Publications

OBJECTIVE

Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin.

DESIGN/SETTING

We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011. We also investigated the role of leptin in these relationships.

SUBJECTS

Participants were aged ≥18 years, English or Spanish speaking, and receiving hemodialysis for at least 3 months.

MAIN OUTCOME MEASURES

Outcome measures of adiposity included body mass index, waist circumference, and body fat measured by bioelectrical impedance spectroscopy.

RESULTS

Mean age was 56 ± 14 years, 39.8% were female, and median serum FGF-23 was 807 pg/mL. In fully adjusted models, FGF-23 was inversely associated with body mass index (-0.24 kg/m per 50% higher FGF-23, 95% confidence interval [CI]: -0.38 to -0.10), waist circumference (-0.44 cm per 50% higher FGF-23, 95% CI: -0.79 to -0.08), and percent body fat (-0.58% per 50% higher FGF-23, 95% CI: -0.79 to -0.37). Leptin was inversely associated with FGF-23. Addition of leptin to body composition models attenuated the associations between FGF-23 and measures of adiposity, but FGF-23 remained significantly associated with percent body fat (-0.17% per 50% higher FGF-23, 95% CI: -0.32 to -0.02).

CONCLUSION

We found a negative association between FGF-23 and adiposity that appears to be mediated in part by leptin. As adipose tissue provides a "protective energy depot" for patients with chronic illness, a decrease in adipose tissue may be one mechanism in which higher FGF-23 levels may contribute to increased mortality in dialysis patients.

BACKGROUND

Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban.

METHODS

An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality.

RESULTS

Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality.

CONCLUSIONS

Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Background

The independent contributions of microbial translocation and liver fibrosis to immune activation in human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV)-infected persons are unclear.

Methods

Multivariable linear regression was used to evaluate whether intestinal fatty acid binding protein (I-FABP: a marker of gut epithelial integrity) and transient elastography-measured liver fibrosis might mediate the association of HIV and HCV with the soluble CD14 (sCD14) level in 120 individuals with HIV and HCV coinfection, 262 with HIV monoinfection, 72 with HCV monoinfection, and 170 without infection.

Results

Coinfected individuals, HIV-monoinfected individuals, and HCV-monoinfected individuals had 37%, 21%, and 12% higher sCD14 levels, respectively, than uninfected individuals, after multivariable adjustment. Additional adjustment for I-FABP level modestly attenuated the association of HIV infection, but attenuation occurred to a lesser extent in the HCV-monoinfected group. Adjustment for liver fibrosis substantially attenuated the association of HCV infection, but attenuation occurred to a lesser extent in the HIV-monoinfected group. Relative to the uninfected group, the primary mediator of the sCD14 level was the I-FABP level in the HIV-infected groups and liver fibrosis in the HCV-monoinfected group.

Conclusion

HIV and HCV are independently and additively associated with higher a sCD14 level. Our findings suggest that microbial translocation contributes to an increased sCD14 level during HIV infection, whereas liver fibrosis plays a stronger role during HCV monoinfection. Coinfected persons may be at greatest risk for progression, because of the independent effects of microbial translocation and liver fibrosis on immune activation.