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Introduction Hypokalemia, including normal range values, Graphical abstract

Background: The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. Methods: We used data from the Third National Health and Nutrition Examination Survey (1988–1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. Results: 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for p for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1–4 (n = 5,346) and specifically in those with CKD stages 3–4 (n = 1,084). Conclusions: Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.

Since 2003, US hypertension guidelines have recommended ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) as first-line antihypertensive therapy in the presence of albuminuria (urine albumin/creatinine ratio ≥300 mg/g). To examine national trends in guideline-concordant ACE inhibitor/ARB utilization, we studied adults participating in the National Health and Nutrition Examination Surveys 2001 to 2018 with hypertension (defined by self-report of high blood pressure, systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg, or use of antihypertensive medications). Among 20 538 included adults, the prevalence of albuminuria ≥300 mg/g was 2.8% in 2001 to 2006, 2.8% in 2007 to 2012, and 3.2% in 2013 to 2018. Among those with albuminuria ≥300 mg/g, no consistent trends were observed for the proportion receiving ACE inhibitor/ARB treatment from 2001 to 2018 among persons with diabetes, without diabetes, or overall. In 2013 to 2018, ACE inhibitor/ARB usage in the setting of albuminuria ≥300 mg/g was 55.3% (95% CI, 46.8%–63.6%) among adults with diabetes and 33.4% (95% CI, 23.1%–45.5%) among those without diabetes. Based on US population counts, these estimates represent 1.6 million adults with albuminuria ≥300 mg/g currently not receiving ACE inhibitor/ARB therapy, nearly half of whom do not have diabetes. ACE inhibitor/ARB underutilization represents a significant gap in preventive care delivery for adults with hypertension and albuminuria that has not substantially changed over time.

Rationale & Objective Persons with chronic kidney disease (CKD) are often unaware of their disease status. Efforts to improve CKD awareness may be most effective if focused on persons at highest risk for progression to kidney failure. Study Design Serial cross-sectional surveys. Setting & Participants Nonpregnant adults (aged ≥20 years) with CKD glomerular filtration rate categories 3-4 (G3-G4) who participated in the National Health and Nutrition Examination Survey from 1999 to 2016 (n = 3,713). Predictor 5-year kidney failure risk, estimated using the Kidney Failure Risk Equation. Predicted risk was categorized as minimal ( Outcome CKD awareness, defined by answering “yes” to the question “Have you ever been told by a doctor or other health professional that you had weak or failing kidneys?” Analytical Approach Prevalence of CKD awareness was estimated within each risk group using complex sample survey methods. Associations between Kidney Failure Risk Equation risk and CKD awareness were assessed using multivariable logistic regression. CKD awareness was compared with awareness of hypertension and diabetes during the same period. Results In 2011 to 2016, unadjusted CKD awareness was 9.6%, 22.6%, 44.7%, and 49.0% in the minimal-, low-, intermediate-, and high-risk groups, respectively. In adjusted analyses, these proportions did not change over time. Awareness of CKD, including among the highest risk group, remains consistently below that of hypertension and diabetes and awareness of these conditions increased over time. Limitations Imperfect sensitivity of the “weak or failing kidneys” question for ascertaining CKD awareness. Conclusions Among adults with CKD G3-G4 who have 5-year estimated risks for kidney failure of 5%

Rationale & Objective Previous studies of inflammation and anemia management in hemodialysis (HD) patients may be biased due to patient differences. We used a self-matched longitudinal design to test whether new inflammation, defined as an acute increase in C-reactive protein (CRP) level, reduces hemoglobin response to erythropoiesis-stimulating agent (ESA) treatment. Study Design Self-matched longitudinal design. Setting & Participants 3,568 new inflammation events, defined as CRP level > 10 mg/L following a 3-month period with CRP level ≤ 5 mg/L, were identified from 12,389 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018) in 10 countries in which CRP is routinely measured. Predictor “After” (vs “before”) observing a high CRP level. Outcomes Within-patient changes in hemoglobin level, ESA dose, and ESA hyporesponsiveness (hemoglobin 6,000 [Japan] or >8,000 [Europe] U/wk). Analytical Approach Linear mixed models and modified Poisson regression. Results Comparing before with after periods, mean hemoglobin level decreased from 11.2 to 10.9 g/dL (adjusted mean change, −0.26 g/dL), while mean ESA dose increased from 6,320 to 6,960 U/wk (adjusted relative change, 8.4%). The prevalence of ESA hyporesponsiveness increased from 7.6% to 12.3%. Both the unadjusted and adjusted prevalence ratios of ESA hyporesponsiveness were 1.68 (95% CI, 1.48-1.91). These associations were consistent in sensitivity analyses varying CRP thresholds and were stronger when the CRP level increase was sustained over the 3-month after period. Limitations Residual confounding by unmeasured time-varying risk factors for ESA hyporesponsiveness. Conclusions In the 3 months after HD patients experienced an increase in CRP levels, hemoglobin levels declined quickly, ESA doses increased, and the prevalence of ESA hyporesponsiveness increased appreciably. Routine CRP measurement could identify inflammation as a cause of worsened anemia. In turn, these findings speak to a potentially important role for anemia therapies that are less susceptible to the effects of inflammation., Graphical Abstract

OBJECTIVEThickened or fatty filum terminale is an occult lesion that can cause tethered cord syndrome requiring surgical untethering. This study’s objectives were to estimate the incidence of tethered fibrofatty filum terminale (TFFT) in a large insured pediatric population, identify predictors of surgery among those TFFT patients, and assess a diagnostic algorithm.METHODSTFFT was defined according to the ICD-9-CM code for cord tethering (742.59), after excluding codes for diastematomyelia, lipomyelomeningocele, terminal myelocystocele, meningocele, and myelomeningocele. Utilizing the Optum Insight database for 2001–2014, the authors identified pediatric patients (< 21 years) in the US who were diagnosed with a tethered cord and estimated the TFFT incidence rates in that source population and the surgical untethering probability among TFFT patients over the 14-year period. Logistic regression was used to estimate the effects (adjusted OR and 95% CI) of age at diagnosis, sex, Charlson Comorbidity Index (CCI) score, diagnosis of Chiari malformation type I, diagnosis of syrinx, and the probability of surgery by US census region. Lastly, to evaluate their algorithm for identifying TFFT from ICD-9 codes, the authors estimated its positive predictive value (PPV) among 50 children who were diagnosed at their institution and met the ICD-9-CM criteria.RESULTSThere were 3218 diagnoses of TFFT, with 482 of these pediatric patients undergoing tethered cord release during the study period. The estimated incidence rate was 12.0 per 100,000/year (95% CI 11.6–12.4 per 100,000/year). The incidence rate was slightly higher in females than in males (12.7 vs 11.4 per 100,000/year). The probability of surgery in the total pediatric TFFT population was 15.0% (95% CI 13.8%–16.2%) and was greater in children with a syrinx (OR 2.2, 95% CI 1.6–3.0), children 7–11 years of age at diagnosis versus < 1 year (OR 1.5, 95% CI 1.1–2.0), CCI score ≥ 3 versus 0 (OR 2.3, 95% CI 1.4–3.8), and residents of the Western vs Northeastern US (OR 2.3, 95% CI 1.6–3.5). In the authors’ own institution’s database, the PPV of TFFT was 35/50 (70.0%, 95% CI 57.3%–82.7%) for identifying tethered cord due to fibrofatty filum terminale among childhood positives.CONCLUSIONSPatients with comorbidities or an associated syrinx showed a higher risk of untethering procedures for TFFT. Also, surgery was appreciably more frequent in the Western US. These findings signify the need for a collaborative prospective cohort study of long-term outcomes for TFFT patients with and without surgery to determine which patients should have surgery.

