Joe Bueti

Serum Creatinine Measurement Immediately After Cardiac Surgery and Prediction of Acute Kidney Injury

BACKGROUND After heart surgery, acute kidney injury (AKI) confers substantial long-term risk of death and chronic kidney disease. We hypothesized that small changes in serum creatinine (SCr) levels measured within a few hours of exit from the operating room could help discriminate those at low versus high risk of AKI. STUDY DESIGN Prospective cohort of 350 elective cardiac surgery patients (valve or coronary artery bypass grafting) recruited in Winnipeg, Canada. Baseline SCr level was obtained at the preoperative visit 2 weeks before surgery. The postoperative SCr level was drawn within 6 hours of completion of surgery and then daily while the patient was in the hospital. PREDICTOR Immediate (ie, <6 hours) postoperative SCr level change (ΔSCr), categorized as within 10% (reference), decrease >10%, or increase >10% relative to baseline. OUTCOME AKI, defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes) consensus definition as an increase in SCr level >0.3 mg/dL within 48 hours or >1.5 times baseline within 1 week. MEASUREMENTS We compared the C statistic of logistic models with and without inclusion of immediate postoperative ΔSCr. RESULTS After surgery, 176 patients (52%) experienced a decrease >10% in SCr level, 26 (7.4%) experienced an increase >10%, and 143 had ΔSCr within ±10% of baseline. During hospitalization, 53 (14%) developed AKI. Bypass pump time, baseline estimated glomerular filtration rate, and European System for Cardiac Operative Risk Evaluation (euroSCORE) were associated with AKI in a parsimonious base logistic model. Added to the base model, immediate postoperative ΔSCr was associated strongly with subsequent AKI and significantly improved model discrimination over the base model (C statistic, 0.78 [95% CI, 0.71-0.85] vs 0.69 [95% CI, 0.62-0.77]; P < 0.001). A ≥10% SCr level decrease predicted significantly lower AKI risk (OR, 0.37; 95% CI, 0.18-0.76), whereas a ≥10% SCr level increase predicted significantly higher (OR, 6.38; 95% CI, 2.37-17.2) AKI risk compared with the reference category. LIMITATIONS We used a surrogate marker of AKI. External validation of our results is warranted. CONCLUSION In elective cardiac surgery patients, measurement of immediate postoperative ΔSCr improves prediction of AKI.

Outcomes of Chronic Dialysis Patients Admitted to the Intensive Care Unit

Admission rates and outcomes of patients who have ESRD and are admitted to an intensive care unit (ICU) are not well defined. We conducted a historical cohort study using a prospective regional ICU database that captured all 11 adult ICUs in Winnipeg, Canada. Between 2000 and 2006, there were 34,965 total admissions to the ICU, 1173 (3.4%) of which were patients with ESRD. The main admission diagnoses among patients with ESRD were cardiac disease (31%), sepsis (15%), and arrest (10%). Compared with other patients in the ICU, those with ESRD were significantly younger but had more diabetes, peripheral arterial disease, and higher APACHE II (Acute Physiology and Chronic Health Evaluation II) scores; mean length of stay in the ICU was similar, however, between these two groups. Restricting the analysis to first admissions to the ICU, unadjusted in-hospital mortality was higher for patients with ESRD (16 versus 11%; P < 0.0001), but this difference did not persist after adjustment for baseline illness severity. In conclusion, although ESRD associates with increased mortality among patients who are admitted to the ICU, this effect is mostly a result of comorbidity.

Acute kidney injury in critically ill patients infected with 2009 pandemic influenza A(H1N1): report from a Canadian Province.

Background 2009 pandemic influenza A(H1N1) has led to a global increase in severe respiratory illness. Little is known about kidney outcomes and dialytic requirements in critically ill patients infected with pandemic H1N1. Study Design Prospective observational study. Setting & Participants 50 patients with pandemic H1N1 admitted to any of 7 intensive care units in Manitoba, Canada, were prospectively followed. Outcome & Measurements Outcomes were kidney injury and kidney failure defined using RIFLE (risk, injury, failure, loss, end-stage disease) criteria or need for dialysis therapy. Results The pandemic H1N1 group was composed of 50 critically ill patients with pandemic H1N1 with severe respiratory syndrome (47 confirmed cases, 3 probable). Kidney injury, kidney failure, and need for dialysis occurred in 66.7%, 66%, and 11% of patients, respectively. Mortality was 16%. Kidney failure was associated with increased death (OR, 11.29; 95% CI, 1.29-98.9), whereas the need for dialysis was associated with an increase in length of stay (RR, 2.38; 95% CI, 2.13-25.75). Limitations Small population studied from single Canadian province; thus, limited generalizability. Conclusions In critically ill patients with pandemic H1N1, kidney injury, kidney failure, and the need for dialysis are common and associated with an increase in mortality and length of intensive care unit stay.

