Use of anti-spike monoclonal antibodies in kidney transplant recipients with COVID-19: Efficacy, ethnic and racial disparities.
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ABSTRACT:
SUBMITTER: Klein EJ
PROVIDER: S-EPMC8652993 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To investigate racial and ethnic differences in graft and recipient survival in elderly kidney transplant recipients.Retrospective cohort.First-time, kidney-only transplant recipients aged 60 and older of age at transplantation transplanted between July 1996 and October 2010 (N = 44,013).United Network for Organ Sharing (UNOS) database.Time to graft failure and death obtained from the UNOS database and linkage to the Social Security Death Index. Neighborhood poverty from 2000 U.S. Census geographic data.Of the 44,013 recipients in the sample, 20% were black, 63% non-Hispanic white, 11% Hispanic, 5% Asian, and the rest "other racial groups." In adjusted Cox models, blacks were more likely than whites to experience graft failure (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.15-1.32), whereas Hispanics (HR = 0.77, 95% CI = 0.70-0.85) and Asians (HR = 0.70, 95% CI = 0.61-0.81) were less likely to experience graft failure. Blacks (HR = 0.84, 95% CI = 0.80-0.88), Hispanics (HR = 0.68, 95% CI = 0.64-0.72), and Asians (HR = 0.62, 95% CI = 0.57-0.68) were less likely than whites to die after renal transplantation.Elderly blacks are at greater risk of graft failure than white transplant recipients but survive longer after transplantation. Asians have the highest recipient and graft survival, followed by Hispanics. Further studies are needed to assess additional factors affecting graft and recipient survival in elderly adults and to investigate outcomes such as quality of life.
| S-EPMC4701211 | biostudies-literature
Project description:Disparities in outcomes for African American (AA) kidney transplant recipients have persisted for 40 years without a comprehensive analysis of evolving trends in the risks associated with this disparity. Here we analyzed U.S. transplant registry data, which included adult Caucasian or AA solitary kidney recipients undergoing transplantation between 1990 and 2009 comprising 202,085 transplantations. During this 20-year period, the estimated rate of 5-year graft loss decreased from 27.6% to 12.8%. Notable trends in baseline characteristics that significantly differed by race over time included the following: increased prevalence of diabetes from 2001 to 2009 in AAs (5-year slope difference: 3.4%), longer time on the waiting list (76.5 more days per 5 years in AAs), fewer living donors in AAs from 2003 to 2009 (5-year slope difference: -3.36%), more circulatory death donors in AAs from 2000-09 (5-year slope difference: 1.78%), and a slower decline in delayed graft function in AAs (5-year slope difference: 0.85%). The absolute risk difference between AAs and Caucasians for 5-year graft loss significantly declined over time (-0.92% decrease per 5 years), whereas the relative risk difference actually significantly increased (3.4% increase per 5 years). These results provide a mixed picture of both promising and concerning trends in disparities for AA kidney transplant recipients. Thus, although the disparity for graft loss has significantly improved, equity is still far off, and other disparities, including living donation rates and delayed graft function rates, have widened during this time.
| S-EPMC5026578 | biostudies-literature
Project description:BackgroundPrevious studies in adult hemodialysis patients have shown that African-American and Hispanic patients have a lower risk of mortality in addition to a lower likelihood of kidney transplantation. However, studies of the association between race and outcomes in pediatric dialysis are sparse and often do not examine outcomes in Hispanic children. The objective was to determine if racial-ethnic disparities in mortality and kidney transplantation outcomes exist in pediatric dialysis patients.MethodsThis was a retrospective cohort analysis of 2,697 pediatric dialysis patients (aged 0-20 years) from a large national dialysis organization (entry period 2001-2011) of non-Hispanic white, African-American, and Hispanic race-ethnicity. Associations between race-ethnicity with mortality and kidney transplantation outcomes were examined separately using competing risks methods. Logistic regression analyses were used to examine the association between race-ethnicity, with outcomes within 1 year of dialysis initiation.ResultsOf the 2,697 pediatric patients in this cohort, 895 were African-American, 778 were Hispanic, and 1,024 were non-Hispanic white. After adjusting for baseline demographics, competing risk survival analysis revealed that compared with non-Hispanic whites, African-Americans had a 64 % higher mortality risk (hazards ratio [HR] = 1.64; 95 % CI 1.24-2.17), whereas Hispanics had a 31 % lower mortality risk (HR = 0.69; 95 % CI 0.47-1.01) that did not reach statistical significance. African-Americans also had higher odds of 1-year mortality after starting dialysis (odds ratio [OR] = 2.08; 95 % CI 0.95-4.58), whereas both African-Americans and Hispanics had a lower odds of receiving a transplant within 1 year of starting dialysis (OR = 0.28; 95 % CI 0.19-0.41 and OR = 0.43; 95 % CI 0.31-0.59 respectively).ConclusionIn contrast to adults, African-American pediatric dialysis patients have worse survival than their non-Hispanic white counterparts, whereas Hispanics have a similar to lower mortality risk. Both African-American and Hispanic pediatric dialysis patients had a lower likelihood of kidney transplantation than non-Hispanic whites, similar to observations in the adult dialysis population.
