significant viral load reductions through day 5 in a chimeric mouse model of HCV. A 3-mg/kg oral dose administered to rats, dogs, or monkeys yielded concentrations in plasma 16 h after dosing that exceeded the half-maximal effective concentration of ITMN-8187. Human microdose pharmacokinetics showed low intersubject variability and prolonged oral absorption with first-order elimination kinetics compatible with once-daily dosing. These preclinical characteristics compare favorably with those of other NS3/4A inhibitors approved for the treatment of chronic HCV infection.

© 2017 Bruce et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Importance: Religiosity has been associated with positive health outcomes. Hypothesized pathways for this association include religious practices, such as church attendance, that result in reduced stress. Objective: The objective of this study was to examine the relationship between religiosity (church attendance), allostatic load (AL) (a physiologic measure of stress) and all-cause mortality in middle-aged adults. Design, setting and participants: Data for this study are from NHANES III (1988-1994). The analytic sample (n = 5449) was restricted to adult participants, who were between 40-65 years of age at the time of interview, had values for at least 9 out of 10 clinical/biologic markers used to derive AL, and had complete information on church attendance. Main outcomes and measures: The primary outcomes were AL and mortality. AL was derived from values for metabolic, cardiovascular, and nutritional/inflammatory clinical/biologic markers. Mortality was derived from a probabilistic algorithm matching the NHANES III Linked Mortality File to the National Death Index through December 31, 2006, providing up to 18 years follow-up. The primary predictor variable was baseline report of church attendance over the past 12 months. Cox proportional hazard logistic regression models contained key covariates including socioeconomic status, self-rated health, co-morbid medical conditions, social support, healthy eating, physical activity, and alcohol intake. Results: Churchgoers (at least once a year) comprised 64.0% of the study cohort (n = 3782). Non-churchgoers had significantly higher overall mean AL scores and higher prevalence of high-risk values for 3 of the 10 markers of AL than did churchgoers. In bivariate analyses non-churchgoers, compared to churchgoers, had higher odds of an AL score 2-3 (OR 1.24; 95% CI 1.01, 1.50) or ≥4 (OR 1.38; 95% CI 1.11, 1.71) compared to AL score of 0-1. More frequent churchgoers (more than once a week) had a 55% reduction of all-cause mortality risk compared with non-churchgoers. (HR 0.45, CI 0.24-0.85) in the fully adjusted model that included AL. Conclusions and relevance: We found a significant association between church attendance and mortality among middleaged adults after full adjustments. AL, a measure of stress, only partially explained differences in mortality between church and non-church attendees. These findings suggest a potential independent effect of church attendance on mortality.

Summary The issue of community or population level screening for health conditions, including chronic kidney disease (CKD), has fueled intense debates over the last several years over the balance of costs versus societal good. In this chapter we review many of the pros and cons of various health screenings for CKD conducted across high and low- and middle-resourced countries. Concerns include trying to balance issues, such as cost-effectiveness, overdiagnosis leading to increased anxiety for patients, and premature labeling of a medical diagnosis, which may impact insurability and/or the cost of medical insurance. Also false negative tests can lead to a sense of reassurance when the actual disease and its risk for progression are present. These concerns are counterbalanced by the potential to detect, prevent, and initiate early treatment for CKD and CKD risk factors, and to mitigate the costly global burden of renal replacement therapy and premature cardiovascular related morbidity and mortality.

Summary Noncommunicable diseases (NCD), including chronic kidney disease (CKD), have become globally recognized as leading causes of premature morbidity and mortality. Three medical conditions: obesity, elevated blood pressure, and elevated blood glucose; and three behavioral factors: tobacco use, alcohol use, and high salt intake, have been identified as major modifiable NCD risk factors. As a result, global targets have been set to address these. Uncontrolled hypertension and poor diabetes control, two of the three prioritized medical conditions, are the two leading causes of kidney failure worldwide. Data from recent studies, however, now concurrently implicate excess body weight as an additional significant contributor to the CKD pandemic. Obstacles to addressing these risk factors and meeting global targets include inadequate public surveillance, substandard prevention, and limited early intervention programs for CKD and CKD risk factors, especially in low- and middle-income countries and low-resourced communities in high-income countries. This chapter will elaborate on the epidemiology and potential strategies to address the three globally targeted medical conditions—diabetes, hypertension, and obesity—and their roles as key CKD risk factors among populations at greatest risk.

