Faculty Bibliography
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241
Long-term outcomes of patients with stable coronary disease and chronic kidney dysfunction: 10-year follow-up of the Medicine, Angioplasty, or Surgery Study II Trial
Background/UNASSIGNED:Chronic kidney disease (CKD) is associated with a worse prognosis in patients with stable coronary artery disease (CAD); however, there is limited randomized data on long-term outcomes of CAD therapies in these patients. We evaluated long-term outcomes of CKD patients with CAD who underwent randomized therapy with medical treatment (MT) alone, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). Methods/UNASSIGNED:Baseline estimated glomerular filtration rate (eGFR) was obtained in 611 patients randomized to one of three therapeutic strategies in the Medicine, Angioplasty, or Surgery Study II trial. Patients were categorized in preserved renal function and mild or moderate CKD groups depending on their eGFR (≥90, 89-60 and 59-30 mL/min/1.73 m2, respectively). The primary clinical endpoint, a composite of overall death and myocardial infarction, and its individual components were analyzed using proportional hazards regression (Clinical Trial registration information: http://www.controlled-trials.com. Registration number: ISRCTN66068876). Results/UNASSIGNED:Of 611 patients, 112 (18%) had preserved eGFR, 349 (57%) mild dysfunction and 150 (25%) moderate dysfunction. The primary endpoint occurred in 29.5, 32.4 and 44.7% (P = 0.02) for preserved eGFR, mild CKD and moderate CKD, respectively. Overall mortality incidence was 18.7, 23.8 and 39.3% for preserved eGFR, mild CKD and moderate CKD, respectively (P = 0.001). For preserved eGFR, there was no significant difference in outcomes between therapies. For mild CKD, the primary event rate was 29.4% for PCI, 29.1% for CABG and 41.1% for MT (P = 0.006) [adjusted hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.07-0.88; P = 0.03 for PCI versus MT; and adjusted HR = 0.48; 95% CI 0.31-0.76; P = 0.002 for CABG versus MT]. We also observed higher mortality rates in the MT group (28.6%) compared with PCI (24.1%) and CABG (19.0%) groups (P = 0.015) among mild CKD subjects (adjusted HR = 0.44, 95% CI 0.25-0.76; P = 0.003 for CABG versus MT; adjusted HR = 0.56, 95% CI 0.07-4.28; P = 0.58 for PCI versus MT). Results were similar with moderate CKD group but did not achieve significance. Conclusions/UNASSIGNED:Coronary interventional therapy, both PCI and CABG, is associated with lower rates of events compared with MT in mild CKD patients >10 years of follow-up. More study is needed to confirm these benefits in moderate CKD.
PMID: 30590726
ISSN: 1460-2385
CID: 3780082
Hemodialysis international. International Symposium on Home Hemodialysis. 2020:24(3):330-334.DOI: 10.1111/hdi.12834
Serum glucose and phosphorus concentrations during continuous renal replacement therapy using commercial replacement solutions with or without phosphorus
INTRODUCTION/BACKGROUND:Continuous venovenous hemofiltration (CVVH) is a common practice in the intensive care unit often associated with electrolyte derangements. Recently, our institution added a phosphate dialysis solution, Phoxillum®, to our formulary as an option for CVVH fluid in addition to the bicarbonate-based Prismasol® products available. We sought to evaluate the impact of Phoxillum in patients who required CVVH when compared to Prismasol with regard to phosphate and glucose management. METHODS:This was a single-center, retrospective, observational cohort analysis approved by Partners Health Care System Institutional Review Board that included patients who received a minimum of 24 hours of either Prismasol 4/2.5 or Phoxillum for CVVH from February 2017 to November 2017. Phosphate and glucose levels were monitored daily while on CVVH. Prevalence of hypoglycemia (glucose <70 mg/dL), hyperglycemia (glucose >180 mg/dL), hypophosphatemia (phosphate <2.5 mg/dL), and hyperphosphatemia (phosphate >4.3 mg/dL) were collected in terms of days of occurrence while on CVVH. Oral and intravenous phosphate repletion requirements were collected for all patients. FINDINGS/RESULTS:Hypophosphatemia occurred more frequently while patients were receiving Prismasol as compared to Phoxillum (130 [24.9%] vs. 13 [6.2%], rate ratio [RR] 0.20 [95% confidence interval-CI = 0.10-0.42, P < 0.0001]), and consequently there was a numerically lower need for intravenous phosphorous repletion in the Phoxillum group (RR = 0.58, 95% CI [0.26, 1.30], P = 0.19]. There was a numerically higher incidence of hyperphosphatemia while patients were on Phoxillum therapy as compared to Prismasol (78 [37%] vs. 145 [27.7%], RR 1.25 [95% CI = 0.84, 1.86, P = 0.27]). There was no difference between the Phoxillum and Prismasol groups in terms of hypoglycemia or hyperglycemia. There was no notable difference in the cost found between the two therapies. DISCUSSION/CONCLUSIONS:The findings suggest that the use of Phoxillum for CVVH may be associated with decreased incidence of hypophosphatemia and a potentially decreased need for phosphate repletion in patients who require CVVH.