| S-EPMC5392236 | biostudies-literature
Project description:BackgroundAlthough kidney transplant improves reproductive function in women with end-stage kidney disease (ESKD), pregnancy in kidney transplant recipients' remains challenging due to the risk of adverse maternal and fetal outcomes.MethodsWe evaluated a retrospective cohort of 7,966 women who were aged 15-45 years and received a kidney transplant between January 1, 2005 and December 31, 2011 from the United States Renal Data System with Medicare as the primary payer for the entire three years after the date of transplantation. Unadjusted and adjusted rates of pregnancy in the first three post-transplant years were calculated, using Poisson regression for the adjustment. Factors associated with pregnancy, including race, were examined using logistic regression.ResultsOverall, 293 pregnancies were identified in 7966 women. The unadjusted pregnancy rate was 13.8 per thousand person-years (PTPY) (95% confidence interval (CI), 12.3-15.5). Pregnancy rates were roughly constant in the years 2005-2011 except in 2005 and 2010. The rate of pregnancy was highest in Hispanic women (21.4 PTPY; 95% CI, 17.2-26.4) and Hispanic women had a higher likelihood of pregnancy as compared to white women (OR, 1.56; CI, 1.12-2.16). Pregnancy rates were lowest in women aged 30-34 years and 35-45 years at transplant, and women aged 30-34 years and 35-45 years at transplant were less likely to ever become pregnant during the follow-up (odds ratio [OR], 0.69; CI, 0.49-0.98 and OR, 0.14; CI 0.09-0.21 respectively) as compared to women aged 25-29 years at time of transplant. Women had higher rates of pregnancy in the second and third-year post-transplant (16.0 PTPY, CI 13.2-19.2 and 16.9 PTPY, CI 14.0-20.4) than in the first-year post-transplant (9.0 PTPY, CI 7.0-11.4). In transplant recipients, pregnancy was more likely in women with ESKD due to cystic disease (OR, 2.42; CI, 1.02-5.74) or glomerulonephritis (OR, 2.14; CI, 1.07-4.31) as compared to women with ESKD due to diabetes.ConclusionHispanic race, younger age, and ESKD cause due to cystic disease or glomerulonephritis are significant factors associated with a higher likelihood of pregnancy. Pregnancy rates have been fairly constant over the last decade. This study improves our understanding of factors associated with pregnancy in kidney transplant recipients.
| S-EPMC6688836 | biostudies-literature
Project description:BackgroundNon-Hispanic black (NHB) and Hispanic patients have lower access to kidney transplantation compared to non-Hispanic whites (NHWs). We examined whether differences in the prevalence of comorbidities that affect eligibility for transplant contribute to disparities in receipt of transplantation.MethodsWe performed a retrospective study of 986 019 adults who started dialysis between 2005 and 2014, according to the United States Renal Data System. We compared prevalence of comorbidities that could influence transplant eligibility by race/ethnicity. We examined time to first transplant by race/ethnicity in this overall cohort and in a very healthy sub-cohort without conditions that could be contraindications to transplantation.ResultsDuring 2.3 years of mean follow-up, 64 892 transplants occurred. NHBs and Hispanics had a lower prevalence of medical barriers to transplantation at the time of dialysis initiation than NHWs, including age >70 years (26% in NHB versus 47% in NHW) and malignancy (4% in Hispanics versus 10% in NHWs). Access to transplant was 65% lower (95% CI, 0.33-0.37) in NHBs and 43% lower (95% CI, 0.54-0.62) in Hispanics (versus NHWs) in the first year after end-stage renal disease, but by Year 4, access to transplantation was not statistically significantly different between Hispanics or NHBs (versus NHWs). In our very healthy cohort, racial and ethnic disparities in access to transplantation persisted up to Year 5 in NHBs and Year 4 in Hispanics after end-stage renal disease onset.ConclusionsDifferences in medical eligibility do not appear to explain racial/ethnic disparities in receipt of kidney transplantation and may mask the actual magnitude of the inequities that are present.
