Amy W. Williams

Acute decompensated heart failure and the cardiorenal syndrome.

Heart failure is one of the leading causes of hospitalizations in the United States. Concomitant and significant renal dysfunction is common in patients with heart failure. Increasingly, the syndrome of heart failure is one of cardiorenal failure, in which concomitant cardiac and renal dysfunctions exist, with each accelerating the progression of the other. One fourth of patients hospitalized for the treatment of acute decompensated heart failure will experience significant worsening of renal function, which is associated with worse outcomes. It remains unclear whether worsening renal function specifically contributes to poor outcomes or whether it is merely a marker of advanced cardiac and renal dysfunction. Diuretic resistance, with or without worsening renal function, is also common in acute decompensated heart failure, although the definition of diuretic resistance, its prevalence, and prognostic implications are less well defined. The term cardiorenal syndrome has been variably associated with cardiorenal failure, worsening renal function, and diuretic resistance but is more comprehensively defined as a state of advanced cardiorenal dysregulation manifest by one or all of these specific features. The pathophysiology of the cardiorenal syndrome is poorly understood and likely involves interrelated hemodynamic and neurohormonal mechanisms. When conventional therapy for acute decompensated heart failure fails, mechanical fluid removal via ultrafiltration, hemofiltration, or hemodialysis may be needed for refractory volume overload. While ultrafiltration can address diuretic resistance, whether ultrafiltration prevents worsening renal function or improves outcomes in patients with cardiorenal syndrome remains unclear. Evidence regarding the potential renal-preserving effects of nesiritide is mixed, and further studies on the efficacy and safety of different doses of nesiritide in heart failure therapy are warranted. Newer therapeutic agents, including vasopressin antagonists and adenosine antagonists, hold promise for the future, and clinical trials of these agents are underway.

Mortality Associated With Nephropathy After Radiographic Contrast Exposure

OBJECTIVE To define outcomes from contrast-induced nephropathy (CIN) after both intra-arterial and intravenous administration of contrast medium. PATIENTS AND METHODS We performed a retrospective case-matched cohort study at Mayo Clinics site in Rochester, MN, from April 1, 2004, to March 31, 2006. All contrast procedures were evaluated for inclusion. Contrast-induced nephropathy was defined as creatinine elevation of 25% or more after contrast exposure or of more than 0.5 mg/dL within 7 days of contrast exposure. Cases of CIN were matched 1:3 with controls by age, sex, pre-procedure creatinine elevation, diabetes mellitus, and type of imaging procedure. RESULTS A total of 809 patients who developed CIN were matched to 2427 patients who did not develop CIN after contrast exposure. In multivariate analyses, CIN was significantly associated with 30-day mortality (odds ratio, 3.37; 95% confidence interval [CI], 2.58-4.41; P<.001) and overall mortality (hazard ratio, 1.57; 95% CI, 1.32-1.86; P<.001) after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. Intravenous contrast administration was a risk factor for 30-day mortality (odds ratio, 2.91; 95% CI, 1.17-7.23; P=.02) and overall mortality (hazard ratio, 3.02; 95% CI, 1.89-4.82; P<.001) compared with intra-arterial administration of contrast after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. CONCLUSION Contrast-induced nephropathy after administration of contrast medium is associated with increased mortality. This risk is higher in patients in whom contrast medium is administered intravenously than in those in whom it is administered intra-arterially.

Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: a retrospective cohort study of 7977 patients at mayo clinic.

BACKGROUND AND OBJECTIVES The role of sodium bicarbonate in preventing contrast nephropathy needs to be evaluated in clinical settings. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective cohort study at Mayo Clinic in Rochester, Minnesota, to assess the risk of contrast nephropathy associated with the use of sodium bicarbonate, N-acetylcysteine, and the combination of sodium bicarbonate with N-acetylcysteine from April 2004 to May 2005. Contrast nephropathy was defined as postexposure creatinine elevation of > or =25% or >0.5 mg/dl within 7 d of contrast exposure. RESULTS A total of 11,516 contrast exposures in 7977 patients had creatinine values available for review before and after contrast exposure. More than 90% of exposures to agents prophylactic for contrast nephropathy were available for analysis. Sodium bicarbonate was used in 268 cases, N-acetylcysteine was used in 616 cases, and both agents were used in combination in 221 cases of contrast exposure. After adjustment for total volume of hydration, medications, age, gender, prior creatinine, contrast iodine load, prior exposure to contrast material, type of imaging study, heart failure, hypertension, renal failure, multiple myeloma, and diabetes mellitus, use of sodium bicarbonate alone was associated with an increased risk of contrast nephropathy compared with no treatment (odds ratio 3.10, 95% confidence interval 2.28 to 4.18; P < 0.001). N-acetylcysteine alone and in combination with sodium bicarbonate was not associated with any significant difference in the incidence of contrast nephropathy. CONCLUSIONS The use of intravenous sodium bicarbonate was associated with increased incidence of contrast nephropathy. Use of sodium bicarbonate to prevent contrast nephropathy should be evaluated further rather than adopted into clinical practice.

