Faculty Bibliography

BACKGROUND:Long-term dialysis patients have a high incidence of myocardial infarction and cardiovascular death, but the incidence of coronary artery disease (CAD) in asymptomatic patients, distribution of coronary obstruction, and relationship between lesion location and mortality are unknown. METHODS:We studied 67 asymptomatic hemodialysis patients who volunteered for coronary angiography. Coronary stenoses of 50% or greater were documented, and the location of each within the proximal, midportion, or distal segment of the coronary vessel was recorded. Patients were followed up until death or renal transplantation. Cox proportional hazards regression was performed to analyze the relationship of lesion location with mortality. RESULTS:Obstructive CAD was common. Twenty-eight subjects (41.7%) had 50% or greater stenosis in at least 1 epicardial vessel, and 19 subjects (28.5%) had evidence of CAD within the proximal third of an epicardial vessel. After a median follow-up of 2.7 years, the presence of proximal CAD was associated with a marked increase in risk of death (adjusted hazard ratio, 3.14; 95% confidence interval, 1.34 to 7.33; P = 0.008) and was associated more strongly with mortality than multivessel disease or left anterior descending disease. CONCLUSION/CONCLUSIONS:CAD is common in asymptomatic dialysis patients, and stenoses frequently are located within the proximal coronary arteries, where they are associated with markedly increased risks of death. Additional studies are needed to determine whether proximal disease is a modifiable risk factor for cardiovascular mortality in dialysis patients.

BACKGROUND:Dialysis patients have a high risk of cardiovascular death but may under-use coronary artery bypass grafting (CABG) because of the risk of peri-operative death. Whether operative mortality in dialysis patients has declined with contemporary techniques is uncertain. We undertook this study in order to compare peri-operative mortality in chronic dialysis (CD) and non-dialysis patients following CABG and to determine whether high levels of comorbidity in CD patients account for identified differences in operative risk. METHODS:This study is a retrospective analysis of the 2001 National Inpatient Sample, a stratified probability sample of over seven million admissions in 33 states. Administrative data and ICD-9CM codes were used to identify dialysis patients, comorbidities, procedures and operative outcomes. Multivariable logistic regression was used to adjust for confounding. RESULTS:In this study, 77 323 non-dialysis patients and 635 dialysis patients underwent CABG. In-hospital death occurred in 11.1% of dialysis patients compared to 3.4% of non-dialysis patients. Rates of stroke, sepsis and pneumonia were also increased in dialysis patients. After adjustment for other surgical risk factors, the odds of in-hospital death were 3.38 (2.54-4.50, P < 0.001) times higher in dialysis than non-dialysis patients. CONCLUSIONS:Operative mortality in dialysis patients remains high despite recent advances in CABG surgery and is not explained by the high rates of comorbidity in dialysis patients. Because there is a very high risk of cardiovascular death without intervention, CABG may nevertheless be a life-saving therapy in CD patients. Randomized trials are needed to better define the optimal role of CABG in dialysis patients.

Chronic kidney disease (CKD) is associated with a high risk of death from coronary artery disease and may modify the response to standard cardiovascular therapies. Treatment of subjects with CKD should ideally be based on evidence from randomized, clinical trials, but how often subjects with CKD have been excluded from these trials is uncertain. We undertook this study in order to quantify how often subjects with moderate to advanced CKD were excluded from large cardiovascular trials. MEDLINE and the reference list of selected articles were searched in order to identify large, randomized, controlled trials of five different coronary artery disease therapies published between 1998 and 2005. Exclusion criteria and reported clinical characteristics of subjects were abstracted. Rates of exclusion and reporting of baseline characteristics of study participants were compared for CKD, diabetes, history of smoking, and hypertension. Eighty-six trials randomizing 411 653 patients were identified. More than 80% of trials excluded subjects with end-stage renal disease and 75.0% excluded patients with CKD. Subjects with diabetes, hypertension, or a history of smoking were excluded less than 4% of the time. Baseline renal function of study participant was reported in only 7% of trials. Patients with CKD are frequently excluded from coronary artery disease trials and renal function of randomized subjects is rarely reported. These findings reinforce the notion that available data on the treatment of coronary artery disease in subjects with CKD have significant limitations and should be generalized to the treatment of subjects with CKD cautiously.

