Overall Infectious Complications Related to Belatacept Conversion in Comparison to Tacrolimus in Kidney Transplant Recipients.

Introduction: Belatacept has demonstrated effectiveness for preventing rejection in kidney transplant and has a favorable side effect profile. Studies assessing long-term infectious complications with belatacept compared to tacrolimus are limited. Project Aims: The purpose of this program evaluation was to determine the proportion of patients who developed an infection when converted to belatacept compared to those on tacrolimus. Design: In this retrospective evaluation, kidney transplant recipients receiving belatacept were matched 1:1 to those receiving tacrolimus, based on transplant date, age, induction immunosuppression, and cytomegalovirus risk. Data collection was initiated in tacrolimus patients on the date of belatacept conversion in the belatacept-matched patients. Data were extracted until study conclusion, death, or discontinuation of belatacept. Patients were stratified into 3 groups based on time of conversion posttransplant, which included early, late, and very late conversion. The primary outcome was the proportion of patients with an infection in belatacept compared to tacrolimus. Outcome data were calculated using chi-square, Fisher's exact test, student's t-test or Mann-Whitney U test where appropriate. Results: A total of 328 matched patients were included in the analysis. More patients on belatacept developed an infection compared to tacrolimus (42.7% vs 29.9%, P = 0.02), which was primarily driven by pneumonia (6.1% vs 0.5%; P = 0.01). Higher incidences of infections were identified in those converted within 6 months from transplant. Conclusions: Belatacept was associated with a higher proportion of patients with infections compared to tacrolimus, particularly in those converted within 6 months from time of transplant.

FcγRIIb on CD11c+ cells modulates serum cholesterol and triglyceride levels and differentially affects atherosclerosis in male and female Ldlr-/- mice.

BACKGROUND AND AIMS: Circulating levels of oxidized lipoprotein (oxLDL) correlate with myocardial infarction risk and atherosclerosis severity. Our previous study demonstrates that oxLDL immune complexes (oxLDL-ICs) can signal through FcγRs on bone marrow-derived dendritic cells (BMDCs) and enhance their activation and inflammatory cytokine secretion. While global FcγR-/- studies have shown that activating FcγRs are proatherogenic, the role of the inhibitory FcγRIIb is unclear. We sought to determine the role of DC-specific FcγRIIb in atherosclerosis. METHODS: Bone marrow chimeras were generated by rescuing lethally irradiated Ldlr-/- mice with hematopoietic cells from littermate CD11c-Cre+ or CD11c-Cre-Fcgr2bfl/fl donors. Four weeks following transplant, recipients were placed on a Western diet for eight weeks. Various tissues and organs were analyzed for differences in inflammation. RESULTS: Quantitation of atherosclerosis in the proximal aorta demonstrated a 58% increase in female CD11c-Cre+Fcgr2bfl/fl recipients, but a surprising 44% decrease in male recipients. Hepatic cholesterol and triglycerides were increased in female CD11c-Cre+Fcgr2bfl/fl recipients. This was associated with an increase in CD36 and MHC Class II expression on hepatic CD11c+CD11b+ DCs in female livers. In contrast, male CD11c-Cre+Fcgr2bfl/fl recipients had decreased hepatic lipids with a corresponding decrease in CD36 and MHC Class II expression on CD11c+ cells. Interestingly, both sexes of CD11c-Cre+Fcgr2bfl/fl recipients had significant decreases in serum cholesterol and TGs with corresponding decreases in liver Fasn transcripts. CONCLUSIONS: The absence of FcγRIIb expression on CD11c+ cells results in sex-dependent alteration in liver inflammation influencing atherogenesis and sex-independent modulation of serum cholesterol and TGs.

An Evaluation of the Incidence of Nephrotoxicity After a Loading Dose of Vancomycin in Patients With Severe Renal Impairment.

BACKGROUND: Loading doses of vancomycin assist in the rapid achievement of target trough concentrations. Patients with renal dysfunction have been excluded from studies evaluating loading doses. OBJECTIVE: The purpose of this study was to investigate nephrotoxicity related to initial vancomycin dose in patients with severe renal dysfunction. METHODS: A retrospective cohort study was approved by the Institutional Review Board of a large, academic health system. Adults were included if they received intravenous vancomycin in the emergency department and presented with creatinine clearance < 30 mL/min. Chronic dialysis patients were excluded. The primary outcome was incidence of nephrotoxicity after an initial high (>20 mg/kg) vs. low (≤20 mg/kg) dose of vancomycin. Secondary outcomes included dialysis, vancomycin concentrations, length of stay, in-hospital mortality, and a composite outcome of nephrotoxicity or dialysis. RESULTS: Of the 927 patients included in the analysis, nephrotoxicity occurred in 7.2% and 13.8% of patients in the high- and low-dose groups, respectively (p < 0.01). Patients in the high-dose group had a reduced risk of nephrotoxicity (relative risk 0.53; 95% confidence interval 0.35-0.78). The reduction in risk remained after fitting a generalized linear model adjusting for weight, age, sex, initial serum creatinine, diabetes, and chronic kidney disease (relative risk 0.61; 95% confidence interval 0.39-0.93). Limitations of this study include its retrospective design and single-center population. CONCLUSION: These data suggest that vancomycin loading doses do not increase nephrotoxicity compared with lower doses in patients with severe renal dysfunction. These patients should be included in future studies relating to vancomycin loading doses.