Faculty Bibliography

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.

Introduction: Albuminuria is a strong risk factor for kidney disease progression and cardiovascular disease as reflected in the KDIGO categories of urinary ACR <30mg/g, 30-300 and >300 mg/g. The CREDENCE trial recruited participants with substantial levels of albuminuria. We examined the relative and absolute effects of canagliflozin according to baseline albuminuria among people in the CREDENCE trial.
Method(s): The CREDENCE double-blind randomised study of 4401 participants with eGFR 30-<90mL/min/1.73m² and urinary albumin:creatinine ratio [uACR]>300-5000mg/g, demonstrated that canagliflozin significantly reduced renal and cardiovascular outcomes including the primary composite of end-stage kidney disease, doubling serum creatinine, or renal or cardiovascular death. We analysed the effect of canagliflozin on these and renal safety outcomes according to categories of baseline uACR of <=1000, >1000-<3000 and >=3000mg/g.
Result(s): At baseline, 2348 (53.4%), 1547 (35.2%), and 506 (11.5%) participants had uACR <=1000, >1000-<3000, >=3000mg/g, respectively. Higher categories of uACR were associated with higher rates of events (Figure). Canagliflozin reduced renal and cardiovascular endpoints, with no statistical evidence the effect varied in different uACR groups (all p heterogeneity >0.17). Canagliflozin led to a greater absolute reduction in renal events in those with higher grades of uACR (number needed to treat [NTT] to prevent one episode of the primary composite: 22 and 8 for uACR >1000-<3000 and >=3000mg/g, respectively). Rates of renal-related adverse events were lower overall with canagliflozin, with greater relative reduction greater in higher grades of uACR (p heterogeneity=0.003). Canagliflozin had no significant effect on the individual events of acute kidney injury, volume depletion, hyperkalaemia, urinary tract infections or hypoglycaemia, with no differences among grades of uACR (all p heterogeneity >0.12).
Conclusion(s): Albuminuria predicts renal and cardiovascular risk at high levels of albuminuria. Canagliflozin safely reduces renal and cardiovascular events in people with type 2 diabetes and substantial albuminuria, with the greatest absolute renal benefit in those with albuminuria of 3000-5000mg/g. [Formula presented]
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BACKGROUND:Continuous renal replacement therapy (CRRT) is commonly employed in the intensive care unit (ICU), though there are no guidelines around the transition between CRRT and intermittent hemodialysis (iHD). Accelerated venovenous hemofiltration (AVVH) is a modality utilizing higher hemofiltration rates (4-5 L/h) with shorter session durations (8-10 h) to "accelerate" the clearance and volume removal that normally is spread out over a 24-h period in CRRT. We examined AVVH as a transition therapy between CRRT and iHD, with the aim of decreasing time on CRRT and providing a more graduated transition for hemodynamically unstable patients requiring RRT. METHODS:Retrospective cohort study describing the clinical outcomes and quality initiative experience of the integration of AVVH into the CRRT program at an academic tertiary care center. Outcomes of interest included mortality, ICU length of stay and readmission rates, and technical characteristics of treatments. RESULTS:In total, 97 patients received a total of 298 AVVH treatments (3.1 ± 3.3 treatments per patient). Totally, 271/298 (91%) treatments were completed successfully. During an average treatment time of 9.5 ± 1.6 h with 4.2 ± 0.5 L/h -replacement fluid rate, urea reduction ratio was 23 ± 26% per 10-h treatment, and net ultrafiltration volume was 2.4 ± 1.3 L/treatment. Inpatient mortality was 32%, mean total hospital length of stay was 54 ± 47 days. Sixty-four out of 97 (66%) patients recovered renal function by discharge. Among those who transferred out of the ICU, 7/62 (11%) patients required readmission to the ICU after developing hypotension on iHD. CONCLUSION/CONCLUSIONS:AVVH can serve as a transition therapy between CRRT and iHD in the ICU and has the potential to decrease total time on CRRT, improve patient mobility, and sustain low ICU readmission rates. Future study is needed to analyze the implications on resource use and cost of this modality.