Background: African Americans (AAs) suffer the widest gaps in chronic kidney disease (CKD) outcomes compared to Caucasian Americans (CAs) and this is because of the disparities that exist in both health and healthcare. In fact, the prevalence of CKD is 3.5 times higher in AAs compared to CAs. The disparities exist at all stages of CKD. Importantly, AAs are 10 times more likely to develop hypertension-related kidney failure and 3 times more likely to progress to kidney failure compared to CAs. Summary: Several factors contribute to these disparities including genetic and social determinants, late referrals, poor care coordination, medication adherence, and low recruitment in clinical trials. Key Messages: The development and implementation of CKD-related evidence-based approaches, such as clinical and social determinant assessment tools for medical interventions, more widespread outreach programs, strategies to improve medication adherence, safe and effective pharmacological treatments to control or eliminate CKD, as well as the use of health information technology, and patient-engagement programs for improved CKD outcomes may help to positively impact these disparities among AAs

Over the last two decades, there has been a general acknowledgement within the scientific community that modern biology is becoming increasingly computational and to be prepared biologists need to build computational skills.We present work in assisting Bioinformatics efforts at minority institutions in the USA funded through a National Institutes of Health (NIH) grant over the last 15 years. The primary aim was to create a program for assisting minority institutions in building multidisciplinary bioinformatics training programs. The program involves four components for immediate and long-term increases in research opportunities at minority institutions. Specifically, we describe the results of a two month internship program. Through pre and post surveys reported by the participants, we have measured the skills levels of the internship participants prior to the training beginning and at the end of the training. The interns in the program have a stated interest in bioinformatics and are drawn exclusively from multiple minority serving institutions (MSIs) across the United States. The results of the incoming surveys indicate that the participants have acquired basic bioinformatics knowledge, but have not acquired general computational science skills needed to be successful practitioners within the field.This program has been a highly successful outreach effort and a very sound and cost-effective use of the Minority Access to Research Careers (MARC) funding program from NIH. Important lessons have been learned about bioinformatics education that should be implemented at the policy level in order to ensure that educators, students and researchers at minority serving institutions can address science problems using state-of-the-art computational methods, computational genomics and Big Data. We offer suggestions based on our experience in working with MSIs and with High Performance Computing (HPC) to help improve the preparation of students for careers as bioinformatics scientists.

Objectives/Hypothesis: To review our experience with the diagnosis and treatment of exercise-induced paradoxical vocal fold motion disorder (EPVFMD). Study Design: Single-institution retrospective review and cohort analysis. Methods: A single-institution retrospective review was performed identifying patients with paradoxical vocal fold motion disorder (PVFMD). Patients with isolated exercise-induced dyspnea were selected for further review. Flexible fiberoptic laryngoscopy (FFL) performed on these patients were reviewed with regard to presence of laryngeal pathology as well as the presence of PVFMD at rest and/or with exertion. The type of therapy was reviewed. Symptom outcomes were graded as complete resolution, improvement, or unchanged following therapy. Results: There were 758 patients who were identified with PVFMD. A total of 104 patients demonstrated symptoms of PVFMD that were only exercise related (EPVFMD). There were 93/104 (89%) patients who underwent a pre- and post-trigger FFL. Of these, 48/93 (52%) patients had no evidence of PVFMD on initial FFL. After subjecting these patients to exertion, 83/93 (89%) had evidence of PVFMD on postexertion FFL, and 39/93 (42%) patients had evidence of PVFMD on both pre-exertion and postexertion FFL. There were 87/104 (84%) patients who had evidence of laryngeal edema, and 23/104 (23%) had one or more laryngeal lesion on examination. A total of 67 patients were enrolled in laryngeal control therapy and attended at least one session, with 48/67 (72%) demonstrating improvement or complete resolution of their symptoms. Conclusions: The diagnosis of EPVFMD is augmented with the addition of provocation testing. Findings of PVFMD can be identified at rest when asymptomatic. Laryngeal control therapy is an effective treatment for EPVFMD. Laryngoscope, 2013

Background African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. Study Design Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. Setting & Participants Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. Predictors Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. Outcomes APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1 . Results The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10 −24 ) and rs136148 (OR, 0.54; additive; P = 1.1 × 10 −7 ) with replication in FIND ( P = 5.0 × 10 −21 and 1.9 × 10 −05 , respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10 −4 ). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene ( NPHS2 ; P = 0.0001). Limitations Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. Conclusions This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.

