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Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial

Mathew, Roy O; Maron, David J; Anthopolos, Rebecca; Fleg, Jerome L; O'Brien, Sean M; Rockhold, Frank W; Briguori, Carlo; Roik, Marek F; Mazurek, Tomasz; Demkow, Marcin; Malecki, Robert; Ye, Zhiming; Kaul, Upendra; Miglinas, Marius; Stone, Gregg W; Wald, Ron; Charytan, David M; Sidhu, Mandeep S; Hochman, Judith S; Bangalore, Sripal
BACKGROUND:]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5. METHODS:This was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5. RESULTS:A total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status. CONCLUSIONS:CKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status. REGISTRATION/BACKGROUND:URL: https://www. CLINICALTRIALS/RESULTS:gov; Unique identifier: NCT01985360.
PMCID:9588677
PMID: 36193750
ISSN: 1941-7705
CID: 5351522

BNT162b2 vaccine effectiveness in chronic kidney disease patients-an observational study

Bielopolski, Dana; Libresco, Gilad; Barda, Noam; Dagan, Noa; Steinmetz, Tali; Yahav, Dafna; Charytan, David M; Balicer, Ran D; Rozen-Zvi, Benaya
Background/UNASSIGNED:Chronic kidney disease (CKD) is a risk factor for severe coronavirus disease 2019 (COVID-19). We aimed to evaluate the real-life effectiveness of the BNT162b2 messenger RNA vaccine for a range of outcomes in patients with CKD compared with matched controls. Methods/UNASSIGNED:) according to demographic and clinical characteristics. Study outcomes included documented infection with severe acute respiratory syndrome coronavirus 2, symptomatic infection, COVID-19-related hospitalization, severe disease and death. Vaccine effectiveness was estimated as the risk ratio (RR) at days 7-28 following the second vaccine dose, using the Kaplan-Meier estimator. Effectiveness measures were also evaluated separately for various stages of CKD. Results/UNASSIGNED:, the risk of severe disease and death was increased compared with controls [RR 6.42 (95% CI 1.85-17.51) and RR 8.81 (95% CI 1.63-13.81), respectively]. The risks for all study outcomes were increased in HD patients compared with controls. Conclusion/UNASSIGNED:for booster shots, pre- and post-exposure prophylaxis and early COVID-19 therapy.
PMCID:9384353
PMID: 36147707
ISSN: 2048-8505
CID: 5335712

Transplant Nephrology

Chonchol, Michel; Gutierrez, Orlando; Rahman, Mahboob; Charytan, David; Rosner, Mitchell
PMID: 35914795
ISSN: 1555-905x
CID: 5287872

Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease: A Post Hoc Analysis From the CREDENCE Trial

Li, Jing-Wei; Arnott, Clare; Heerspink, Hiddo J L; MBiostat, Qiang Li; Cannon, Christopher P; Wheeler, David C; Charytan, David M; Barraclough, Jennifer; Figtree, Gemma A; Agarwal, Rajiv; Bakris, George; de Zeeuw, Dick; Greene, Tom; Levin, Adeera; Pollock, Carol; Zhang, Hong; Zinman, Bernard; Mahaffey, Kenneth W; Perkovic, Vlado; Neal, Bruce; Jardine, Meg J
Background The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events. Methods and Results The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m2, over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P<0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59-0.86]; P<0.001). The absolute risk difference per 1000 patients treated over 2.5 years was -44 (95% CI, -67 to -21) first cardiovascular events and -73 (95% CI, -114 to -33) total events. Conclusions Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events. Registration Information URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02065791.
PMID: 35929472
ISSN: 2047-9980
CID: 5288332

Hydralazine-Isosorbide Dinitrate Use in Patients With End-Stage Kidney Disease on Dialysis

