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Background: Depressive symptoms, assessed by using self-report scales, are present at a striking rate of 45% in patients with chronic kidney disease (CKD) at dialysis therapy initiation. These scales may emphasize somatic symptoms of anorexia, sleep disturbance, and fatigue, which may coexist with chronic disease symptoms and lead to overestimation of depression diagnosis. No study has validated these scales in patients with CKD before dialysis therapy initiation.Study Design: We conducted a diagnostic test study in participants with CKD to investigate the screening characteristics of 2 depression self-report scales against a gold-standard structured psychiatric interview.Setting& Participants: 272 consecutively recruited outpatients with stages 2 to 5 CKD not treated by dialysis were studied.Index Tests: The Beck Depression Inventory (BDI) and the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR(16)) depression screening scales were administered to all participants.Reference Test: A structured Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based interview, the Mini International Neuropsychiatric Interview, was administered by trained persons blinded to self-report scale scores.Results: 57 of 272 (21%) patients had major depression according to the reference test. The best cutoff scores by means of receiver/responder operating characteristic curves to identify a major depressive episode were 11 for the BDI and 10 for the QIDS-SR(16). Sensitivities were 89% (95% confidence interval [CI], 78 to 96; BDI) and 91% (95% CI, 80 to 97; QIDS-SR(16)), whereas specificities were 88% (95% CI, 83 to 92; BDI) and 88% (95% CI, 83 to 92; QIDS-SR(16)). The positive and negative likelihood ratios for these cutoff scores were 7.6 and 0.1 (BDI) and 7.5 and 0.1 (QIDS-SR(16)).Limitations: Single-center study and a sample not representative of US demographics.Conclusions: We found that a BDI score of 11 or higher was a sensitive and specific cutoff value for identifying a major depressive episode in patients with CKD not on dialysis therapy. Both the BDI and QIDS-SR(16) are effective screening tools. [ABSTRACT FROM AUTHOR]

Background: Depression is prevalent in long-term dialysis patients and is associated with death and hospitalization. Whether depression is present through all chronic kidney disease (CKD) stages or appears after dialysis therapy initiation is not clear. We determined the prevalence of a major depressive episode and other psychiatric illnesses by using a structured gold-standard clinical interview and demographic and clinical variables associated with major depressive episode in patients with CKD.Study Design: Observational cross-sectional study using a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based structured interview administered by trained persons to 272 consecutive participants. Multivariable logistic regression was used to determine demographic and clinical variables associated with major depressive episode.Setting& Participants: Patients with stages 2 to 5 CKD not treated by using dialysis were consecutively approached and enrolled from a Veterans Affairs CKD clinic.Predictors: Demographic and clinical variables.Outcome: Major depressive episode diagnosed by using a structured Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based interview, the Mini International Neuropsychiatric Interview.Results: The cohort had a mean age of 64.5 +/- 12.0 years. Thirty-eight percent were African American, and 55% had diabetes mellitus. Percentages of patients with stages 2, 3, 4, and 5 CKD were 6%, 38%, 41%, and 14%, respectively. Mean hemoglobin level was 12.5 +/- 2.0 g/dL. The prevalence of a major depressive episode was 21% and did not vary significantly among different CKD stages. Variables associated with a major depressive episode were diabetes mellitus, comorbid psychiatric illness, and history of drug or alcohol abuse.Limitations: Single-center study composed of primarily male veterans.Conclusions: One in 5 patients with CKD had a major depressive episode. Patients with CKD should be screened routinely for depression given this high prevalence and the independent association of depression with poor outcomes in patients with end-stage renal disease receiving maintenance dialysis. [ABSTRACT FROM AUTHOR]

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m 2 , 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = -0.36 √(ml/min/1.73 m 2 ), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m 2 ) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m 2 ) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J. Grodin receives fees for scientific consulting from Pfizer, Eidos/BridgeBio, Astra-Zeneca, and Sarepta.

Background: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking., Objectives: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency., Methods: Participants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models., Results: Clustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts., Conclusions: The authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality., Competing Interests: Funding Support and Author Disclosures Dr Pandey has received research support from the National Institute of Health (5R01MD017529, R21HL169708) and grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon Therapies, Medtronic, Edward Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, and Emmi Solutions; has received nonfinancial support from Pfizer and Merck; and is also a consultant for Palomarin Inc with stock compensation. Dr Segar has received honoraria from Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Fonarow has done consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Allen reports grant funding from American Heart Association, National Institutes of Health, and PCORI; and consulting fees from Amgen, Boston Scientific, Cytokinetics, Novartis, and WCG ACI Clinical. Dr Pandey has received grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Bayer, Edwards Lifesciences, Medtronic, Sarfez Pharmacuticals, Novo Nordisk, and Roche Diagnostics; has received support from Pfizer and Merck; and is a consultant for Palomarin Inc with stock compensation. Dr Khan serves as an advisory board member for Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens immediately before hemodialysis and persists through the dialysis treatment. Little is known about associated risk factors or pathophysiology, although it may relate to a classic conditioning response. Postdialysis fatigue (PDF) develops or worsens after hemodialysis and may persist for hours. There is no consensus on how to measure PDF. Estimates for the prevalence of PDF range from 20%-86%, likely due to variation in methods of ascertainment and participant characteristics. Several hypotheses seek to explain the pathophysiology of PDF, including inflammation, hypothalamic-pituitary-adrenal axis dysregulation, and osmotic and fluid shifts, but none is currently supported by compelling or consistent data. PDF is associated with several clinical factors, including cardiovascular and hemodynamic effects of the dialysis procedure, laboratory abnormalities, depression, and physical inactivity. Clinical trials have reported hypothesis-generating data about the utility of cold dialysate, frequent dialysis, clearance of large middle molecules, treatment of depression, and exercise as potential treatments. Existing studies are often limited by sample size, lack of a control group, observational design, or short intervention duration. Robust studies are needed to establish the pathophysiology and management of this important symptom., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