PMID: 32351011
ISSN: 1542-4758
CID: 4427702
Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series
Background/UNASSIGNED:There is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights. Methods/UNASSIGNED:We present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center. Findings/UNASSIGNED: = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing. Interpretation/UNASSIGNED:In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis. Funding/UNASSIGNED:None.
PMCID:7316051
PMID: 32766543
ISSN: 2589-5370
CID: 4555682
Clinical journal of the American Society of Nephrology : CJASN. 2020:15(6):880-882.DOI: 10.2215/CJN.05180420
Impending Shortages of Kidney Replacement Therapy for COVID-19 Patients
PMID: 32345750
ISSN: 1555-905x
CID: 4412262
Clinical journal of the American Society of Nephrology : CJASN. 2020:15(6):805-812.DOI: 10.2215/CJN.06810619
Intradialytic Hypotension and Cardiac Arrhythmias in Patients Undergoing Maintenance Hemodialysis: Results from the Monitoring in Dialysis Study
BACKGROUND AND OBJECTIVES/OBJECTIVE:Patients receiving maintenance hemodialysis (HD) have a high incidence of cardiac events, including arrhythmia and sudden death. Intradialytic hypotension (IDH) is a common complication of HD and is associated with development of reduced myocardial perfusion, a potential risk factor for arrhythmia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:(decline in systolic BP 0-20 mm Hg from predialysis systolic BP) with clinically significant arrhythmia (bradycardia≤40 bpm for ≥6 seconds, asystole≥3 seconds, ventricular tachycardia ≥130 bpm for ≥30 seconds, or patient-marked events) during HD. RESULTS:was associated with a seven-fold higher rate (incidence rate ratio, 7.2; 95% confidence interval, 2.1 to 25.4). CONCLUSIONS:IDH is common in patients on maintenance HD and is associated with a greater risk of developing intradialytic clinically significant arrhythmia.
PMID: 32381584
ISSN: 1555-905x
CID: 4437292
Canagliflozin and risk of skin and soft tissue infections in people with diabetes mellitus and kidney disease-a post-hoc analysis of the credence trial [Meeting Abstract]
Background and Aims: The skin's hypertonic microenvironment has a hypothesized protective antimicrobial function that may be disrupted by SGLT2i. The association between sodiumglucose cotransporter inhibitors (SGLT2i) and genital mycotic infections is well established, but it is not known if these agents increase the risk of other skin and soft tissue infections (SSTI).We aimed to describe SSTI in the CREDENCE trial, and determine whether canagliflozin affects the risk of skin and soft tissue infections (SSTIs) overall and in subgroups.
Method(s): We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Infections reported as adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with a sensitivity analysis conducted in the intention-to-treat population. Univariable time-to first-event regression models were assessed.
Result(s): Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious. Drug was continued in 290/373 (78%) of first events, with similar frequency of subsequent events between groups (31/133 (23%) and 33/157 (21%) for those continuing canagliflozin and placebo respectively). In both cases of necrotising fasciitis, drug was withdrawn and the participants recovered.Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11) (Figure 1). Results were similar in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33), and in the predefined subgroups.
