Patrick Cunningham Ahearn, MD, MAS

All Publications

• Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities. Transplantation direct Caldwell, J. S., Parvathinathan, G., Stedman, M. R., Ahearn, P., Tan, J. C., Cheng, X. S. 2024; 10 (7): e1653

  Abstract

  Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities.We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death.We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10).Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

  View details for DOI 10.1097/TXD.0000000000001653

  View details for PubMedID 38881747

  View details for PubMedCentralID PMC11177818

• Analysis of Cross-sectional and Longitudinal HLA and Anti-viral Responses After COVID Infection in Renal Allograft Recipients: Differences and Correlates. Transplantation Girnita, A. L., Wang, L., Colovai, A. I., Ahearn, P., Azzi, Y., Menon, M. C., Fernandez-Vina, M., Gebel, H. M., Steve Woodle, E., Cravedi, P., Maltzman, J. S., Akalin, E. 2022

  Abstract

  BACKGROUND: Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti-SARS-CoV-2 antibodies.METHODS: This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein.RESULTS: Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti-SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti-SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti-SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1).CONCLUSIONS: Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti-SARS-CoV-2 antibodies were high IgA/IgM.

  View details for DOI 10.1097/TP.0000000000004277

  View details for PubMedID 36070571

• Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN Ahearn, P. n., Johansen, K. L., Tan, J. C., McCulloch, C. E., Grimes, B. A., Ku, E. n. 2021

  Abstract

  Women with kidney failure have lower access to kidney transplantation compared with men, but the magnitude of this disparity may not be uniform across all kidney diseases. We hypothesized that the attributed cause of kidney failure may modify the magnitude of the disparities in transplant access by sex.We performed a retrospective cohort study of adults who developed kidney failure between 2005 and 2017 according to the United States Renal Data System. We used adjusted Cox models to examine the association between sex and either access to waitlist registration or deceased-donor kidney transplantation, and tested for interaction between sex and the attributed cause of kidney failure using adjusted models.Among a total of 1,478,037 patients, 271,111 were registered on the waitlist and 89,574 underwent deceased-donor transplantation. The rate of waitlisting was 6.5 per 100 person-years in women and 8.3 per 100 person-years for men. In adjusted analysis, women had lower access to the waitlist (hazard ratio, 0.89; 95% confidence interval, 0.89 to 0.90) and to deceased-donor transplantation after waitlisting (hazard ratio, 0.96; 95% confidence interval, 0.94 to 0.98). However, there was an interaction between sex and attributed cause of kidney disease in adjusted models (P<0.001). Women with kidney failure due to type 2 diabetes had 27% lower access to the kidney transplant waitlist (hazard ratio, 0.73; 95% confidence interval, 0.72 to 0.74) and 11% lower access to deceased-donor transplantation after waitlisting compared with men (hazard ratio, 0.89; 95% confidence interval, 0.86 to 0.92). In contrast, sex disparities in access to either the waitlist or transplantation were not observed in kidney failure secondary to cystic disease.The disparity in transplant access by sex is not consistent across all causes of kidney failure. Lower deceased-donor transplantation rates in women compared with men are especially notable among patients with kidney failure attributed to diabetes.

  View details for DOI 10.2215/CJN.09140620

  View details for PubMedID 33500250

• Delayed Kinetics of IgG, but not IgA, Anti-spike Antibodies in Transplant Recipients following SARS-CoV-2 Infection. J Am Soc Nephrol. Cravedi, P. 2021

  View details for DOI 10.1681/ASN.2021040573

• Trends in Cardiovascular Mortality Among a Cohort of Children and Young Adults Starting Dialysis in 1995 to 2015. JAMA network open Ku, E., McCulloch, C. E., Ahearn, P., Grimes, B. A., Mitsnefes, M. M. 2020; 3 (9): e2016197

  Abstract

  Importance: Survival of patients receiving dialysis has improved during the last 2 decades. However, few studies have examined temporal trends in the attributed causes of death (especially cardiovascular-related) in young populations.Objective: To determine temporal trends and risk of cause-specific mortality (ie, cardiovascular and infectious) for children and young adults receiving dialysis.Design, Setting, and Participants: This retrospective cohort study examined the records of children and young adults (aged <30 years) starting dialysis between 1995 and 2015 according to the United States Renal Data System database. Analyses were performed between June 2019 and June 2020. Fine-Gray models were used to examine trends in risk of different cardiovascular-related deaths. Models were adjusted for age, sex, race, neighborhood income, cause of end-stage kidney disease, insurance type, and comorbidities. Analyses were performed separately for children (ie, age <18 years) and young adults (between ages 18 and 30 years). Follow-up was censored at death or administratively, and transplantation was treated as a competing event.Exposures: Calendar year.Main Outcomes and Measures: Cardiovascular cause-specific mortality.Results: A total of 80 189 individuals (median [interquartile range] age, 24 [19-28] years; 36 259 [45.2%] female, 29 508 [36.8%] Black, and 15 516 [19.3%] Hispanic white) started dialysis and 16 179 experienced death during a median (interquartile range) of 14.3 (14.0-14.7) years of follow-up. Overall, 40.2% of deaths were from cardiovascular-related causes (6505 of 16 179 patients). In adjusted analysis, risk of cardiovascular-related death was stable initially but became statistically significantly lower after 2006 (vs 1995) in those starting dialysis as either children (subhazard ratio [SHR], 0.74; 95% CI, 0.55-1.00) or adults (SHR, 0.90; 95% CI, 0.83-0.98). Risk of sudden cardiac death improved steadily for all age groups, but to a greater degree in children (SHR, 0.31; 95% CI, 0.20-0.47) vs young adults (SHR, 0.64; 95% CI, 0.56-0.73) comparing 2015 vs 1995. Risk of stroke became statistically significantly lower around 2010 (vs 1995) for children (SHR, 0.40; 95% CI, 0.18-0.88) and young adults (SHR, 0.76; 95% CI, 0.59-0.99).Conclusions and Relevance: In this study, the risk of cardiovascular-related death declined for children and young adults starting dialysis during the last 2 decades, but trends differed depending on age at dialysis initiation and the specific cause of death. Additional studies are needed to improve risk of cardiovascular disease in young populations.

  View details for DOI 10.1001/jamanetworkopen.2020.16197

  View details for PubMedID 32902652