Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease.

Importance: Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective: To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants: This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures: Incident use of TNF inhibitors. Main Outcomes and Measures: The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results: Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance: In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients.

Background: Oral iron is the predominant route of iron replacement (IRT) but its benefits and safety are unclear in patients with chronic kidney disease (CKD). Methods: We examined the association of oral IRT vs no IRT with end-stage kidney disease (ESKD) and mortality in a national cohort of US Veterans. We identified 17 413 incident new users of oral IRT with estimated glomerular filtration rates <60 mL/min/1.73 m2 and 32 530 controls who did not receive any IRT during 2004-18. We used propensity score-overlap weighting to account for differences in key baseline characteristics associated with the use of oral IRT. We examined associations using competing risk regression and Cox models. Results: In the cohort of 49 943 patients, 1616 (3.2%) patients experienced ESKD and 28 711 (57%) patients died during a median follow-up of 1.9 years. Oral IRT was not associated with ESKD [subhazard ratio (HR) (95% confidence interval, CI) 1.00 (0.84-1.19), P = .9] and was associated with higher risk of all-cause mortality [HR (95% CI) 1.06 (1.01-1.11), P = .01]. There was significant heterogeneity of treatment effect for mortality, with oral IRT associated with higher mortality in the subgroups of patients without congestive heart failure (CHF), anemia or iron deficiency. In patient with blood hemoglobin <10 g/dL oral IRT was associated with significantly lower mortality. Conclusion: Oral IRT was associated with lower mortality only in patients with anemia. In patients without anemia, iron deficiency or CHF, the risk-benefit ratio of oral IRT should be further examined.

Association of iron therapy with incidence of chronic kidney disease.

OBJECTIVE: We investigated the association of oral iron replacement with the incidence of chronic kidney disease (CKD) in a population with normal kidney function to study the effects of iron replacement on the development of new onset CKD. METHODS: In a national cohort of US Veterans with no pre-existing CKD, we identified 33 894 incident new users of oral iron replacement and a comparable group of 112 780 patients who did not receive any iron replacement during 2004-2018. We examined the association of oral iron replacement versus no iron replacement with the incidence of eGFR <60 mL/min/1.73 m2 and the incidence of urine albumin creatinine ratio (UACR) ≥30 mg/g in competing risk regressions and in Cox models. We used propensity score weighing to account for differences in key baseline characteristics associated with the use of oral iron replacement. RESULTS: In the cohort of 146 674 patients, a total of 18 547 (13%) patients experienced incident eGFR <60 mL/min/1.73 m2 , and 16 117 patients (11%) experienced new onset UACR ≥30 mg/g. Oral iron replacement was associated with significantly higher risk of incident eGFR <60 mL/min/1.73 m2 (subhazard ratio, 95% confidence interval [CI]: 1.3 [1.22-1.38], p < .001) and incident albuminuria (subhazard ratio, 95% CI: 1.14 [1.07-1.22], p < .001). CONCLUSION: Oral iron replacement is associated with higher risk of new onset CKD. The long-term kidney safety of oral iron replacement should be tested in clinical trials.

Medical Faculty and Medical Student Opinions on the Utility of Questions to Teach and Evaluate in the Clinical Environment.

Objectives: We sought to report medical student and faculty perceptions of the purpose and utility of questions on clinical rounds. Methods: We developed and administered a survey to third and fourth-year medical students and teaching physicians. The survey elicited attitudes about using questions to teach on rounds in both benign and malignant learning environments. Results: Ninety-seven percent of faculty and 85% of students predicted they will use questions to teach. Nine percent of students described learning-impairing stress during benign bedside teaching. Fifty-nine percent of faculty felt questions were mostly for teaching; 74% of students felt questions were mostly for evaluation. Forty-six percent of students felt questions underestimated their knowledge. Students felt questions were more effective for classroom teaching than bedside teaching. Faculty and students agreed that a malignant environment detrimentally affected learning and performance. Conclusions: Students and faculty supported the use of questions to teach and evaluate, especially in benign teaching environments. Many students described stress severe enough to affect their learning and performance, even when questioned in benign teaching environments. Faculty underestimated the degree to which students experience stress-related learning impairment and the degree to which students see questions as evaluation rather than teaching. Nearly half of students felt that questions underestimated their own knowledge. Students feel more stress and less learning when questioned with a patient present. Faculty must realize that even in the best learning environment some students experience stress-impaired learning and performance, perhaps because of the conflict between learning and evaluation.