Summary Background and objectives Conventional lipid profiles usually cannot predict cardiovascular outcomes in chronic disease states. We hypothesized that novel lipoprotein subfraction concentrations and LDL particle size measurements better predict mortality in maintenance hemodialysis (MHD) patients. Design, setting, participants, & measurements Mortality-predictability of LDL particle diameter and lipoprotein subfraction concentrations, measured by novel ion mobility, was examined in a cohort of 235 hemodialysis patients who were followed for up to 6 years using Cox models with adjustment for important covariables. Results Patients were 54 ± 14 years old (mean ± SD) and included 45% women with total, LDL and HDL cholesterol levels of 143 ± 42, 76 ± 29, and 37 ± 12 mg/dl, respectively. Over 6 years, 71 patients (31%) died. Conventional lipid profile was not associated with mortality. The death hazard ratio (HR, 95% confidence interval) of the highest versus lowest quartiles of very small and large LDL particle concentrations were 2.43 (1.03 to 5.72) and 0.38 (0.15 to 0.96), respectively. Across increasing quartiles of LDL particle diameter, death HRs were 1.00, 0.93 (0.46 to 1.87), 0.43 (0.21 to 0.89), and 0.45 (0.31 to 1.00), respectively. Conclusions Whereas conventional lipid profile cannot predict mortality in MHD patients, larger novel LDL particle diameter or higher large LDL particle concentrations appear predictive of greater survival, whereas higher very small LDL particle concentration is associated with higher death risk. Examining lipoprotein subfraction modulation in chronic diseases is indicated.

In this study, tests were performed with modified tires at the various front and rear positions on seventeen different vehicles to determine the effect of a full tire tread belt separation on a vehicle at highway speeds. The driver's steering and braking inputs were measured along with the vehicle responses during the event. The results show that the forces of a full tread belt separation generally do not force a vehicle out of a driver's control and that only small steering corrections are required to remain in the original lane of travel during the tread belt separation event. Additionally, forces due to the separating tires do not result in violent hop or tramp suspension responses during the separation event. 2011 SAE International.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested that low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence, or lack thereof, of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Background Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. Conclusions The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population. Copyright © 2009 John Wiley & Sons, Ltd.

Editorial American Journal of Nephrology Am J Nephrol 2016;44:81–83 DOI: 10.1159/000447098 Published online: July 14, 2016 Racial Disparities in End-of-Life Issues in Patients with Chronic Kidney Disease Keith C. Norris Susanne B. Nicholas Chronic kidney disease (CKD) affects nearly 15% of adults in the United States (US) and is associated with a progressive increase in the risk of premature morbidity and mortality as kidney function deteriorates [1] . Patients receiving replacement therapy (RRT) are at the highest risk for mortality, and end-of-life (EOL) issues including advanced care planning (ACP) and hospice care have been increasingly promoted in this subset of patients [2] . In fact, during the time period 2000–2012, the percentage of Medicare beneficiaries with end-stage renal disease (ESRD) admitted to the intensive or coronary care unit during the last 90 days of life rose from 50 to 63%, while those who died in the hospital decreased from 47 to 41% [2] . Additionally, the percentage of patients who discon- tinued maintenance dialysis treatments before death in- creased from 19 to 25%, while patients with ESRD receiv- ing hospice care at the time of death increased from 11 to 25%, suggesting a substantial increase in the use of ACP and EOL options. Of note, for the subset of patients who opted to discon- tinue dialysis treatments, the use of hospice services be- tween 2004 and 2012 increased substantially (from 59 to 80%), leading to a significant reduction in Medicare costs per person during the last week of life [2] . While major gains that have been made in the use of hospice services © 2016 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/ajn have been seen across all racial/ethnic groups, Black and Hispanic patients still remain less likely to discontinue dialysis or utilize hospice care compared to their white peers [2] . The discussion of EOL is always challenging, but pa- tients receiving RRT have already transitioned through many of the hurdles that accompany the period of pre- ESRD care. By contrast, patients with advanced stages of CKD who are not receiving RRT present a unique dilem- ma, as their risk for a major adverse event is also great, but many are overwhelmed by concerns regarding pro- gression to RRT, deteriorating health, struggling with di- etary and medication recommendations, coordinating care for associated comorbidities related to their underly- ing disease(s), and selecting an RRT modality [3] . In ad- dition, they are often trying to navigate these multiple complex issues in the face of declining cognitive function- ing from the underlying disease, progressive azotemia, depression, and/or polypharmacy [3] . Thus, much less is known about how to best approach EOL care issues in patients with CKD who are not yet receiving RRT. To fur- ther complicate the issue, there are many patient-level factors such as language, race/ethnicity, religion, age and socioeconomic status that may further influence recep- tivity to and individual prioritization of EOL issues. Keith C. Norris, MD, PhD Department of Medicine 911 Broxton Avenue, Suite 103 Los Angeles, CA 90024 (USA) E-Mail kcnorris @ mednet.ucla.edu Downloaded by: UCLA Biomedical Library 149.142.243.20 - 7/18/2016 10:54:25 PM Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, Calif. , USA

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.

Patients with chronic kidney disease (CKD) suffer from an increased prevalence of cardiovascular disease (CVD) risk factors, and a high rate of premature CV morbidity and mortality. The confluence of CV risk factors, in the context of cardio-metabolic perturbations that vary as renal function declines, complicates strategies for the care of patients with CKD. Understanding the ex­isting evidence for effective CVD treatment strategies can help providers better care for these patients, navigate the complex treat­ment guidelines, which often differ across major organizations, and minimize the con­flicting recommendations that new studies may pose. A pragmatic approach is to target a BP Ethn Dis. 2015;25(4):515- 520; doi:10.18865/ed.25.4.515

Approximately 346 million individuals worldwide and 25.8 million individuals in the U.S. have diabetes (1,2). The high prevalence of diabetes results in a persistently increased prevalence of diabetic nephropathy, which is the leading cause of kidney failure and premature cardiovascular mortality (3). In the U.S., diabetic nephropathy is represented disproportionately in several minority populations including American Indians (4). Of the American Indian tribes in which type 2 diabetes develops at an alarming rate in children as a result of childhood obesity, the Pima Indians tend to have even higher rates of diabetic nephropathy (up to 65%; age-group 45–74 years) and concomitant end stage renal disease (ESRD; as high as 3.5 times) compared with white Americans (5–7). Fasting hyperglycemia and hemoglobin A1C are strong predictors of albuminuria in Pima Indians. Research has established that strict control of plasma glucose in the prediabetic stage can preempt a diagnosis of diabetes in some indigenous peoples (8). Further, in Pima Indians, the combination of macroalbuminuria and worsening estimated glomerular filtration rate (eGFR) strongly predict ESRD and death (9). Several large, well-designed clinical trials in diabetic cohorts have shown that blockade of the renin angiotensin system (RAS) prevents the progression of microalbuminuria to macroalbuminuria as well as the progression of macroalbuminuria to overt proteinuria and subsequent ESRD (10–12). Despite the fact that RAS blockade has shown no effect on primary prevention of diabetic nephropathy in mainly white, normotensive, normoalbuminuric, type 1 diabetic individuals, the importance of defining the renal outcome of RAS blockade in high-risk Pima Indians in particular cannot be overstated. Indeed, primary prevention of diabetic nephropathy in Pima Indians could potentially …

To date, there has not been direct visualization of the anatomic location of direct His bundle pacing (DHBP) leads in the human heart. The absence of such data has contributed to disagreement about the location of DHBP leads with respect to the plane of the tricuspid valve.1,2 We present an autopsy study of a patient who had previously had a DHBP lead implanted, showing unequivocally that the lead is implanted on the atrial side of the tricuspid annulus. An 81-year-old man with diabetes died of sepsis secondary to a lower-extremity infection. Two years prior, the patient presented with symptoms of congestive heart failure and presyncope. He had a history of coronary artery bypass graft and myocardial infarction with mild to moderate left ventricular dysfunction (ejection fraction, 40%–45%). β-blockade therapy was limited by sinus bradycardia and frequent Wenckebach block. The patient was noninducible for ventricular arrhythmias, and a pacemaker was recommended for chronotropic incompetence and AV block. To prevent pacemaker-induced electric dyssynchrony, we implanted a DHBP lead. DHBP lead implantation was performed as previously described.3 Briefly, an octapolar mapping catheter was used to map the His bundle. A pacing lead was actively fixed adjacent to bipolar electrodes recording a His potential (SelectSecure lead, model 3830, delivered …

Chronic kidney disease (CKD) is a national public health problem that afflicts persons of all segments of society. While racial/ethnic disparities in advanced CKD including dialysis dependent populations have been well established, the finding of differences in CKD incidence, prevalence and progression across different socioeconomic groups and racial and ethnic strata has only recently started to receive significant attention. Socioeconomics may exert both interdependent and independent effects on CKD and its complications, and may confound racial and ethnic disparities. Socioeconomic constellations influence not only access to quality care for CKD risk factors and CKD treatment, but may mediate many of the cultural and environmental determinants of health that are becoming more widely recognized as impacting complex medical disorders. In this manuscript we have reviewed the available literature pertaining to the role of socioeconomic status and economic factors in both non-dialysis dependent CKD and end-stage-renal disease. Advancing our understanding of the role of socioeconomic factors in patients with or at risk for CKD can lead to improved strategies for disease prevention and management.

For many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostatespecific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADCw) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy.