Faculty Bibliography
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Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice
Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatment and placebo groups who had eGFR measured at both baseline and week three. The eGFR was categorized at week three as greater than a 10% decline; between 0 and 10% decline; and no decline. Long-term eGFR trajectories and safety outcomes were estimated in each category of acute eGFR change by linear mixed effects models and Cox regression after adjustment for baseline characteristics and medications use. Significantly more participants in the canagliflozin (45%) compared to the placebo (21%) group experienced an acute drop in eGFR over 10%. An over 30% drop occurred infrequently (4% of participants with canagliflozin and 2% with placebo). The odds ratio for a drop in eGFR over 10% with canagliflozin compared to placebo was significant at 3.03 (95% confidence interval 2.65, 3.47). Following the initial drop in eGFR, multivariable adjusted long-term eGFR trajectories, as well as overall and kidney safety profiles, in those treated with canagliflozin were similar across eGFR decline categories. Thus, although acute drops in eGFR over 10% occurred in nearly half of all participants following initiation of canagliflozin, the clinical benefit of canagliflozin was observed regardless. Additionally, safety outcomes were similar among subgroups of acute eGFR drop.
PMID: 33316282
ISSN: 1523-1755
CID: 4759462
An Exploratory Qualitative Study of Patient and Caregiver Perspectives of Ambulatory Kidney Palliative Care
OBJECTIVES/UNASSIGNED:The ideal clinical model to deliver palliative care to patients with advanced kidney disease is currently unknown. Internationally, ambulatory kidney palliative care clinics have emerged with positive outcomes, yet there is limited data from the United States (US). In this exploratory study we report perceptions of a US-based ambulatory kidney palliative care clinic from the perspective of patient and caregiver attendees. The objective of this study was to inform further improvement of our clinical program. METHODS/UNASSIGNED:Semi-structured interviews were conducted to elicit the patient and caregiver experience. Eleven interviews (8 patients with chronic kidney disease stage IV or V and 3 caregivers) were analyzed using qualitative description design. RESULTS/UNASSIGNED:We identified 2 themes: "Communication addressing the emotional and physical aspects of disease" and "Filling gaps in care"; Subthemes include perceived value in symptom management, assistance with coping with disease, engagement in advance care planning, program satisfaction and patient activation. SIGNIFICANCE OF RESULTS/UNASSIGNED:Qualitative analysis showed that attendees of an ambulatory kidney palliative care clinic found the clinic enhanced the management of their kidney disease and provided services that filled current gaps in their care. Shared experiences highlight the significant challenges of life with kidney disease and the possible benefits of palliative care for this population. Further study to determine the optimal model of care for kidney palliative care is needed. Inclusion of the patient and caregiver perspective will be essential in this development.
PMID: 33438435
ISSN: 1938-2715
CID: 4746812
Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19
Importance:Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective:To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants:The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures:Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures:Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results:Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance:Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
PMCID:7577201
PMID: 33080002
ISSN: 2168-6114
CID: 4683922
AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19
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.
PMID: 33067383
ISSN: 1533-3450
CID: 4642792
Management of Coronary Disease in Patients with Advanced Kidney Disease
BACKGROUND:Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS:We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS:At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS:Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
PMID: 32227756
ISSN: 1533-4406
CID: 5451232
Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York City
Background:The COVID-19 pandemic strained hospital resources in New York City, including those for providing dialysis. New York University Medical Center and affiliations, including New York City Health and Hospitals/Bellevue, developed a plan to offset the increased needs for KRT. We established acute peritoneal dialysis (PD) capability, as usual dialysis modalities were overwhelmed by COVID-19 AKI. Methods:Observational study of patients requiring KRT admitted to Bellevue Hospital during the COVID surge. Bellevue Hospital is one of the largest public hospitals in the United States, providing medical care to an underserved population. There were substantial staff, supplies, and equipment shortages. Adult patients admitted with AKI who required KRT were considered for PD. We rapidly established an acute PD program. A surgery team placed catheters at the bedside in the intensive care unit; a nephrology team delivered treatment. We provided an alternative to hemodialysis and continuous venovenous hemofiltration for treating patients in the intensive-care unit, demonstrating efficacy with outcomes comparable to standard care. Results:From April 8, 2020 to May 8, 2020, 39 catheters were placed into ten women and 29 men. By June 10, 39% of the patients started on PD recovered kidney function (average ages 56 years for men and 59.5 years for women); men and women who expired were an average 71.8 and 66.2 years old. No episodes of peritonitis were observed; there were nine incidents of minor leaking. Some patients were treated while ventilated in the prone position. Conclusions:Demand compelled us to utilize acute PD during the COVID-19 pandemic. Our experience is one of the largest recently reported in the United States of which we are aware. Acute PD provided lifesaving care to acutely ill patients when expanding current resources was impossible. Our experience may help other programs to avoid rationing dialysis treatments in health crises.
PMCID:8815539
PMID: 35372895
ISSN: 2641-7650
CID: 5219412
Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial
Background:Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown. Methods:., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E' velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography. Results:=0.19. Conclusions:ISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo.
PMCID:8815530
PMID: 35372900
ISSN: 2641-7650
CID: 5219422
Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York City
ORIGINAL:0015108
ISSN: n/a
CID: 4874982
Independent predictors of heart failure in patients with type 2 diabetes and chronic kidney disease: Modeling from the CREDENCE trial [Meeting Abstract]
Background: SGLT2 inhibitors have been shown to reduce hospitalization for heart failure (HHF). We sought to determine independent baseline predictors for HHF specifically in a population with type 2 diabetes and chronic kidney disease (CKD).