Conclusion(s): Although other studies suggest that SGLT2i may reduce the sodium content of the skin, we found that canagliflozin does not increase the risk of skin and soft tissue infections, overall or in any subgroup, in people with type 2 diabetes mellitus and albuminuric chronic kidney disease. (Figure Presented)
Method(s): We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Infections reported as adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with a sensitivity analysis conducted in the intention-to-treat population. Univariable time-to first-event regression models were assessed.
Result(s): Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious. Drug was continued in 290/373 (78%) of first events, with similar frequency of subsequent events between groups (31/133 (23%) and 33/157 (21%) for those continuing canagliflozin and placebo respectively). In both cases of necrotising fasciitis, drug was withdrawn and the participants recovered.Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11) (Figure 1). Results were similar in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33), and in the predefined subgroups.
Conclusion(s): Although other studies suggest that SGLT2i may reduce the sodium content of the skin, we found that canagliflozin does not increase the risk of skin and soft tissue infections, overall or in any subgroup, in people with type 2 diabetes mellitus and albuminuric chronic kidney disease. (Figure Presented)
EMBASE:633422527
ISSN: 1460-2385
CID: 4694872
Canagliflozin and risk of genital infections and urinary tract infections in people with diabetes mellitus and kidney disease-a post-hoc analysis of the credence trial [Meeting Abstract]
Background and Aims: To describe genital mycotic infections (GMI) and urinary tract infections (UTI) in the CREDENCE trial, determine whether canagliflozin increased the risk of these infections overall and in subgroups, and describe predictors of risk for genital mycotic infections.
Method(s): The CREDENCE trial randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to canagliflozin 100mg daily or placebo. We analysed the risk of GMI and UTI with canagliflozin compared to placebo overall and in patient subgroups. The primary analysis was conducted in the on-treatment population, as the more conservative approach with sensitivity analyses conducted using an intention-to-treat population. When canagliflozin increased risk, we determined patient risk factors for GMIs using multivariable Cox regression models adjusting for age, gender, race, markers of disease severity (body mass index (BMI), haemoglobin A1c, diabetes duration, other glucose lowering medications at baseline and kidney function).
Result(s): Overall 31/2905 (1.1%) men and 32/1492 (2.1%) women experienced 91 GMIs and 166/2905 (5.7%) men and 300/1492 (20.1%) women experienced 669 UTIs. Canagliflozin increased the risk of GMI (HR 3.83 [95% CI 2.08-7.06] p<0.0001). The hazard ratio for canagliflozin compared to placebo was consistent across most subgroups, though the risk with canagliflozin was greater in those with a higher BMI (HR 5.91 [95% CI 2.65-13.15] for BMI >=30 kg/m2 vs HR 1.36 [95% CI 0.47-3.92] for BMI<30 kg/m2, p interaction=0.03) and was higher in men (HR 9.30 [95% CI 2.83-30.60] vs HR 2.10 [95% CI 1.00-4.45] for men and women respectively, p interaction= 0.04). In those who were randomised to canagliflozin, independent risk factors for GMI were higher BMI (HR 1.53 [95% CI 1.29-1.83] per 5 units p<0.0001) and longer diabetes duration (HR 1.18 [95% CI 1.01-1.40] per 5 years p=0.04). Canagliflozin did not affect the risk of UTI over placebo (HR 1.08 [95% CI 0.90-1.29] p=0.42) overall or in any subgroup, however risk was higher in women (HR 1.23 [95% CI 0.98-1.54] vs HR 0.82 [0.60-1.11] for women and men respectively, p interaction=0.04).58/669 (8.7%) UTIs but no GMIs were reported as serious. Drug was continued in 56/63 (89%) of first GMIs, with similar frequency of subsequentGMI in those continuing on canagliflozin (13/43, 30.2%) or placebo (4/13, 30.8%). Drug was continued in 385/466 (82.6%) first UTIs, with similar frequency of subsequent UTIs in those continuing on cangliflozin (50/199 (25.1%) or placebo 49/186 (26.3%). All findings were similar when conducted using an intention-to-treat approach.