We previously developed and validated a model to predict acute kidney injury (AKI) in hospitalized coronavirus disease 2019 (COVID-19) patients and found that the variables with the highest importance included a history of chronic kidney disease and markers of inflammation. Here, we assessed model performance during periods when COVID-19 cases were attributable almost exclusively to individual variants. Electronic Health Record data were obtained from patients admitted to 19 hospitals. The outcome was hospital-acquired AKI. The model, previously built in an Inception Cohort , was evaluated in Delta and Omicron cohorts using model discrimination and calibration methods. A total of 9104 patients were included, with 5676 in the Inception Cohort , 2461 in the Delta cohort, and 967 in the Omicron cohort. The Delta Cohort was younger with fewer comorbidities, while Omicron patients had lower rates of intensive care compared with the other cohorts. AKI occurred in 13.7% of the Inception Cohort , compared with 13.8% of Delta and 14.4% of Omicron (Omnibus p = 0.84). Compared with the Inception Cohort (area under the curve (AUC): 0.78, 95% confidence interval (CI): 0.76-0.80), the model showed stable discrimination in the Delta (AUC: 0.78, 95% CI: 0.75-0.80, p = 0.89) and Omicron (AUC: 0.74, 95% CI: 0.70-0.79, p = 0.37) cohorts. Estimated calibration index values were 0.02 (95% CI: 0.01-0.07) for Inception , 0.08 (95% CI: 0.05-0.17) for Delta , and 0.12 (95% CI: 0.04-0.47) for Omicron cohorts, p = 0.10 for both Delta and Omicron vs Inception . Our model for predicting hospital-acquired AKI remained accurate in different COVID-19 variants, suggesting that risk factors for AKI have not substantially evolved across variants.

Background: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD)., Methods: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm., Results: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1β in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups., Conclusions: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. (clinicaltrials.gov # NCT03649711)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America., Methods: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT)., Results: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ 2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28)., Conclusions: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Kidney disease is a common finding in patients with heart failure and can significantly impact treatment decisions and outcomes. Abnormal kidney function is currently determined in clinical practice using filtration markers in the blood to estimate glomerular filtration rate, but the manifestations of kidney disease in the setting of heart failure are much more complex than this. In this manuscript, we review novel biomarkers that may provide a more well-rounded assessment of kidney disease in patients with heart failure., Recent Findings: Galectin-3, ST2, FGF-23, suPAR, miRNA, GDF-15, and NAG may be prognostic of kidney disease progression. L-FABP and suPAR may help predict acute kidney injury (AKI). ST2 and NAG may be helpful in diuretic resistance. Several biomarkers may be useful in determining prognosis of long-term kidney disease progression, prediction of AKI, and development of diuretic resistance. Further research into the mechanisms of kidney disease in heart failure utilizing many of these biomarkers may lead to the identification of therapeutic targets., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Natriuretic peptide levels are elevated in persons with chronic kidney disease (CKD) stages 1-3, but it remains unclear whether this is associated with extracellular volume excess or early cardiovascular changes. We hypothesized that patients with CKD stages 1-3 would have evidence of cardiovascular changes, which would associate with brain natriuretic peptide (BNP), amino-terminal-pro-BNP (NT-pro-BNP), and patient-reported symptoms.Outpatients with CKD stages 1-3 and non-CKD controls were enrolled. Cardiovascular parameters included extracellular water (ECW) normalized to body weight measured using whole-body multifrequency bioimpedance spectroscopy, and total peripheral resistance index (TPRI) and cardiac index measured by impedance cardiography. Dyspnea, fatigue, depression, and quality of life were quantified using questionnaires.Among 21 participants (13 with CKD), median (IQR) BNP was 47.0 (28.0-302.5) vs 19.0 (12.3-92.3) pg/mL, p=0.07, and NT-pro-BNP was 245.0 (52.0-976.8) vs 26.0 (14.5-225.8) pg/mL, p=0.08, in the CKD and control groups, respectively. Those with CKD had higher pulse pressure (79 (66-87) vs 64 (49-67) mm Hg, p=0.046) and TPRI (3721 (3283-4278) vs 2933 (2745-3198) dyn×s/cm 5 /m 2 , p=0.01) and lower cardiac index (2.28 (2.08-2.78) vs 3.08 (2.43-3.37) L/min/m 2 , p=0.02). In the overall cohort, natriuretic peptides correlated with pulse pressure (BNP r=0.59; NT-pro-BNP r=0.58), cardiac index (BNP r=-0.76; NT-pro-BNP r=-0.62), and TPRI (BNP r=0.48), p<0.05 for each, but not with ECW/weight. TPRI and blood pressure correlated moderately with symptoms.Elevated natriuretic peptides may coincide with low cardiac index and elevated peripheral resistance in patients with CKD stages 1-3. The role of these biomarkers to detect subclinical cardiovascular changes needs to be further explored., Competing Interests: Competing interests: PNVB is an associate editor for the Journal of Investigative Medicine. SN reports receiving personal fees from AstraZeneca (Data Safety Monitoring Board) Bayer, Boehringer Ingelheim, and Eli Lilly and Co and Vifor; receiving grants from Keryx and receiving research funding from the Department of Veterans Affairs Health Services Research & Development outside the submitted work. SV reports research funding from VA HSR&D, NIH, World Heart Federation, Tahir, and Jooma Family; and honoraria from the American College of Cardiology in his role as the Associate Editor for Innovations, acc.org, outside of this work. WW reports personal fees from Akebia/Otsuka, AstraZeneca, Bayer, Boehringer-Ingelheim/Lilly, GlaxoSmithKline, Janssen, Merck, Pharmacosmos, and Reata, outside of this work. The remaining authors have nothing to disclose., (The interpretation and reporting of these data are the responsibility of the authors and in no way should be viewed as official policy or interpretation of the Department of Veterans Affairs or the US government.Peter Van Buren is an Associate Editor; please add the disclosure to the competing interests statement.Final comment from a reviewer (please check with the authors at the galley stage):"In discussion there is just a sentence with typo that needs fixing: "Our exploratory results generate hypotheses that subclinical changes in cardiovascular parameters that may exist in patients with CKD stages 1-3."I believe extra word "that" should be removed.")