Mavrakanas, Thomas A; Soomro, Qandeel H; Charytan, David M
Introduction/UNASSIGNED:The combination of hydralazine-isosorbide dinitrate (H-ISDN) has potential as a heart failure (HF) therapy in the setting of maintenance dialysis. Methods/UNASSIGNED:In this retrospective study, we analyzed the efficacy of H-ISDN using United States Renal Data System (USRDS) data. We identified all adult patients with a history of HF on maintenance dialysis between January 1, 2011, and December 31, 2016, with at least 1 prescription for H-ISDN. Baseline characteristics, prescriptions, and outcomes were retrieved from institutional and physician claims. The primary outcome was death from any cause. Additional outcomes included cardiovascular death, sudden cardiac death, hospitalization for HF, an inpatient diagnosis of myocardial infarction (MI), or new-onset atrial fibrillation. Stabilized inverse probability weights were estimated using relevant baseline characteristics and were used in Cox proportional hazards regression. Results/UNASSIGNED:We identified 6306 patients who were treated with H-ISDN and 75,509 patients who did not receive H-ISDN. The crude all-cause mortality rate was lower in patients treated with H-ISDN (16.0 events/100 patient years [PYs]) than in nonusers (27.9/100-PY). H-ISDN use was independently associated with lower mortality: hazard ratio (HR) 0.48 (95% CI 0.43-0.54). Cardiovascular death and sudden cardiac death were less common among H-ISDN users than nonusers, Weighted HR was 0.62 (95% CI 0.53-0.71) and 0.62 (95% CI 0.52-0.73), respectively. In contrast, HF admission and MI were more frequent in patients treated with H-ISDN (195.5 and 18.0 events/100-PY) compared with nonusers (73.4 and 10.2 events/100-PY). Conclusion/UNASSIGNED:H-ISDN therapy may improve cardiovascular outcomes in maintenance dialysis patients with HF.
PMCID:9171697
PMID: 35685328
ISSN: 2468-0249
CID: 5283272

Automated Determination of Left Ventricular Function Using Electrocardiogram Data in Patients on Maintenance Hemodialysis

Vaid, Akhil; Jiang, Joy J; Sawant, Ashwin; Singh, Karandeep; Kovatch, Patricia; Charney, Alexander W; Charytan, David M; Divers, Jasmin; Glicksberg, Benjamin S; Chan, Lili; Nadkarni, Girish N
BACKGROUND AND OBJECTIVES/OBJECTIVE:Left ventricular ejection fraction is disrupted in patients on maintenance hemodialysis and can be estimated using deep learning models on electrocardiograms. Smaller sample sizes within this population may be mitigated using transfer learning. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:) pretrained on patients not on hemodialysis and fine-tuned on patients on hemodialysis. We assessed the ability of the models to classify left ventricular ejection fraction into clinically relevant categories of ≤40%, 41% to ≤50%, and >50%. We compared performance by area under the receiver operating characteristic curve. RESULTS:=1309), respectively. For the same tasks, model 1 achieved area under the receiver operating characteristic curves of 0.74, 0.55, and 0.71, respectively; model 2 achieved area under the receiver operating characteristic curves of 0.71, 0.55, and 0.69, respectively, and model 3 achieved area under the receiver operating characteristic curves of 0.80, 0.51, and 0.77, respectively. We found that predictions of left ventricular ejection fraction by the transfer learning model were associated with mortality in a Cox regression with an adjusted hazard ratio of 1.29 (95% confidence interval, 1.04 to 1.59). CONCLUSION/CONCLUSIONS:A deep learning model can determine left ventricular ejection fraction for patients on hemodialysis following pretraining on electrocardiograms of patients not on hemodialysis. Predictions of low ejection fraction from this model were associated with mortality over a 5-year follow-up period. PODCAST/UNASSIGNED:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_06_CJN16481221.mp3.
PMID: 35667835
ISSN: 1555-905x
CID: 5248242

A Pilot Randomized Controlled Trial of Integrated Palliative Care and Nephology Care [Meeting Abstract]

Scherer, Jennifer; Rau, Megan; Krieger, Anna; Xia, Yuhe; Brody, Abraham; Zhong, Hua; Charytan, David; Chodosh, Joshua
ISI:000802790300134
ISSN: 0885-3924
CID: 5246832

Risk Factors for Fracture in Patients with Coexisting Chronic Kidney Disease and Type 2 Diabetes: An Observational Analysis from the CREDENCE Trial

Young, Tamara K; Toussaint, Nigel D; Di Tanna, Gian Luca; Arnott, Clare; Hockham, Carinna; Kang, Amy; Schutte, Aletta E; Perkovic, Vlado; Mahaffey, Kenneth W; Agarwal, Rajiv; Bakris, George L; Charytan, David M; Heerspink, Hiddo J L; Levin, Adeera; Pollock, Carol; Wheeler, David C; Zhang, Hong; Jardine, Meg J
Background/UNASSIGNED:The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods/UNASSIGNED:Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results/UNASSIGNED:Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88-2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01-1.06), female sex (HR 2.49, CI 1.70-3.65), previous fracture (HR 2.30, CI 1.58-3.34), Asian race (HR 1.74, CI 1.09-2.78), vitamin D therapy requirement (HR 2.05, CI 1.31-3.21), HbA1c (HR 1.14, CI 1.00-1.32), prior cardiovascular event (HR 1.60, CI 1.10-2.33), and serum albumin (HR 0.41, CI 0.23-0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92-1849.51, SBC range 1875.60-1948.04). Conclusion/UNASSIGNED:Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.
PMCID:9168808
PMID: 35677742
ISSN: 2314-6753
CID: 5248452

Utilization of Palliative Care for Patients with Acute Kidney Injury and COVID-19 (S541) [Meeting Abstract]

Scherer, J; Rau, M; Qian, Y; Soomro, Q; Sullivan, R; Zhong, H; Linton, J; Chodosh, J; Charytan, D
Outcomes: 1. Understand the historical use of palliative care for patients with acute kidney injury (AKI) 2. Describe the use of palliative care for patients with AKI and COVID-19 during the surge at our institution 3. Describe the associations of palliative care with subsequent health care utilization such as hospice use, ICU time, and mechanical ventilation Original Research Background: Acute kidney injury (AKI) is a common morbidity seen in patients with COVID-19 and is associated with high mortality. Palliative care is valuable for these patients yet is historically underused in AKI. Research Objectives: To describe the use of palliative care and subsequent health care utilization by COVID-19 patients with AKI.
Method(s): A retrospective analysis of NYU's electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. AKI was defined by the AKI Network creatinine criteria. Regression models examined characteristics associated with a receiving palliative care and discharge to hospice versus death in the hospital.
Result(s): Patientswith COVID-19 and AKI were more likely than those without AKI to receive palliative care (42% vs 7%, p < 0.001); however, consults came significantly later (10 days from admission vs 5 days, p < 0.001). 66% of patients initiated on renal replacement therapy (RRT) received palliative care versus 37% (p < 0.001) of those with AKI not on RRT, also later in timing (12 days from admission vs 9 days, p = 0.002). Patients with AKI had a significantly longer stay, more ICU admissions, use of mechanical ventilation, discharges to hospice (6% vs 3%), and changes in code status (34% vs 7%, p < 0.001) than those without AKI. Among those who received palliative care, AKI both without RRT (adjusted odds ratio [aOR] 0.51, 95% confidence interval [CI] 0.27-0.95) and with RRT (aOR 0.18, 95% CI 0.04-0.67) was associated with a lower likelihood of discharge to hospice versus hospital death compared to those without AKI.
Conclusion(s): Palliative care was used more for patients with AKI and COVID-19 than historically reported, yet this consultation came later in the hospital course and did not avoid invasive interventions despite high mortality. Implications for Research, Policy, or Practice: These data can lead to further exploration of earlier timing of palliative care consultation in AKI.
Copyright
EMBASE:2017644107
ISSN: 1873-6513
CID: 5240182

Obesity Related Glomerulopathy in Adolescent Women: The Effect of Body Surface Area

Bielopolski, Dana; Singh, Neha; Bentur, Ohad S; Renert-Yuval, Yael; MacArthur, Robert; Vasquez, Kimberly S; Moftah, Dena S; Vaughan, Roger D; Charytan, David M; Kost, Rhonda G; Tobin, Jonathan N
Background/UNASSIGNED:, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG. Methods/UNASSIGNED:or 135 ml/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to creatinine clearance. Results/UNASSIGNED:Serum creatinine values and hyperfiltration prevalence according to BSA-standardized eGFR were similar, 13%-15%, across body mass index (BMI) groups. The prevalence of hyperfiltration determined by absolute eGFR differed across BMI groups: underweight, 2%; normal weight, 6%; overweight, 17%; and obese, 31%. This trend paralleled the rise in creatinine clearance across BMI groups. Conclusions/UNASSIGNED:Absolute eGFR more readily identifies early ORG than the currently used formulae, which are adjusted to a standardized BSA and are not representative of current population BMI measures. Using absolute eGFR in clinical practice and research may improve the ability to identify, intervene, and reverse early ORG, which has great importance with increasing obesity rates.
PMCID:8967610
PMID: 35368563
ISSN: 2641-7650
CID: 5219382