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Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

ABSTRACT: Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 ?mol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 ?mol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

SUBMITTER: Eder M

PROVIDER: S-EPMC6585795 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Eder Michael M Schwarz Christoph C Kammer Michael M Jacobsen Niels N Stavroula Masouridi Levrat ML Cowan Morton J MJ Chongkrairatanakul Tepsiri T Gaston Robert R Ravanan Rommel R Ishida Hideki H Bachmann Anette A Alvarez Sergio S Koch Martina M Garrouste Cyril C Duffner Ulrich A UA Cullis Brett B Schaap Nicolaas N Medinger Michael M Sørensen Søren Schwartz SS Dauber Eva-Maria EM Böhmig Georg G Regele Heinz H Berlakovich Gabriela A GA Wekerle Thomas T Oberbauer Rainer R

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20180713 2

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem ce ...[more]

PMID: 29900661

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Project description:Background and objectivesIn the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described.Design, setting, participants, & measurementsUsing registry-linked data, we compared National Kidney Registry (n=2363) recipients to control kidney transplant recipients (n=54,497) (February 2008 to December 2017). We estimated the risk of death-censored graft failure and mortality using inverse probability of treatment weighted Cox regression. The parsimonious model adjusted for recipient factors (age, sex, black, race, body mass index ≥30 kg/m2, diabetes, previous transplant, preemptive transplant, public insurance, hepatitis C, eGFR, antibody depleting induction therapy, year of transplant), donor factors (age, sex, Hispanic ethnicity, body mass index ≥30 kg/m2), and transplant factors (zero HLA mismatch).ResultsNational Kidney Registry recipients were more likely to be women, black, older, on public insurance, have panel reactive antibodies >80%, spend longer on dialysis, and be previous transplant recipients. National Kidney Registry recipients were followed for a median 3.7 years (interquartile range, 2.1-5.6; maximum 10.9 years). National Kidney Registry recipients had similar graft failure (5% versus 6%; log-rank P=0.2) and mortality (9% versus 10%; log-rank P=0.4) incidence compared with controls during follow-up. After adjustment for donor, recipient, and transplant factors, there no detectable difference in graft failure (adjusted hazard ratio, 0.95; 95% confidence interval, 0.77 to 1.18; P=0.6) or mortality (adjusted hazard ratio, 0.86; 95% confidence interval, 0.70 to 1.07; P=0.2) between National Kidney Registry and control recipients.ConclusionsEven after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

Project description:Delayed renal allograft survival (delayed graft function [DGF]) after deceased donor kidney transplantation is associated with an increased risk of allograft loss. Inflammatory response and apoptosis are associated with increased risk of DGF.Cross-sectional study.We first recruited 616 recipients of kidneys from 512 deceased kidney donors, and donor DNA was genotyped. These recipients, who were included in a prospective cohort study of 9 transplant centers in the Delaware Valley region, had their DGF outcome obtained through medical record abstraction. We then identified the recipient (n = 349) of the contralateral deceased kidney donor, if not part of the cohort, through the US Renal Data System registry. The final cohort consisted of 965 recipients of deceased donor kidneys from 512 donors.Donor single-nucleotide polymorphisms in genes for tumor necrosis factor alpha (TNF), transforming growth factor beta1 (TGFB1), interleukin 10 (IL10), p53 (TP53), and heme oxygenase 1 (HMOX1).DGF, defined as the need for dialysis therapy in the first week posttransplantation. Secondary outcomes included acute rejection and estimated glomerular filtration rate.Information for DGF, acute rejection, and estimated glomerular filtration rate for recipients in the Delaware Valley Cohort was obtained through medical record abstraction. For other recipients, information for DGF was obtained from United Network for Organ Sharing forms and Centers for Medicare & Medicaid Services claims in the US Renal Data System registry.No association was detected between the TGFB1, IL10, TP53, and HMOX1 genes and DGF. The G allele of the TNF polymorphism rs3093662 was associated with DGF in an adjusted analysis (odds ratio, 1.85 compared with A allele; 95% confidence interval, 1.16 to 2.96; P = 0.01). However, this association did not achieve statistical significance after adjusting for multiple comparisons.Inadequate sample size for infrequent genotypes and multiple comparisons.Because of the low frequency of donor single-nucleotide polymorphisms of interest, a larger sample size and replication are necessary to confirm these findings on the association of donor genotypes with DGF.

Dataset Information

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Publications

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

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