Several studies have found reduced use of recommended medications after myocardial infarction (MI) in patients with impaired kidney function. However, the reasons for such undertreatment are not well understood. A total of 1380 Medicare patients who survived at least 90 d after MI and had prescription drug coverage through Pennsylvania's medication assistance program for the elderly were studied. Filled prescriptions were used to assess use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta blockers, and statins within 90 d of MI. Patients' demographics, comorbidities, and health care utilization before MI also were ascertained. We used logistic regression to test the association between kidney function and postdischarge use of each medication. Overall, 619 (45%) patients filled a prescription for a beta blocker, 675 (49%) received an ACEI or ARB, and 406 (29%) received a statin after discharge but within 90 d after their admission for MI. Reduced kidney function was associated with both lower beta blocker and statin use (P = 0.01 and P = 0.002, respectively), but after multivariate adjustment, these associations disappeared (P = 0.23 and P = 0.62, respectively). Use of ACEI or ARB was nearly half in patients with estimated GFR <30 ml/min compared with patients with better kidney function in univariate and multivariate analyses (P < 0.001). Analyses using serum creatinine measurements rather than estimations of GFR yielded similar results. Differences in other characteristics such as age, rather than kidney function, may be responsible for much or all the reported reduction in use of preventive medications after MI seen in patients with chronic kidney disease.

BACKGROUND:Chronic kidney disease is a risk factor for death in the year following myocardial infarction or coronary angioplasty. Whether the risk is similar after coronary stenting, whether impaired renal function is associated with an increased risk of cardiovascular death or myocardial infarction (MI) after coronary stenting and whether this risk is maintained beyond the first year are uncertain. METHODS:We analyzed the long-term risks of MI or the combination of cardiovascular death and non-fatal MI in patients participating in 4 coronary stenting trials with mandated, prospective long-term follow-up. Cox proportional hazards models were used to adjust for confounding and to generate multivariable odds ratios. RESULTS:Patients (n=1,228) were followed for a median of 5 years. There were 125 MIs and 55 cardiovascular deaths. Patients with a serum creatinine>or=1.3 mg/dL had markedly elevated risks of cardiovascular death and MI that emerged during the first year and were maintained throughout follow-up. The adjusted hazard ratio of MI was 2.14 (p=0.006) while the adjusted hazard ratio of a combined end point of MI or cardiovascular death was 2.13 (p=0.001). The risks were similar in patients with moderate (serum creatinine 1.3-1.9 mg/dL) or advanced chronic kidney disease. CONCLUSIONS:The presence of even mild chronic kidney disease is associated with a high risk of cardiovascular death and MI following coronary stenting. Further research to address the causes of the association and to define the best therapy for these patients is necessary.

BACKGROUND:The presence of aortic atherosclerosis has been identified as a major risk factor for stroke after coronary artery bypass grafting (CABG). Whether aortic atherosclerosis is similarly related to the risk of acute renal failure (ARF), a common and important complication of CABG, is unknown. METHODS:Rates of postoperative ARF were analyzed using data from 1,117 randomized patients in a multicenter controlled trial comparing standard CABG with CABG plus an experimental aortic catheter. Aortic atherosclerosis was prospectively measured using transesophageal echocardiography. The association of aortic atherosclerosis with postoperative renal failure was analyzed using multivariable logistic regression to adjust for confounding by baseline and intraoperative conditions. RESULTS:Baseline creatinine clearance <40 ml/min and systolic hypertension were strong predictors of postoperative acute renal failure. Neither mild nor moderate aortic atherosclerosis was associated with the development of acute renal failure. Patients with moderate aortic atherosclerosis had a lower risk of acute renal failure (odds ratio = 0.53, p = 0.20) than those with lesser degrees of atherosclerosis. CONCLUSIONS:Our results demonstrate that the presence of significant aortic atherosclerosis does not increase the risk of acute renal failure following CABG, and they suggest that cholesterol embolization from the aorta to the renal circulation is an infrequent cause of acute renal failure after bypass surgery. Strategies to decrease cholesterol embolization from the aorta are unlikely to significantly lower the rate of renal failure following bypass surgery.