High dietary glycaemic index (GI) and glycaemic load (GL) may increase cancer risk. However, limited information was available on GI and/or GL and head and neck cancer (HNC) risk. We conducted a pooled analysis on 8 case-control studies (4081 HNC cases; 7407 controls) from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of HNC, and its subsites, from fixed- or mixed-effects logistic models including centre-specific quartiles of GI or GL. GI, but not GL, had a weak positive association with HNC (ORQ4 vs. Q1 = 1.16; 95% CI = 1.02–1.31). In subsites, we found a positive association between GI and laryngeal cancer (ORQ4 vs. Q1 = 1.60; 95% CI = 1.30–1.96) and an inverse association between GL and oropharyngeal cancer (ORQ4 vs. Q1 = 0.78; 95% CI = 0.63–0.97). This pooled analysis indicates a modest positive association between GI and HNC, mainly driven by laryngeal cancer.

Purpose: Mortality among first-year hemodialysis (HD) patients remains unacceptably high. To address this problem, we estimate the proportions of early HD deaths that are potentially preventable by modifying known risk factors. Methods: We included 15,891 HD patients (within 60 days of starting HD) from 21 countries in the Dialysis Outcomes and Practice Patterns Study (1996-2015), a prospective cohort study. Using Cox regression adjusted for potential confounders, we estimated the fraction of first-year deaths attributable to one or more of twelve modifiable risk factors (the population attributable fraction, AF) identified from the published literature by comparing predicted survival based on risk factors observed vs counterfactually set to reference levels. Results: The highest AFs were for catheter use (22%), albumin = 160 mm Hg, phosphorus = 5.5 mg/dL, hemoglobin = 12 g/dL, and white blood cell count >10,000/mu L. AFs for ferritin, calcium, and PTH were 10 mg/L was 21% in facilities where it was routinely measured. Conclusion: A substantial proportion of first-year HD deaths could be prevented by successfully modifying a few risk factors. Highest priorities should be decreasing catheter use and limiting malnutrition/inflammation whenever possible.

We hypothesized that high incidence rates of end-stage renal disease (ESRD) in certain counties of the U.S. are partly due to patients with a type of ESRD resembling chronic kidney disease of uncertain etiology (CKDu), which has been observed in Central America and other countries. Using data on 338,126 incident ESRD patients from the United States Renal Data System (USRDS) (2011 - 2013) and the Behavior Risk Factor Surveillance System (BRFSS) Supplement on county-level variables (2006), we describe both patient-level and county-level characteristics in counties with the highest quartile of ESRD incidence rate standardized for age, sex, and race (> 420 cases/million population/year) compared to the rest of the U.S. and two specific "hotspots" of ESRD: the San Joaquin Valley and the Rio Grande Valley. Logistic regression was used to examine characteristics associated with patients who had either missing cause of ESRD or "unknown" listed as the primary cause of ESRD. High incidence rates of ESRD were observed in southern Texas, the Southeast and parts of California (including the San Joaquin valley area), while low rates were seen in the Northwest and the Mountain Regions. The median crude incidence rate of ESRD was 335 (range 0 - 2,341) new cases per million population per year among counties. Significant predictors of missing/unknown primary cause of ESRD included: older age, white or unknown race, non-Hispanic ethnicity, lack of comorbidities at ESRD onset, lower estimated glomerular filtration rate (eGFR) at initiation, and lack of pre-dialysis care. Large areas of the U.S. have very high rates of ESRD incidence. We cannot confirm that CKDu is present in the U.S. based on this preliminary work. This topic therefore requires further investigation, as many of these patients may well be undocumented aliens working as farm laborers and therefore not registered in the USRDS. .

BackgroundAnemia at hemodialysis (HD) initiation is common. Correcting low hemoglobin (Hgb) before HD initiation may improve survival by avoiding potential harms of chronic anemia, high doses of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in the early HD period, and/or rapid Hgb rise.MethodsWe included 4604 incident HD patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study Phases 4–5 (2009–15). Because low Hgb at HD start may reflect comorbidity or ESA hyporesponse, we restricted our analysis to the 80% of patients who achieved Hgb ≥10 g/dL 91–120 days after HD start (Month 4).ResultsAbout 53% of these patients had Hgb ConclusionsEven among patients with Hgb ≥10 g/dL 3 months later, anemia at HD initiation was common and associated with elevated mortality. A more proactive approach to anemia management in advanced chronic kidney disease (CKD) may thus improve survival on HD, though long-term prospective studies of non-dialysis CKD patients are needed.

Background and objectives Calcimimetic drugs used to treat secondary hyperparathyroidism are being considered for inclusion in the Medicare ESRD Prospective Payment System bundle after an evaluation period. Understanding of utilization patterns of calcimimetics across dialysis facilities may help align financial incentives with clinical objectives. Our study’s purpose was to describe the distribution of cinacalcet prescription across United States hemodialysis facilities and to explore factors that may influence cinacalcet utilization. Design, setting, participants, & measurements We used monthly cross-sectional data from the Dialysis Outcomes and Practice Patterns Study in 2014 to characterize the distribution of cinacalcet prescription across 203 United States hemodialysis facilities (10,521 patients). On the basis of associations with parathyroid hormone levels from patient-level analyses, we used linear mixed-effects regressions to estimate the associations between three facility-level exposures (black race, Results The mean percentage of patients in each facility with cinacalcet prescription was 23% in June 2014 (median, 22%; interquartile range, 13%–30%). Adjusted for facility-level and nonexposure patient-level variables, the difference in prevalence of cinacalcet prescription between facilities with the highest and lowest quartiles of percentage of black patients was 7.8% (95% confidence interval [95% CI], 0.8% to 14.8%; P for trend =0.03). The adjusted prevalence difference was 7.3% for the percentage of patients aged Conclusions Facilities treating more patients who are black, under age 65 years, and having dialysis vintage ≥3 years have higher average levels of cinacalcet prescription. However, these differences were strongly attenuated after accounting for the unbalanced distributions of these patient case-mix variables.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Background Population rates of obesity, hypertension, diabetes, age, and race can be used in simulation models to develop projections of ESRD incidence and prevalence. Such projections can inform long-range planning for ESRD resources needs. Methods We used an open compartmental simulation model to estimate the incidence and prevalence of ESRD in the United States through 2030 on the basis of wide-ranging projections of population obesity and ESRD death rates. Population trends in age, race, hypertension, and diabetes were on the basis of data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey and the US Census. Results The increase in ESRD incidence rates within age and race groups has leveled off and/or declined in recent years, but our model indicates that population changes in age and race distribution, obesity and diabetes prevalence, and ESRD survival will result in a 11%–18% increase in the crude incidence rate from 2015 to 2030. This incidence trend along with reductions in ESRD mortality will increase the number of patients with ESRD by 29%–68% during the same period to between 971,000 and 1,259,000 in 2030. Conclusions The burden of ESRD will increase in the United States population through 2030 due to demographic, clinical, and lifestyle shifts in the population and improvements in RRT. Planning for ESRD resource allocation should allow for substantial continued growth in the population of patients with ESRD. Future interventions should be directed to preventing the progression of CKD to kidney failure.