Conclusion(s): Canagliflozin increased the risk of genital mycotic infections but not urinary tract infections. The risk of genital mycotic infections from canagliflozin over placebo was higher in men and those with higher BMI. In those treated with canagliflozin, higher BMI and longer diabetes duration independently predicted infection. Most participants continued treatment following their first infection with similar recurrence rates in the canagliflozin and placebo groups.These findings will be useful in clinical care, and help identify those at greatest risk for genital infections with canagliflozin treatment
Method(s): The CREDENCE trial randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to canagliflozin 100mg daily or placebo. We analysed the risk of GMI and UTI with canagliflozin compared to placebo overall and in patient subgroups. The primary analysis was conducted in the on-treatment population, as the more conservative approach with sensitivity analyses conducted using an intention-to-treat population. When canagliflozin increased risk, we determined patient risk factors for GMIs using multivariable Cox regression models adjusting for age, gender, race, markers of disease severity (body mass index (BMI), haemoglobin A1c, diabetes duration, other glucose lowering medications at baseline and kidney function).
Result(s): Overall 31/2905 (1.1%) men and 32/1492 (2.1%) women experienced 91 GMIs and 166/2905 (5.7%) men and 300/1492 (20.1%) women experienced 669 UTIs. Canagliflozin increased the risk of GMI (HR 3.83 [95% CI 2.08-7.06] p<0.0001). The hazard ratio for canagliflozin compared to placebo was consistent across most subgroups, though the risk with canagliflozin was greater in those with a higher BMI (HR 5.91 [95% CI 2.65-13.15] for BMI >=30 kg/m2 vs HR 1.36 [95% CI 0.47-3.92] for BMI<30 kg/m2, p interaction=0.03) and was higher in men (HR 9.30 [95% CI 2.83-30.60] vs HR 2.10 [95% CI 1.00-4.45] for men and women respectively, p interaction= 0.04). In those who were randomised to canagliflozin, independent risk factors for GMI were higher BMI (HR 1.53 [95% CI 1.29-1.83] per 5 units p<0.0001) and longer diabetes duration (HR 1.18 [95% CI 1.01-1.40] per 5 years p=0.04). Canagliflozin did not affect the risk of UTI over placebo (HR 1.08 [95% CI 0.90-1.29] p=0.42) overall or in any subgroup, however risk was higher in women (HR 1.23 [95% CI 0.98-1.54] vs HR 0.82 [0.60-1.11] for women and men respectively, p interaction=0.04).58/669 (8.7%) UTIs but no GMIs were reported as serious. Drug was continued in 56/63 (89%) of first GMIs, with similar frequency of subsequentGMI in those continuing on canagliflozin (13/43, 30.2%) or placebo (4/13, 30.8%). Drug was continued in 385/466 (82.6%) first UTIs, with similar frequency of subsequent UTIs in those continuing on cangliflozin (50/199 (25.1%) or placebo 49/186 (26.3%). All findings were similar when conducted using an intention-to-treat approach.
Conclusion(s): Canagliflozin increased the risk of genital mycotic infections but not urinary tract infections. The risk of genital mycotic infections from canagliflozin over placebo was higher in men and those with higher BMI. In those treated with canagliflozin, higher BMI and longer diabetes duration independently predicted infection. Most participants continued treatment following their first infection with similar recurrence rates in the canagliflozin and placebo groups.These findings will be useful in clinical care, and help identify those at greatest risk for genital infections with canagliflozin treatment
EMBASE:633422365
ISSN: 1460-2385
CID: 4694882
Oxalate Nephropathy in an Oxalobacter formigenes-Negative Subject [Case Report]
PMCID:7210700
PMID: 32405600
ISSN: 2468-0249
CID: 4431442
Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial
BACKGROUND:Canagliflozin reduced renal and cardiovascular events in people with type 2 diabetes in the CREDENCE trial. We assessed efficacy and safety of canagliflozin by initial estimated glomerular filtration rate (eGFR). METHODS:) and linear mixed effects models to analyze the effects on eGFR slope. RESULTS:). CONCLUSIONS:. Absolute benefits for renal outcomes were greatest in subgroups with lower eGFR. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER/UNASSIGNED:Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), NCT02065791.
PMID: 32354987
ISSN: 1533-3450
CID: 4438642
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
