Faculty Bibliography

In medicine, there are progresses which radically transform practices, change recommendations and win unanimous support in the medical community. There are some which divide, questioning principles that seemed established. There are also small advances, which can answer the questions that internists ask themselves in the daily care of their patients. Here are several articles published in 2017, read and commented for you by hospitalists, selected according to their impact on the medical world.

AIM/OBJECTIVE:This study aims to describe the variability of pre-dialysis troponin values in stable haemodialysis patients and compare the performance of single versus fluctuating or persistently elevated troponins in predicting a composite of mortality and cardiac arrest, myocardial infarction or stroke. METHODS:A total of 128 stable ambulatory chronic haemodialysis patients were enrolled. Pre-dialysis troponin I was measured for three consecutive months. The patients were followed for 1 year. A troponin elevation (>0.06 μg/L) was considered high risk, and patients were classified into three risk groups: (i) patients who had normal troponin levels on all three measurements; (ii) patients with at least one elevated and one normal troponin value; and (iii) patients with elevated troponin values on all measurements. RESULTS:A total of 81 patients had all three troponin values in the normal range; 29 had fluctuating values; 18 had all three values elevated. Twenty-seven deaths or composite events were observed: eight in the first risk group, 10 in the second and nine in the third. Persistently elevated and fluctuating troponin values were associated with higher mortality and cardiovascular event rate. Serial troponin measurement had a higher sensitivity for the composite outcome than single troponin measurement when either fluctuating or persistently elevated values were considered to confer high risk. CONCLUSION/CONCLUSIONS:Most haemodialysis patients do not have elevated troponin levels at baseline. Troponin levels that remain elevated or fluctuate are associated with worse outcomes. A serial troponin measurement strategy is associated with better sensitivity and higher negative predictive value compared with single troponin measurement.

BACKGROUND AND OBJECTIVES/OBJECTIVE:It is unknown whether echocardiographic parameters are independently associated with the cardiorenal syndrome. No direct comparison of the natural history of various cardiorenal syndrome types has been conducted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:Our retrospective cohort study enrolled adult patients with at least one transthoracic echocardiography between 2004 and 2014 at a single health care system. Information on comorbidities was extracted using condition-specific diagnostic codes. All-cause mortality was the primary outcome among patients with cardiorenal syndrome types 1-4. Myocardial infarction and stroke were the secondary outcomes. RESULTS:<0.001). Patients with acute cardiorenal syndrome and type 4 had increased risk of myocardial infarction and stroke compared with patients with CKD without cardiorenal syndrome. CONCLUSIONS:Up to 19% of patients with a chronic form of cardiorenal syndrome will subsequently develop an acute syndrome. Development of acute or type 4 cardiorenal syndrome is independently associated with mortality, the acute form having the worst prognosis.

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single-center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm³ in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post-transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High-risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18-3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52-1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16-2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97-2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.

AIMS OF THE STUDY/OBJECTIVE:The optimal timing of renal replacement therapy (RRT) initiation in acute kidney injury (AKI) remains a matter of debate. A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted to better estimate the effects of early initiation of RRT compared with late initiation of RRT among patients with AKI and in patients at risk for AKI. METHODS:A Medline literature research was conducted in PubMed for RCTs in adult patients with AKI that compared different RRT initiation strategies (early vs late). The meta-analysis outcomes were in-hospital or ≤60 day mortality, and renal recovery. RESULTS:Nine trials meeting inclusion criteria and four trials investigating preventive dialysis in patients at risk for AKI were identified. Early initiation of RRT was not associated with reduced in-hospital or 60-day mortality: risk ratio (RR) 0.91, 95% confidence interval (CI) 0.72-1.16, p = 0.46, I2 = 49%). When only the four trials that offered RRT within 6 to 12 hours of eligibility were included in the analysis, the results were similar (RR 0.93, 95% CI 0.82-1.06) without significant heterogeneity. The percentage of patients among survivors who recovered enough kidney function to be off dialysis was similar with early compared with late RRT: RR 1.02, 95% CI 0.99-1.06, p = 0.16. Early initiation of RRT was associated with higher incidence of catheter-related infections: RR 1.82, 95% CI 1.03-3.21, p = 0.04. No survival benefit was identified in patients undergoing preventive dialysis: RR 0.85 (95% CI 0.52-1.41, p = 0.54). CONCLUSIONS:Early RRT in patients with AKI (or at risk for AKI) does not appear to provide a significant reduction in mortality rates compared with late RRT. The data did not suggest any apparent impact on renal recovery with early dialysis.