This cross-sectional study examines whether removal of the Black race coefficient from a glomerular filtration rate (GFR) estimating equation is associated with a change in the estimated prevalence of chronic kidney disease (CKD) in the general Black population and among Black veterans in the US.

INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p(interaction) = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p(interaction) = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p(interaction)

Background Although there is some evidence of positive associations between both the glycemic index (GI) and glycemic load (GL) with cancer risk, the relationships with lung cancer risk remain largely unexplored. We evaluated the associations between GI and GL with lung cancer. Methods The analyses were performed using data from a population-based case-control study recruited between 1999 and 2004 in Los Angeles County. Dietary factors were collected from 593 incident lung cancer cases and 1026 controls using a modified food frequency questionnaire. GI and GL were estimated using a food composition table. Adjusted odds ratios (ORs) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. Results Dietary GI was positively associated with lung cancer (OR for upper vs. lower tertile = 1.62; 95 % CI: 1.17, 2.25). For histologic subtypes, positive associations were observed between GI and adenocarcinoma (OR for upper vs. lower tertile = 1.82; 95 % CI: 1.22, 2.70) and small cell carcinoma (OR for upper vs. lower tertile = 2.68; 95 % CI: 1.25, 5.74). No clear association between GL and lung cancer was observed. Conclusion These findings suggest that high dietary GI was associated with increased lung cancer risk, and the positive associations were observed for both lung adenocarcinoma and small cell lung carcinoma. Replication in an independent dataset is merited for a broader interpretation of our results.

Angelo Karaboyas,1,2 Hal Morgenstern,3 Nancy L Fleischer,2 Douglas E Schaubel,4,5 Bruce M Robinson1,6 1Arbor Research Collaborative for Health, Ann Arbor, MI, USA; 2University of Michigan, Department of Epidemiology, Ann Arbor, MI, USA; 3University of Michigan, Departments of Epidemiology and Environmental Health Sciences, School of Public Health, and Department of Urology, Medical School, Ann Arbor, MI, USA; 4University of Michigan, Department of Biostatistics, Ann Arbor, MI, USA; 5University of Pennsylvania, Department of Biostatistics, Epidemiology and Informatics, Philadelphia, PA, USA; 6University of Michigan, Department of Internal Medicine, Ann Arbor, MI, USACorrespondence: Angelo KaraboyasArbor Research Collaborative for Health, 3700 Earhart Road, Ann Arbor, MI 48105, USATel +1 (734) 665-4108Email Angelo.Karaboyas@ArborResearch.orgBackground: Reproducibility of clinical and epidemiologic research is important to generalize findings and has increasingly been scrutinized. A recently published randomized trial, PIVOTAL, evaluated high vs low intravenous iron dosing strategies to manage anemia in hemodialysis patients in the UK. Our objective was to assess the reproducibility of the PIVOTAL trial findings using data from a well-established cohort study, the Dialysis Outcomes and Practice Patterns Study (DOPPS).Methods: To overcome the absence of randomization in the DOPPS, we applied the parametric g-formula, an extension of standardization to longitudinal data. We estimated the effect of a proactive high-dose vs reactive low-dose iron supplementation strategy on all-cause mortality (primary outcome), hemoglobin, two measures of iron concentration (ferritin and TSAT), and erythropoiesis-stimulating agent dose over 12 months of follow-up in 6325 DOPPS patients.Results: Comparing high- vs low-iron dose strategies, the 1-year mortality risk difference was 0.020 (95% CI: 0.008, 0.031) and risk ratio was 1.20 (95% CI: 1.07, 1.33), compared with null 1-year findings in the PIVOTAL trial. Differences in secondary outcomes were directionally consistent but of lesser magnitude than in the PIVOTAL trial.Conclusion: Our findings are somewhat consistent with the recent PIVOTAL trial, with discrepancies potentially attributable to model misspecification and differences between the two study populations. In addition to the importance of our results to nephrologists and hence hemodialysis patients, our analysis illustrates the utility of the parametric g-formula for generalizing results and comparing complex and dynamic treatment strategies using observational data.Keywords: reproducibility, causal inference, nephrology, dialysis, anemia, iron

BACKGROUND: Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis. METHODS: We employed an observational cohort study design using data collected from patients maintained on long-term hemodialysis between 1996 and 2015 in facilities across 12 developed countries participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The main outcome was discontinuation of dialysis therapy. We analyzed the association between several patient characteristics and time to dialysis discontinuation by country and phase of study entry. RESULTS: A total of 259 343 DOPPS patients contributed data to the study, of whom 48 519 (18.7%) died during the study period. Of the decedents, 5808 (12.0%) discontinued dialysis before death. Rates of discontinuation were higher within the first few months after initiation of dialysis, among older adults, among those with a greater number of comorbidities and among those living in an institution. After adjustment for age, sex, dialysis duration, diabetes and dialysis era, rates of discontinuation were highest in Canada, the United States and Australia/New Zealand (33.8, 31.4 and 21.5 per 1000/yr, respectively) and lowest in Japan and Italy (< 0.1 per 1000/yr). Crude discontinuation rates were highest in dialysis facilities that were more likely to offer comprehensive conservative renal care to older adults. INTERPRETATION: We found persistent international variation in average rates of dialysis discontinuation not explained by differences in patient case-mix. These differences may reflect physician-, facility- and society-level differences in clinical practice. There may be opportunities for international cross-collaboration to improve support for patients with end-stage renal disease who prefer a more conservative approach.

