Factors affecting willingness to receive a kidney transplant among minority patients at an urban safety-net hospital: a cross-sectional survey

Abstract Background In the US, African Americans (AAs) are four times more likely to develop end stage renal disease (ESRD) but half as likely to receive a kidney transplant as whites. Patient interest in kidney transplantation is a fundamental step in the kidney transplant referral process. Our aim was to determine the factors associated with the willingness to receive a kidney transplant among chronic kidney disease (CKD) patients in a predominantly minority population. Methods CKD patients from an outpatient nephrology clinic at a safety-net hospital (n = 213) participated in a cross-sectional survey from April to June, 2013 to examine the factors associated with willingness to receive a kidney transplant among a predominantly minority population. The study questionnaire was developed from previously published literature. Multivariable logistic regression analysis was used to determine factors associated with willingness to undergo a kidney transplant. Results Respondents were primarily AAs (91.0 %), mostly female (57.6 %) and middle aged (51.6 %). Overall, 53.9 % of participants were willing to undergo a kidney transplant. Willingness to undergo a kidney transplant was associated with a positive perception towards living kidney donation (OR 7.31, 95 % CI: 1.31–40.88), willingness to attend a class about kidney transplant (OR = 7.15, CI: 1.76–29.05), perception that a kidney transplant will improve quality of life compared to dialysis (OR = 5.40, 95 % CI: 1.97–14.81), and obtaining information on kidney transplant from other sources vs. participant’s physician (OR =3.30, 95 % CI: 1.13–9.67), when compared with their reference groups. Conclusion It is essential that the quality of life benefits of kidney transplantation be known to individuals with CKD to increase their willingness to undergo kidney transplantation. Availability of multiple sources of information and classes on kidney transplantation may also contribute to willingness to undergo kidney transplantation, especially among AAs.http://deepblue.lib.umich.edu/bitstream/2027.42/116033/1/12882_2015_Article_186.pd

Transferrinfection. A Highly Efficient Way to Express Gene Constructs in Eukaryotic Cells

No abstract available

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation

Background African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years

Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA+ cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Attribution of cause of end-stage renal disease among patients with systemic lupus erythematosus: the Georgia Lupus Registry

OBJECTIVE: Whether using provider-attributed end-stage renal disease (ESRD) cause of systemic lupus erythematosus (SLE) in national surveillance data captures the entire population of patients with SLE and ESRD remains uncertain. Our goal was to examine attributed cause of ESRD in US surveillance data among patients with SLE who have developed ESRD. METHODS: Data from a national registry of treated ESRD (United States Renal Data System (USRDS)) were linked to the population-based Georgia Lupus Registry (GLR). The provider-attributed cause of ESRD was extracted from the USRDS for each validated patient with SLE in the GLR (diagnosed through 2004) who initiated treatment for ESRD through 2012. The percentage of these patients with SLE whose ESRD was subsequently attributed to SLE in the USRDS was calculated, overall and by patient characteristics. RESULTS: Among 251 patients with SLE who progressed to ESRD, 78.9% had SLE as their attributed cause of ESRD. Of the remaining 53 patients, 43.4%, 18.9% and 15.6% had ESRD attributed to hypertension, diabetes mellitus type II and non-SLE-related glomerulonephritis, respectively. Attribution of ESRD to SLE was higher among patients aged ≤30 (87.9–93.9%) vs >30 (52.6%; p<0.001) but did not differ by sex or race. Having Medicaid (86.2%) or no insurance (93.5%) was associated with greater attribution of ESRD to SLE than having private insurance (72.5%; p=0.02), as was having two or more providers state a diagnosis of SLE (89.0% vs 73.5% with a rheumatologist diagnosis alone; p=0.008). CONCLUSIONS: These estimates indicate that USRDS-based studies may underreport ESRD among US patients with SLE. However, observed patterns of differential attribution of ESRD cause, particularly by age, suggest that providers may be correctly attributing ESRD to causes other than SLE among some patients with SLE