BACKGROUND:Beta-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are standard therapies after myocardial infarction (MI) in the general population. Their use and association with mortality in elderly dialysis patients after MI have not been studied sufficiently. METHODS:Claims records from Medicare and Medicaid patients aged 65 years and older who participated in prescription benefit plans of 2 eastern states were used to identify dialysis patients with MI between 1995 and 2003. Study outcomes were outpatient use of beta-blockers, statins, and ACE inhibitors and/or ARBs within 90 days after MI. We used multivariate logistic regression to assess predictors of such use. Multivariate Cox regression was applied to test for associations between beta-blocker, statin, and ACE-inhibitor and/or ARB use and 1-year mortality. RESULTS:We identified 902 dialysis patients who were hospitalized with MI. Of these, 39.5% died within 90 days and 63.6% died within 1 year after MI. Of 494 patients who were discharged within 21 days or less and survived longer than 90 days, 31.0% were administered an ACE inhibitor and/or ARB; 19.4%, a statin; and 34.2%, a beta-blocker after discharge. Use of ACE inhibitors and/or ARBs was associated with a 30% reduction in 1-year mortality (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50 to 0.98), whereas statin (HR, 0.97; 95% CI, 0.65 to 1.45) and beta-blocker use (HR, 1.05; 95% CI, 0.78 to 1.43) were not. CONCLUSION/CONCLUSIONS:Elderly dialysis patients have excessively high mortality and low use of standard therapies after MI. Only ACE inhibitors and/or ARBs were associated with a reduced risk for death at 1 year in this population. Whether the high mortality rate in this population is attributable to such low use of preventive cardiovascular medications remains uncertain.

BACKGROUND:Dialysis patients have an excessive risk of cardiovascular death after myocardial infarction (MI). Underutilization of cardiac therapies may partially explain this risk, but whether patients on maintenance dialysis have differential rates of coronary angiography or revascularization during admission for MI compared with patients not on dialysis and whether these differences are explained by the presence of comorbid illness were uncertain. METHODS:We analyzed 154,692 patients with a primary diagnosis of MI in the 2001 National Inpatient Sample, and we compared procedure use in patients on long-term dialysis, patients with non-dialysis-dependent chronic kidney disease (CKD), or normal renal function. RESULTS:Dialysis patients and patients with dialysis-independent CKD were significantly less likely to undergo coronary angiography than patients with normal renal function (39% and 34% vs 56%). They were also less likely to undergo coronary revascularization (19% and 23% vs 41%) or to have a coronary intervention after diagnostic angiography (46% and 62% vs 70%). After adjustment, these differences remained, with a lower likelihood of angiography (42% and 45% vs 56%), revascularization (22% and 31% vs 41%), or coronary intervention after diagnostic angiography (52% and 66% vs 70%). CONCLUSIONS:Despite a high mortality rate after MI, patients on dialysis are markedly less likely than patients with dialysis-independent CKD or normal renal function to undergo diagnostic angiography or coronary revascularization after admission for MI. Additional studies to determine how these disparities are related to mortality are warranted.

Commercial serological assays for the presence of anti-glomerular basement membrane (GBM) antibodies are thought to be indicative of Goodpasture's syndrome. We report a case in which commercial tests inaccurately suggested that a patient with a pulmonary-renal syndrome had Goodpasture's disease. Additional laboratory testing using recombinant type IV collagen NC1 domain proteins showed that the autoantibodies in question were not directed against the Goodpasture antigen (the alpha3NC1 domain), but against the alpha2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the alpha2NC1 domain. Further investigation showed that this patient has decreased alpha3 and alpha5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.