Richard Formica
· Professor of Medicine (Nephrology) and Professor of Surgery (Transplant); Director of Transplant Medicine, Internal Medicine; Director Outpatient Transplantation Service, Transplantation Center, Yale New Haven Hospital; Medical Director Adult Kidney Transplantation, Transplantation Center, Yale New Haven HospitalVerifiedYale University · Nephrology
Active 1969–2026
About
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Research topics
- Internal medicine
- Medicine
- Intensive care medicine
- Cardiology
- Chemistry
- Surgery
- Psychology
- Pharmacology
- Anesthesia
Selected publications
A Sliding Scale AdaptiVe Expedited rescue algorithm for deceased donor kidney transplantation
American Journal of Transplantation · 2026-03-01
articleSenior authorPlacing Organ Allocation Out of Sequence in the Proper Context
The American Journal of Bioethics · 2026-01-02
article1st authorCorrespondingTransplantation · 2025-09-03 · 2 citations
article1st authorCorrespondingAlthough maintenance immunosuppression with calcineurin inhibitors (CNIs) has greatly reduced rejection rates in renal transplant recipients, long-term use can contribute to eventual nephrotoxicity, potentially leading to allograft injury and loss. Several clinical trials have shown that, compared with CNIs, belatacept-based maintenance immunosuppression can improve renal function, reduce the incidence of de novo donor-specific antibodies, and improve long-term patient/graft survival. However, the US Food and Drug Administration-approved belatacept-based regimen is also associated with higher acute rejection (AR) rates than CNI-based immunosuppression. Recent data from clinical trials and real-world studies suggest that initial posttransplant treatment with CNI-based immunosuppression followed by conversion to a belatacept-based regimen can lower the AR risk while preserving patient and renal health. This review article summarizes the available data pertaining to belatacept treatment protocols, with a focus on conversion to belatacept. Also discussed are studies of protocol modifications intended to further mitigate AR risks and belatacept-related outcomes in special populations, such as patients receiving marginal kidneys and those at risk of new-onset diabetes. Overall, the available data suggest that conversion from CNI- to belatacept-based immunosuppression ≥6 mo posttransplant appears to be effective in lowering the AR risk compared with belatacept use in the de novo setting or conversion <6 mo posttransplant. The addition of an extended transient or low-dose CNI treatment to de novo belatacept or a prolonged CNI taper in the conversion setting may also help lower the AR risk. However, additional studies will be needed to optimize the many variables applicable to belatacept treatment, particularly for different patient subgroups.
The role of eplet matching in solid organ transplantation
Frontiers in Transplantation · 2025-12-08 · 1 citations
articleOpen accessIntroduction: Donor-recipient compatibility remains a central determinant of transplant success, yet conventional antigen-level human leukocyte antigen (HLA) matching provides limited resolution for predicting alloimmune risk. Molecular matching at the eplet level, which quantifies structural motifs on HLA molecules recognized by B- and T-cells, has emerged as a promising strategy to refine immunologic risk assessment. Methods: We conducted a scoping review of 98 studies encompassing 286,101 solid organ transplant (SOT) recipients across kidney, heart, lung, liver, pancreas, and combined grafts. Data on HLA typing approaches, eplet mismatch (epMM) algorithms, thresholds, and associations with clinical outcomes were systematically extracted and synthesized. Results: donor-specific antibodies, antibody mediated rejection, and graft dysfunction. Reported epMM thresholds varied but were most robust for class II loci, while findings for class I loci were less consistent. Observed differences in epMM thresholds and effect sizes reflected both organ-specific immunobiology and methodological heterogeneity, including variation in typing resolution, mismatch algorithms, immunosuppression exposure, and study design. Conclusion: Eplet matching demonstrates significant potential to improve risk stratification and long-term graft outcomes across SOT. However, clinical translation is limited by inconsistent methods, equity concerns, and the absence of standardized epMM thresholds. Prospective studies, harmonized molecular typing, and integration with allocation frameworks are needed to establish the clinical utility and policy implications of molecular-level HLA matching.
Skin Elasticity: A Potential Surrogate Marker for Facial Allograft Skin Fibrosis—A Case Series
Clinical Transplantation · 2025-06-01 · 2 citations
articleINTRODUCTION: Rejection represents a major and common complication in vascularized composite allotransplantation (VCA). Over time, recurrent acute or chronic rejection can lead to vascular and dermal fibrosis and potentially graft loss. To date, a non-invasive monitoring tool to capture chronic graft changes among VCA recipients has not been established. This pilot study aims to assess the potential value of noninvasive skin elasticity measurements for surveillance of longitudinal fibrosis of facial allografts. METHODS: Viscoelasticity was non-invasively assessed via triplicate measurements of the transplanted facial skin on bilateral cheeks and native skin on bilateral upper arms in six face transplant recipients using the well-established Cutometer Dual MPA 580. Data were statistically compared with recipient/donor age, post-transplant years (PTYs), and cumulative rejection burden (CRB), smoking status, ethnicities, and immunosuppressive regimens. RESULTS: A significant (p < 0.05) negative linear relationship between CRB and the Cutometer parameters R2 (gross elasticity), R5 (net elasticity), and R7 (elasticity recovery) was found, which was not observed in control measurements of native skin of VCA recipients. Results were ranked into a three-level severity scale. Comparison with PTYs further revealed a significant negative linear relationship with R2 and R5 values. No statistically significant correlation was detected across R values when evaluated against recipient/donor age, smoking status, ethnicity, or immunosuppressive regimens. CONCLUSIONS: Although diagnosis and monitoring of rejection-associated degenerative skin changes currently still rely on biopsies, this exploratory study identifies skin elasticity as a promising surrogate marker for facial allograft fibrosis.
2. The Potential Role of Eplet Matching in Vascularized Composite Allotransplantation
Transplantation · 2025-06-01
articleIntroduction: Eplet matching represents a paradigm shift in transplant immunology, refining donor-recipient HLA compatibility assessment by focusing on specific polymorphic amino acid clusters rather than whole antigens. In solid organ transplantation, especially kidney transplantation, reduced eplet mismatches have been associated with lower risks of de novo donor-specific antibody (dnDSA) formation and improved graft survival. In vascularized composite allotransplantation (VCA), particularly high allograft immunogenicity, associated with frequent rejections and a high immunosuppressive burden, as well as the elective character of these reconstructive transplantations demand best possible immunogenic risk stratification and donor selection. Methods: Eplet-based mismatches of ten face transplantations, conducted within 2009-2020, were assessed with the HLA Matchmaker program while T cell-mediated alloimmunity was predicted with the PIRCHE (Predicted Indirectly Recognizable HLA Epitopes) algorithm. One case involved a facial re-transplantation due to severe chronic rejection. For this patient eplet matching for both respective donors were performed. The tissue used for these analyses included frozen PBMCs of recipients and frozen donor lymph nodes provided by the New England Donor Services. The relative cumulative rejection burden was calculated as the product of the total amount of days of all bioptically verified rejection episodes since transplantation (defined as Banff scores ≥2) multiplied by the weighted average Banff score of each rejection episode divided by the sum of years since transplantation (CRB = Total rejection days x weighed average Banff score/ years since transplantation). Statistical analysis of eplet mismatching and PIRCHE results with respective CRBs was performed. Established high-risk HLA mismatching thresholds associated with dnDSA development in kidney transplantation were included in the statistical analysis. Results: HLA Matchmaker analysis detected a mean overall mismatching of 31.36 HLA Class I (range 0-66), 41.09 class II (range 0-79), 11.55 HLA-DQ (range 0-27), and 19.45 HLA-DRB1 and -DRB345 (range 0-42) molecules. The mean PIRCHE score was 58.09 (range 0-111). In the single case of facial re-transplantation high mismatching scores were found between the recipient and the first rejected allograft (HLA-DQ: 9, HLA-DRB1, -DRB345: 25, PIRCHE: 102) while zero mismatching was present between the recipient and the second allograft donor (HLA-DQ: 0, DLA-DRB1, -DRB345: 0, PIRCHE: 0). Simple linear regression and correlation models revealed a significant positive linear relationship between CRB and HLA-A mismatching (r=07664, R2=0.5874, p=0.0097). Differentiation between low-/high-risk HLA-DQ, -DRB1/-DRB345 mismatch thresholds HLA‐DR <7 and HLA‐DQ <9) revealed two transplantations with low alloimmune risk with a mean CRB of 19.48, one case of intermediate alloimmune risk (≥7 HLA‐DR and ≥9 HLA‐DQ eplet mismatches) with a mean CRB of 32.52 and seven high-risk mismatching results with a mean CRB of 91.88. Conclusion: The results of this first piloting study show a correlation of low eplet mismatching with low CRB in VCA, suggesting great clinical potential of eplet matching for optimizing donor selection as well as individualized risk assessment and tailored immunosuppression in VCA recipients. More data from larger studies is needed to verify the potential clinical value of eplet matching in VCA and further explore the specific role of HLA-A in VCA.
Transplantation · 2025-01-27 · 3 citations
articleThe organ donation and transplantation system in the United States is governed by a unique public-private partnership, largely driven by high-caliber volunteer contributions. The system includes a Board of Directors, and multiple committees responsible for the development and implementation of transplant policies. The Organ Procurement and Transplantation Network (OPTN) is undergoing a modernization effort supported by the Securing the US OPTN Act (H.R. 2544), enacted September 22, 2023.1 This legislation is designed to improve the management and efficiency of the US organ transplantation system.2,3 Key provisions of the law include allowing the US Department of Health and Human Services to award multiple contracts or grants to operate the OPTN (previously managed by a single contractor), and removing the $7M budgetary cap.4 As part of modernization and securing the independence of a fiduciary Board of Directors, the Independent Network of Volunteers for Equitable and Safe Transplants was created to support the volunteer experts (professionals and patients). These volunteer experts have always been tasked with (1) developing organ allocation policies, (2) overseeing OPTN membership (hospitals, organ procurement organization, and others), and (3) supporting the implementation of new policies alongside a government contractor. We sought to evaluate the economic value of the volunteer hours from committee and board members. We used publicly available data including membership data on the 26 active committees and the Board of Directors (599 positions filled by 459 individual volunteers) and committee meeting schedules from June 2023 to June 2024, available on the OPTN website. During that time, 502 meetings occurred, with a mean of 23.94 participants; assuming each meeting lasted at least 1 h, this conservatively represents 12,019 volunteer hours. OPTN volunteer tasks are executive level; consequently, we valued volunteers’ time at $110.95 /h. (corresponding to a $221,900 annual salary, based on the National Institutes of Health salary cap). Applying this rate to the calculated number of person-hours yields a conservative estimate of $1,333,508.10 for the annual value of this volunteer effort. However, volunteer duties extend beyond board meeting attendance. The OPTN’s 2016–2017 committee volunteer engagement survey reported that volunteers annually volunteered 41,762 h of service. Applying the hourly rate to the total number of hours contributed yields an estimated value of $4,633,493.90. Even this estimate may be conservative since the survey excluded board members, who presumably contribute the most time, and this estimate is meant to give a general sense of the scope of manpower devoted to OPTN committees rather than an attempt to estimate a precise dollar figure. This level of volunteer effort is unique in the US healthcare system, and the expertise provided is invaluable. Given the high value of the volunteer effort, it is unlikely that the government could use or purchase comparable services. Moreover, the extensive involvement of numerous professionals who volunteer their time enriches the diversity of perspectives considered, thereby diminishing the influence of any single vested interest or conflict of interest in the establishment of the OPTN and its policies about organ transplantation. While restructuring the system brings major changes, federal lawmakers and administrators should understand that the minimum calculated monetary value of the volunteer effort is nearly 50% of what the government contract has heretofore provided. While we push forward to constantly improve the system for patients and the American public, the fluid nature of the field requires a volunteer network that has a broad diversity of expertise, experience, geography, sex, ethnicity, creed, and race. ACKNOWLEDGMENTS The completion of this article was conducted with funding from the National Institute of Diabetes and Digestive and Kidney Diseases for award 5R01DK132395-02, entitled “Continuous Allocation Score Design For Guaranteeing Equity and Reducing Discards in Kidney and Liver Transplantation.”
Kidney International Reports · 2025-02-03 · 8 citations
articleOpen accessIntroduction: We recently discovered 2 urinary exosomal mRNA signatures to identify and differentiate T-cell-mediated rejection (TCMR) from antibody-mediated rejection (ABMR) in kidney transplant recipients. Here, we developed Exosome Transplant Rejection Urine (ExoTRU), a urinetest based on a 4-gene signature from the previous discovery cohort, showed its clinical utility in a new cohort of kidney transplant recipients undergoing clinically indicated biopsies, and validated it through a separate laboratory in an independent-cohort of patients. Methods: A workflow suited for clinical laboratories was developed, allowing for smaller urine volumes and widely standardized qPCR instrumentation. A total of 226 urine samples from 214 patients were paired with clinically indicated biopsies. Urinary exosomal mRNAs levels were evaluated for previously defined targets. Results: Four mRNAs (IL32, B2M, CXCL11, and PGK1) performed well in distinguishing biopsies with rejection or significant inflammation from those without inflammation, achieving 94% sensitivity, 62% positive predictive value, and 52% specificity. Patients who tested positive by the signature but negative by biopsy were nearly twice as likely to experience adverse outcomes in the 5-year follow-up period, including subsequent rejection, thereby showing the limitations of kidney biopsies and the prognostic potential of molecular signatures. The evaluation of an independent validation cohort showed similar performance, achieving an area under the curve (AUC) of 0.838. Another 6-gene signature distinguished TCMR from ABMR, with an AUC of 0.756. Conclusion: Exosomal mRNA gene signatures identified patients with different stages and classes of rejection, including early stage and significant inflammation, enabling improved decision-making and patient management and reducing unnecessary biopsies by 45%. This represents a potential tool for risk stratification based on poor outcomes in patients with positive signatures.
The kidneys’ effect on the survival of multi-organ transplant recipients
The Journal of Heart and Lung Transplantation · 2025-08-18
editorial1st authorCorrespondingTransplantation · 2025-06-01
articleIntroduction: Rejection still represents a major and common complication in vascularized composite allotransplantation (VCA). Overtime recurrent and/or chronic rejection lead to vascular and dermal fibrosis, and potentially graft loss. To date, a non-invasive monitoring tool, to capture chronic graft changes among VCA recipients, has not been established. In kidney/liver transplantation, the loss in tissue elasticity has been associated with allograft rejection and fibrosis. This pilot study aims to assess the potential value of skin elasticity measurements for monitoring of rejection-related chronic changes of facial allografts. Methods: Viscoelasticity of transplanted facial skin was non-invasively assessed via triplicate measurements on bilateral cheeks in six face transplant recipients using the well-established Cutometer® dual MPA580 (C+K electronic GmbH). Data was correlated with recipient/donor age, post-transplant duration, and cumulative rejection burden (CRB). The latter was estimated as the product of the total amount of days of bioptically verified rejection episodes since transplantation (Banff scores ≥2) multiplied by the weighted average Banff score of each rejection episode (CRB = total rejection days x average Banff score; analogous to pack-years calculation for smoking). Results: Spearman rank correlation revealed statistical significance between CRB and the cutometer parameters R2 (measure of gross elasticity; R2= 0.8292, p=0.0121), R5 (measure of net elasticity; R2= 0.8496, p=0.0090), and R7 (measure of elasticity recovery; R2= 0.8883, p=0.0049), which was ranked into a three-level severity scale. No statistically significant correlation was detected across R2, R5, or R7 when evaluated against recipient age, donor allograft age, or years post-transplantation (p>0.05). Conclusion: This exploratory study identified that a significant negative linear relationship exists between degree of CRB and measured viscoelasticity of the skin. Higher CRB corresponded with significantly decreased cutometer R values, indicating decreased viscoelasticity of the skin. Longitudinal allograft rejection as seen in VCA transplantation, can manifest with definitive skin changes including vascular narrowing, adnexa deterioration, skin atrophy, and deep tissue fibrosis, all of which may be reflected in the reduced viscoelastic properties of the skin captured by the cutometer. Therefore, the cutometer may hold potential as a quantitative clinical tool for non-invasive surveillance of graft performance, specifically evaluating VCA patients for chronic rejection and/or the cumulative impact of repeated acute rejections over time.
Frequent coauthors
- 37 shared
Sanjay Kulkarni
Yale University
- 20 shared
David C. Mulligan
- 14 shared
William S. Asch
- 13 shared
Darren Stewart
New York University
- 11 shared
Margaret J. Bia
Yale University
- 11 shared
Mark I. Aeder
University Hospitals of Cleveland
- 11 shared
Martin Kauke-Navarro
Yale New Haven Hospital
- 11 shared
John J. Friedewald
Northwestern University
Awards & honors
- Lifetime Achievement Award (2022)
- Regional Award (2022)
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