Serum Creatinine-to-Cystatin-C Ratio as a Potential Muscle Mass Surrogate and Racial Differences in Mortality.

OBJECTIVES: Serum creatinine-based estimated glomerular filtration rate equations and muscle mass are powerful markers of health and mortality risk. However, the serum creatinine-to-cystatin-C ratio may be a better indicator of health status. The objective of this study was to describe the relationship between creatinine-to-cystatin-C ratio and all-cause mortality when stratifying patients as per race and as per chronic kidney disease status. METHODS: This was a retrospective cohort study examining black and nonblack US veterans between October 2004 and September 2019, with baseline cystatin C and creatinine data from those not on dialysis during the study period. Veterans were divided into four creatinine-to-cystatin-C ratio groups: <0.75, 0.75-<1.00, 1.0-<1.25, and ≥1.25. The primary outcome of interest was all-cause mortality subsequent to the cystatin C laboratory measure. RESULTS: Among 22,316 US veterans, the mean (± standard deviation) age of the cohort was 67 ± 14 years, 5% were female, 82% were nonblack, and 18% were black. The proportion of black veterans increased across creatinine-to-cystatin-C ratio groups. In the fully adjusted model, compared with the reference (creatinine-to-cystatin-C ratio: 1.00-<1.25), a creatinine-to-cystatin-C ratio <0.75 had the highest mortality risk among both black and nonblack veterans (nonblack: hazard ratio [HR] [95% confidence interval {CI}]: 3.01 [2.78-3.26] and black: 4.17 [3.31-5.24]). A creatinine-to-cystatin-ratio ≥1.25 was associated with lower death risk than the referent in both groups (nonblack: HR [95% CI]: 0.89 [0.80-0.99] and black: HR [95% CI]: 0.55 [0.45-0.69]). However, there was a significant difference in the effect by race (Wald's P-value: <0.01). CONCLUSIONS: Higher creatinine-to-cystatin-C ratios indicate better health status and are strongly associated with lower mortality risk regardless of the kidney function level, and the relation was similar for both black and nonblack veterans, but with different strengths of effect across racial groups. Thereby, use of a fixed race coefficient in estimating kidney function may be biased.

Patient preferences and comfort for cancer survivorship models of care: results of an online survey.

PURPOSE: Workforce shortages will impact oncologists' ability to provide both active and survivorship care. While primary care provider (PCP) or survivorship clinic transition has been emphasized, there is little evidence regarding patient comfort. METHODS: We developed an online survey in partnership with patient advocates to assess survivors' comfort with PCP or survivorship clinic care and distributed the survey to online, cancer-specific patient communities from June to August 2020. Descriptive and logistic regression analyses were conducted. RESULTS: A total of 975 surveys were complete. Most respondents were women (91%) and had private insurance (65%). Thirty-six cancer types were reported. Ninety-three percent had a PCP. Twenty-four percent were comfortable seeing a PCP for survivorship care. Higher odds of comfort were seen among respondents who were Black or had stage 0 cancer; female sex was associated with lower odds. Fifty-five percent were comfortable with a survivorship clinic. Higher odds of comfort were seen with lymphoma or ovarian cancer, > 15 years from diagnosis, and non-US government insurance. Lower odds were seen with melanoma, advanced stage, Medicaid insurance, and one late effect. Preference for PCP care was 87% for general health, 32% for recurrence monitoring, and 37% for late effect management. CONCLUSIONS: One quarter of cancer survivors were comfortable with PCP-led survivorship care and about half with a survivorship clinic. Most preferred oncologist care for recurrence monitoring and late-effect management. IMPLICATIONS FOR CANCER SURVIVORS: Patient preference and comfort should be considered when developing survivorship care models. Future efforts should focus on facilitating patient-centered transitions to non-oncologist care.

