Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. CONCLUSIONS: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Antihypertensive Medication Use Trajectories After Bariatric Surgery: A Matched Cohort Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the most effective and durable treatment for obesity. We aimed to compare the trajectories of antihypertensive medication (AHM) use among obese individuals treated and not treated with MBS. METHODS: Adults with a body mass index of ≥35 kg/m2 were identified in the Merative Database (US employer-based claims database). Individuals treated with versus without MBS were matched 1:1 using baseline demographic and clinical characteristics as well as AHM utilization. Monthly AHM use was examined in the 3 years after the index date using generalized estimating equations. Subanalyses investigated rates of AHM discontinuation, AHM initiation, and apparent treatment-resistant hypertension. RESULTS: The primary cohort included 43 206 adults who underwent MBS matched with 43 206 who did not. Compared with no MBS, those treated with MBS had sustained, markedly lower rates of AHM use (31% versus 15% at 12 months; 32% versus 17% at 36 months). Among patients on AHM at baseline, 42% of patients treated with MBS versus 7% treated medically discontinued AHM use (P<0.01). The risk of apparent treatment-resistant hypertension was 3.41× higher (95% CI, 2.91-4.01; P<0.01) 2 years after the index date in patients who did not undergo MBS. Among those without hypertension treated with MBS versus no MBS, 7% versus 21% required AHM at 2 years. CONCLUSIONS: MBS is associated with lower rates of AHM use, higher rates of AHM discontinuation, and lower rates of AHM initiation among patients not taking AHM. These findings suggest that MBS is both an effective treatment and a preventative measure for hypertension.

Development of a risk-prediction model for primary aldosteronism in veterans with hypertension.

BACKGROUND: Rates of screening for primary aldosteronism in patients who meet the criteria are exceedingly low (1%-3%). To help clinicians prioritize screening in patients most likely to benefit, we developed a risk-prediction model. METHODS: Using national Veterans Health Administration data, we identified patients who met the criteria for primary aldosteronism screening between 2000 and 2019. We performed multivariable logistic regression to identify characteristics associated with positive primary aldosteronism testing before generating a risk-scoring system based on the coefficients (0< ß < 0.5 = 1 pt, 0.5 ≤ ß < 1 = 2 pts, 1 ≤ ß < 1.5 = 3 pts) and then tested the system performance using an internal validation cohort. RESULTS: We identified 502,190 patients who met primary aldosteronism screening criteria, of whom 1.6% were screened and 15% tested positive. Based on the regression model, we generated a risk-scoring system based on a total of 9 possible points in which age under 50, absence of smoking history, and resistant hypertension each scored 1 point; elevated serum sodium 2 points; and hypokalemia 3 points. Rates of positive screening increased with risk score, with 5.6% to 6.7% of those scoring 0 points testing positive; 7.9% to 9.0% 1 point; 8.6% to 10% 2 points; 13% to 14% 3 points; 21% 4 points; 22% to 38% 5 points; 27% to 38% 6 points; 42% to 49% 7 points; and 50% to 51% ≥8 points. CONCLUSION: In hypertensive patients who meet the criteria for primary aldosteronism screening, rates of positive screening range from 5.6% to 51%. Use of our risk-predication model incorporating these factors can identify patients most likely to benefit from testing.

Proteomic Correlates of the Urinary Protein/Creatinine Ratio in Heart Failure With Preserved Ejection Fraction.

Proteinuria is common in heart failure with preserved ejection fraction (HFpEF), but its biologic correlates are poorly understood. We assessed the relation between 49 plasma proteins and the urinary protein/creatinine ratio (UPCR) in 365 participants in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. Linear regression and network analysis were used to represent relations between protein biomarkers and UPCR. Higher UPCR was associated with older age, a greater proportion of female gender, smaller prevalence of previous myocardial infarction, and greater prevalence of diabetes, insulin use, smoking, and statin use, in addition to a lower estimated glomerular filtration rate, hematocrit, and diastolic blood pressure. Growth differentiation factor 15 (GDF-15; ß = 0.15, p <0.0001), followed by N-terminal proatrial natriuretic peptide (NT-proANP; ß = 0.774, p <0.0001), adiponectin (ß = 0.0005, p <0.0001), fibroblast growth factor 23 (FGF-23, ß = 0.177; p <0.0001), and soluble tumor necrosis factor receptors I (ß = 0.002, p <0.0001) and II (ß = 0.093, p <0.0001) revealed the strongest associations with UPCR. Network analysis showed that UPCR is linked to various proteins primarily through FGF-23, which, along with GDF-15, indicated node characteristics with strong connectivity, whereas UPCR did not. In a model that included FGF-23 and UPCR, the former was predictive of the risk of death or heart-failure hospital admission (standardized hazard ratio 1.83, 95% confidence interval 1.49 to 2.26, p <0.0001) and/or all-cause death (standardized hazard ratio 1.59, 95% confidence interval 1.22 to 2.07, p = 0.0005), whereas UPCR was not prognostic. Proteinuria in HFpEF exhibits distinct proteomic correlates, primarily through its association with FGF-23, a well-known prognostic marker in HFpEF. However, in contrast to FGF-23, UPCR does not hold independent prognostic value.