Rationale & Objective Normalization of parathyroid hormone (PTH), serum calcium, and phosphorus levels may prevent coronary and bone disease in hemodialysis (HD) patients. We describe the trajectory of these mineral bone disorder parameters and treatments during the first 5 years of HD by international region and race. Study Design Prospective cohort study. Setting & Participants 33,517 US black/African American, US non-black/African American, European, and Japanese HD patients from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 5 (2009-2015). Predictor Time since HD initiation. Outcomes Monthly cross-sections of mineral bone disorder parameters (PTH, serum calcium, and phosphorus) and medications (cinacalcet, active vitamin D, and phosphate binders). Results Mean PTH levels declined precipitously during the first 4 months of HD in all 4 groups, then steadily increased during the next 4.5 years in the United States/Europe but not in Japan. 3 years after HD initiation (month 36), mean PTH level was highest in US black/African Americans (496 pg/mL), despite greater prescription of cinacalcet (23%) and active vitamin D (85%), and lowest in Japan (151 pg/mL). Mean serum calcium and phosphorus levels increased during the first 4 months of HD. By month 36, the mean calcium level was lower in Japan (8.8 mg/dL) than United States/Europe (9.0-9.1 mg/dL), while the mean phosphorus level was lower in Europe (4.8 mg/dL) than United States/Japan (5.1-5.3 mg/dL). Limitations Lack of data for medication dosages; most patients were not followed from HD onset. Conclusions Large differences exist in the levels, trajectories, and therapies for PTH, calcium, and phosphorus by country and race in the first 5 years of HD. Higher PTH levels were observed in the United States, especially among black/African American patients, despite greater use of cinacalcet and active vitamin D than in Japan or Europe. Potential contributors to differences in PTH levels should be explored to study their impact on PTH management strategies and consequent bone and cardiovascular complications., Graphical abstract

INTRODUCTION: We aimed to estimate the effects of a family history of colorectal cancer (CRC) or esophageal cancer on the risk of Barrett's esophagus (BE) and identify variants in cancer genes that may explain the association. METHODS: Men scheduled for screening colonoscopy were recruited to undergo upper endoscopy. Cases and noncases were screenees with and without BE, respectively. The effects of family histories on BE were estimated with logistic regression, adjusting for the potential confounders. We additionally recruited men recently diagnosed with BE by clinically indicated endoscopies. Banked germline DNA from cases of BE with ≥2 first-degree relatives (FDRs) with CRC and/or an FDR with esophageal cancer underwent next-generation sequencing using a panel of 275 cancer genes. RESULTS: Of the 822 men screened for CRC who underwent upper endoscopy, 70 were newly diagnosed with BE (8.5%). BE was associated with family histories of esophageal cancer (odds ratio = 2.63; 95% confidence interval = 1.07–6.47) and CRC in ≥2 vs 0 FDRs (odds ratio = 3.73; 95% confidence interval = 0.898–15.4). DNA analysis of subjects with both BE and a family history of cancer identified one or more germline variants of interest in genes associated with cancer predisposition in 10 of 14 subjects, including the same novel variant in EPHA5 in 2 unrelated individuals. DISCUSSION: We found an increased risk for BE associated with a family history of esophageal cancer or CRC. Although analysis of germline DNA yielded no clinically actionable findings, discovery of the same EPHA5 variant of uncertain significance in 2 of 14 cases merits additional investigation.

Head and neck cancer (HNC) risk prediction models based on risk factor profiles have not yet been developed. We took advantage of the large database of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, including 14 US studies from 1981–2010, to develop HNC risk prediction models. Seventy percent of the data were used to develop the risk prediction models; the remaining 30% were used to validate the models. We used competing-risk models to calculate absolute risks. The predictors included age, sex, education, race/ethnicity, alcohol drinking intensity, cigarette smoking duration and intensity, and/or family history of HNC. The 20-year absolute risk of HNC was 7.61% for a 60-year-old woman who smoked more than 20 cigarettes per day for over 20 years, consumed 3 or more alcoholic drinks per day, was a high school graduate, had a family history of HNC, and was non-Hispanic white. The 20-year risk for men with a similar profile was 6.85%. The absolute risks of oropharyngeal and hypopharyngeal cancers were generally lower than those of oral cavity and laryngeal cancers. Statistics for the area under the receiver operating characteristic curve (AUC) were 0.70 or higher, except for oropharyngeal cancer in men. This HNC risk prediction model may be useful in promoting healthier behaviors such as smoking cessation or in aiding persons with a family history of HNC to evaluate their risks.

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA's Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed. Among 7 million VA users in fiscal year 2014, CKD was identified using either a strict or liberal operational definition in 1.1 million (16.4%) and 2.5 million (36.3%) veterans, respectively. Most were identified using an estimated glomerular filtration rate laboratory phenotype, some through proteinuria assessment, and very few through International Classification of Diseases, Ninth Revision coding. The VA spent ∼$18 billion for the care of patients with CKD without KRT, most of which was for CKD stage 3, with higher per-patient costs by CKD stage. VA-REINS can be leveraged for disease surveillance, population health management, and improving the quality and value of care, thereby enhancing VA's capacity as a patient-centered learning health system for US veterans.

Background Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

BACKGROUND: To better understand the relation between sleep problems and CKD, we examined temporal trends in the prevalence of self-reported sleep problems in adults in the United States and their associations with CKD and all-cause mortality. METHODS: Using data from 27,365 adult participants in five biannual National Health and Examination Surveys (2005–2006 through 2013–2014), we studied five self-reported sleep problems—trouble sleeping, sleep disorder, nocturia (urinating ≥2 times/night), inadequate sleep (9 hours/night)—plus a composite index. We conducted three types of analysis: temporal trends in the prevalence of each sleep measure by CKD status, using model-based standardization; cross-sectional analysis of associations between four CKD measures and each sleep measure, using logistic regression; and survival analysis of the association between each sleep measure and mortality, using Cox regression. RESULTS: The prevalence of trouble sleeping and sleep disorder increased over the five surveys by 4% and 3%, respectively, whereas the other sleep problems remained relatively stable. All sleep problems, except inadequate sleep, were more common during the study period among adults with CKD than without CKD (40% versus 21% for nocturia; 5% versus 2% for excessive sleep; 30% versus 25% for trouble sleeping; 12% versus 8% for sleep disorder). Both eGFR 9 versus 7–9 hours/night=1.7; 95% CI, 1.3 to 2.1; and for nocturia=1.2; 95% CI, 1.1 to 1.4). CONCLUSIONS: The high prevalence of sleep problems among persons with CKD and their associations with mortality suggest their potential importance to clinical practice. Future work could examine the health effects of identifying and treating sleep problems in patients with CKD.