Novel insights in classic versus relative glomerular hyperfiltration and implications on pharmacotherapy.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) assessment and its estimation (eGFR) is a long-lasting challenge in medicine and public health. Current eGFR formulae are indexed for standardized body surface area (BSA) of 1.73 m2, ignoring persons and populations wherein the ratio of BSA or metabolic rate to nephron number might be different, due to increased BSA, increased metabolic rate or reduced nephron number. These equations are based on creatinine, cystatin C or a combination of the two, which adds another confounder to eGFR assessment. Unusually high GFR values, also known as renal hyperfiltration, have not been well defined under these equations. RECENT FINDINGS: Special conditions such as solitary kidney in kidney donors, high dietary protein intake, obesity and diabetes are often associated with renal hyperfiltration and amenable to errors in GFR estimation. In all hyperfiltration types, there is an increased intraglomerular pressure that can be physiologic, but its persistence over time is detrimental to glomerulus leading to progressive glomerular damage and renal fibrosis. Hyperfiltration might be underdiagnosed due to BSA standardization embedded in the formula. Hence, timely intervention is delayed. Reducing intraglomerular pressure in diabetes can be achieved by SGLT2 inhibitors or low protein diet to reverse the glomerulopathy process. SUMMARY: Accurate identification of glomerular hyperfiltration as a pre-CKD condition needs accurate estimation of GFR in the above normal range should establish a threshold for timely intervention.

Serum Low-Density Lipoprotein Cholesterol and Cardiovascular Disease Risk Across Chronic Kidney Disease Stages (Data from 1.9 Million United States Veterans).

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage.

Cohort Study and Bias Analysis of the Obesity Paradox Across Stages of Chronic Kidney Disease.

OBJECTIVE: In advanced chronic kidney disease (CKD), patients with obesity often have better outcomes than patients without obesity, often called the 'obesity paradox'. Yet, in CKD, the prevalence of inflammation increases as CKD progresses. Although a potential confounder, inflammation may be left unaccounted in obesity-mortality studies. We examined the associations of body mass index (BMI) with all-cause and cause-specific mortality across CKD stages, with consideration for uncontrolled confounding due to unmeasured inflammation. METHODS: We investigated 2,703,512 patients with BMI data between 2004 and 2006. We used Cox models to examine the associations of BMI with all-cause, cardiovascular, and cancer mortality, (ref: BMI 25-<30 kg/m2), adjusted for clinical characteristics and stratified by CKD stages. To address uncontrolled confounding, we performed bias analysis using a weighted probabilistic model of inflammation given the observed data applied to weighted Cox models. RESULTS: The cohort included 5% females and 14% African Americans. In adjusted analyses, the associations of the BMI with all-cause and cardiovascular mortality showed a reverse J-shape, where a higher BMI (>40 kg/m2) was associated with a higher risk. Conversely, a lower mortality risk was observed with a BMI 30-<35 kg/m2 across all CKD stages and for BMI >40 kg/m2 in CKD stage 4/5. Cancer mortality analyses showed an inverse relationship. Bias analysis for uncontrolled confounding suggested that independent of inflammation, the obesity paradox was present. CONCLUSION: We observed the presence of the obesity paradox in this study. This association was consistent in advanced CKD and in our bias analysis, suggesting that inflammation may not fully explain the observed BMI-mortality associations including in patients with CKD.

Novel Protein to Phosphorous Ratio Score Predicts Mortality in Hemodialysis Patients.

OBJECTIVE: Lowering serum phosphorus in people on hemodialysis may improve their survival. However, prior studies have shown that restricting dietary protein intake, a major source of phosphorus, is associated with higher mortality. We hypothesized that a novel metric that incorporates both these values commensurately can improve survival prediction. METHODS: We used serum phosphorous and normalized protein catabolic rate (nPCR), a surrogate of dietary protein intake, to form a new metric R that was used to examine the associations with mortality in 63,016 people on hemodialysis (HD) of one year after treatment initiation. Survival models were adjusted for case-mix, malnutrition-inflammation cachexia syndrome (MICS), and residual kidney function (RKF). RESULTS: Individuals treated with hemodialysis were divided into five groups in accordance with R value. Group 1 included sick individuals with high phosphorous and low nPCR. Group 5 included individuals with low phosphorous and high nPCR. After 1-year follow-up, survival difference between the groups reflected R value, where an increase in R was associated with improved survival. The association of R with mortality was strengthened by adjustment in demographic variables and attenuated after adjustment to MICS. Mortality associations in accordance with R were not influenced by residual kidney function (RKF). CONCLUSION: The novel protein to phosphorus ratio score R predicts mortality in people on dialysis, probably reflecting both nutrition and inflammation state independent of RKF. The metric enables better phosphorus monitoring, although adequate dietary protein intake is ensured and may improve the prediction of outcomes in the clinical setting.

Polypharmacy and Frailty among Hemodialysis Patients.