Method(s): CREDENCE randomized 4401 participants with type 2 diabetes and CKD to canagliflozin 100 mg versus placebo. We evaluated the baseline clinical and demographic factors using multivariate regression modeling to identify the independent predictors of HHF.
Result(s): Overall, 230 participants (89 canagliflozin; 141 placebo) had at least 1 HHF event. Canagliflozin reduced the incidence of HHF compared with placebo (4.0% vs 6.4%; HR 0.61; 95% CI 0.47-0.80). Participants with HHF events postrandomization were older (65.8 vs 62.9 y), and had a longer duration of diabetes (17.4 vs 15.7 y), higher prevalence of prior HF (30.4% vs 14.0%), higher urinary albumin:creatinine ratio (1347 vs 904 mg/g), lower estimated glomerular filtration rate (51.5 vs 56.4 mL/min/1.73m2), and higher prevalence of prior cardiovascular disease (65.7% vs 49.6%) compared to those without HHF. Independent predictors of HHF are shown in the Table.
Conclusion(s): HHF is common in patients with type 2 diabetes and CKD. Canagliflozin reduces HHF by 39% compared with placebo. Higher urinary albumin:creatinine ratio was the most potent predictor of HHF and should be part of patient risk assessment. (Table Presented)
Method(s): CREDENCE randomized 4401 participants with type 2 diabetes and CKD to canagliflozin 100 mg versus placebo. We evaluated the baseline clinical and demographic factors using multivariate regression modeling to identify the independent predictors of HHF.
Result(s): Overall, 230 participants (89 canagliflozin; 141 placebo) had at least 1 HHF event. Canagliflozin reduced the incidence of HHF compared with placebo (4.0% vs 6.4%; HR 0.61; 95% CI 0.47-0.80). Participants with HHF events postrandomization were older (65.8 vs 62.9 y), and had a longer duration of diabetes (17.4 vs 15.7 y), higher prevalence of prior HF (30.4% vs 14.0%), higher urinary albumin:creatinine ratio (1347 vs 904 mg/g), lower estimated glomerular filtration rate (51.5 vs 56.4 mL/min/1.73m2), and higher prevalence of prior cardiovascular disease (65.7% vs 49.6%) compared to those without HHF. Independent predictors of HHF are shown in the Table.
Conclusion(s): HHF is common in patients with type 2 diabetes and CKD. Canagliflozin reduces HHF by 39% compared with placebo. Higher urinary albumin:creatinine ratio was the most potent predictor of HHF and should be part of patient risk assessment. (Table Presented)
EMBASE:634164634
ISSN: 1522-9645
CID: 4811402
The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial [Meeting Abstract]
Background and aims: Individuals with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are at high risk for hospitalized heart failure (HHF) and these events are reduced by canagliflozin (CANA). We investigated whether the effect of CANA on HHF or cardiovascular (CV) death differs by key participant characteristics.
Material(s) and Method(s): CREDENCE randomized participants with T2DM and CKD to CANA or matching placebo. In this analysis, we assessed the effect of CANA on the prespecified secondary outcome of HHF/CV death by baseline characteristics. Hazard ratios (HRs) and 95% CIs were estimated with Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity.
Result(s): Of 4401 trial participants, 432 experienced a HHF/CV death event over a median follow-up of 2.6 years. Participants at higher risk included those with a history of CV disease or HF, lower eGFR, higher UACR and baseline use of loop diuretics. CANA reduced the risk of HHF/CV death by 31% in the overall population (HR 0.69, 95% CI 0.57, 0.83), with consistent effect across a broad range of participant subgroups including those at high risk (all Pinteraction>0.246; Figure). The effect of CANA on HHF alone (HR 0.61, 95% CI 0.47-0.80) was also similar across most key participant subgroups (all Pinteraction>0.10).
Conclusion(s): CANA consistently reduces the risk of HHF/CV death and of HHF in T2DM and CKD across a broad range of participant subgroups, including those with and without prior HF
Material(s) and Method(s): CREDENCE randomized participants with T2DM and CKD to CANA or matching placebo. In this analysis, we assessed the effect of CANA on the prespecified secondary outcome of HHF/CV death by baseline characteristics. Hazard ratios (HRs) and 95% CIs were estimated with Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity.
Result(s): Of 4401 trial participants, 432 experienced a HHF/CV death event over a median follow-up of 2.6 years. Participants at higher risk included those with a history of CV disease or HF, lower eGFR, higher UACR and baseline use of loop diuretics. CANA reduced the risk of HHF/CV death by 31% in the overall population (HR 0.69, 95% CI 0.57, 0.83), with consistent effect across a broad range of participant subgroups including those at high risk (all Pinteraction>0.246; Figure). The effect of CANA on HHF alone (HR 0.61, 95% CI 0.47-0.80) was also similar across most key participant subgroups (all Pinteraction>0.10).
Conclusion(s): CANA consistently reduces the risk of HHF/CV death and of HHF in T2DM and CKD across a broad range of participant subgroups, including those with and without prior HF
EMBASE:633995301
ISSN: 1432-0428
CID: 4774282