Background: Cardiac dysfunction and cardiovascular (CV) events are prevalent among patients with chronic kidney disease (CKD) without overt obstructive coronary artery disease (CAD) but the mechanisms remain poorly understood. Coronary microvascular dysfunction (CMD) has been proposed as a link between abnormal renal function and impairment of cardiac function and CV events. We sought to investigate the relationships between CKD, CMD, cardiac dysfunction and adverse CV outcomes. Methods: Patients undergoing cardiac stress positron emission tomography (PET), echocardiogram and renal function ascertainment at Brigham and Women's Hospital were studied longitudinally. Patients free of overt coronary (summed stress score < 3 & without history of ischemic heart disease), valvular and end-organ disease were followed for adverse composite outcome of death, hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was determined from PET. Echocardiograms were used to measure cardiac mechanics: diastolic (lateral and septal E/e') and systolic [global longitudinal (GLS), radial (GRS) and circumferential strain (GCS)]. Image analyses and event adjudication were blinded. The associations between estimated glomerular filtration rate (eGFR), CFR, diastolic, systolic indices and adverse CV outcomes were assessed in adjusted models and mediation analyses. Results: 352 patients (median age 65 years, 63% women and 22% black) were studied. 35% of patients had eGFR<60 ml/min/1.73 m², median LVEF of 62% and median CFR of 1.8. eGFR and CFR were associated with diastolic and systolic indices, as well as future CV events (all p<0.05). In multivariable models, CFR but not eGFR was independently associated with cardiac mechanics and CV events. The associations between eGFR, cardiac mechanics and CV events were partly mediated via CFR. Conclusions: CMD but not eGFR was independently associated with abnormal cardiac mechanics and an increased risk of CV events. CMD may mediate the effect of CKD on abnormal cardiac function and CV events in those without overt CAD.

Traditional management of diabetes mellitus has focused on glycemic control, beginning with lifestyle changes, followed by metformin, and then other classes of antiglycemic agents.¹ Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular (CV) events, including CV death, myocardial infarction (MI) and heart failure, and slow progression of renal dysfunction, including prevention of end-stage kidney disease (ESKD).^2-3 Because initial clinical trials included mostly patients with baseline HbA1c >7%, current guidelines have recommended this class as add-on therapy for patients whose HbA1c is not at goal, typically ≥7%.¹ We hypothesized that there would be similar benefits on CV and renal endpoints regardless of baseline HbA1c, including those with HbA1c <7%.

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.

Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.We evaluated an observational cohort of 8,217 individuals with stage 3-5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20-1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16-1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21-1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.

BACKGROUND/AIMS/OBJECTIVE:Chronic kidney disease (CKD) is common among patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse clinical outcomes. This study aims to identify whether the association of CKD with HFpEF is independent of underlying echocardiographic abnormalities. MATERIALS/METHODS:We conducted a retrospective cohort study including patients without prevalent heart failure referred for echocardiography. Patients with serial echocardiograms, baseline left ventricular ejection fraction (LVEF) ≥50% and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were matched 1:1 with patients with eGFR <60 mL/min/1.73 m2 for age (±5 years), sex, history of hypertension or diabetes, use of renin-angiotensin inhibitors, and LVEF (±5%). A secondary analysis included patients with preserved LVEF and normal left ventricular mass index matched for the same parameters except use of renin-angiotensin inhibitors. RESULTS:Patients with CKD were at increased risk for HFpEF admission: crude hazard ratio (HR) 1.79 (95% confidence interval [CI] 1.38-2.32, p < 0.001) and adjusted HR (for coronary disease, loop diuretics, left atrial diameter) 1.64 (95% CI 1.22-2.21, p = 0.001). LVEF and left ventricular diameter decreased over time in both groups but no difference was observed in rate of dropping. Results were similar in the secondary analysis (crude HR 1.99, 95% CI 1.07-3.71, p = 0.03 and HR adjusted for left atrial diameter 1.98, 95% CI 1.05-3.75, p = 0.04). Rate of change was similar for LVEF, pulmonary artery pressure, and left ventricular mass index in both groups. CONCLUSION/CONCLUSIONS:CKD is independently associated with incident HFpEF despite a similar change in relevant echocardiographic parameters in patients with or without CKD.