Introduction This study examined state-level variation in chronic kidney disease (CKD) awareness using national estimates of disease awareness among adults in the U.S. with CKD. Methods Data on U.S. adults were obtained from two national, population-based surveys: (1) the Behavioral Risk Factor Surveillance System (BRFSS 2011; n =506,467), a state-level phone survey containing information on self-reported kidney disease; and (2) the National Health and Nutrition Examination Survey (NHANES 2005–2012; n =20,831), containing physical health examination, surveys containing data on self-reported kidney disease, risk factors, and laboratory values. CKD was defined as an estimated glomerular filtration rate of 15–59 mL/minute/1.73 m 2 or urinary albumin-to-creatinine ratio >30 mg/g. As BRFSS does not include laboratory data, CKD status for each person was imputed (multiple) based on a logistic regression model predicting NHANES CKD status. CKD awareness in each state was estimated as the weighted proportion of BRFSS participants with imputed CKD who reported having kidney disease. Results Overall, estimated CKD awareness was 9.0% (95% CI=8.0%, 10.0%), ranging from 5.8% (95% CI=4.8%, 6.8%) in Iowa to 11.7% (95% CI=9.7%, 13.7%) in Arizona. Awareness was greater among adults with hypertension (12.0%) and diabetes (15.3%) than among adults without those conditions, and lower in Hispanics (6.0%) than in non-Hispanic whites (8.8%), non-Hispanic blacks (9.9%), and other racial/ethnic groups (12.7%). Conclusions Among individuals with CKD, awareness of their condition was very low and varied approximately twofold among states. This is the first study to estimate awareness of kidney disease by state for the U.S. adult population.

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend

Background This study’s objective was to identify adverse events following common orthopaedic procedures, and to estimate the incidence rates and risks of these events and their associations with age, sex, and comorbidities. Methods This retrospective cohort study manually reviewed and extracted electronic medical data on the incidence and predictors of adverse events that occurred within 90 days of the 50 most frequent orthopaedic surgeries at an academic hospital in 2010. We also extracted demographic data, baseline comorbidities, and duration of follow-up (≤90 days). Patients were scored on the Charlson Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). We estimated incidence rates and risks for all events and associations using regression methods. Prolonged pain 42-days post-surgery was treated as a separate outcome. Results We included 1,552 patients; average age was 53.4 years, and 51.7% were female. A total of 1,148 adverse events were identified in 729 patients. The incidence rate of all adverse events was 10 events per 1,000 person-days at risk; 47% of all patients experienced at least one adverse event within 90 days. The most frequent events were prolonged pain (31% of all adverse events) and persistent swelling (7%). We found positive associations between both comorbidity scores and the incidence rate and 90-day risk of all adverse events, excluding pain, adjusting for age and sex (neither of which was associated with adverse events); the association was stronger for the FCI than for the CCI. For total hip arthroplasty (THA) and total knee arthroplasty (TKA), the incidence rate of all adverse events, excluding pain, was positively associated with both comorbidity scores and age; the 90-day risk was positively associate with the FCI score and male sex. The prevalence of prolonged pain at 42 days was greater in patients with higher FCI scores; for THA and TKA only, pain prevalence was greater in those with higher FCI scores and in men. Conclusions Adverse events are frequent following common orthopaedic procedures. The incidence is greatest for patients with more functional comorbidities. For THA and TKA procedures, being male and being older are also associated with a greater incidence of adverse events.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Background: Hypothesizing that statins may be useful as adjuvant treatment for renal anemia, we examined the association between statin prescription (Rx) and erythropoiesis-stimulating agent (ESA) hyporesponsiveness in Japanese hemodialysis (HD) patients prescribed ESAs. Methods: We examined 3,602 patients in 60 HD facilities dialyzed 3 times/week for ≥4 months from the Japan Dialysis Outcomes and Practice Patterns Study phases 3-5 (2005-2015). Statin Rx was reported at the end of a 4-month interval (baseline) for each patient. ESA hyporesponsiveness in the subsequent 4 months was then defined as a binary indicator (mean hemoglobin [Hgb] level 6,000 units/week) and separately as the ESA resistance index (ERI; mean ESA dose/[dry weight × mean Hgb]). We used adjusted logistic and linear regressions to evaluate the associations between statin Rx and ESA hyporesponsiveness. Results: At baseline, 16.2% of patients reported statin Rx; 12.8% were classified as having ESA hyporesponsiveness during 4 months of follow-up. Compared to patients without statin Rx, patients with statin Rx had lower odds of ESA hyporesponsiveness (OR 0.87; 95% CI 0.66-1.15). Similarly, the ERI was lower for those with statin Rx than without (ratio of means, 0.94; 95% CI 0.89-0.99) after adjustment for possible confounders. Conclusions: Our results suggest that statins may slightly reduce ESA hyporesponsiveness in HD patients. However, any causal inference is limited by the observational study design and unmeasured compliance with statin Rx.

Background Although incidence rates of end-stage renal disease (ESRD) in the United States are reported routinely by the US Renal Data System (USRDS), risks (probabilities) are not reported. Short- and long-term risk estimates need to be updated and expanded to minority populations, including Native Americans, Asian/Pacific Islanders, and Hispanics. Study Design Risk estimation from surveillance data in large populations using life-table methods. A competing-risks framework was applied by constructing a hypothetical cohort followed from birth to death. Setting & Participants Total US population. Incidence and mortality rates of ESRD were obtained from the USRDS; all-cause mortality rates were obtained from CDC WONDER. Predictors Age, sex, race/ethnicity, and year. Outcomes 10-year to lifetime risks (cumulative incidence) of ESRD. Results Among males, lifetime risks of ESRD from birth using 2013 data were 3.1% (95% CI, 3.0%-3.1%) for non-Hispanic whites, 8.0% (95% CI, 7.9%-8.2%) for non-Hispanic blacks, 3.8% (95% CI, 3.4%-4.9%) for non-Hispanic Native Americans, 5.1% (95% CI, 4.8%-5.4%) for non-Hispanic Asians/Pacific Islanders, and 6.2% (95% CI, 6.1%-6.4%) for Hispanics. Among females, lifetime risks were 2.0% (95% CI, 2.0%-2.1%) for non-Hispanic whites, 6.8% (95% CI, 6.7%-6.9%) for non-Hispanic blacks, 3.6% (95% CI, 3.3%-4.2%) for non-Hispanic Native Americans, 3.8% (95% CI, 3.6%-4.0%) for non-Hispanic Asian/Pacific Islanders, and 4.3% (95% CI, 4.2%-4.5%) for Hispanics. Lifetime risk of ESRD from birth increased from 3.5% in 2000 to 4.0% in 2013 in males and decreased from 3.0% to 2.8% in females. Limitations Standard life-time assumption of fixed age-specific rates over time and possible ESRD misclassification. To be useful in clinical practice, this application will require additional predictors (eg, comorbid conditions and chronic kidney disease stage). Conclusions ESRD risk in the United States varies more than 2-fold among racial/ethnic groups for both sexes.