Rationale & Objective: Acute kidney injury (AKI) is common in patients hospitalized with COVID-19, but validated, predictive models for AKI are lacking. We aimed to develop the best predictive model for AKI in hospitalized patients with coronavirus disease 2019 and assess its performance over time with the emergence of vaccines and the Delta variant., Study Design: Longitudinal cohort study., Setting & Participants: Hospitalized patients with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction result between March 1, 2020, and August 20, 2021 at 19 hospitals in Texas., Exposures: Comorbid conditions, baseline laboratory data, inflammatory biomarkers., Outcomes: AKI defined by KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria., Analytical Approach: Three nested models for AKI were built in a development cohort and validated in 2 out-of-time cohorts. Model discrimination and calibration measures were compared among cohorts to assess performance over time., Results: Of 10,034 patients, 5,676, 2,917, and 1,441 were in the development, validation 1, and validation 2 cohorts, respectively, of whom 776 (13.7%), 368 (12.6%), and 179 (12.4%) developed AKI, respectively ( P  = 0.26). Patients in the validation cohort 2 had fewer comorbid conditions and were younger than those in the development cohort or validation cohort 1 (mean age, 54 ± 16.8 years vs 61.4 ± 17.5 and 61.7 ± 17.3 years, respectively, P  < 0.001). The validation cohort 2 had higher median high-sensitivity C-reactive protein level (81.7 mg/L) versus the development cohort (74.5 mg/L; P  < 0.01) and higher median ferritin level (696 ng/mL) versus both the development cohort (444 ng/mL) and validation cohort 1 (496 ng/mL; P  < 0.001). The final model, which added high-sensitivity C-reactive protein, ferritin, and D-dimer levels, had an area under the curve of 0.781 (95% CI, 0.763-0.799). Compared with the development cohort, discrimination by area under the curve (validation 1: 0.785 [0.760-0.810], P  = 0.79, and validation 2: 0.754 [0.716-0.795], P  = 0.53) and calibration by estimated calibration index (validation 1: 0.116 [0.041-0.281], P  = 0.11, and validation 2: 0.081 [0.045-0.295], P  = 0.11) showed stable performance over time., Limitations: Potential billing and coding bias., Conclusions: We developed and externally validated a model to accurately predict AKI in patients with coronavirus disease 2019. The performance of the model withstood changes in practice patterns and virus variants., (© 2022 The Authors.)

Background: Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y 12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients., Methods: In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed., Results: Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel., Conclusions: More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention., Competing Interests: S.S. Hedayati reports honoraria from the American College of Physicians for participation in Nephrology MKSAP and the American Society of Nephrology Post-Graduate Education Program; and an advisory or leadership role for the American Heart Association (study sections), ACP, and the MKSAP Nephrology Committee. B. Martin reports consultancy for eMaxHealth LLC; honoraria from the Institute of Clinical and Economic Review (ICER) as a member of the Midwest Comparative Effectiveness Public Advisory Council; and patents or royalties for Trestle Tree LLC. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Rationale & Objective: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population., Study Design: Observational study., Setting & Participants: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease., Exposure: Estimated glomerular filtration rate (eGFR)., Outcome: NT-proBNP and hsTnT at baseline., Analytical Approach: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT., Results: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m 2 , 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m 2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60])., Limitations: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting., Conclusions: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: S.S. Hedayati reports honoraria from the American College of Physicians for participation in Nephrology MKSAP, American Society of Nephrology Post-Graduate Education Program, and is a scientific advisor for the American Heart Association, study sections, ACP, MKSAP Nephrology Committee. All remaining authors have nothing to disclose.

Background: Acute kidney injury (AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce., Methods: Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit., Results: Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity (P < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included., Conclusions: Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas., (© 2022. The Author(s).)