Long-term outcomes of end-stage renal disease patients admitted to the ICU

BACKGROUND End-stage renal disease (ESRD) patients admitted to the intensive care unit (ICU) have poor survival and high rates of readmission; however, little evidence exists on long-term outcomes. We set out to investigate the long-term (6 and 12 months) survival of ESRD patients admitted to the ICU and whether differential survival could be explained by dialysis modality and vascular access. METHODS We compared the admission characteristics, outcomes and readmission rates of 619 ESRD [95 peritoneal dialysis (PD), 334 hemodialysis with a catheter (HD CVC), 190 hemodialysis with an AV fistula (HD AVF)] patients admitted to 11 ICUs in Winnipeg, Manitoba, Canada. Parametric and nonparametric tests were used as appropriate to determine differences in baseline characteristics. Multivariable Cox and logistic regression was used to assess outcomes between the groups. RESULTS The 6- and 12-month crude survival was 62 and 52%, respectively. In a univariate model, modality and vascular access were associated with an increased hazard ratio (HR) of death [PD HR 1.60 95% confidence interval (CI) 1.20-2.13, HD CVC HR 1.55 95% CI 1.25-1.93] compared to patients on HD with an AVF. In three different multivariate adjusted models, this association persisted with HRs for death of 1.63-1.75 for PD and 1.50-1.58 for HD CVC. CONCLUSIONS Overall long-term survival of ESRD patients after admission to the ICU is poor. Being on PD or being dialyzed with a catheter was independently associated with an increased mortality.

Underutilization of peritoneal dialysis: the role of the nephrologist's referral pattern

BACKGROUND The incidence of end-stage renal disease is increasing, placing a tremendous burden on health care resources. Peritoneal dialysis (PD) is cheaper than hemodialysis and has many potential advantages and few contraindications as an initial modality selection. This study examined differences in patient PD attempt rates between nephrologists using technique survival and mortality as outcomes. METHODS We performed a retrospective review of the Manitoba Renal Program databases from January 2004 to January 2010. Analysis of 630 patients who commenced dialysis and had demographic data available was performed. A genetic matching algorithm was used to balance potential differences between patient characteristics. Each nephrologist was then compared against their peers to calculate a PD attempt rate. The highest attempt rate group was compared with the lowest. RESULTS When comparing PD attempt rates between groups, all the results were significant. PD technique survival at >90 days showed no significant differences (P = 0.42). Patient mortality at >90 days was also not significant when comparing groups (P = 0.14). CONCLUSIONS Our data suggest that when comparing the low- with high-attempt groups, the factors limiting PD utilization do not include on-site availability of PD, case mix, funding, patient location or reimbursement. Aggressive approaches of starting more patients on PD did not lead to lower technique survival or higher mortality rates. If the PD attempt rate was maximized, a significant amount of money and resources could be saved or directed toward helping a larger population without significant harm to patients.

The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial

BACKGROUND AND OBJECTIVES Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events. RESULTS Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, -4.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons >10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level >6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP. CONCLUSION Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis.

The Role of Functional Status in Discharge to Assisted Care Facilities and In-Hospital Death Among Dialysis Patients

BACKGROUND Functional status is an important component in the assessment of hospitalized patients. We set out to determine the scope, severity, and prognostic significance of impaired functional status in acutely hospitalized dialysis patients. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 1,286 hospitalized dialysis patients admitted and discharged from 1 of 11 area hospitals in Manitoba, Canada, from September 2003 to September 2010 with an activity of daily living (ADL) assessment within 24 hours of admission. PREDICTOR The 12-point ADL score assesses 6 domains (bathing, toileting, dressing, incontinence, feeding, and transferring) and scores them as independent or supervision only (score, 0), partial assistance (1), and full assistance (2). Thus, higher score indicates worse functional status. Parametric and nonparametric tests were used as appropriate to determine differences in baseline characteristics. OUTCOMES Multivariable logistic regression and Cox proportional hazards assessed the association between functional status, in-hospital death, and discharge to an assisted care facility. RESULTS During the study period, 250 (19.4%) and 72 (5.6%) patients experienced the outcomes of in-hospital death or discharge to an assisted care facility. Abnormalities in functional status were present in >70% of the cohort. ADL score within 24 hours of admission combined with age differentiated risks of death and discharge to an assisted care facility home, ranging from 4.8%-46.6% and 0.6%-17.8%, respectively. After adjustment, ORs of death and discharge to an assisted care facility were 1.16 (95% CI, 1.11-1.22; P < 0.001; C statistic = 0.79) and 1.25 (95% CI, 1.14-1.36; P < 0.001; C statistic = 0.91) per 1-point increase in ADL score, respectively. Findings were consistent after accounting for the competing outcomes of in-hospital death or discharge to an assisted care facility versus discharge to home. LIMITATIONS A 1-time measurement of ADLs could not differentiate temporary from long-term deterioration in functional status. CONCLUSIONS Impaired functional status is common at the time of admission in the dialysis population. A single ADL score measurement at admission combined with age is highly predictive of poor outcomes in the hospitalized dialysis population.