BACKGROUND: Both polypharmacy and frailty are highly prevalent among the patients on hemodialysis and associated with adverse outcomes; however, little is known about the association between them. METHODS: We examined 337 patients enrolled in the ACTIVE/ADIPOSE dialysis cohort study between 2009 and 2011. The number of prescribed medications and frailty were assessed at baseline, 12, and 24 months. Frailty was defined based upon the Fried's frailty phenotype. We used logistic regression with generalized estimating equations to model the association of the number of medications and frailty at baseline and over time. A competing-risk regression analysis was also used to assess the association between the number of medications and incidence of frailty. RESULTS: The mean number of medications was 10 ± 5, and 94 patients (28%) were frail at baseline. Patients taking >11 medications showed higher odds for frailty than the patients taking fewer than 8 medications (OR 1.54, 95% CI 1.05-2.26). During the 2-year of follow-up, 87 patients developed frailty among those who were nonfrail at baseline. Compared with the patients taking fewer than 8 medications, the incidence of frailty was approximately 2-fold in those taking >11 medications (sub-distribution hazard ratio 2.15, 95% CI 1.32-3.48). CONCLUSIONS: Using a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients.

Changing Institutional Culture Around Hospice Using LEAN Tools to Improve Hospice Utilization in a Veteran Population.

BACKGROUND: Longer hospice length of stay improves the palliation of symptoms, quality of life, and the dying process for patients and their caregivers. We used a Lean designed Rapid Improvement Event (RIE) to facilitate earlier entry into hospice. MEASURES: Our primary outcome was hospice length of stay. Secondary outcomes were avoiding unwanted inpatient utilization and hospice location. INTERVENTIONS: We conducted a five-day RIE utilizing Lean tools targeting the inpatient medicine wards. OUTCOMES: Hospice length of stay increased from a median (interquartile range [IQR]) of 11 (7,27) days prior to 37 (7,73) days following the RIE. Home hospice and outside Skilled Nursing Home (SNF) hospice use increased while use of the onsite VA hospice decreased. CONCLUSIONS/LESSONS LEARNED: LEAN tools can be used successfully to improve end of life outcomes in an inpatient VA setting. The 90-day sustainment period following the RIE uncovers barriers to implementation and allows for adjustments to implementation.

Impact of Circulating N-Acylethanolamine Levels with Clinical and Laboratory End Points in Hemodialysis Patients.

BACKGROUND: Patients with ESRD on maintenance hemodialysis (MHD) are particularly susceptible to dysregulation of energy metabolism, which may manifest as protein energy wasting and cachexia. In recent years, the endocannabinoid system has been shown to play an important role in energy metabolism with potential relevance in ESRD. N-acylethanolamines are a class of fatty acid amides which include the major endocannabinoid ligand, anandamide, and the endogenous peroxisome proliferator-activated receptor-α agonists, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). METHODS: Serum concentrations of OEA and PEA were measured in MHD patients and their correlations with various clinical/laboratory indices were examined. Secondarily, we evaluated the association of circulating PEA and OEA levels with 12-month all-cause mortality. RESULTS: Both serum OEA and PEA levels positively correlated with high-density lipoprotein-cholesterol levels and negatively correlated with body fat and body anthropometric measures. Serum OEA levels correlated positively with serum interleukin-6 (IL-6) (rho = 0.19; p = 0.004). Serum PEA and IL-6 showed a similar but nonsignificant trend (rho = 0.12; p = 0.07). Restricted cubic spline analyses showed that increasing serum OEA and PEA both trended toward higher mortality risk, and these associations were statistically significant for PEA (PEA ≥4.7 pmol/mL; reference: PEA <4.7 pmol/mL) after adjustments in a Cox model (hazard ratio 2.99; 95% confidence interval 1.04, 8.64). CONCLUSIONS: In MHD patients, OEA and PEA are significantly correlated with variables related to lipid metabolism and body mass. Additionally, higher serum levels of PEA are associated with mortality risk. Future studies are needed to examine the potential mechanisms responsible for these findings and their clinical implications.

Predialysis Potassium Variability and Postdialysis Mortality in Patients With Advanced CKD.