Depression disproportionately affects patients with kidney disease, including those with nondialysis chronic kidney disease, end-stage kidney disease requiring dialysis, and kidney transplant recipients. Patients across the spectrum of kidney disease should be screened for depression every 6 to 12 months using self-report questionnaires, followed by an interview with a clinician to confirm the presence of sadness or anhedonia when depressive symptoms are identified. Pharmacologic treatment with selective serotonin reuptake inhibitors has not consistently shown benefit compared with placebo and may be associated with serious adverse outcomes including cardiovascular events, bleeding, and fractures. However, based on the availability of alternative therapies, a watchful trial with close monitoring for therapeutic and adverse effects is reasonable. Several clinical trials have suggested that cognitive behavioral therapy and physical activity improve depressive symptoms when compared with a control group. Given the low risk associated with these therapies, they should be recommended to patients who have access and are amenable to such interventions. Future trials are needed to study therapeutic options for depression in nondialysis chronic kidney disease, peritoneal dialysis, or kidney transplant recipients, as well as alternative pharmacologic therapy and combination therapies. Given improvement in depressive symptoms with placebo in existing trials, inclusion of a control group is paramount., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Kidney transplant recipients with coronavirus disease 2019 (COVID-19) are at increased risk for adverse outcomes, such as acute kidney injury (AKI), intensive care unit (ICU) admission, and death. The association of inflammatory biomarkers with outcomes and the impact of changes in immunosuppression on biomarker levels are unknown., Methods: We investigated factors associated with a composite of AKI, ICU admission, or death, and whether immunosuppression changes correlated with changes in inflammatory biomarkers and outcomes in kidney transplant recipients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction., Results: Of 59 patients, 50% had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . Patients who discontinued calcineurin inhibitors (CNIs) had higher peak high-sensitivity C-reactive protein (hs-CRP) than those who maintained the same dose (median, 344; interquartile range [IQR], 145-374 vs median, 41; IQR, 22-116 mg/L, P = .03). Of the patients, 73% were hospitalized, 22% had admissions to the ICU, and 20% died. Of the 56% with AKI, 35% required dialysis. All patients with AKI but without pulmonary manifestations recovered to 10% of baseline creatinine levels. Factors associated with the composite outcome were eGFR <60 mL/min/1.73 m 2 (odds ratio [OR], 5.833; 95% confidence interval [CI], 1.880-18.099; P = .002), hs-CRP (OR, 1.011/unit increase; 95% CI, 1.002-1.021; P = .019), white blood cell count (OR, 1.173/unit increase; 95% CI, 1.006-1.368; P = .041), and decreased or discontinued CNI (OR, 4.286; 95% CI, 1.353-13.572; P = .013). eGFR<60 mL/min/1.73 m 2 (OR, 11.176; 95% CI, 1.581-79.001; P = .016), and peak hs-CRP (OR, 1.010/unit increase; 95% CI, 1.000-1.020; P = .049) remained associated with the composite in the multivariable model., Conclusions: Kidney transplant recipients with COVID-19 have high rates of ICU admissions, AKI, and death. Those with eGFR<60 mL/min/1.73 m 2 are at highest risk. CNI reduction is associated with higher inflammatory biomarkers, correlating with worse outcomes. More studies are needed to determine if this association should drive clinical management., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Although oral P2Y 12 inhibitors (P2Y12-Is) are one of the most commonly prescribed medication classes in patients with end stage kidney disease on dialysis (ESKD), scarce data exist regarding their benefits and risks., Methods: We compared effectiveness and safety of clopidogrel, prasugrel, and ticagrelor in a longitudinal study using the United States Renal Data System registry of Medicare beneficiaries with ESKD. Individuals who filled new P2Y12-I prescriptions between 2011 and 2015 were included and followed until death or censoring. The primary exposure variable was P2Y12-I assignment. The primary outcome variable was death. Secondary outcomes included cardiovascular (CV) death, coronary revascularization, and gastrointestinal (GI) hemorrhage. Survival analyses were performed after propensity matching., Results: Of 44,619 patients with ESKD who received P2Y12-Is, 95% received clopidogrel ( n  = 42,523), 3% prasugrel ( n  = 1205), and 2% ticagrelor ( n  = 891). To balance baseline differences, propensity-matching was performed: 1:6 for prasugrel ( n  = 1189) versus clopidogrel ( n  = 7134); 1:4 for ticagrelor ( n  = 880) versus clopidogrel ( n  = 3520); and 1:1 for ticagrelor versus prasugrel ( n  = 880). Prasugrel was associated with a reduced risk for death versus clopidogrel and ticagrelor (adjusted hazard ratio [HR] = 0.82; 95% CI: 0.73-0.93 and 0.78; 95% CI: 0.64-0.95). Compared with clopidogrel, prasugrel reduced risk for coronary revascularization (HR = 0.91; 95% CI: 0.86-0.96). There were no differences in GI hemorrhage between P2Y12-Is., Conclusion: In patients with ESKD, prasugrel compared with others reduced risk of death possibly by reducing risk for coronary revascularizations and without worsening gastrointestinal hemorrhage. Future trials are imperative to compare efficacy and safety of P2Y12-Is in patients with ESKD., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID-19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID-19. Methods and Results In a large multicenter registry including 8574 patients with COVID-19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end-stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all-cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new-onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end-stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46-2.03]; stage 2 HR, 1.83 [95% CI, 1.52-2.20]; stage 3 HR, 1.69 [95% CI, 1.44-1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74-2.71]; stage 2 HR, 2.70 [95% CI, 2.07-3.51]; stage 3 HR, 3.06 [95% CI, 2.52-3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all-cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID-19.

Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19)., Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival., Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used., Setting: 67 hospitals in the United States., Participants: Adults with COVID-19 admitted to a participating ICU., Measurements: Time to death, censored at hospital discharge, or date of last follow-up., Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35])., Limitation: Observational design., Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation., Primary Funding Source: None.

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease. We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with chronic kidney disease. We studied US Veterans with nondialysis chronic kidney disease stages 1-5 and hypertension on nondiuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic versus any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over 6 months after second agent prescription. Cox proportional hazards regression measured associations of BPV with a primary cardiovascular event composite (fatal or nonfatal myocardial infarction or ischemic stroke; heart failure hospitalization). Secondary outcomes included all-cause death, each primary outcome component, end-stage kidney disease, and cardiovascular death. There were 31 394 participants in each group. BPV was associated with composite cardiovascular events, hazard ratio (95% CI) at second, third, fourth, and fifth versus first quintile: 1.79 (1.53-2.11), 2.32 (1.99-2.71), 2.60 (2.24-3.02), and 3.12 (2.68-3.62). Diuretics attenuated associations between the fourth and fifth BPV quintiles with composite events ( P interaction =0.03 and 0.04, respectively). BPV was associated with all secondary outcomes except end-stage kidney disease, with no diuretic interactions. BPV was associated with cardiovascular events and death but not end-stage kidney disease in patients with chronic kidney disease, with attenuated associations with cardiovascular events in the diuretic-treated group at high BPV quintiles. Future studies should investigate whether other antihypertensive classes modify these risks.

Background: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT)., Methods: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients., Results: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission., Conclusions: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission., (Copyright © 2021 by the American Society of Nephrology.)

Importance: Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear., Objective: To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF., Design, Setting, and Participants: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020., Main Outcomes and Measures: Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models., Results: Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44)., Conclusions and Relevance: In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.

Purpose of Review: It remains controversial whether existing therapies, including pharmacologic and psychological interventions, are effective for treatment of depression in patients with chronic kidney disease (CKD) and end-stage kidney disease., Recent Findings: Most studies of depression treatment were underpowered or uncontrolled. The CKD Antidepressant Sertraline Trial showed no benefit of a serotonin-selective reuptake inhibitor (SSRI), sertraline, over double-blind matched placebo for the treatment of depressive symptoms in patients with nondialysis CKD. A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression showed improvement in depressive symptoms from baseline in both groups and a marginal benefit of sertraline over CBT that was of unclear clinical significance, given the lack of an active control group. SSRIs are associated with poor tolerability in clinical trials and serious adverse outcomes in large retrospective studies., Summary: Although the data do not support unlimited use of SSRIs in patients with CKD or end-stage kidney disease, it is reasonable to initiate a cautious trial of sertraline while closely monitoring for depressive symptom improvement and adverse effects. CBT is a low-risk, possibly effective intervention to treat major depressive disorder in patients with kidney disease who have access to such treatments.

