Faculty Bibliography

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: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.

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.

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: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.

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.

BACKGROUND:Anti-glomerular basement membrane (GBM) antibodies occasionally occur in Alport patients after renal allograft transplantation. METHODS:We report a patient with Alport's syndrome who lost four transplants each within the first year post transplantation. We searched for the presence of anti-GBM antibodies using recombinant NC1 domains of type IV collagen. Immunoblotting, enzyme linked immunosorbent assay (ELISA), and immunofluorescence were used to detect the presence of antibodies against the glomerular basement membrane. RESULTS:High antibody titers to the alpha3 chain (the Goodpasture antigen) and alpha5 chain of type IV collagen were detected. Review of pathologic specimens showed features of vascular rejection in all specimens. CONCLUSION/CONCLUSIONS:The association of high titer anti-GBM antibodies and vascular rejection may be important. When vascular rejection occurs in Alport patients, the presence of anti-GBM antibodies should be sought. Recombinant anti-GBM assays should be used if standard anti-GBM testing is equivocal.

Theophylline is commonly used in the treatment of bronchospastic lung disease. In addition to gastrointestinal and cardiac dysfunction, hypokalaemia, lactic and ketoacidosis can complicate theophylline overdose. Clinicians frequently fail to identify theophylline's role when complications develop. A case of an 80-year-old man who developed profound metabolic disturbances while hospitalized is presented. The typical causes of these abnormalities were absent, theophylline levels were elevated, and the patient recovered after theophylline was held. Based on our case and review of the literature, we discuss the reasons why theophylline toxicity is under-recognized, and propose mechanisms for the rare metabolic abnormalities identified in this case. A high index of suspicion for theophylline toxicity should be maintained and it should be considered when unexplained acidosis or hypokalaemia occur.