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Biomedical subjects

Wolfgang C Winkelmayer

Publications and source records attributed to Wolfgang C Winkelmayer.

At least 19 recordsLinked to original sources
PubMed2006

The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival.

BACKGROUND: Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function. METHODS: We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003. Actual and functional graft survival was compared between users and nonusers of ACEI/ARB using exposure propensity score models and time-dependent Cox regression models. RESULTS: Ten-year actual graft survival averaged 44% in the ACEI/ARB group, but only 32% in patients without ACEI/ARB (P=0.002). The hazard ratio of actual graft failure was 0.58 (95% confidence interval: 0.35-0.80, P=0.002) for ACEI/ARB users compared with nonconsumers. Seventy-one percent of subjects with ACEI/ARB had a functional graft at 10 years versus 64% of ACEI/ARB nonusers (P=0.027). The hazard ratio of functional graft loss was 0.48 (95% confidence interval: 0.24-0.91, P=0.025). CONCLUSIONS: Use of ACEI/ARB in patients experiencing delayed allograft function was associated with longer actual and functional transplant survival.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

A prospective study of anaemia and long-term outcomes in kidney transplant recipients.

BACKGROUND: Anaemia is prevalent in kidney transplant recipients (KTR), and only few KTR with anaemia receive treatment with erythropoietin. Some have claimed that this undertreatment might contribute to suboptimal outcomes such as mortality and cardiovascular events in these patients. However, no evidence is currently available that anaemia is actually associated with such risks in KTR. METHODS: We merged two cohorts of KTR to study the associations between anaemia and two outcomes: all-cause mortality and kidney allograft loss. Detailed information on the demographic and clinical characteristics of these 825 patients was available at baseline. As recommended by the American Society of Transplantation, anaemia was considered present if the haemoglobin concentration was < or =13 g/dl in men or < or =12 g/dl in women. Patients were followed using the Austrian Dialysis and Transplant Registry. RESULTS: After 8.2 years of follow-up, 251 patients died and 401 allografts were lost. In multivariate analyses, anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80-1.45), but it was associated with 25% greater risk of allograft loss (HR = 1.25; 95% CI: 1.02-1.59). This association was even more pronounced in death-censored analyses. Analyses using haemoglobin as a continuous variable or in categories also found no association with mortality. CONCLUSIONS: Anaemia may not be associated with mortality in KTR. In light of the recent findings of increased mortality in chronic kidney disease patients with higher haemoglobin treatment target, further evidence is needed to guide clinicians in the treatment of anaemia in these patients.

Anemia↗
PubMed2006

Renal dysfunction increases the risk of saphenous vein graft occlusion: results from the Post-CABG trial.

OBJECTIVES: Saphenous vein grafts are common among patients with a history of coronary artery bypass graft (CABG) surgery. Chronic kidney disease (CKD) is an established cardiovascular risk factor, but its role in graft disease has not been evaluated. METHODS AND RESULTS: The Post-CABG Trial randomized 1351 patients who had undergone CABG surgery 1-11 years earlier to high- or low-dose lovastatin and to low-dose warfarin or placebo. Coronary angiography was conducted at baseline and after a median follow-up time of 4.2 years. Subjects were grouped according to their baseline estimated glomerular filtration rate (eGFR). The primary trial endpoint was significant graft disease progression assessed angiographically. Additional pre-defined endpoints included occlusion of grafts patent at baseline, change in minimum lumen diameter, and a composite endpoint of recurrent clinical events. Decreasing eGFR was associated with an increased risk of graft occlusion (P(trend)=0.040), but not substantial atherosclerotic progression (P(trend)=0.30), per-graft change in minimum lumen diameter (P(trend)=0.067), or recurrent clinical events (P(trend)=0.86). We did not observe significant effect modification of treatment effects by the presence of CKD. CONCLUSIONS: CKD may be associated with increased risk of atherosclerotic plaque disruption rather than atherosclerotic progression in saphenous vein grafts.

Aged↗
PubMed2006

Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure.

Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

Acute Kidney Injury↗
PubMed2006

Endothelial progenitor cells in kidney transplant recipients.

BACKGROUND: Lower concentrations of endothelial progenitor cells (EPCs) may be associated with increased cardiovascular risk. EPC counts and their correlates have not yet been studied in kidney transplant recipients (KTR). METHODS: We cross-sectionally studied EPC counts in 105 middle-aged KTR (mean estimated glomerular filtration rate 45.2 ml/min/1.73 m; range: 5.4 to 117.5). Using univariate and multivariate linear regression assuming a gamma distribution of the outcome, we examined the associations between counts of cultured EPCs and traditional cardiovascular disease risk factors (hypertension, diabetes, hyperlipidemia, smoking), kidney function, and immunosuppressive agents, amongst others. RESULTS: The median count of cultured EPCs was 34 cells per high-power field (interquartile range: 19 to 64), comparable to healthy individuals. From multivariate analyses, we found independent inverse associations between counts of cultured EPCs and body mass index, mean arterial pressure, and history of cardiovascular disease. Statin use was associated with greater EPC counts, whereas patients receiving azathioprine or angiotensin II receptor treatment had lower EPC counts (all P<0.01). CONCLUSIONS: This study suggests negative associations in KTR between EPC counts and body mass index, and blood pressure, whereas statin use was associated with greater EPC counts. These findings raise the hypothesis whether EPCs are responsible, at least in part, for the well established associations between these factors and cardiovascular outcomes in KTR.

Antigens, CD↗
PubMed2006

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation.

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.

Adult↗
PubMed2006

Predicting survival in patients requiring renal replacement therapy after cardiac surgery.

BACKGROUND: We sought to develop and internally validate a prediction score for all-cause in-hospital mortality in patients who have acute renal failure and require renal replacement therapy after cardiac surgery. METHODS: From January 1992 to July 2001, 136 of 14,000 patients (0.9%) had acute renal failure requiring renal replacement therapy after cardiac surgery. Multivariate logistic regression analysis, based on pre-renal replacement therapy variables, was used to construct a predictive score for all causes of in-hospital mortality. Subsequently, the score was validated in 27 patients who underwent surgery between August 2001 and March 2003. RESULTS: In-hospital mortality was 58% (79 of 136). From the logistic regression model, we assigned a score (range, 0 to 6) based on the presence of independent predictors of operative mortality (preoperative creatinine < or = 1.5 mg/dL [odds ratio (OR) = 5.0], hypertension [OR = 4.4], predialysis coma [OR = 9.6], sepsis [OR = 6.4], and total bilirubin > or = 2 mg/dL [OR = 5.6]). Higher scores strongly predicted mortality: patients who scored 3 or higher before the initiation dialysis (n = 54), had a mortality rate of 94% (51 of 54). In contrast, patients who scored 1 or less on this scale (n = 36), had a mortality of 16% (6 of 36). In the validation cohort, the sensitivity of the new score at the cutoff of 2 or fewer points versus 3 or more points was 0.71, the specificity was 0.90, the positive predictive value was 0.92, and the negative predictive value was 0.64. CONCLUSIONS: The prediction score represents a simple and accurate tool for predicting in-hospital mortality associated with renal replacement therapy for cardiac surgery patients before the institution of this resource-intensive treatment.

Acute Kidney Injury↗
PubMed2006

Genetic aspects of hyperhomocysteinemia in chronic kidney disease.

Patients with chronic kidney disease who are on dialysis or with a kidney transplant have higher total plasma homocysteine concentrations than individuals who are free from kidney disease. Several single-nucleotide polymorphisms of genes encoding enzymes that are involved in homocysteine metabolism have been studied in these patients. These polymorphisms are located in genes encoding of 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase, methionine synthase, cystathionine beta-synthase, glutamate carboxy peptidase II, reduced folate carrier 1, and transcobalamin II. Among the single-nucleotide polymorphisms studied, only MTHFR 677C>T was associated consistently with total plasma homocysteine levels, but there currently is no evidence of any association between MTHFR 677C>T genotype and long-term outcomes.

Chronic Disease↗
PubMed2006

Poor short-term survival and low use of cardiovascular medications in elderly dialysis patients after acute myocardial infarction.

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: 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.

Aged↗
PubMed2006

Prognostic associations between lipid markers and outcomes in kidney transplant recipients.