Background: Inflammatory biomarkers are elevated in patients with CKD and associated with poor outcomes. Major depressive disorder (MDD) is prevalent in CKD and associated with inflammation. No studies investigated the effect of MDD treatment on plasma inflammatory biomarkers in patients with nondialysis CKD., Methods: In a prespecified analysis of the randomized, double-blind CKD Antidepressant Sertraline Trial, we investigated whether treatment with sertraline versus placebo or response to treatment would affect plasma levels of albumin, prealbumin, IL-6, and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 12 weeks of treatment. We also explored whether somatic versus nonsomatic depressive symptoms, measured using the Quick Inventory of Depressive Symptomatology, and quality-of-life subscales, measured using the Kidney Disease Quality of Life Short Form, were associated with baseline levels of these inflammatory biomarkers., Results: Of the 193 participants, mean age was 58.4 (SD 13) years and 58% were black, 42% were white, and 18% were Hispanic. Higher baseline hsCRP correlated with somatic depressive symptoms ( r =0.21; P =0.01), fatigue ( r =0.22; P =0.005), and poorer physical functioning ( r =-0.26; P =0.001). There was no change in hsCRP in the sertraline group. hsCRP increased in placebo nonresponders from baseline (median, 3.7 mg/L; interquartile range [IQR], 1.7-10.0 mg/L) to exit (median, 4.9 mg/L; IQR, 1.8-8.8 mg/L; P =0.01). The change from baseline to exit differed between placebo responders (median, -0.4 mg/L; IQR, -9.3 to 0.2 mg/L) and nonresponders (median, 0.8 mg/L; IQR, -0.1 to 3.9 mg/L; P =0.008). There were no differences in changes in albumin, prealbumin, or IL-6 from baseline in any group., Conclusions: Among patients with CKD and MDD, hsCRP correlated with somatic symptoms of depression and fatigue, but not with nonsomatic symptoms. Sertraline treatment was not associated with a longitudinal change in hsCRP from baseline regardless of treatment effect on depressive symptoms, but those who failed to respond to placebo had an increase in hsCRP over time. This area deserves further investigation., Clinical Trial Registry Name and Registration Number: CKD Antidepressant Sertraline Trial (CAST), NCT00946998., Competing Interests: M. Trivedi has served as an advisor or consultant to the following organizations: Allergan Sales LLC, Alkermes, Arcadia Pharmaceuticals Inc., AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Eli Lilly & Company, Evotec, Johnson & Johnson, Lundbeck, MedAvante, Merck, MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Roche Products Ltd., SHIRE Development, Takeda, and Tal Medical/Puretech Venture. M. Trivedi reports personal fees from Acadia, Akili Interactive (other), Alto Neuroscience Inc., Applied Clinical Intelligence LLC, Axome Therapeutics, Boehringer Ingelheim, Engage Health Media, GreenLight VitalSign6 Inc., Health Care Global Village, Janssen-Cilag, Janssen Research and Development LLC, Jazz Pharmaceuticals, Medscape LLC, Navitor Pharmaceuticals Inc, Otsuka Pharmaceutical Development & Commercialization Inc., Otsuka America Pharmaceutical Inc, Perception Neuroscience Holdings Inc., Pharmerit International LP, Policy Analysis Inc., Rexahn Pharmaceuticals Inc., Sage Therapeutics, Signant Health, SK Life Science Inc., and The Baldwin Group Inc. He also reports grants from the National Institute of Mental Health, Patient-Centered Outcomes Research Institute, Cancer Prevention Research Institute of Texas, other from Oxford University Press, and other from American Psychiatric Association (Deputy Editor for American Journal of Psychiatry), outside the submitted work. The coauthors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Introduction: Depression comorbid with chronic disease may be mediated by inflammation. We sought to characterize relationships between inflammatory biomarkers and depressive symptoms in patients with chronic kidney disease and end-stage kidney disease., Methods: A systematic literature search was conducted by 2 authors up to March 19, 2019, for studies of patients with chronic kidney disease or end-stage kidney disease evaluating circulating inflammatory biomarkers associated with depression of chronic disease: albumin, C-reactive protein (CRP), high-sensitivity CRP, interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1. Standardized mean differences in biomarkers between individuals with and without depression were computed and analyzed using mixed effects models. Correlations between biomarkers and the severity of depressive symptoms were computed., Results: Thirty-four studies (5652 participants) compared biomarkers between depressed and nondepressed individuals. Individuals with depression had lower albumin levels (standardized mean difference, -0.37; 95% confidence interval [CI], -0.61 to -0.13), higher CRP levels (standardized mean difference, 0.76; 95% CI, 0.16-1.37), and higher IL-6 levels (standardized mean difference, 0.42; 95% CI, 0.21-0.63). Studies were heterogeneous for albumin, CRP, high-sensitivity CRP, and tumor necrosis factor-α. Twenty-three studies (3047 participants) investigated correlations between biomarkers and depressive symptoms. The severity of depressive symptoms correlated with albumin ( Z  = -0.25; 95% CI, -0.36 to -0.14), high-sensitivity CRP ( Z  = 0.28; 95% CI, 0.13-0.43), and IL-6 ( Z  = 0.34; 95% CI, 0.18-0.49). There was heterogeneity across studies of IL-6. Only 6 studies (321 participants) investigated the effect of antidepressant treatment on inflammatory biomarkers, which was insufficient to combine in meta-analysis., Conclusion: Lower albumin and higher IL-6 were associated with both the presence and severity of depression, CRP with the presence of depression, and high-sensitivity CRP with the severity of depressive symptoms. The effect of interventions to lower inflammation in patients with kidney disease and depression deserves investigation., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background: Major Depressive Disorder (MDD) can lead to adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Although one of the proposed mechanisms is heightened platelet activation, effects of MDD and its treatment with a selective serotonin reuptake inhibitor (SSRI) on platelet function in patients with CKD remain unclear., Methods: In a pre-specified analysis, changes from baseline to 12 weeks in whole blood platelet aggregation (WBPA) and plasma levels of E-selectin and P-selectin on treatment with sertraline vs. placebo were investigated in 175 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73m 2 ) and MDD (MDD+/CKD+) in a randomized, double-blind trial. Correlations between severity of depressive symptoms and platelet function were also analyzed. In order to investigate whether differences in platelet function were due to presence of CKD or MDD, we compared a subgroup of 49 MDD+/CKD+ patients with eGFR < 30 ml/min/1.73m 2 to 43 non-depressed CKD controls (28 CKD with eGFR < 30 ml/min/1.73m 2 [MDD-/CKD+] and 15 individuals with eGFR ≥90 ml/min/1.73m 2 [MDD-/CKD-]., Results: In MDD+/CKD+ individuals, there were no significant correlations between severity of depressive symptoms and platelet function, and no significant changes in platelet function after 12 weeks of treatment with sertraline vs. placebo. There were no significant differences in platelet function among MDD+/CKD+ patients and controls without MDD except in WBPA to 10 μM ADP (P = 0.03). WBPA to ADP was lower in the MDD-/CKD- group (8.0 Ω [5.0 Ω, 11.0 Ω]) as compared to the MDD-/CKD+ group (12.5 Ω [8.0 Ω, 14.5 Ω]), P = 0.01, and the MDD+/CKD+ group (11.0 Ω [8.0 Ω, 15.0 Ω]), P < 0.01., Conclusions: Heightened ADP-induced platelet aggregability was observed in CKD patients compared to controls with normal kidney function, regardless of presence of comorbid MDD, and treatment with sertraline did not affect platelet function. These findings suggest that increased platelet activation may not be a major contributory underlying mechanism by which depression may lead to worse cardiovascular outcomes in patients with CKD. Future studies should include positive MDD controls without CKD to confirm our findings., Trial Registration: ClinicalTrials.gov identifier numbers: CAST Study: NCT00946998 (Recruitment Status: Completed. First Posted: July 27, 2009. Results First Posted: January 30, 2018). WiCKDonASA Study: NCT01768637 (Recruitment Status: Completed. First Posted: January 15, 2013. Results First Posted: April 19, 2019).