Rationale & Objective Native Hawaiians and Pacific Islanders (NHPI) have been reported to have the highest rates of incident end-stage kidney disease (ESKD) compared with other races in the United States. However, these estimates were likely biased upward due to the exclusion of nearly half the NHPI population that reports multiple races in the US Census. We sought to estimate the incidence rate of ESKD, including individuals reporting multiple races, and describe the clinical characteristics of incident cases by race and location. Study Design Health care database study. Setting & Participants US residents of the 50 states and 3 Pacific Island territories of the United States whose ESKD was recorded in the US Renal Data System (USRDS) between 2007 and 2016, as well as US residents recorded in the 2010 Census. Predictors Age, sex, race, body mass index, primary cause of ESKD, comorbid conditions, estimated glomerular filtration rate, pre-ESKD nephrology care, and hemoglobin A1c level among ESKD cases. Outcome Initiation of maintenance dialysis or transplantation for kidney failure. Analytical Approach Crude ESKD incidence rates (cases/person-years) were estimated using both single- and multiple-race reporting. Results Even after inclusion of multirace reporting, NHPI had the highest ESKD incidence rate among all races in the 50 states (921 [95% CI, 904-938] per million population per year)—2.7 times greater than whites and 1.2 times greater than blacks. Also using multirace reporting, the NHPI ESKD incident rate in the US territories was 941 (95% CI, 895-987) per million population per year. Diabetes was listed as the primary cause of ESKD most frequently for NHPI and American Indians/Alaska Natives. Sensitivity analysis adjusting for age and sex demonstrated greater differences in rates between NHPI and other races. Diabetes was the primary cause of ESKD in 60% of incident NHPI cases. Patients with ESKD living in the territories had received less pre-ESKD nephrology care than had patients living in the 50 states. Limitations Different methods of race classification in the USRDS versus the US Census. Conclusions NHPI living in the 50 US states and Pacific territories had the highest rates of ESKD incidence compared with other races. Further research and efforts are required to understand the reasons for and define how best to address this racial disparity.

IntroductionThe relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied.MethodsIndividual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots.ResultsOverall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR= 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR= 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR= 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR= 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR= 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets.ConclusionsBoth being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.

Objectives: \ud This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.\ud \ud Materials and Methods: \ud We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.\ud \ud Results: \ud For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.\ud \ud Conclusion: \ud Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

Background Patient-reported measures are increasingly recognized as important predictors of clinical outcomes in peritoneal dialysis (PD). We sought to understand associations between patient-reported perceptions of the advantages and disadvantages of PD and clinical outcomes. Methods In this cohort study, 2760 PD patients in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) completed a questionnaire on their PD experience, between 2014 and 2017. In this questionnaire, PDOPPS patients rated 17 aspects of their PD experience on a 5-category ordinal scale, with responses scored from − 2 (major disadvantage) to + 2 (major advantage). An advantage/disadvantage score (ADS) was computed for each patient by averaging their response scores. The ADS, along with each of these 17 aspects, were used as exposures. Outcomes included mortality, transition to hemodialysis (HD), patient-reported quality of life (QOL), and depression. Cox regression was used to estimate associations between ADS and mortality, transition to HD, and a composite of the two. Logistic regression with generalized estimating equations was used to estimate cross-sectional associations of ADS with QOL and depression. Results While 7% of PD patients had an ADS

Author(s): Saran, Rajiv; Robinson, Bruce; Abbott, Kevin C; Agodoa, Lawrence YC; Bragg-Gresham, Jennifer; Balkrishnan, Rajesh; Bhave, Nicole; Dietrich, Xue; Ding, Zhechen; Eggers, Paul W; Gaipov, Abduzhappar; Gillen, Daniel; Gipson, Debbie; Gu, Haoyu; Guro, Paula; Haggerty, Diana; Han, Yun; He, Kevin; Herman, William; Heung, Michael; Hirth, Richard A; Hsiung, Jui-Ting; Hutton, David; Inoue, Aya; Jacobsen, Steven J; Jin, Yan; Kalantar-Zadeh, Kamyar; Kapke, Alissa; Kleine, Carola-Ellen; Kovesdy, Csaba P; Krueter, William; Kurtz, Vivian; Li, Yiting; Liu, Sai; Marroquin, Maria V; McCullough, Keith; Molnar, Miklos Z; Modi, Zubin; Montez-Rath, Maria; Moradi, Hamid; Morgenstern, Hal; Mukhopadhyay, Purna; Nallamothu, Brahmajee; Nguyen, Danh V; Norris, Keith C; O'Hare, Ann M; Obi, Yoshitsugu; Park, Christina; Pearson, Jeffrey; Pisoni, Ronald; Potukuchi, Praveen K; Repeck, Kaitlyn; Rhee, Connie M; Schaubel, Douglas E; Schrager, Jillian; Selewski, David T; Shamraj, Ruth; Shaw, Sally F; Shi, Jiaxiao M; Shieu, Monica; Sim, John J; Soohoo, Melissa; Steffick, Diane; Streja, Elani; Sumida, Keiichi; Kurella Tamura, Manjula; Tilea, Anca; Turf, Megan; Wang, Dongyu; Weng, Wenjing; Woodside, Kenneth J; Wyncott, April; Xiang, Jie; Xin, Xin; Yin, Maggie; You, Amy S; Zhang, Xiaosong; Zhou, Hui; Shahinian, Vahakn

Background There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.

Background The putative benefits of cinacalcet therapy for management of secondary hyperparathyroidism (SHPT) are thought to be most manifested when patients are taking it consistently and as prescribed. Real-world descriptions of cinacalcet prescription discontinuation and reinitiation in European hemodialysis patients are lacking. To address this knowledge gap, we used Dialysis Outcomes and Practice Patterns Study (DOPPS) data, based on dialysis facility medical records, from seven European countries to estimate rates and predictors of cinacalcet prescription discontinuation and reinitiation in hemodialysis patients and to describe the trajectories of CKD-MBD laboratory values after discontinuation. Methods Cox regression analyses were used to predict (1) cinacalcet discontinuation among 613 patients with ≥3 consecutive months without cinacalcet prescription immediately prior to a new cinacalcet prescription and (2) cinacalcet reinitiation among 415 patients with a newly discontinued cinacalcet prescription immediately after ≥3 consecutive months of prescribed use. Results Cinacalcet was discontinued in 21 and 35% of new users after 6 and 12 months, respectively. Cinacalcet was reinitiated in 38 and 49% of newly-discontinued users after 6 and 12 months, respectively. Predictors of discontinuation included lower parathyroid hormone (PTH) in the previous month (

Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background and objectivePrevious reports indicated that patients on thrice-weekly hemodialysis (HD) had higher mortality rates after the 3-day interdialytic interval. However, day-of-the-week patterns of emergency department (ED) visits and hospitalizations remain under-investigated.MethodsWe conducted a retrospective cohort study of HD patients on thrice-weekly dialysis, using 2013 data from the United States Renal Data System (USRDS). We estimated crude incidence rates of ED visits and hospitalizations by day of the week and dialysis schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday). Using Poisson regression, we estimated case-mix adjusted rate ratios of all-cause ED visits and hospitalizations, and adjusted rates of cause-specific ED visits and hospitalizations.ResultsWe identified 241,093 eligible HD patients in 2013, who had 514,773 ED visits and 301,674 hospitalizations that year. Three distinct but related patterns of outcome events were observed. Crude and adjusted incidence rates of all-cause, cardiovascular, and infection-related ED visits and hospitalizations, but not vascular-access-related events, were higher on all three HD treatment days ("dialysis-day effect"). Rates for ED visits and hospitalizations were lower on weekends than weekdays, rising appreciably from Sunday to Monday for both dialysis schedules ("post-weekend effect"); and rates were highest after the long 3-day interval between dialysis sessions for both dialysis schedules ("interdialytic-gap effect"). In contrast, rates of hospitalizations not preceded by an ED visit were nearly the same Monday through Friday and lower on weekends for both dialysis schedules.ConclusionsHigher rates of ED visits and hospitalizations on the days of HD sessions and early in the week are a public-health concern that should stimulate research to explain these patterns and reduce the excessive morbidity and associated costs among patients on thrice-weekly HD, while improving quality of care and patient experience with dialysis.

To the Editor: The prognostic importance of residual kidney function (RKF) for maintenance hemodialysis (HD) patients has previously been recognized.1, 2, 3, 4, 5, 6 In previous studies, monitoring of RKF typically required urine collection preceding the HD session and a predialysis blood sample from the end of collection to compute the renal clearance of urea/creatinine (ie, urinary urea/creatinine divided by serum concentration2, 4, 5) and more specifically, renal Kt/Vurea.3 Urine volume, the prerequisite for RKF, can also be estimated by patient self-report.7 In the present analysis of the DOPPS, we evaluated predictors and outcomes of self-reported urine volume; specifically, whether a positive response to the question: “Did the patient have urine output > 200 mL/d or 1 cup/day at the time of enrollment?” was associated with mortality during follow-up periods of 2 to 3 years.

Author(s): Bragg-Gresham, Jennifer; Morgenstern, Hal; McClellan, William; Saydah, Sharon; Pavkov, Meda; Williams, Desmond; Powe, Neil; Tuot, Delphine; Hsu, Raymond; Saran, Rajiv; Centers for Disease Control and Prevention CKD Surveillance System | Abstract: BackgroundConsiderable geographic variation exists in the prevalence of chronic kidney disease across the United States. While some of this variability can be explained by differences in patient-level risk factors, substantial variability still exists. We hypothesize this may be due to understudied environmental exposures such as air pollution.MethodsUsing data on 1.1 million persons from the 2010 5% Medicare sample and Environmental Protection Agency air-quality measures, we examined the association between county-level particulate matter ≤2.5 μm (PM2.5) and the prevalence of diagnosed CKD, based on claims. Modified Poisson regression was used to estimate associations (prevalence ratios [PR]) between county PM2.5 concentration and individual-level diagnosis of CKD, adjusting for age, sex, race/ethnicity, hypertension, diabetes, and urban/rural status.ResultsPrevalence of diagnosed CKD ranged from 0% to 60% by county (median = 16%). As a continuous variable, PM2.5 concentration shows adjusted PR of diagnosed CKD = 1.03 (95% CI: 1.02-1.05; pl0.001) for an increase of 4 μg/m3 in PM2.5. Investigation by quartiles shows an elevated prevalence of diagnosed CKD for mean PM2.5 levels ≥14 μg/m3 (highest quartile: PR = 1.05, 95% CI: 1.03-1.07), which is consistent with current ambient air quality standard of 12 μg/m3, but much lower than the level typically considered healthy for sensitive groups (~40 μg/m3).ConclusionA positive association was observed between county-level PM2.5 concentration and diagnosed CKD. The reliance on CKD diagnostic codes likely identified associations with the most severe CKD cases. These results can be strengthened by exploring laboratory-based diagnosis of CKD, individual measures of exposure to multiple pollutants, and more control of confounding.

Background Little is known about the prevalence of functional impairment in peritoneal dialysis (PD) patients, its variation by country, and its association with mortality or transfer to hemodialysis. Methods A prospective cohort study was conducted in PD patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) (2014 – 2017). Functional status (FS) was assessed by combining self-reports of 8 instrumental and 5 basic activities of daily living, using the Lawton-Brody and the Katz questionnaires. Summary FS scores, ranging from 1.25 (most dependent) to 13 (independent), were based on the patient's ability to perform each activity with or without assistance. Logistic regression was used to estimate the odds ratio (OR; 95% confidence interval [CI]) of a FS score < 11 comparing each country with the United States (US). Cox regression was used to estimate the hazard ratio (HR; 95% CI) for the effect of a low FS score on mortality and transfer to hemodialysis, adjusting for case mix. Results Of 2,593 patients with complete data on FS, 48% were fully independent (FS = 13), 32% had a FS score 11 to < 13, 14% had a FS score 8 to < 11, and 6% had a FS score < 8. Relative to the US, low FS scores (< 11; more dependent) were more frequent in Thailand (OR = 10.48, 5.90 – 18.60) and the United Kingdom (UK) (OR = 3.29, 1.77 – 6.08), but similar in other PDOPPS countries. The FS score was inversely and monotonically associated with mortality but not with transfer to hemodialysis; the HR, comparing a FS score < 8 vs 13, was 4.01 (2.44 – 6.61) for mortality and 0.91 (0.58 – 1.43) for transfer to hemodialysis. Conclusion Regional differences in FS scores observed across PDOPPS countries may have been partly due to differences in regional patient selection for PD. Functional impairment was associated with mortality but not with permanent transfer to hemodialysis.

The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure, an important risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, it is unclear whether adherence to a DASH diet confers protection against future ESRD, especially among those with pre-existing CKD and hypertension. We examined whether a DASH diet is associated with lower risk of ESRD among 1,110 adults aged ≥ 20 years with hypertension and CKD (estimated glomerular filtration rate, eGFR 30-59 ml/min/1.73 m2) enrolled in the National Health and Nutrition Examination Survey (1988-1994). Baseline DASH diet accordance score was assessed using a 24-hour dietary recall questionnaire. ESRD was ascertained by linkage to the U.S. Renal Data System registry. We used the Fine-Gray competing risks method to estimate the relative hazard (RH) for ESRD after adjusting for sociodemographics, clinical and nutritional factors, eGFR, and albuminuria. Over a median follow-up of 7.8 years, 18.4% of subjects developed ESRD. Compared to the highest quintile of DASH diet accordance, there was a greater risk of ESRD among subjects in quintiles 1 (RH=1.7; 95% CI 1.1-2.7) and 2 (RH 2.2; 95% CI 1.1-4.1). Significant interactions were observed with diabetes status and race/ethnicity, with the strongest association between DASH diet adherence and ESRD risk observed in individuals with diabetes and in non-Hispanic blacks. Low accordance to a DASH diet is associated with greater risk of ESRD in adults with moderate CKD and hypertension, particularly in non-Hispanic blacks and persons with diabetes.