The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis

BACKGROUND Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). STUDY DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. SELECTION CRITERIA FOR STUDIES Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. INTERVENTION Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). OUTCOMES Cardiovascular and all-cause mortality, hyperkalemia, serum potassium level, hypotension, change in blood pressure, and gynecomastia. RESULTS We identified 9 trials including 829 patients. The overall quality of evidence was low due to methodologic limitations in most of the included trials. The relative risk (RR) for cardiovascular mortality was 0.34 (95% CI, 0.15-0.75) for MRA-treated compared with control patients. The RR for all-cause mortality was 0.40 (95% CI, 0.23-0.69). The RR for hyperkalemia for MRA treatment was 3.05 (95% CI, 1.21-7.70). Sensitivity analyses demonstrated wide variability in RRs for cardiovascular mortality, all-cause mortality, and hyperkalemia, suggesting further uncertainty in the confidence of the primary results. LIMITATIONS Trial quality and size insufficient to robustly and precisely identify a treatment effect. CONCLUSIONS Given the uncertainty of both the benefits and harms of MRAs in dialysis, large high-quality trials are required.

Thrice weekly warfarin administration in haemodialysis patients

BACKGROUND Medication adherence in haemodialysis patients is often challenging due to a high pill burden, complex and dynamic medication regimens and limited patient self-interest in care. The purpose of this study was to investigate the time within target INR and safety profile of thrice weekly warfarin administration in haemodialysis patients with a clinical indication for anticoagulation and documented nonadherence to medications. METHODS Thirty-seven patients from two haemodialysis units in Winnipeg, Manitoba, Canada, were recruited, and 17 patients were treated with thrice weekly warfarin and compared to 20 patients treated with daily warfarin therapy. The patients were followed for 1 year with weekly international normalized ratio (INR), dosage and adverse events recorded. The primary outcome was percentage of time with INR in target and sub (<1.5)- and supra (>4)-therapeutic INR. Adverse events were recorded in the two groups. RESULTS The thrice weekly group had a higher burden of comorbidity (Charlson comorbidity index of 6.35 +/- 1.77 versus 4.55 +/- 1.64, P = 0.003) compared to the daily dosage group. In the thrice weekly dosage group, time within target INR was higher (56.9 versus 49.3%, P = 0.008), and time with supra-therapeutic INR > 4 lower (2.7 versus 4.3%, P = 0.03). Total bleeding events (7 versus 6) and major bleeding events (3 versus 2 events) were similar between the two groups. CONCLUSION In this pilot study, thrice weekly warfarin appears to be a safe and feasible dosing strategy in a select patient population. A randomized controlled trial of thrice weekly warfarin is warranted.

End-stage renal disease status and critical illness in the elderly.

BACKGROUND AND OBJECTIVES Elderly patients (> 65 years old) are a rapidly growing demographic in the ESRD and intensive care unit (ICU) populations, yet the effect of ESRD status on critical illness in elderly patients remains unknown. Reliable estimates of prognosis would help to inform care and management of this frail and vulnerable population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The effect of ESRD status on survival and readmission rates was examined in a retrospective cohort of 14,650 elderly patients (>65 years old) admitted to 11 ICUs in Winnipeg, Manitoba, Canada between 2000 and 2006. Logistic regression models were used to adjust odds of mortality and readmission to ICU for baseline case mix and illness severity. RESULTS Elderly ESRD patients had twofold higher crude in-hospital mortality (22% versus 13%, P < 0.0001) and readmission rate (6.4 versus 2.7%, P = 0.001). After adjustment for illness severity alone or illness severity and case mix, the odds ratio for mortality decreased to 0.85 (95% CI: 0.57 to 1.25) and 0.82 (95% CI: 0.55 to 1.23), respectively. In contrast, ESRD status remained significantly associated with readmission to ICU after adjustment for other risk factors (OR 2.06 [95% CI: 1.32, 3.22]). CONCLUSIONS Illness severity on admission, rather than ESRD status per se, appears to be the main driver of in-hospital mortality in elderly patients. However, ESRD status is an independent risk factor for early and late readmission, suggesting that this population might benefit from alternative strategies for ICU discharge.