| S-EPMC7067676 | biostudies-literature
Project description:BACKGROUND Disparities research has traditionally focused on patient-level variables to ascertain predominant risk factors driving differences in outcomes for African-American (AA) kidney transplant recipients. Our objectives were to determine the magnitude and impact of transplant center variability for graft outcome disparities. MATERIAL AND METHODS This was a retrospective cohort study analyzing 25 years of U.S. national transplant registry data at both the patient and center levels using univariate descriptive statistics and multivariable modeling. RESULTS A total of 257,024 recipients from 191 centers were analyzed; AAs represented 31.1% of recipients. After adjusting for baseline characteristics, AAs had 42% higher risk of graft loss (aHR 1.42, 95% CI 1.39 to 1.45; p<0.001). Center variability for graft outcome disparities in AAs was significant (race*center interaction term p<0.05), with the aHRs ranging from 0.5 to 4.9; 46% of centers demonstrated a non-statistically significant disparity (aHR p>0.05) and 25% of centers had a large AA disparity (aHR >1.75). In a more recent transplant time period (2000-14), overall racial disparities decreased but center-level disparities increased in variability. Center-level factors significantly associated with increasing disparity included higher acute rejection rates, fewer transplants per year, longer length of stay, lower use of calcineurin inhibitors (CNI), and lower living donor rates. CONCLUSIONS There is evidence of significant center-level variability in graft outcome disparities for AA kidney recipients. Further, there appears to be a number of center-level factors associated with this variability, including acute rejection rates, CNI use, number of transplants per year, and, in recent years, low living donor rates.
| S-EPMC6019128 | biostudies-literature
Project description:Racial disparities persist in the United States renal transplantation process. Previous studies suggest that the distance between a patient's residence and the transplant facility may associate with disparities in transplant waitlisting. We examined this possibility in a cohort study using data for incident, adult ESRD patients (1998 to 2002) from the ESRD Network 6, which includes Georgia, North Carolina, and South Carolina. We linked data with the United Network for Organ Sharing (UNOS) transplant registry through 2005 and with the 2000 U.S. Census geographic data. Of the 35,346 subjects included in the analysis, 12% were waitlisted, 57% were black, 50% were men, 20% were impoverished, 45% had diabetes as the primary etiology of ESRD, and 73% had two or more comorbidities. The median distance from patient residence to the nearest transplant center was 48 mi. After controlling for multiple covariates, distance from patient residence to transplant center did not predict placement on the transplant waitlist. In contrast, race, neighborhood poverty, gender, age, diabetes, hypertension, body mass index, albumin, and the use of erythropoietin at dialysis initiation was associated with waitlisting. As neighborhood poverty increased, the likelihood of waitlisting decreased for blacks compared with whites in each poverty category; in the poorest neighborhoods, blacks were 57% less likely to be waitlisted than whites. This study suggests that improving the allocation of kidneys may require a focus on poor communities.
| S-EPMC2689891 | biostudies-literature
Project description:BackgroundMorbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.MethodsWe performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.ResultsThere were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.ConclusionsBamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.
| S-EPMC8967616 | biostudies-literature
Project description:IntroductionKidney transplant recipients (KTRs) are at high risk of severe COVID-19, even when they are fully vaccinated. Additional booster vaccinations or passive immunization with prophylactic monoclonal antibodies are recommended to increase their protection against severe COVID-19.MethodsHere, we describe the neutralization of SARS-CoV-2 Delta, Omicron BA.1, BA.2, BA.4, and BA.5 variants, firstly by 39 serum samples from vaccinated KTRs exhibiting anti-spike antibody concentrations ≥264 binding antibody units (BAU)/mL and, secondly, by tixagevimab/cilgavimab.ResultsNo neutralization was observed for 18% of the KTRs, while serum from only 46% of patients could neutralize the five variants. Cross-neutralization of the Delta and Omicron variants occurred for 65-87% of sera samples. The anti-spike antibody concentration correlated with neutralization activity for all the variants. The neutralization titers against the Delta variant were higher in vaccinated KTRs who had previously presented with COVID-19, compared to those KTRs who had only been vaccinated. Breakthrough infections occurred in 39% of the KTRs after the study. Tixagevimab/cilgavimab poorly neutralizes Omicron variants, particularly BA.5, and does not neutralize BQ.1, which is currently the most prevalent strain.DiscussionAs a result, sera from seropositive vaccinated KTRs had poor neutralization of the successive Omicron variants. Several Omicron variants are able to escape tixagevimab/cilgavimab.
| S-EPMC10095161 | biostudies-literature