Background: Although depression is common among patients receiving maintenance hemodialysis, data on their acceptance of treatment and on the comparative efficacy of various therapies are limited., Objective: To determine the effect of an engagement interview on treatment acceptance (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for treating depression in patients receiving hemodialysis., Design: Multicenter, parallel-group, open-label, randomized controlled trial. (ClinicalTrials.gov: NCT02358343)., Setting: 41 dialysis facilities in 3 U.S. metropolitan areas., Participants: Patients who had been receiving hemodialysis for at least 3 months and had a Beck Depression Inventory-II score of 15 or greater; 184 patients participated in phase 1, and 120 subsequently participated in phase 2., Intervention: Engagement interview versus control visit (phase 1) and 12 weeks of CBT delivered in the dialysis facility versus sertraline treatment (phase 2)., Measurements: The primary outcome for phase 1 was the proportion of participants who started depression treatment within 28 days. For phase 2, the primary outcome was depressive symptoms measured by the Quick Inventory of Depressive Symptoms-Clinician-Rated (QIDS-C) at 12 weeks., Results: The proportion of participants who initiated treatment after the engagement or control visit did not differ (66% vs. 64%, respectively; P = 0.77; estimated risk difference, 2.1 [95% CI, -12.1 to 16.4]). Compared with CBT, sertraline treatment resulted in lower QIDS-C depression scores at 12 weeks (effect estimate, -1.84 [CI, -3.54 to -0.13]; P = 0.035). Adverse events were more frequent in the sertraline than the CBT group., Limitation: No randomized comparison was made with no treatment, and persistence of treatment effect was not assessed., Conclusion: An engagement interview with patients receiving maintenance hemodialysis had no effect on their acceptance of treatment for depression. After 12 weeks of treatment, depression scores were modestly better with sertraline treatment than with CBT., Primary Funding Source: Patient-Centered Outcomes Research Institute, Dialysis Clinic, Kidney Research Institute, and National Institute of Diabetes and Digestive and Kidney Diseases.

Background: Fatigue, although common and associated with outcomes in dialysis-dependent chronic kidney disease (CKD), has not been studied in nondialysis chronic kidney disease (CKD-ND) patients., Methods: In this longitudinal cohort of 266 outpatients with CKD-ND stages 2-5, we measured self-reported fatigue on 3 scales-Quick Inventory of Depression Symptomatology-Self Report (QIDS-SR16), Beck Depression Inventory-I (BDI-I), and short form 12 health survey (SF-12) questionnaires and evaluated the prespecified composite of progression to dialysis initiation, death, or hospitalization after 12 months. Logistic and linear regression assessed characteristics associated with fatigue. Survival analysis measured associations of fatigue with outcomes., Results: Mean age was 64.4 ± 12.0 years, and mean estimated glomerular filtration rate (eGFR) was 31.6 ± 16.7 mL/min/1.73 m2. Fatigue was common, with 69.2% reporting fatigue on QIDS-SR16 and 77.7% on BDI-I. Unemployment, comorbidities, use of antidepressant medications, and lower hemoglobin correlated with fatigue. There were 126 outcome events. Participants that reported any versus no fatigue on QIDS-SR16 were more likely to reach the composite, hazard ratio (HR) 1.70 (95% CI 1.11-2.59), which persisted after adjusting for demographics, comorbidities, substance abuse, hemoglobin, albumin, eGFR, and calcium-phosphorus product, HR 1.63 (1.05-2.55). Fatigue severity by the SF-12 was also associated with outcomes independent of demographics, comorbidities, and substance abuse, HR per unit increase 1.18 (1.03-1.35). No association was observed with fatigue on the BDI-I., Conclusion: Fatigue affected about 2/3 of CKD-ND patients and associated with unemployment, comorbidities, antidepressant medication use, and anemia. Fatigue measured by the QIDS-SR16 and SF-12 independently predicted outcomes in CKD patients. Eliciting the presence of fatigue may be a clinically significant prognostic assessment in CKD patients., (© 2019 S. Karger AG, Basel.)

Patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) are 10 times more likely to die of cardiovascular (CV) diseases than the general population, and dialysis-dependent patients are at even higher risk. Although traditional CV risk factors are highly prevalent in individuals with CKD, these patients were often excluded from studies targeting modification of these risks. Although treatment of hypertension is beneficial in CKD, the best target blood pressure has not been established. Trial data showed that renin-angiotensin-aldosterone blockade may prevent CV events in patients with CKD. The risks of aspirin may equal the benefits in NDD-CKD samples, and there are no trials testing aspirin in dialysis-dependent patients. Lipid-lowering therapy improves CV outcomes in NDD-CKD, but not in dialysis-dependent patients. Strict glycemic control prevents CV events in nonalbuminuric individuals, but showed no benefit in those with baseline albuminuria with albumin excretion > 300mg/g, and there are no data in dialysis-dependent patients. Data for lifestyle modifications, such as weight loss, physical activity, and smoking cessation, are mostly observational and extrapolated from non-CKD samples. This comprehensive review summarizes the best existing evidence and current clinical guidelines for modification of traditional risk factors for the prevention of CV events in patients with CKD and identifies knowledge gaps., (Published by Elsevier Inc.)

Background: Monocyte chemoattractant protein-1 -(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored., Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events., Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = -0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4-2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0-2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1-2.3]) after adjusting for CV risk factors., Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD., (© 2018 S. Karger AG, Basel.)