Cancer Therapy-Related Hypertension: A Scientific Statement From the American Heart Association.

Contemporary anticancer drugs have significantly improved cancer survival at the expense of cardiovascular toxicities, including heart disease, thromboembolic disease, and hypertension. One of the most common side effects of these drugs is hypertension, especially in patients treated with vascular endothelial growth factor inhibitors, as well as tyrosine kinase inhibitors and proteasome inhibitors. Adjunctive therapy, including corticosteroids, calcineurin inhibitors, and nonsteroidal anti-inflammatories, as well as anti-androgen hormone therapy for prostate cancer, may further increase blood pressure in these patients. Cancer therapy-induced hypertension is often dose limiting, increases cardiovascular mortality in cancer survivors, and is usually reversible after interruption or discontinuation of treatment. The exact molecular mechanisms underlying hypertension are unclear, but recent discoveries indicate an important role for reduced nitric oxide generation, oxidative stress, endothelin-1, prostaglandins, endothelial dysfunction, increased sympathetic outflow, and microvascular rarefaction. In addition, genetic polymorphisms in vascular endothelial growth factor receptors are implicated in vascular endothelial growth factor inhibitor-induced hypertension. Diagnosis, management, and follow-up of cancer therapy-induced hypertension follow national hypertension guidelines because evidence-based clinical trials specifically addressing patients who develop hypertension as a result of cancer therapy are currently lacking. Rigorous baseline assessment of patients before therapy is started requires particular emphasis on assessing and treating cardiovascular risk factors. Hypertension management follows guidelines for the general population, although special attention should be given to rebound hypotension after termination of cancer therapy. Management of these complex patients requires collaborative care involving oncologists, cardiologists, hypertension specialists, primary care professionals, and pharmacists to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure-lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.

The Association Between Socioeconomic Factors and Incident Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort (CRIC).

BACKGROUND: The association between socioeconomic factors and development of peripheral artery disease (PAD) has not been as well characterized compared to other cardiovascular diseases. We sought to define how annual income, sex, race, and education level are associated with newly diagnosed PAD in a well-characterized, diverse set of adults with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multicenter, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic and clinical data including ankle brachial index (ABI) and interventions were collected at baseline, as well as yearly during follow-up visits. Annual income was categorized as: <$25,000, $25,000-50,000, $50,000-100,000, or above $100,000. We excluded those with pre-existing PAD, defined as enrollment ABI of <0.9 or >1.4, or missing income data. Cox proportional hazards regression was used to estimate the risk for incident PAD during CRIC enrollment, defined as a drop in ABI to <0.90 or a confirmed PAD intervention, including revascularization or amputation. RESULTS: A total of 3,313 patients met inclusion criteria, the mean age was 58.7 years, 56% were male, and 42% were Black. Over a median follow-up of 10.1 years, 639 participants (19%) were newly diagnosed with PAD. After adjusting for cardiovascular risk factors, all lower levels of annual household income were associated with increased incidence of PAD (income <$25,000 HR 1.7, 95% CI 1.1-2.4, P = 0.008; income $25,000-50,000 HR 1.5, 95% CI 1.1-2.3, P = 0.009; income $50,000-100,000 HR 1.6, 95% CI 1.2-2.4, P = 0.004), relative to a baseline annual income of >$100,000 (overall P-value = 0.02). In the multivariable model, there was no association between education level and PAD incidence (P = 0.80). Black race (HR 1.2, 95% CI 1.0-1.5, P = 0.023) and female sex (HR 1.7, 95% CI 1.4-2.0, P < 0.001) were independently associated with PAD incidence. Multiple imputation analysis provided similar results. CONCLUSIONS: In the CRIC, a multi-center cohort of prospectively followed CKD patients undergoing yearly CVD surveillance, lower annual household income, female sex, and Black race were significantly associated with the PAD incidence. In contrast, level of education was not independently associated with incident PAD.

Acute Kidney Injury in Deceased Organ Donors and Kidney Transplant Outcomes: A National Cohort Study Using a Novel Data Source.

OBJECTIVE: The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement. BACKGROUND: Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool. METHODS: Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus "ideal comparator" kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively. RESULTS: We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01-1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m 2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL. CONCLUSION: Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.

Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis.

AIMS: Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS. METHODS AND RESULTS: We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance. CONCLUSIONS: Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.

Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Clinical and Proteomic Correlates of Plasma ACE2 (Angiotensin-Converting Enzyme 2) in Human Heart Failure.

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.

Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone.

OBJECTIVES: This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy. BACKGROUND: Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: Among TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone. RESULTS: Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe. CONCLUSIONS: We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions.