Outcomes of Arteriovenous Fistula Creation after the Fistula First Initiative

BACKGROUND AND OBJECTIVES The arteriovenous fistula (AVF) is the preferred hemodialysis access, but AVF-failure rate is high, and complications from AVF placement are rarely reported. There is no clear consensus on predictors of AVF patency. This study determined AVF outcomes and patency predictors at Mayo Clinic Rochester following the Fistula First Initiative. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective cohort study of AVFs placed at Mayo Clinic from January 2006 through December 2008 was performed. The AVF placement-associated primary and secondary failure rates, complications, interventions, and hospitalizations were examined. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine primary and secondary patency and associated predictors. RESULTS During this time frame, 317 AVFs were placed in 293 individual patients. The primary failure rate was 37.1% after excluding patients not initiated on hemodialysis during follow-up (n = 38) or those with indeterminate outcome (37 lost to follow-up; six died; two transplanted). Of usable AVFs, 11.4% later failed. AVF creation incurred complications and hospitalization in 21.2% and 12.3% of patients, respectively. The risk for reduced primary patency was increased by diabetes (HR, 1.54; 95% CI, 1.14 to 2.07); the risk for reduced primary and secondary patency was decreased with larger arteries (HR, 0.83; 95% CI, 0.73 to 0.94; and HR, 0.69; 95% CI, 0.56 to 0.84, respectively). CONCLUSIONS Primary failure remains a major issue in the post-Fistula First era. Complications from AVF placement must be considered when planning AVF placement. Our data demonstrate that artery size is the main predictor of AVF patency.

Impact of Short Daily Hemodialysis on Restless Legs Symptoms and Sleep Disturbances

BACKGROUND AND OBJECTIVES Restless legs syndrome (RLS) and sleep disturbances are common among in-center hemodialysis patients and are associated with increased morbidity/mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The FREEDOM study is an ongoing prospective cohort study investigating the benefits of home short daily hemodialysis (SDHD) (6 times/week). In this interim report, we examine the long-term effect of SDHD on the prevalence and severity of RLS, as measured by the International Restless Legs Syndrome (IRLS) Study Group rating scale, and sleep disturbances, as measured by the Medical Outcomes Study sleep survey. RESULTS 235 participants were included in this report (intention-to-treat cohort), of which 127 completed the 12-month follow-up (per-protocol cohort). Mean age was 52 years, 55% had an arteriovenous fistula, and 40% suffered from RLS. In the per-protocol analysis, among patients with RLS, the mean IRLS score improved significantly at month 12, after adjustment for use of RLS-related medications (18 versus 11). Among patients with moderate-to-severe RLS (IRLS score ≥15), there was an even greater improvement in the IRLS score (23 versus 13). The intention-to-treat analysis yielded similar results. Over 12 months, there was decline in the percentage of patients reporting RLS (35% versus 26%) and those reporting moderate-to-severe RLS (59% versus 43%). There was a similar and sustained 12-month improvement in several scales of the sleep survey, after adjustment for presence of RLS and use of anxiolytics and hypnotics. CONCLUSIONS Home SDHD is associated with long-term improvement in the prevalence and severity of RLS and sleep disturbances.