BACKGROUND: Hyperlipidemia is highly prevalent in kidney transplant recipients, but the prognostic significance for mortality and allograft survival in these patients has not been established sufficiently. METHODS: We prospectively enrolled 733 kidney transplant recipients between 1996 and 1998. Clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplantation procedures and organ donor were obtained from the Eurotransplant Foundation database. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, independent relations of fasting plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels to risk for death from any cause and risk for kidney allograft loss were examined. RESULTS: During a median follow-up of 6.1 years, 154 patients died and 260 kidney allografts were lost. After careful multivariate adjustment, there were no significant associations between TG and TC levels and patient mortality. Patients in the highest quartile of TG and TC levels had no difference in risks for mortality compared with patients in the lowest quartile of these parameters (hazards ratio, 0.81; 95% confidence interval, 0.51 to 1.28; hazards ratio, 0.68; 95% confidence interval, 0.42 to 1.10, respectively). Similarly, no associations were found with allograft loss. Further analysis of associations between high-density lipoprotein cholesterol or low-density lipoprotein cholesterol categories and patient mortality or kidney allograft loss did not show associations. CONCLUSION: Elevated levels of TC or its subfractions and elevated TG levels are not associated with increased risk for patient mortality or allograft loss in these kidney transplant recipients.

Biomarkers↗
PubMed2006

Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation.

Thymoglobulin is used effectively as an induction agent in kidney transplantation, but the optimal dose is not well established. We evaluated the degree and durability of T-cell clearances with two different thymoglobulin regimens in adult kidney transplant recipients (KTR). Seven KTR received a 3-day thymoglobulin-based induction of 1.0 mg/kg/day while nine received 1.5 mg/kg/day, in addition to maintenance immunosuppression. Lymphocyte subsets were monitored for 6 months. Renal function, infections and malignancies were monitored for 24 months. T-cell subsets were significantly lower by day 30 with the thymoglobulin 1.5 mg/kg/day regimen when compared with the 1.0 mg/kg/day regimen; this trend was sustained at 6-month (CD3(+): 438 +/- 254 vs. 1001 +/- 532 cells/mm(3), P = 0.016). Renal function between the two groups was not significantly different at 6- and 24-months post-transplant. One case of BK Virus viremia in the 1.5 mg/kg/day thymoglobulin group was detected. No acute rejection episodes, cytomegalovirus infections, or malignancies were noted in either group. Thymoglobulin induction was efficacious in both groups, but with a significantly sustained T-cell clearance in the 1.5 mg/kg/day regimen. A more profound T-cell clearance within the first 6 months postinduction therapy may translate into a decreased risk of immunological injury and improved long-term outcome after kidney transplantation.

Aged↗
PubMed2006

Angiotensin inhibition after myocardial infarction: does drug class matter?

BACKGROUND: Angiotensin converting enzyme-inhibitors (ACEI) and angiotensin-II-receptor blockers (ARB) are equally efficacious in reducing mortality after MI, although the latter are far more costly. Little is known about their relative use after MI in typical care settings, and about their relative effectiveness outside the clinical trial setting. OBJECTIVES: To assess temporal trends in the relative use of ACEI and ARB after myocardial infarction, and to test for differences in 1-year survival between users of these drug classes. DESIGN: Retrospective closed cohort study. PATIENTS: Medicare beneficiaries who survived >90 days after myocardial infarction, had full prescription drug coverage, and who filled a prescription for either ACEI or ARB within 90 days of myocardial infarction. MEASUREMENTS: Relative use of ACEI versus ARB over time. Adjusted relative 1-year mortality between ACEI and ARB users. RESULTS: Between 1995 and 2004, 14,190 patients met inclusion criteria. Mean age was 80 years, 75% were female, and 90% were white. Overall, 88% received an ACEI, and 12% an ARB, with the proportion receiving an ARB increasing from 2% (1995) to 25% (2004; P<.001). Multivariate-adjusted 1-year mortality did not differ between ARB and ACEI users (HR: 1.04; 95% confidence interval: 0.88 to 1.22). The findings were similar for new users of ACEI/ARB, and for those with preexisting heart failure. CONCLUSIONS: ARB users had the same 1-year mortality after myocardial infarction as ACEI users in routine care. Use of more costly ARB has increased dramatically over time, to a quarter of ACEI/ARB users, despite the lack of a therapeutic advantage for most patients.

Aged↗
PubMed2006

Efficacy and safety of angiotensin II receptor blockade in elderly patients with diabetes.

OBJECTIVE: While national guidelines recommend ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy in patients with diabetes and nephropathy, guidelines concerning elderly patients with diabetes have not endorsed these drugs. We sought to assess the nephroprotective efficacy and safety of ARB therapy in elderly patients by conducting age-specific subgroup analyses using data from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. RESEARCH DESIGN AND METHODS: We studied 1,513 patients with type 2 diabetes and nephropathy who randomly received either losartan or placebo. We tested for effect modification by age of the effect of losartan on the incidence of the predefined end points (doubling of serum creatinine, end-stage renal disease [ESRD], or death) and the risk of adverse events. RESULTS: Of 1,513 participants, 421 (27.8%) were aged >65 years (maximum age 74 years). Age did not modify the efficacy of losartan in reducing the risk of the primary outcome, a composite of doubling of serum creatinine, ESRD, or death (P(interaction) = 0.66) or its individual components (all P(interaction) > 0.44). In patients aged >65 years, losartan reduced the risk of ESRD by 50% (95% CI 30-81, P = 0.005). We found no evidence that older patients were more likely to experience adverse events from losartan such as a rise in serum creatinine or hyperkalemia than younger patients. CONCLUSIONS: Elderly patients had the same level of benefits and risks as younger patients from treatment with losartan. Underuse of ACEI and ARB therapy in elderly patients because of the perceived lack of efficacy or a greater risk of adverse events appears unjustified.

Aged↗
PubMed2005

Cost-effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine therapy for blacks with heart failure.

BACKGROUND: Fixed-dose combination of isosorbide dinitrate/hydralazine (ISDN/HYD) improved clinical outcomes in the African-American Heart Failure Trial (A-HeFT). We assessed the resource use, costs of care, and cost-effectiveness of ISDN/HYD therapy in the A-HeFT trial population. METHODS AND RESULTS: We obtained resource use data from A-HeFT, assigning costs through the use of US federal sources. Excluding indirect costs, we summarized the within-trial experience and modeled cost-effectiveness over extended time horizons, including a US societal lifetime reference case. During the mean trial follow-up of 12.8 months, the ISDN/HYD group incurred fewer heart failure-related hospitalizations (0.33 versus 0.47 per subject; P=0.002) and shorter mean hospital stays (6.7 versus 7.9 days; P=0.006). When study drug costs were excluded, both heart failure-related and total healthcare costs were lower in the ISDN/HYD group (mean per-subject heart failure-related costs, 5997 dollars versus 9144 dollars; P=0.04; mean per-subject total healthcare costs, 15,384 dollars versus 19,728 dollars; P=0.03). With an average daily drug cost of 6.38 dollars, ISDN/HYD therapy was dominant (reduced costs and improved outcomes) over the trial duration. Assuming that no additional benefits accrue beyond the trial, we project the cost-effectiveness of ISDN/HYD therapy using heart failure-related costs to be 16,600 dollars/life-year at 2 years after enrollment, 37,100 dollars/life-year at 5 years, and 41,800 dollars/life-year over lifetime (reference case). CONCLUSIONS: ISDN/HYD therapy, previously shown to improve clinical outcomes, also reduced resource use and costs in A-HeFT, primarily because of a large reduction in hospitalizations. Long-term use of ISDN/HYD therapy should be associated with a favorable cost-effectiveness profile in this population.

Black People↗
PubMed2005

Habitual caffeine intake and the risk of hypertension in women.

CONTEXT: Caffeine acutely increases blood pressure, but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain. OBJECTIVE: To examine the association between caffeine intake and incident hypertension in women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study conducted in the Nurses' Health Studies (NHSs) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years (1990-1991 to 2002-2003 questionnaires). Caffeine intake and possible confounders were ascertained from regularly administered questionnaires. We also tested the associations with types of caffeinated beverages. MAIN OUTCOME MEASURE: Incident physician-diagnosed hypertension. RESULTS: During follow-up, 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II. In both cohorts, no linear association between caffeine consumption and risk of incident hypertension was observed after multivariate adjustment (NHS I, P for trend = .29; NHS II, P for trend = .53). Using categorical analysis, an inverse U-shaped association between caffeine consumption and incident hypertension was found. Compared with participants in the lowest quintile of caffeine consumption, those in the third quintile had a 13% and 12% increased risk of hypertension, respectively (95% confidence interval in NHS I, 8%-18%; in NHS II, 6%-18%). When studying individual classes of caffeinated beverages, habitual coffee consumption was not associated with increased risk of hypertension. By contrast, consumption of cola beverages was associated with an increased risk of hypertension, independent of whether it was sugared or diet cola (P for trend <.001). CONCLUSION: No linear association between caffeine consumption and incident hypertension was found. Even though habitual coffee consumption was not associated with an increased risk of hypertension, consumption of sugared or diet cola was associated with it. Further research to elucidate the role of cola beverages in hypertension is warranted.

Caffeine↗
PubMed2005

Long-term patient and graft survival in the eurotransplant senior program: a single-center experience.

BACKGROUND: The Eurotransplant Senior Program (ESP) was launched in 1999, targeted to increase the supply of donor kidneys to the elderly. This program requires local allocation of kidneys from cadaveric donors >>65 years to recipients >>65 years. METHODS: Of all patients >>65 years who received a kidney transplant in 1999-2002 at our center, 59 patients were transplanted through the ESP protocol (ESP group), and 44 patients received a transplant from a younger donor (EuroTransplant Kidney Allocation System, ETKAS group). Recipients were followed for up to 5.3 years using the Austrian Dialysis and Transplant Registry. Outcomes studied included all-cause mortality and allograft loss. RESULTS: Age, sex, and comorbid conditions did not differ by group. Donor age was higher (69 vs. 36 years; P < 0.001) and cold ischemia time shorter in the ESP group (10 vs. 15 hr; P < 0.001). Number of HLA mismatches was greater in the ESP group (3.8 vs. 3.0; P = 0.003). ESP patients were more likely to receive induction therapy and less likely to receive cyclosporine A. Primary nonfunction, delayed graft function, operative mortality, rate of acute rejection episodes, and length of stay did not differ by group. Although serum creatinine at discharge was higher in ESP patients (1.7 vs. 1.4 mg/dL; P < 0.001), 4-year mortality (hazard ratio [HR] = 0.68; 95% CI: 0.31-1.49) and graft loss (HR = 0.61; 95% CI: 0.29-1.28) tended to be less. CONCLUSIONS: Long-term patient and graft survival were comparable between elderly patients who received their organ via the ESP and the regular ETKAS algorithm.

Aged↗
PubMed2005

The hepatotoxicity of antifungal medications in bone marrow transplant recipients.

BACKGROUND: Systemic antifungal medications can be lifesaving but can also have important toxicities. With a number of new antifungal drugs being introduced, there is a compelling need to define the toxicities associated with existing therapies. METHODS: We identified cases of hepatotoxicity among patients who underwent bone marrow transplantation and selected matched control subjects from the same population. Multivariable logistic regression modeling was used to control for patient characteristics in evaluating the relationship between hepatotoxicity and exposure to antifungal medications. Follow-up analyses were performed for patients who continued receiving antifungal medications after developing hepatotoxicity. RESULTS: The unadjusted incidence of hepatotoxicity was 0.78 cases per 100 patient-days of exposure to amphotericin deoxycholate, 0.98 for fluconazole, and 1.50 for liposomal amphotericin B. Case-control analyses found that liposomal amphotericin B was associated with a substantial increase in the risk of hepatotoxicity in these patients (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.61-6.88); a smaller increase in risk was found for fluconazole (OR, 1.99; 95% CI, 1.21-3.26). There was no statistically significant association between amphotericin B deoxycholate and the development of hepatotoxicity. Patients had greater elevations of serum transaminase values associated with exposure to larger cumulative doses of liposomal amphotericin B. In the follow-up analysis of patients who developed hepatotoxicity and who continued receiving antifungal medication, one-third of those receiving liposomal amphotericin B had marked increases in bilirubin levels, as opposed to 8% of patients treated with fluconazole. CONCLUSIONS: In these bone marrow transplant recipients, liposomal amphotericin B and fluconazole were both associated with increased risk of hepatotoxicity, independent of other treatments received or patient characteristics; the magnitude of the risk was larger for liposomal amphotericin B. Patients who develop hepatotoxicity appear to tolerate continued therapy with fluconazole, but a large fraction of those who received liposomal amphotericin B have worsening conditions with continued treatment.

Adult↗