Bariatric surgery before and after kidney transplantation: long-term weight loss and allograft outcomes.

BACKGROUND: Severe obesity is frequently a barrier to kidney transplantation, and kidney transplant recipients often have significant weight gain following transplantation. OBJECTIVES: The goals of this study were to evaluate the long-term risks and benefits of bariatric surgery before and after kidney transplantation. SETTING: University Hospital, United States. METHODS: We performed a retrospective cohort study of 43 patients who had pretransplantation bariatric surgery and 21 patients who had posttransplantation bariatric surgery from 1994 to 2017 with propensity-score matching to identify matched controls using national registry data. RESULTS: Body mass index at the time of transplantation was similar in patients who underwent bariatric surgery before versus after transplantation (32 versus 34 kg/m2, P = .172). There was no significant difference in body mass index in the 5 years after bariatric surgery among patients who underwent bariatric surgery before versus after kidney transplantation (36 versus 32 kg/m2, P = 0.814). Compared with matched controls, bariatric surgery before (n = 38) and after (n = 18) kidney transplantation was associated with a decreased risk of allograft failure (hazard ratio .31 [95% confidence interval .29-0.33] and .85 [95% confidence interval .85-.86] for pre- and posttransplant, respectively) and mortality (hazard ratio .57 [95% confidence interval .53-.61] and .80 [95% confidence interval .79-.82] for pre- and posttransplant, respectively). CONCLUSIONS: Bariatric surgery before and after kidney transplantation results in similar maintenance of weight loss and improved long-term allograft survival compared with matched controls. Bariatric surgery appears to be a safe and reasonable approach to weight loss both before and after transplantation.

Correction to: The Association of Body Mass Index with Postoperative Outcomes After Elective Paraesophageal Hernia Repair.

In this paper, the first author's name was incorrectly tagged.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. EXPOSURE: HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. OUTCOMES: Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. ANALYTICAL APPROACH: After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. RESULTS: Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. LIMITATIONS: No data for HCV viral load or liver biopsy. CONCLUSIONS: HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

National Postoperative Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease and End-Stage Kidney Disease.

PURPOSE: Obesity is a major risk factor for end-stage kidney disease (ESKD) and is often a barrier to kidney transplantation. However, limited evidence exists evaluating postoperative bariatric surgery outcomes in patients with chronic kidney disease (CKD) and ESKD. MATERIALS AND METHODS: We performed a retrospective cohort study of patients who underwent bariatric surgery in 2015-2016 using the national Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program dataset. Propensity score matching was used to balance characteristics across patients with CKD and ESKD vs. those without CKD. RESULTS: There were 323,034 patients without CKD, 1694 patients with CKD, and 925 patients with ESKD who underwent bariatric surgery. Patients with CKD and ESKD had a significantly increased risk of 30-day reoperation (CKD odds ratio [OR] 2.25 95% confidence interval [CI] 1.45-3.51; ESKD OR 3.10, 95% CI 1.72-5.61) and readmission (CKD OR 1.98, 95% CI 1.53-2.56; ESKD OR 2.97, 95% CI 2.05-4.31) compared to patients without CKD; mortality risk was elevated in patients with ESKD (OR 11.59, 95% CI 6.71-20.04) but not in those with CKD (OR 1.00, 95% CI 0.32-3.11). Rates of adverse outcomes were < 15% across all groups. There were 12, 50, and 172 deaths per 1000 person-years among patients without CKD, with CKD, and with ESKD, respectively. CONCLUSION: Patients with CKD and ESKD experienced higher risk of postbariatric surgery complications compared to those without kidney disease, although absolute complication rates were low across all groups. CKD and ESKD should not be perceived as contraindications to bariatric surgery.

Hypertension in Cancer Patients and Survivors: Epidemiology, Diagnosis, and Management.

Cancer patients and survivors of cancer have a greater burden of cardiovascular disease compared to the general population. Much of the elevated cardiovascular risk in these individuals is likely attributable to hypertension, as individuals with cancer have a particularly high incidence of hypertension following cancer diagnosis. Treatment with chemotherapy is an independent risk factor for hypertension due to direct effects of many agents on endothelial function, sympathetic activity, and renin-angiotensin system activity as well as nephrotoxicity. Diagnosis and management of hypertension in cancer patients requires accurate blood pressure measurement and consideration of potential confounding factors, such as adjuvant treatments and acute pain, that can temporarily elevate blood pressure readings. Home blood pressure monitoring can be a useful tool to facilitate longitudinal blood pressure monitoring for titration of antihypertensive medications. Selection of antihypertensive agents in cancer patients should account for treatment-specific morbidities and target organ injury.

Disparity in access to kidney allograft offers among transplant candidates with human immunodeficiency virus.

BACKGROUND: Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus. METHODS: We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period. RESULTS: Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79-0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68-0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92-1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12-1.36). CONCLUSIONS: HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed.