Long-Term Survival after Kidney Transplantation

Hariharan, Sundaram; Israni, Ajay K.; Danovitch, Gabriel M.

doi:10.1056/nejmra2014530

Cited by 352 publications

(238 citation statements)

References 99 publications

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“…Therefore, one of the major goals in transplant medicine is to prolong the time of allograft survival, especially as more and more allografts with extended donor criteria have to be used to overcome organ shortage (2,(24)(25)(26)(27)(28). Despite major improvements in transplant patient care and therein immunosuppressive treatment, acute and chronic rejection processes often irreversibly damaging renal allograft tissues are The relative frequencies are derived from the respective total number of samples in each status group.…”

Section: Discussionmentioning

confidence: 99%

“…still a major risk for premature allograft loss (1,2,29). Strategies to completely prevent allograft rejection are still missing, and diagnostic procedures for early detection of rejection are still suboptimal.…”

Section: Discussionmentioning

confidence: 99%

“…Despite a steady improvement of patient and organ survival after renal transplantation, allograft rejection continues to pose a risk of graft damage. In the first week and month after transplantation, T-cell-mediated rejection (TCMR) in particular is more common, while later antibody-mediated rejection (ABMR) accounts for the majority of immunological graft damages (1,2).…”

Section: Introductionmentioning

confidence: 99%

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A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment

et al. 2022

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Background: In an earlier monocentric study, we have developed a novel non-invasive test system for the prediction of renal allograft rejection, based on the detection of a specific urine metabolite constellation. To further validate our results in a large real-world patient cohort, we designed a multicentric observational prospective study (PARASOL) including six independent European transplant centers. This article describes the study protocol and characteristics of recruited better patients as subjects.Methods: Within the PARASOL study, urine samples were taken from renal transplant recipients when kidney biopsies were performed. According to the Banff classification, urine samples were assigned to a case group (renal allograft rejection), a control group (normal renal histology), or an additional group (kidney damage other than rejection).Results: Between June 2017 and March 2020, 972 transplant recipients were included in the trial (1,230 urine samples and matched biopsies, respectively). Overall, 237 samples (19.3%) were assigned to the case group, 541 (44.0%) to the control group, and 452 (36.7%) samples to the additional group. About 65.9% were obtained from male patients, the mean age of transplant recipients participating in the study was 53.7 ± 13.8 years. The most frequently used immunosuppressive drugs were tacrolimus (92.8%), mycophenolate mofetil (88.0%), and steroids (79.3%). Antihypertensives and antidiabetics were used in 88.0 and 27.4% of the patients, respectively. Approximately 20.9% of patients showed the presence of circulating donor-specific anti-HLA IgG antibodies at time of biopsy. Most of the samples (51.1%) were collected within the first 6 months after transplantation, 48.0% were protocol biopsies, followed by event-driven (43.6%), and follow-up biopsies (8.5%). Over time the proportion of biopsies classified into the categories Banff 4 (T-cell-mediated rejection [TCMR]) and Banff 1 (normal tissue) decreased whereas Banff 2 (antibody-mediated rejection [ABMR]) and Banff 5I (mild interstitial fibrosis and tubular atrophy) increased to 84.2 and 74.5%, respectively, after 4 years post transplantation. Patients with rejection showed worse kidney function than patients without rejection.Conclusion: The clinical characteristics of subjects recruited indicate a patient cohort typical for routine renal transplantation all over Europe. A typical shift from T-cellular early rejections episodes to later antibody mediated allograft damage over time after renal transplantation further strengthens the usefulness of our cohort for the evaluation of novel biomarkers for allograft damage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment

et al. 2022

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“…The survival advantages of transplantation over long-term dialysis are known if a given patient with end-stage kidney disease is suitable for a transplant. A major challenge is to optimize modifiable variables that could improve long-term survival [ 34 ], and with the present study, we aimed to assess the impact of recipient demographic characteristics of sex, ethnicity, and BMI on kidney grafts retrieved from LDs.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Recipient Demographics on Outcomes from Living Donor Kidneys: Systematic Review and Meta-Analysis

Bellini

Nozdrin

Pengel

et al. 2021

JCM

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Background and Aims: Recipient demographics affect outcomes after kidney transplantation. The aim of this study was to assess, for kidneys retrieved from living donors, the effect of recipient sex, ethnicity, and body mass index (BMI) on delayed graft function (DGF) and one-year graft function, incidence of acute rejection (AR), and recipient and graft survivals. Methods: A systematic review and meta-analysis was performed. EMBASE and MEDLINE databases were searched using algorithms through Ovid. Web of Science collection, BIOSIS, CABI, Korean Journal database, Russian Science Citation Index, and SciELO were searched through Web of Science. Cochrane database was also searched. Risk of bias was assessed using the NHBLI tools. Data analysis was performed using Revman 5.4. Mean difference (MD) and risk ratio (RR) were used in analysis. Results: A total of 5129 studies were identified; 24 studies met the inclusion criteria and were analysed. Female recipients were found to have a significantly lower serum creatinine 1-year-post renal transplantation (MD: −0.24 mg/dL 95%CI: −0.18 to −0.29 p < 0.01) compared to male recipients. No significant difference in survival between male and female recipients nor between Caucasians and Africans was observed (p = 0.08). However, Caucasian recipients had a higher 1-year graft survival compared to African recipients (95% CI 0.52−0.98) with also a lower incidence of DGF (RR = 0.63 p < 0.01) and AR (RR = 0.55 p < 0.01). Recipient obesity (BMI > 30) was found to have no effect on 1-year recipient (p = 0.28) and graft survival (p = 0.93) compared to non-obese recipients although non-obese recipients had a lower rate of DGF (RR = 0.65 p < 0.01) and AR (RR = 0.81 p < 0.01) compared to obese recipients. Conclusions: Gender mismatch between male recipients and female donors has negative impact on graft survival. African ethnicity and obesity do not to influence recipient and graft survival but negatively affect DGF and AR rates.

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“…Renal transplantation is the established treatment of choice for kidney failure, as it confers both the highest survival and the best quality of life compared to other renal replacement therapies ( 1 ). Despite continuous advances in the field of solid organ transplantation, long-term outcomes of kidney allografts have only modestly improved in the last decades.…”

Section: Introductionmentioning

confidence: 99%

Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives

Podestà

Sykes

2022

Front. Immunol.

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Chronic rejection and immunosuppression-related toxicity severely affect long-term outcomes of kidney transplantation. The induction of transplantation tolerance – the lack of destructive immune responses to a transplanted organ in the absence of immunosuppression – could potentially overcome these limitations. Immune tolerance to kidney allografts from living donors has been successfully achieved in humans through clinical protocols based on chimerism induction with hematopoietic cell transplantation after non-myeloablative conditioning. Notably, two of these protocols have led to immune tolerance in a significant fraction of HLA-mismatched donor-recipient combinations, which represent the large majority of cases in clinical practice. Studies in mice and large animals have been critical in dissecting tolerance mechanisms and in selecting the most promising approaches for human translation. However, there are several key differences in tolerance induction between these models and humans, including the rate of success and stability of donor chimerism, as well as the relative contribution of different mechanisms in inducing donor-specific unresponsiveness. Kidney allograft tolerance achieved through durable full-donor chimerism may be due to central deletion of graft-reactive donor T cells, even though mechanistic data from patient series are lacking. On the other hand, immune tolerance attained with transient mixed chimerism-based protocols initially relies on Treg-mediated suppression, followed by peripheral deletion of donor-reactive recipient T-cell clones under antigenic pressure from the graft. These conclusions were supported by data deriving from novel high-throughput T-cell receptor sequencing approaches that allowed tracking of alloreactive repertoires over time. In this review, we summarize the most important mechanistic studies on tolerance induction with combined kidney-bone marrow transplantation in humans, discussing open issues that still need to be addressed and focusing on techniques developed in recent years to efficiently monitor the alloresponse in tolerance trials. These cutting-edge methods will be instrumental for the development of immune tolerance protocols with improved efficacy and to identify patients amenable to safe immunosuppression withdrawal.

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Long-Term Survival after Kidney Transplantation

Cited by 352 publications

References 99 publications

A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment

A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment

The Impact of Recipient Demographics on Outcomes from Living Donor Kidneys: Systematic Review and Meta-Analysis

Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives

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