Combined liver–kidney transplantation with positive crossmatch: Role of delayed kidney transplantation

Goggins, William C.; Ekser, Burçin; Rokop, Zachary P.; Lutz, Andrew J.; Mihaylov, Plamen; Mangus, Richard S.; Fridell, Jonathan A.; Powelson, John A.; Kubal, Chandrashekhar A.

doi:10.1016/j.surg.2021.05.012

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…While there is a paucity of data on this topic, there are some data that delayed kidney transplants might reduce total and class I donor specific antibodies during the window period before the kidney transplant. 26 As with all historical studies there is missing data, but the dataset is large, which should minimize the impact. The study is subject to misclassification bias, but there is no reason to suspect differential misclassification between the groups.…”

Section: Discussionmentioning

confidence: 99%

“…It becomes challenging to determine whether the underlying immunologic changes before and after the kidney or changes in immune suppression are contributing to any differences in rejection rates. While there is a paucity of data on this topic, there are some data that delayed kidney transplants might reduce total and class I donor specific antibodies during the window period before the kidney transplant 26 . As with all historical studies there is missing data, but the dataset is large, which should minimize the impact.…”

Section: Discussionmentioning

confidence: 99%

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Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone

Ghali,

Ibrahim,

Hodge

et al. 2024

Clinical Transplantation

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BackgroundSimultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a “safety net” policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown.MethodsWe performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss.ResultsSixty‐six thousand seventy‐nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan‐Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups.ConclusionKALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK.Brief summaryPatients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone

Ghali,

Ibrahim,

Hodge

et al. 2024

Clinical Transplantation

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“…There are also cases in the literature of living donor liver transplants who developed acute AMR after desensitization to perform DSA and were successfully treated with bortezomib and everolimus therapy[ 25 ]. In this regard, in sensitized combined liver-kidney transplant recipients, the “delayed” kidney transplant approach was associated with a significant reduction in total and class I DSAs after liver transplantation before kidney transplantation[ 26 ], allowing therapeutic interventions such as plasmapheresis, providing optimal results similar to those of crossmatched recipients.…”

Section: Hla Antibodies and Hla / Kir ...mentioning

confidence: 99%

Human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes are important in transplant immunology in the liver

Muro¹,

Legáz²

2023

World J Gastroenterol

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Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even de novo autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.

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“…The current understanding of pre-existing DSA in SLK transplantation suggests that class I DSA at the time of transplant poses little risk to either transplant. When high levels of class I DSA are crossed, staggering the transplants to allow the liver time to absorb the DSA before implantation of the kidney transplant limits the degree of antibody-mediated damage to the kidney and may prevent ABMR ( 36 ). The same cannot be said for class II DSA where minimal adsorption by the liver is observed and immunomodulation leading to decreases in DSA requires months.…”

Section: Recipients With Pre-transplant Hla Dsa and Outcomesmentioning

confidence: 99%

Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection

Parajuli

Hidalgo²,

Foley³

2022

Front. Transplant.

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Simultaneous liver and kidney (SLK) transplantation is considered the best treatment modality among selected patients with both chronic kidney disease (CKD) and end-stage liver disease (ESLD). Since the first SLK transplant in 1983, the number of SLK transplants has increased worldwide, and particularly in the United States since the implementation of the MELD system in 2002. SLK transplants are considered a relatively low immunological risk procedure evidenced by multiple studies displaying the immunomodulatory properties of the liver on the immune system of SLK recipients. SLK recipients demonstrate lower rates of both cellular and antibody-mediated rejection on the kidney allograft when compared to kidney transplant-alone recipients. Therefore, SLK transplants in the setting of preformed donor-specific HLA antibodies (DSA) are a common practice, at many centers. Acceptance and transplantation of SLKs are based solely on ABO compatibility without much consideration of crossmatch results or DSA levels. However, some studies suggest an increased risk for rejection for SLK recipients transplanted across high levels of pre-formed HLA DSA. Despite this, there is no consensus regarding acceptable levels of pre-formed DSA, the role of pre-transplant desensitization, splenectomy, or immunosuppressive management in this unique population. Also, the impact of post-transplant DSA monitoring on long-term outcomes is not well-studied in SLK recipients. In this article, we review recent and relevant past articles in this field with a focus on the immunological risk factors among SLK recipients, and strategies to mitigate the negative outcomes among them.

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Combined liver–kidney transplantation with positive crossmatch: Role of delayed kidney transplantation

Cited by 8 publications

References 24 publications

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone

Human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes are important in transplant immunology in the liver

Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection

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