INTRODUCTION: Patients with advanced non-dialysis-dependent chronic kidney disease (NDD-CKD) are prone to potassium (K) imbalances due to reduced kidney function. Both hypo- and hyperkalemia are associated with increased mortality; however, it is unclear if K variability before dialysis initiation is associated with outcomes after dialysis initiation. METHODS: We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 1, 2007, through March 31, 2015, who had at least 1 K measurement each year over a 3-year period before transition (3-year prelude). For each patient, a linear mixed-effects model was used to regress K over time (in years) over the 3-year prelude to derive K variability (square root of the average squared distance between the observed and estimated K). The main outcomes of interest were 6-month all-cause and cardiovascular mortality after dialysis initiation. Multivariable Cox and Fine-Gray competing risk regression adjusted for 3-year prelude K intercept, K slope (per year), demographics, smoking status, comorbidities, length of hospitalizations, body mass index, vascular access type, medications, average estimated glomerular filtration rate, and number of K measurements over the 3-year prelude were used to assess the association of K variability (expressed as quartiles) with all-cause and cardiovascular mortality, respectively. RESULTS: Higher prelude K variability was associated with higher multivariable-adjusted risk of all-cause mortality but not cardiovascular mortality (adjusted hazard/subhazard ratios [95% confidence interval] for highest quartile [vs. lowest] of K variability, 1.14 [1.03-1.25] and 0.99 [0.85-1.16] for all-cause and cardiovascular mortality, respectively). CONCLUSION: Higher K variability is associated with higher all-cause mortality after dialysis initiation.

"Going Flat" After Mastectomy: Patient-Reported Outcomes by Online Survey.

BACKGROUND: The Going Flat movement aims to increase awareness and acceptance of mastectomy alone as a viable option for patients. Little is known about motivations and satisfaction with surgical outcomes in this population. METHODS: An online survey was administered to 931 women who had a history of uni- or bilateral mastectomy for treatment of breast cancer or elevated breast cancer risk without current breast mound reconstruction. Satisfaction with outcome and surgeon support for the patient experience were characterized using 5-level scaled scores. RESULTS: Mastectomy alone was the first choice for 73.7% of the respondents. The top two reasons for going flat were desire for a faster recovery and avoidance of a foreign body placement. Overall, the mean scaled satisfaction score was 3.72 ± 1.17 out of 5. In the multivariable analysis, low level of surgeon support for the decision to go flat was the strongest predictor of a satisfaction score lower than 3 (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.59-5.72; p < 0.001). Dissatisfaction also was more likely among respondents reporting a body mass index (BMI) of 30 kg/m2 or higher (OR, 2.74; 95% CI, 1.76-4.27; p < 0.001) and those undergoing a unilateral procedure (OR, 1.99; 95% CI, 1.29-3.09; p = 0.002). Greater satisfaction was associated with receiving adequate information about surgical options (OR, 0.48; 95% CI, 0.32-0.69; p < 0.0001) and having a surgeon with a specialized breast surgery practice (OR, 0.56; 95% CI, 0.38-0.81; p = 0.002). CONCLUSIONS: Most patients undergoing mastectomy alone are satisfied with their surgical outcome. Surgeons may optimize patient experience by recognizing and supporting a patient's decision to go flat.

Dietary Potassium Intake and Mortality in a Prospective Hemodialysis Cohort.

OBJECTIVES: Among hemodialysis patients, clinical practice guidelines recommend dietary potassium restriction given concerns about potential hyperkalemia leading to malignant arrhythmias and mortality. However, there are sparse data informing recommendations for dietary potassium intake in this population. We thus sought to examine the relationship between dietary potassium intake and death risk in a prospective cohort of hemodialysis patients. DESIGN AND METHODS: Among 415 hemodialysis patients from the prospective "Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease" cohort recruited across 16 outpatient dialysis clinics, information regarding dietary potassium intake was obtained using Food Frequency Questionnaires administered over October 2011 to March 2015. We first examined associations of baseline dietary potassium intake categorized as tertiles with mortality risk using Cox regression. We then examined clinical characteristics associated with low dietary potassium intake (defined as the lowest tertile) using logistic regression. RESULTS: In expanded case-mix Cox analyses, patients whose dietary potassium intake was in the lowest tertile had higher mortality (ref: highest tertile) (adjusted hazard ratio 1.74, 95% confidence interval 1.14-2.66). These associations had even greater magnitude of risk following adjustment for laboratory and nutritional covariates (adjusted hazard ratio 2.65, 95% confidence interval 1.40-5.04). In expanded case-mix restricted cubic spline analyses, there was a monotonic increase in mortality risk with incrementally lower dietary potassium intake. In expanded case-mix logistic regression models, female sex; higher serum bicarbonate; and lower dietary energy, protein, and fiber intake were associated with low dietary potassium intake. CONCLUSIONS: In a prospective cohort of hemodialysis patients, lower dietary potassium intake was associated with higher mortality risk. These findings suggest that excessive dietary potassium restriction may be deleterious in hemodialysis patients, and further studies are needed to determine the optimal dietary potassium intake in this population.