PURPOSE OF REVIEW:This review article focuses on the most significant cardiovascular complications in dialysis patients [sudden cardiac death (SCD), acute coronary syndromes, heart failure, and atrial fibrillation]. RECENT FINDINGS:Current and ongoing research aims to quantify the rate and pattern of significant arrhythmia in dialysis patients and to determine the predominant mechanism of SCD. Preliminary findings from these studies suggest a high rate of atrial fibrillation and that bradycardia and asystole may be more frequent than ventricular arrhythmia as a cause of sudden death. A recently published matched cohort study in dialysis patients who received a defibrillator for primary prevention showed that there was no significant difference in mortality rates between defibrillator-treated patients and propensity-matched controls. Two randomized controlled trials are currently recruiting participants and will hopefully answer the question of whether implantable or wearable cardioverter defibrillators can prevent SCD. An observational study using United States Renal Data System data demonstrated how difficult it is to keep hemodialysis patients on warfarin, as more than two-thirds discontinued the drug during the first year. The ISCHEMIA-CKD trial may provide answers about the optimal strategy for the treatment of atherosclerotic coronary disease in patients with advanced chronic kidney disease. SUMMARY:The article reviews the diagnosis of acute coronary syndromes in dialysis patients, current literature on myocardial revascularization, and data on fatal and nonfatal cardiac arrhythmia. The new classification of heart failure in end-stage renal disease is reviewed. Finally, available cohort studies on warfarin for stroke prevention in dialysis patients with atrial fibrillation are reviewed.

OBJECTIVE:Diabetes mellitus is a well-established risk factor for atherosclerotic disease, but its role in the occurrence of venous thromboembolism (VTE) has not been elucidated. We conducted a meta-analysis of published cohort and case-control studies to assess whether diabetes mellitus is a risk factor for VTE. RESEARCH DESIGN AND METHODS/METHODS:We systematically searched MEDLINE and EMBASE for case-control and prospective cohort studies assessing association between the risk of venous thromboembolism and diabetes. Odds ratios (OR) from case-control studies were combined while for prospective studies hazard ratios (HR) were combined. Models with random effects were used. Meta-analyses were conducted separately for raw and adjusted measures of association. RESULTS:24 studies were identified including 10 cohort studies (274,501 patients) and 14 case-control studies (1,157,086 patients). Meta-analysis of the prospective cohort studies demonstrated a significant association between diabetes and VTE (HR 1.60; 95% CI 1.35 to 1.89). This association was no longer present after analysis of multi-adjusted HRs (HR 1.10; 95% CI 0.77 to 1.56). Meta-analysis of case-control studies showed a significant association between diabetes and VTE (OR 1.57; 95%CI 1.17 to 2.12), but this association was no longer present when adjusted ORs were used (OR 1.18; 95%CI 0.89 to 1.56). CONCLUSIONS:The increased risk of VTE associated with diabetes mainly results from confounders rather than an intrinsic effect of diabetes on venous thrombotic risk. Therefore, no specific recommendations should apply for the management of diabetic patients at risk for VTE.

BACKGROUND:An elevated troponin level is commonly found in asymptomatic patients on hemodialysis (HD) and is associated with higher risk of mortality and major adverse cardiovascular events. The underlying mechanism for the association between adverse outcomes and elevated troponin levels has not been elucidated. METHODS:Two hundred thirty-six stable chronic HD patients from 2 tertiary care centers were enrolled in this study. We measured pre-dialysis troponin I levels with routine monthly bloods for 3 consecutive months. Troponin I was considered to be elevated if it exceeded the laboratory reference range of 0.06 μg/l. RESULTS:The study population had a mean age of 67.5, 56% were male, 47% had diabetes and 28% had pre-existing coronary artery disease. Eighty-eight positive troponin values were recorded (13% of the available values) in 52 patients. In a repeated measures linear random effects model (univariate analysis), high ultrafiltration (UF), high inter-dialytic weight gain, and duration of the dialysis session, but not intra-dialytic hypotension, were associated with troponin I elevation. In the multivariate model, only high UF explained troponin I elevation (p = 0.04). The intraclass correlation coefficient was found to be 5.8%, suggesting that observed variability is within and not between subjects, with session-related parameters being more important than inter-individual differences. CONCLUSIONS:A high UF rate during HD is associated with a biochemical evidence of myocardial injury. If confirmed, efforts to avoid rapid UF, protect residual kidney function or minimize weight gain between sessions may impact cardiovascular outcomes in this high-risk population.