Improved Biochemical Variables, Nutrient Intake, and Hormonal Factors in Slow Nocturnal Hemodialysis: A Pilot Study

OBJECTIVE To determine whether slow nocturnal hemodialysis (SNHD) can be safely performed in patients with end-stage renal disease to improve the biochemical and clinical outcome. MATERIAL AND METHODS We conducted an 8-week pilot study in nondiabetic adult patients, who underwent dialysis 6 nights per week for 8 hours each night. A dialysate flow rate of 300 mL/min and a blood flow rate of 250 mL/min, through an internal jugular dual-lumen venous catheter, were used. The equipment used was a COBE Centry System 3 dialysis machine and Fresenius F-80 (1.8 m2) or Baxter CT 190 (1.9 m2) dialyzers. Five patients were enrolled in the study. RESULTS Two patients did not complete the study because of catheter-related infections--one at day 7 and one after 4 weeks of SNHD. All patients had improved blood pressure control, and no intradialytic adverse events occurred. Dietary intake improved, urea and creatinine levels significantly decreased, and weekly delivery of dialysate increased on SNHD. Potassium, chloride, beta 2-microglobulin, phosphorus, calcium, and high-density lipoprotein cholesterol all improved on SNHD. Serum testosterone increased in the three men on SNHD, but parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone remained unchanged. Erythropoietin levels increased on SNHD, despite no change in exogenous erythropoietin doses in three patients and discontinuation of administration of erythropoietin in one. The following biochemical factors did not change significantly: serum sodium, bicarbonate, vitamin B12, folate, alkaline phosphatase, total cholesterol, triglycerides, and albumin. CONCLUSION Higher doses of hemodialysis benefit nutrition, improve biochemical variables, and may improve many hormonal systems.

Outcome of Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting Renal Function and Mortality After 3.8 Years

Background— There are few data regarding medium-term outcome of coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction, particularly in the modern era, and even less assessing preoperative factors that might identify patients at highest risk. Methods and Results— Three hundred seventy-nine consecutive patients with LV ejection fraction ≤35%, who underwent isolated first CABG between 1995 and 1999 were studied. Potential preoperative and perioperative predictors of outcome were recorded and patients followed-up for a median of 3.8 years. The primary study end-point was all-cause mortality. The 30-day, 1-year, and 3-year survival rates were 94.5%, 88%, and 81%, respectively. The independent predictors of mortality were preoperative estimated glomerular filtration rate (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97 to 0.99 per mL/min/1.73m2; P<0.001) and age (HR, 1.03; 95% CI, 1.01 to 1.06 per year; P=0.005). Conclusions— Patients with significant LV systolic dysfunction undergoing isolated CABG using contemporary techniques have a good medium-term survival. Renal dysfunction is the strongest independent predictor of mortality.

Improved preservation of residual renal function in chronic hemodialysis patients using polysulfone dialyzers

Our objective was to determine whether patients with chronic renal failure requiring maintenance hemodialysis retain intrinsic renal function longer when using reprocessed polysulfone (PS) membrane hemodialyzers or single-use cellulose acetate (CA) membrane hemodialyzers. Fifty consecutive patients with residual renal function (urea clearance > 2.0 mL/min) using PS dialyzers were compared with a retrospective, disease- and time-matched population of patients using CA dialyzers. Endogenous urea clearance was measured every 3 months in all patients with remaining residual function. Other data collected included age, sex, cause of chronic renal failure, use of angiotensin-converting enzyme inhibitors or calcium channel blockers, and hemodynamic stability during hemodialysis. All patients were observed for at least 6 months while using a single type of dialyzer. Study end points included loss of residual renal function (urea clearance < 1.0 mL/min), death, transplant, transfer to peritoneal dialysis, or change of dialyzer. The PS and CA groups of patients were well matched for sex, age, initial renal clearance, predialysis blood pressure, and hemodynamic stability during hemodialysis. The PS patients had a higher delivered Kt/V (1.34 +/- 0.30 [mean +/- SD]) than the CA patients (1.06 +/- 0.20). The PS group had a higher average urea clearance than the CA group after 4 to 9 months of dialysis (2.8 +/- 2.6 mL/min v 1.7 +/- 1.6 mL/min, respectively), after 10 to 15 months of chronic dialysis (2.0 +/- 2.4 mL/min v 1.1 +/- 1.5 mL/min, respectively), and after 16 to 21 months of dialysis (1.3 +/- 1.9 mL/min v 0.5 +/- 1.1 mL/min, respectively; all P < 0.03, t-test). After 22 to 24 months of dialysis, the difference between the two groups was not significant. When comparing patients with identical causes of chronic renal failure, there were no differences between the PS and CA groups for those with diabetes mellitus, tubulointerstitial disease, or polycystic disease. Patients with parenchymal renal disease (glomerulonephritis or nephrosclerosis) had markedly better retention of intrinsic renal function with PS than with CA dialyzers (all P < 0.01). Kaplan-Meier analysis for retention of intrinsic renal function showed that PS patients with parenchymal renal disease had a mean of 23 months before loss of intrinsic renal function, whereas for CA patients the mean was 11 months before loss of intrinsic renal function (P = 0.0005). Cellulose acetate patients lost renal function at an average rate of 0.27 +/- 0.22 mL/min/mo, whereas for PS patients the rate was 0.14 +/- 0.56 mL/min/mo (P = 0.06, rank sum). CA patients with parenchymal renal disease lost renal function at a rate of 0.29 +/- 0.22 mL/min/mo, whereas for PS patients the rate was 0.0 +/- 0.8 mL/min/mo (P = 0.004, rank sum). Age, sex, and the use of either angiotensin-converting enzyme inhibitors or calcium channel blockers did not have an effect on the loss of intrinsic renal function. Patients with nondiabetic parenchymal renal disease receiving chronic hemodialysis with hydrogen peroxide/peroxyacetic acid-reprocessed PS dialyzers and a higher Kt/V lose residual renal function at a slower rate than disease-matched patients using single-use CA dialyzers. Our findings provide further evidence that the choice of dialyzer membrane may have an effect on intrinsic renal function.

Slow Nocturnal and Short Daily Hemodialysis: A Comparison

The disadvantages of thrice weekly hemodialysis (HD) have been described by many (1–8). The large fluid and solute shifts that occur during thrice weekly HD lead to increased cellular and vascular stress. Despite adequate solute clearance as measured by urea kinetics, morbidity and mortality continue to be unacceptable in the HD population and rehabilitation is unusual. Previously published data from this center (9) and others (10, 11) have shown improved patient well-being, biochemical parameters, nutrient intake, and hormonal factors, and less intraand interdialytic weight changes and improved blood pressure control when patients are dialyzed 6 nights per week for 8 hours per night using the slow nocturnal methods. The only adverse effects noted on slow nocturnal hemodialysis (SNHD) were related to the central venous catheters used for the dialysis access. For those patients who, due to disposition issues (nursing home residents, etc.), physical impairment, psychosocial issues, or personal preferences are not able to do home SNDH, short daily hemodialysis (DHD) at home, or incenter is an option. The purpose here was to determine the safety of DHD and the clinical and biochemical outcomes in patients on DHD and compare these findings to our previously published experience with SNHD (9).

The positive impact of a facilitated peer mentoring program on academic skills of women faculty

BackgroundIn academic medicine, women physicians lag behind their male counterparts in advancement and promotion to leadership positions. Lack of mentoring, among other factors, has been reported to contribute to this disparity. Peer mentoring has been reported as a successful alternative to the dyadic mentoring model for women interested in improving their academic productivity. We describe a facilitated peer mentoring program in our institutions department of medicine.MethodsNineteen women enrolled in the program were divided into 5 groups. Each group had an assigned facilitator. Members of the respective groups met together with their facilitators at regular intervals during the 12 months of the project. A pre- and post-program evaluation consisting of a 25-item self-assessment of academic skills, self-efficacy, and academic career satisfaction was administered to each participant.ResultsAt the end of 12 months, a total of 9 manuscripts were submitted to peer-reviewed journals, 6 of which are in press or have been published, and another 2 of which have been invited to be revised and resubmitted. At the end of the program, participants reported an increase in their satisfaction with academic achievement (mean score increase, 2.32 to 3.63; P = 0.0001), improvement in skills necessary to effectively search the medical literature (mean score increase, 3.32 to 4.05; P = 0.0009), an improvement in their ability to write a comprehensive review article (mean score increase, 2.89 to 3.63; P = 0.0017), and an improvement in their ability to critically evaluate the medical literature (mean score increased from 3.11 to 3.89; P = 0.0008).ConclusionsThis facilitated peer mentoring program demonstrated a positive impact on the academic skills and manuscript writing for junior women faculty. This 1-year program required minimal institutional resources, and suggests a need for further study of this and other mentoring programs for women faculty.