Donal N. Reddan

Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes

Background—Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results—A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions—Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.

Secondary analysis of the CHOIR trial epoetin-α dose and achieved hemoglobin outcomes

Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.

Chronic Kidney Disease, Mortality, and Treatment Strategies among Patients with Clinically Significant Coronary Artery Disease

Cardiovascular disease is an important cause of mortality among patients with chronic kidney disease (CKD). This study describes associations between CKD, cardiac revascularization strategies, and mortality among patients with CKD and cardiovascular disease. All patients undergoing cardiac catheterization at Duke University Medical Center (1995 to 2000) with documented stenosis > or =75% of at least one coronary artery and available creatinine data were included. CKD was staged using creatinine clearance (CrCl) derived from the Cockcroft-Gault formula (normal, > or = 90 ml/min; mild, 60 to 89 ml/min; moderate, 30 to 59 ml/min; severe, 15 to 29 ml/min). Cox proportional-hazard regression estimated the relationship between clinical variables, including CrCl and percutaneous coronary artery intervention (PCI), coronary artery bypass grafting (CABG), medical management, and patient survival. There were 4584 patients included, and 24% had CrCl <60 ml/min. Each 10-ml/min decrement in CrCl was associated with an increase in mortality (hazard ratio, 1.14; P < 0.0001). CABG was associated with a survival benefit among patients with both normal renal function and patients with CKD compared with medical management. In patients with normal renal function, CABG was not associated with survival benefit over PCI. However, in patients with CKD, CABG was associated with improved survival. PCI was associated with a survival benefit compared with medical management among patients with normal, mildly, and moderately impaired renal function. Among patients with severe CKD, PCI was not associated with improved survival. CABG is associated with greater mortality reduction than PCI in severe CKD.

Intradialytic Blood Volume Monitoring in Ambulatory Hemodialysis Patients: A Randomized Trial

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.

National Profile of Practice Patterns for Hemodialysis Vascular Access in the United States

The Centers for Medicare & Medicaid Services (CMS), national End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project is a data collection initiative to identify opportunities for improvement of care to adult, Medicare maintenance dialysis beneficiaries. This analysis of 1999 CPM data characterizes the profile of hemodialysis vascular access in the United States and identifies determinants of vascular access type 2 yr after the translation of vascular access clinical practice guideline statements into national CPMs. CPM data were collected during October to December 1999 and stratified by the 18 regional ESRD networks. Univariate and multivariable analyses were conducted to examine associations of access type with demographic, laboratory, and geographic variables. Multivariable logistic regression analyses were performed to identify independent variables associated with access type. A total of 8154 hemodialysis patients were sampled; 17% (n = 1399) were incident. Twenty-eight percent were dialyzed through an autologous arteriovenous fistula (AVF), 49% through a prosthetic graft (AVG), and 23% through a percutaneous catheter. Independent predictors of having a catheter for hemodialysis were female gender, white race, incident to hemodialysis status, and lower hemoglobin and serum albumin. For patients with a fistula or AVG, female gender (odds ration [OR], 2.46 [2.18 to 2.78]) and black race (OR, 1.70 [1.50 to 1.93]) were the strongest predictors of dialysis through an AVG. Other predictors of dialysis through an AVG were older age, increased body mass index (BMI), diabetes mellitus as the cause of ESRD, and lower serum albumin. Even in adjusted analyses, there was significant geographic variability with respect to hemodialysis access type. Despite translation of practice guidelines for hemodialysis vascular access into national CPMs, there is substantial geographic variability and gender and racial disparity in angioaccess allocation in the United States. Quality improvement strategies to improve the prevalence of fistulae should focus on selected regions and include physician education about their practice patterns and potential biases.

A secondary analysis of the CHOIR trial shows that comorbid conditions differentially affect outcomes during anemia treatment

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

Management of small renal tumors: an overview

The incidental finding of a small renal mass poses a therapeutic dilemma. The traditional treatment of clinically important masses has been radical nephrectomy. Recently, nephron-sparing surgery has emerged as a viable alternative; and experimental minimally invasive percutaneous tissue ablation techniques, including cryotherapy and radiofrequency ablation, are being evaluated. In this review, we discuss the dilemma posed by frequent renal imaging and the increased proportion of incidental tumors being detected, the limitations of needle biopsies for histologic diagnosis, nephron-conserving and minimally invasive surgery, and the possible merits of radiofrequency ablation and cryotherapy. We envision a defined role for minimally invasive percutaneous or extracorporeal ablation of small renal tumors.

Trends in Anemia Management among US Hemodialysis Patients

This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from 58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis

Vascular access site thrombosis is a major cause of morbidity in patients receiving hemodialysis. The role of hypercoagulable states in recurrent vascular access site thrombosis remains poorly understood. Data are limited regarding systemic anticoagulation to improve access graft patency, because of concern about hemorrhagic complications. We determined the prevalence of hypercoagulable states and clinical outcome (thrombotic and hemorrhagic) after initiation of antithrombotic therapy in a series of patients with recurrent vascular access site thrombosis. We evaluated 31 patients who had sustained 119 thrombotic events that resulted in vascular access graft failure during the year before evaluation. Sixty-eight percent of patients tested had elevated concentrations of antibody to anticardiolipin or topical bovine thrombin, and 18% of patients tested had heparin-induced antibodies. More than 90% of patients had elevated factor VIII concentration, 62% had elevated fibrinogen concentrations, and 42% had elevated C-reactive protein concentrations. Twenty-nine patients were given antithrombotic therapy: 13 with warfarin sodium, 12 with unfractionated heparin (UFH), and 11 with low molecular weight heparin (LMWH). Seven patients received more than one antithrombotic agent, sequentially. Nineteen patients have had no thrombotic events since beginning antithrombotic therapy (10 with warfarin, 3 with UFH, 6 with LMWH). Mean follow-up was 8.6 months (median, 7 months). Eight patients sustained 10 bleeding complications (5 with warfarin, 3 with UFH, and 2 with LMWH). In conclusion, hypercoagulable states are common in patients with recurrent vascular access site thrombosis. Antithrombotic therapy may increase vascular access graft patency, but is associated with significant risk for hemorrhage. Prospective studies are needed to evaluate the role and safety of antithrombotic agents in improving vascular access graft patency.

Racial Inequity in America's ESRD Program

The end‐stage renal disease (ESRD) program has a significant overrepresentation of racial and ethnic minority groups. The increased susceptibility of nonwhite populations to ESRD has not been fully explained and probably represents a complex interplay of genetic, cultural, and environmental influences. Because the program delivers care under a uniform health care payment system, it represents a unique environment in which to explore variation in health care delivery. A number of disparities in outcomes and delivery of ESRD care have been noted for racial minority participants. These include possible overdiagnosis of hypertensive nephrosclerosis, decreased provision of renal replacement therapy, limited referral for home dialysis modalities, underprescription of dialysis, increased use of synthetic grafts rather than fistulas as permanent angioaccess, and delayed wait‐listing for renal transplantation. Transplantation inequities mean that black patients are likely to remain on dialysis relatively longer, so that their susceptibility to less than optimal processes of care increases disproportionately. Improved survival and quality of life (QOL) for blacks with ESRD may have encouraged provider complacency about racial disparities in the ESRD program and in particular about referral for transplantation. It is also apparent that minority ESRD patients may, similar to their non‐ESRD counterparts, be referred less frequently for invasive cardiovascular (CV) procedures. Despite these observations of inequality in ESRD care, the adjusted mortality for minority participants in the ESRD program are better than for the majority population. This seeming paradox may define an opportunity to improve outcomes for minorities with ESRD even more.