Importance: Major depressive disorder (MDD) is prevalent among patients with chronic kidney disease (CKD) and is associated with morbidity and mortality. The efficacy and adverse events of selective serotonin reuptake inhibitors in these patients are unknown., Objective: To determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD., Design, Setting, and Participants: The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) was a randomized, double-blind, placebo-controlled trial involving 201 patients with stage 3, 4, or 5 non-dialysis-dependent CKD, who were enrolled at 3 US medical centers. The Mini Neuropsychiatric Interview was used to establish MDD. The first participant was randomized in March 2010 and the last clinic visit occurred in November 2016., Interventions: After a 1-week placebo run-in, participants were randomized to sertraline (n = 102) for 12 weeks at an initial dose of 50 mg/d (escalated to a maximum dose of 200 mg/d based on tolerability and response) or matching placebo (n = 99)., Main Outcomes and Measures: The primary outcome was improvement in depressive symptom severity from baseline to 12 weeks determined by the 16-item Quick Inventory of Depression Symptomatology-Clinician Rated (QIDS-C16) (score range, 0-27; minimal clinically important difference, 2 points). Secondary outcomes included improvement in quality of life (Kidney Disease Quality of Life Survey-Short Form; score range, 0-100; higher scores indicate more favorable quality of life) and adverse events., Results: There were 201 patients (mean [SD] age, 58.2 [13.2] years; 27% female) randomized. The primary analysis included 193 patients who had at least 1 outcome assessment after randomization. The mean (SD) baseline QIDS-C16 score was 14.0 (2.4) in the sertraline group (n = 97) and 14.1 (2.4) in the placebo group (n = 96). The median participation time was 12.0 weeks and the median achieved dose was 150 mg/d, which was not significantly different between the groups. The QIDS-C16 score changed by -4.1 in the sertraline group and by -4.2 in the placebo group (between-group difference, 0.1 [95% CI, -1.1 to 1.3]; P = .82). There was no significant between-group difference in change in patient-reported overall health on the Kidney Disease Quality of Life Survey (median score, 0 in the sertraline group vs 0 in the placebo group; between-group difference, 0 [95% CI, -10.0 to 0]; P = .61). Nausea or vomiting occurred more frequently in the sertraline vs placebo group (22.7% vs 10.4%, respectively; between-group difference, 12.3% [95% CI, 1.9% to 22.6%], P = .03), as well as diarrhea (13.4% vs 3.1%; between-group difference, 10.3% [95% CI, 2.7% to 17.9%], P = .02)., Conclusions and Relevance: Among patients with non-dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non-dialysis-dependent CKD., Trial Registration: clinicaltrials.gov Identifier: NCT00946998.

Background: Cardiac troponin T and brain natriuretic peptide (BNP) are elevated in >50% of dialysis patients and are associated with poor outcomes. Few data investigated these associations in earlier chronic kidney disease (CKD)., Methods and Results: We studied whether CKD modified associations of elevated BNP, N-terminal-pro-BNP, high-sensitivity cardiac troponin T, coronary artery calcification, and left ventricular hypertrophy with all-cause death and cardiovascular death/events in 3218 multiethnic individuals followed for 12.5 years, and whether biomarkers added prognostic information to traditional cardiovascular risk factors in CKD. Of the cohort, 279 (9%) had CKD. There were 296 deaths and 218 cardiovascular deaths/events. Of non-CKD individuals, 7% died and 6% had cardiovascular death/event versus 32% and 30% of CKD participants, P <0.001 for both. The interaction between BNP and CKD on death was significant ( P =0.01): the adjusted hazard ratio in CKD was 2.05, 95% CI (1.34, 3.14), but not significant in non-CKD, 1.04 (0.76, 1.41). CKD modified the association of high-sensitivity cardiac troponin T with cardiovascular death/event, adjusted hazard ratio 3.34 (1.56, 7.18) in CKD versus 1.65 (1.16, 2.35) in non-CKD, interaction P =0.09. There was an interaction between N-terminal-pro-BNP and CKD for death in those without prior cardiovascular disease. Addition of each biomarker to traditional risk factors improved risk prediction, except coronary artery calcification was not discriminatory for cardiovascular death/event in CKD., Conclusions: Cardiac biomarkers, with the exception of coronary artery calcification, prognosticated outcomes in early-stage CKD as well as, if not better than, in non-CKD individuals, even after controlling for estimated glomerular filtration rate, and added to information obtained from traditional cardiovascular risk factors alone., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events., (Copyright © 2017 by the American Society of Nephrology.)

Objective: Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients., Design: Retrospective cohort study., Setting: Urban academic medical center ICU., Patients: ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded., Interventions: None., Measurements and Main Results: A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury-/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease-; and 1.5 L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury., Conclusions: Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is "Patient Centered-Research", in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases., (Copyright © 2016 by the American Society of Nephrology.)

Objective: Because there is overlap between somatic symptoms of depression and symptoms of chronic kidney disease (CKD), it is unclear if self-reported depression rating scales can be used accurately in predialysis CKD patients, especially if CKD and other comorbidities are symptomatic. We assessed the performance of two depression scales - the Beck Depression Inventory (BDI) and the Quick Inventory of Depression Symptomatology (QIDS-SR16) - by CKD stage, diagnosis of diabetes and total medical comorbidity burden - using item response theory (IRT) in a sample of 272 predialysis CKD patients., Methods: We performed IRT by low versus high CKD stage, diabetes versus no diabetes and high (>3 diagnoses) versus low medical comorbidity burden., Results: IRT models of each rating scale were affected in a limited way by CKD stage, diabetes and medical comorbidity burden. Sleep disturbances on the QIDS-SR16 were more discriminatory for depression in diabetics and those with high comorbidity burden. Pessimism and guilt from the BDI compared to QIDS-SR16 were more discriminatory of depression in the high CKD and high comorbidity groups, respectively., Conclusions: Overall item differences were modest, and chronic disease severity by CKD stage, diabetes mellitus or other medical comorbidities did not appreciably contribute to differences in scale performance., (Copyright © 2016. Published by Elsevier Inc.)

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes., (Published by Elsevier Inc.)