How patients experience endocrine therapy for breast cancer: an online survey of side effects, adherence, and medical team support.

PURPOSE: Many patients with hormone receptor-positive (HR+) breast cancer do not adhere to endocrine therapy (ET), and treatment-related side effects are often discussed by participants in online breast cancer forums. Our aim was to survey this unique group of patients about their ET-related experiences. METHODS: We partnered with patients active in breast cancer social media communities to develop a survey assessing ET-related side effects and medical team communication. Patients with a history of HR+ breast cancer who had received a recommendation to take ET were eligible to participate in the anonymous, online survey. RESULTS: Respondents included 2353 women and 54 men. Aromatase inhibitors were the most commonly used medication. Side effects were reported by 91.2%, were more often experienced by women than men (p < 0.001), and were primarily related to medication type. Approximately one-third of respondents discontinued therapy early. While most felt supported by their medical team, 31.5% reported that their side effects were dismissed or minimized. Survey respondents most frequently reported that a healthy diet and exercise, yoga/acupuncture, and vitamins/supplements were helpful in managing ET-related side effects. CONCLUSIONS: ET-related side effects are very common, and one-third discontinued treatment early. Lifestyle changes and complementary therapies can be important tools for side effect management. One-third of patients did not feel that their side effects were taken seriously. IMPLICATIONS FOR CANCER SURVIVORS: This is the largest survey of ET use by participants in online breast cancer communities. Further research is needed to identify strategies to improve treatment adherence and to better manage ET-related side effects.

The quest for cardiovascular disease risk prediction models in patients with nondialysis chronic kidney disease.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, traditional CVD risk prediction equations do not work well in patients with CKD, and inclusion of kidney disease metrics such as albuminuria and estimated glomerular filtration rate have a modest to no benefit in improving prediction. RECENT FINDINGS: As CKD progresses, the strength of traditional CVD risk factors in predicting clinical outcomes weakens. A pooled cohort equation used for CVD risk prediction is a useful tool for guiding clinicians on management of patients with CVD risk, but these equations do not calibrate well in patients with CKD, although a number of studies have developed modifications of the traditional equations to improve risk prediction. The reason for the poor calibration may be related to the fact that as CKD progresses, associations of traditional risk factors such as BMI, lipids and blood pressure with CVD outcomes are attenuated or reverse, and other risk factors may become more important. SUMMARY: Large national cohorts such as the US Veteran cohort with many patients with evolving CKD may be useful resources for the developing CVD prediction models; however, additional considerations are needed for the unique composition of patients receiving care in these healthcare systems, including those with multiple comorbidities, as well as mental health issues, homelessness, posttraumatic stress disorders, frailty, malnutrition and polypharmacy. Machine learning over conventional risk prediction models may be better suited to handle the complexity needed for these CVD prediction models.

Association of lactate dehydrogenase with mortality in incident hemodialysis patients.

BACKGROUND: Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients. METHODS: We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition-inflammation complex syndrome. RESULTS: There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14-1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality. CONCLUSIONS: Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients.

Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin.

Anemia is a frequent comorbidity of chronic kidney disease (CKD) and is associated with a considerable burden because of decreased patient health-related quality of life and increased healthcare resource utilization. Based on observational data, anemia is associated with an increased risk of CKD progression, cardiovascular events, and all-cause mortality. The current standard of care includes oral or intravenous iron supplementation, erythropoiesis-stimulating agents, and red blood cell transfusion. However, each of these therapies has its own set of population-specific patient concerns, including increased risk of cardiovascular disease, thrombosis, and mortality. Patients receiving dialysis or those who have concurrent diabetes or high blood pressure may be at greater risk of developing these complications. In particular, treatment with high doses of erythropoiesis-stimulating agents has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Resistance to erythropoiesis-stimulating agents remains a therapeutic challenge in a subset of patients. Hypoxia-inducible factor transcription factors, which regulate several genes involved in erythropoiesis and iron metabolism, can be stabilized by a new class of drugs that act as inhibitors of hypoxia-inducible factor prolyl-hydroxylase enzymes to promote erythropoiesis and elevate hemoglobin levels. Here, we review the burden of anemia of chronic kidney disease, the shortcomings of current standard of care, and the potential practical advantages of hypoxia-inducible factor prolyl-hydroxylase inhibitors in the treatment of patients with anemia of CKD.