Author(s): Saran, Rajiv; Robinson, Bruce; Abbott, Kevin C; Agodoa, Lawrence YC; Bhave, Nicole; Bragg-Gresham, Jennifer; Balkrishnan, Rajesh; Dietrich, Xue; Eckard, Ashley; Eggers, Paul W; Gaipov, Abduzhappar; Gillen, Daniel; Gipson, Debbie; Hailpern, Susan M; Hall, Yoshio N; Han, Yun; He, Kevin; Herman, William; Heung, Michael; Hirth, Richard A; Hutton, David; Jacobsen, Steven J; Jin, Yan; Kalantar-Zadeh, Kamyar; Kapke, Alissa; Kovesdy, Csaba P; Lavallee, Danielle; Leslie, Janet; McCullough, Keith; Modi, Zubin; Molnar, Miklos Z; Montez-Rath, Maria; Moradi, Hamid; Morgenstern, Hal; Mukhopadhyay, Purna; Nallamothu, Brahmajee; Nguyen, Danh V; Norris, Keith C; O'Hare, Ann M; Obi, Yoshitsugu; Park, Christina; Pearson, Jeffrey; Pisoni, Ronald; Potukuchi, Praveen K; Rao, Panduranga; Repeck, Kaitlyn; Rhee, Connie M; Schrager, Jillian; Schaubel, Douglas E; Selewski, David T; Shaw, Sally F; Shi, Jiaxiao M; Shieu, Monica; Sim, John J; Soohoo, Melissa; Steffick, Diane; Streja, Elani; Sumida, Keiichi; Tamura, Manjula K; Tilea, Anca; Tong, Lan; Wang, Dongyu; Wang, Mia; Woodside, Kenneth J; Xin, Xin; Yin, Maggie; You, Amy S; Zhou, Hui; Shahinian, Vahakn

The benefits of renin angiotensin-aldosterone system inhibitors (RAASi) are well-established in the general population, particularly among those with diabetes, congestive heart failure (CHF), or coronary artery disease (CAD). However, conflicting evidence from trials and concerns about hyperkalemia limit RAASi use in hemodialysis patients, relative to other antihypertensive agents, including beta blockers and calcium channel blockers. Therefore, we investigated prescription patterns and associations with mortality for RAASi and other antihypertensive agents using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS). Cox regression was used to estimate the effect of the prescription of RAASi and other antihypertensive agents at study entry on mortality in 11,421 incident (120 days or less) hemodialysis and 37,124 prevalent (over 120 days) hemodialysis patients from DOPPS phases 2-5 (2002-2015). Over 95% of RAASi were angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. RAASi prevalence was 39% and varied minimally by CHF and CAD. The adjusted hazard ratio for RAASi (vs. no RAASi) was 0.89 (95% confidence interval 0.80-0.99) among incident and 0.94 (0.90-0.99) among prevalent hemodialysis patients, with no convincing evidence of interaction with diabetes, CAD or CHF. Inverse associations with mortality were also observed for beta blockers and calcium channel blockers, and were stronger for angiotensin receptor blockers than angiotensin-converting enzyme inhibitors, but this latter finding requires further study. Thus, our observations suggest a relatively small survival benefit of RAASi and other antihypertensive agents in hemodialysis patients, though randomized prospective studies are needed to potentially change prescribing criteria.

Background The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin–mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ. Methods Data from 18 261 patients in Phases 4 and 5 (2009–15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders. Results Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region. Conclusion The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.

There have been few published studies on differences between Blacks and Whites in the estimated effects of alcohol and tobacco use on the incidence of head and neck cancer (HNC) in the United States. Previous studies have been limited by small numbers of Blacks. Using pooled data from 13 US case–control studies of oral, pharyngeal, and laryngeal cancers in the International Head and Neck Cancer Epidemiology Consortium, this study comprised a large number of Black HNC cases (n = 975). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for several tobacco and alcohol consumption characteristics. Blacks were found to have consistently stronger associations than Whites for the majority of tobacco consumption variables. For example, compared to never smokers, Blacks who smoked cigarettes for > 30 years had an OR 4.53 (95% CI 3.22–6.39), which was larger than that observed in Whites (OR 3.01, 95% CI 2.73–3.33; pinteraction < 0.0001). The ORs for alcohol use were also larger among Blacks compared to Whites. Exclusion of oropharyngeal cases attenuated the racial differences in tobacco use associations but not alcohol use associations. These findings suggest modest racial differences exist in the association of HNC risk with tobacco and alcohol consumption. © 2018, Springer International Publishing AG, part of Springer Nature.

Background: Dietary acid load (DAL) contributes to the risk of CKD and CKD progression. We sought to determine the relation of DAL to racial/ethnic differences in the risk of end-stage renal disease (ESRD) among persons with CKD. Methods: Among 1,123 non-Hispanic black (NHB) and non-Hispanic white (NHW) National Health and Nutrition Examination Survey III participants with estimated glomerular filtration rate 15–59 mL/min/1.73 m2, DAL was estimated using the Remer and Manz net acid excretion (NAEes) formula and 24-h dietary recall. ESRD events were ascertained via linkage with Medicare. A competing risk model (accounting for death) was used to estimate the hazard ratio (HR) for treated ESRD, comparing NHBs with NHWs, adjusting for demographic, clinical and nutritional factors (body surface area, total caloric intake, serum bicarbonate, protein intake), and NAEes. Additionally, whether the relation of NAEes with ESRD risk varied by race/ethnicity was tested. Results: At baseline, NHBs had greater NAEes (50.9 vs. 44.2 mEq/day) than NHWs. It was found that 22% developed ESRD over a median of 7.5 years. The unadjusted HR comparing NHBs to NHWs was 3.35 (95% CI 2.51–4.48) and adjusted HR (for factors above) was 1.68 (95% CI 1.18–2.38). A stronger association of NAE with risk of ESRD was observed among NHBs (adjusted HR per mEq/day increase in NAE 1.21, 95% CI 1.12–1.31) than that among NHWs (HR 1.08, 95% CI 0.96–1.20), p interaction for race/ethnicity × NAEes = 0.004. Conclusions: Among US adults with CKD, the association of DAL with progression to ESRD is stronger among NHBs than NHWs. DAL is worthy of further investigation for its contribution to kidney outcomes across race/ethnic groups.

For years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in–center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance.