Faculty Bibliography

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.

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.
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INTRODUCTION/BACKGROUND:Obesity is more prevalent among African American individuals, increasing the risk for cardiorenal morbidity. We explored interactions between race, BMI, and the risk of hyperfiltration associated with obesity-related glomerulopathy (ORG). METHODS:We created a cohort of female adolescents from electronic health records. Glomerular filtration rate (GFR) was estimated in two ways: (A) using standard age recommended formulae and (B) absolute eGFR - adjusted to individual body surface area (BSA). Multivariate logistic regression was used to analyze the contribution of risk factors for ORG-associated hyperfiltration defined as 135 mL/min/1.73 m2 or 135 mL/min, according to BMI group. Pearson's coefficient was used to assess correlation with creatinine clearance (CrCl). RESULTS:The final cohort included 7,315 African American and 15,102 non-African American adolescent females, with CrCl available for internal validation in 207 non-African American and 107 African American individuals. Compared with non-African American ethnicity, African American ethnicity was independently associated with a lower risk of hyperfiltration with standard eGFR calculations (odds ratio [OR] = 0.57, 95% confidence intervals [CIs] 0.45-0.71), associations were enhanced for absolute eGFR (OR = 0.81, 95% CI 0.69-0.95). Absolute eGFR values agreed better with CrCl (r = 0.63), compared to standard indexed eGFR formulae. Proportions classified as hyperfiltration changed with standard versus absolute eGFR; they were similar across BMI groups with the first and reflected obesity with the later. CONCLUSION/CONCLUSIONS:Adjusting to individual BSA improves estimation of GFR and identification of obesity-related hyperfiltration. More accurate and earlier ascertainment of obesity-related hyperfiltration may have important consequences for preservation of kidney function.

BACKGROUND AND OBJECTIVES/OBJECTIVE:AKI is a common complication of coronavirus disease 2019 (COVID-19) and is associated with high mortality. Palliative care, a specialty that supports patients with serious illness, is valuable for these patients but is historically underutilized in AKI. The objectives of this paper are to describe the use of palliative care in patients with AKI and COVID-19 and their subsequent health care utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We conducted a retrospective analysis of New York University Langone Health electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. Regression models were used to examine characteristics associated with receiving a palliative care consult. RESULTS:=0.002). Despite greater use of palliative care, patients with AKI had a significantly longer length of stay, more intensive care unit admissions, and more use of mechanical ventilation. Those with AKI did have a higher frequency of discharges to inpatient hospice (6% versus 3%) and change in code status (34% versus 7%) than those without AKI. CONCLUSIONS:Palliative care was utilized more frequently for patients with AKI and COVID-19 than historically reported in AKI. Despite high mortality, consultation occurred late in the hospital course and was not associated with reduced initiation of life-sustaining interventions. PODCAST/UNASSIGNED:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_24_CJN11030821.mp3.

Background The myocardial cytoskeleton functions as the fundamental framework critical for organelle function, bioenergetics and myocardial remodeling. To date, impairment of the myocardial cytoskeleton occurring in the failing heart in patients with advanced chronic kidney disease has been largely undescribed. Methods and Results We conducted a 3-arm cross-sectional cohort study of explanted human heart tissues from patients who are dependent on hemodialysis (n=19), hypertension (n=10) with preserved renal function, and healthy controls (n=21). Left ventricular tissues were subjected to pathologic examination and next-generation RNA sequencing. Mechanistic and interference RNA studies utilizing in vitro human cardiac fibroblast models were performed. Left ventricular tissues from patients undergoing hemodialysis exhibited increased myocardial wall thickness and significantly greater fibrosis compared with hypertension patients (P<0.05) and control (P<0.01). Transcriptomic analysis revealed that the focal adhesion pathway was significantly enriched in hearts from patients undergoing hemodialysis. Hearts from patients undergoing hemodialysis exhibited dysregulated components of the focal adhesion pathway including reduced β-actin (P<0.01), β-tubulin (P<0.01), vimentin (P<0.05), and increased expression of vinculin (P<0.05) compared with controls. Cytoskeletal adaptations in hearts from the hemodialysis group were associated with impaired mitochondrial bioenergetics, including dysregulated mitochondrial dynamics and fusion, and loss of cell survival pathways. Mechanistic studies revealed that cytoskeletal changes can be driven by uremic and metabolic abnormalities of chronic kidney disease, in vitro. Furthermore, focal adhesion kinase silencing via interference RNA suppressed major cytoskeletal proteins synergistically with mineral stressors found in chronic kidney disease in vitro. Conclusions Myocardial failure in advanced chronic kidney disease is characterized by impairment of the cytoskeleton involving disruption of the focal adhesion pathway, mitochondrial failure, and loss of cell survival pathways.

AIM/OBJECTIVE:- Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. METHODS:- The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event. The effect of canagliflozin and predictors of neuropathy events were estimated using Cox regression analysis. In sensitivity analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, and non-autonomic neuropathy events. RESULTS:- Almost half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years of follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). Independent factors associated with higher risk of experiencing neuropathy events were non-white race, younger age, higher glycated haemoglobin and lower estimated glomerular filtration rate. The incidence of neuropathy events was similar in people randomized to canagliflozin and placebo (334/2202 vs. 323/2199; HR 1.04, 95% CI 0.89 to 1.21, P = 0.66). Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93, 95% CI 0.69 to 1.25, P = 0.63), diabetic neuropathy (HR 0.91, 95% CI 0.68 to 1.22, P = 0.52), or non-autonomic neuropathy (HR 1.03, 95% CI 0.87 to 1.21, P = 0.77). The lack of effect on neuropathy events was consistent in subgroup analyses. CONCLUSION/CONCLUSIONS:- Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. Future large randomized studies with prespecified neuropathy endpoints are required to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy.

RATIONALE AND OBJECTIVE/OBJECTIVE:Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN/METHODS:A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS/METHODS:4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS/METHODS:Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES/RESULTS:). RESULTS:, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS/CONCLUSIONS:Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION/CONCLUSIONS:Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.

BACKGROUND:Acute kidney injury (AKI) requiring kidney replacement therapy (KRT) is associated with high mortality and utilization. We evaluated the use of an AKI-Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes including mortality, hospital and ICU length of stay. METHODS:We conducted a 12-month controlled study in the ICUs of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a "sham" control form in 4-6-week blocks. The primary outcome was risk of inpatient mortality. Pre-specified secondary outcomes included 30-day mortality, 60-day mortality and hospital and ICU length of stay. Generalized estimating equations were used to estimate the impact of the AKI-SCAMP on mortality and length of stay. RESULTS:There were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% vs 47% control). AKI-SCAMP use was associated with significantly reduced ICU length of stay (mean 8 (95% CI 8-9) vs 12 (95% CI 10-13) days; p = <0.0001) and hospital length of stay (mean 25 (95% CI 22-29) vs 30 (95% CI 27-34) days; p = 0.02). Patients in the AKI-SCAMP group less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% vs 7%, p=0.003). CONCLUSIONS:Use of the AKI-SCAMP tool for AKI-KRT was not significantly associated with inpatient mortality but was associated with reduced ICU and hospital length of stay and use of KRT in cases of physician-perceived treatment futility.