Clinical Transplantation最新文献

Introduction

Procurements from controlled donation after circulatory death donors (cDCD donors) are increasing in France, with systematic abdominal normothermic regional perfusion (A-NRP). However, some procedures are aborted due to technical difficulties to cannulate, which could be avoided by exclusive surgical femoral cannulation. The objective of this study was to describe the results of organ procurement and kidney transplantation following withdrawal of life sustaining therapy (WLST) with exclusive femoral surgical cannulation.

Material and Methods

We performed a retrospective analysis of all the kidney procurement procedures from cDCD donors with femoral cannulation performed by our surgical team and the subsequent kidney transplantations performed in our center.

Results

We performed 60 procurements from cDCD donors and 52 subsequent kidney transplantations. Thirty-six (60%) WLST took place in the intensive care unit (ICU) and 24 (40%) were performed in the operating room (OR). Arterial and venous femoral surgical cannulation was successfully achieved within the authorized timeframe in 100% of cases with a median time of 15 min (Q1–Q3: 12–18).

Conclusion

This single-center experience highlights the feasibility of exclusive surgical femoral cannulation for NRP initiation, with high technical success and favorable ischemia times.

Background

Kidney transplant recipients are at increased risk for infections such as BK virus, with few treatment options. This study assessed how nonidentical but compatible ABO blood types influence BKPyV-DNAemia risk.

Methods

We conducted a retrospective single-center study from 1/1/2011 to 1/12/2021, focusing on BK viremia (>10 000 copies/mL in two consecutive measurements one week apart) within the first posttransplant year. We used stepwise forward regression for multivariate analysis.

Results

Of the 1244 transplants, 1084 involved identical blood types. The percentage of living donor grafts was 63.3% (787 cases), with 98.8% (158 cases) in the mismatched blood type group. There were 78 significant BK viremia episodes in the first year, occurring in 5.5% of matched and 11.3% of mismatched blood type recipients (OR 2.16, p = 0.006). For living donors, the viremia rate was 6% overall, with 4.6% in the matched blood type group and 11.4% in the mismatched blood type group (OR 2.22, p = 0.001). Multivariate analysis revealed an increased risk of mismatched blood types in living donor grafts (OR = 2.75, p = 0.002).

Conclusions

This study revealed an association between blood type mismatch and increased BK viremia in kidney transplant recipients, highlighting a modifiable risk factor for clinicians in organ procurement.

Introduction

There are no effective therapeutic agents for preventing or treating delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs). Donor and recipient factors are important to predicting DGF and associated outcomes, which we hypothesize differed over time.

Methods

DDKTRs were stratified by transplant year into four eras—E1 (2000–2005), E2 (2006–2011), E3 (2012–2017), and E4 (2018–2021). We analyzed risk factors for DGF, along with one-year uncensored graft failure (UCGF), death-censored graft failure (DCGF), death with a functioning graft (DWFG), and acute rejection (AR) by era.

Results

A total of 3085 DDKTRs were included (E1: 804, E2: 882, E3: 909, E4: 490). The proportion of patients with DGF differed significantly by era. Duration of DGF and median dialysis count were lower in recent eras.

In E1-E4, donation after circulatory death, higher donor terminal serum creatinine, and pretransplant duration of dialysis were risk factors for DGF, while preemptive transplant was associated with lower odds of DGF. Other factors were not consistently associated with DGF across eras.

The risk of one-year AR was significantly lower in E3 (aHR: 0.46; 95% CI: 0.30–0.69, p < 0.001) and E4 (aHR: 0.16; 95% CI: 0.07–0.36, p < 0.001) compared to E1. There were trends towards decreased risk for UCGF and DWFG in E2, E3, and E4.

Conclusion

Some risk factors for DGF remained consistent, while others differed. Likely due to improved management, the risk for AR in the DGF setting improved in recent eras. There were trends of improved uncensored graft and patient survival in recent eras.

Background

Antibodies to donor HLA (DSA) and non-HLA antigens are associated with detrimental outcomes in kidney, heart, and lung transplants. Such data are scarce in liver transplants (LTx). We aim to study the roles of DSA and non-HLA antibodies in T-cell-mediated rejection (TCMR) of LTx.

Methods

Allograft biopsies (n = 103) from adult LTx recipients were studied. Biopsy-paired serums were retrospectively tested for anti-angiotensin II type 1 receptor (AT1R) and the Luminex panel of 60 non-HLA Antibodies.

Results

TCMR was detected in 59 of 103 (57.3%) biopsies. Twenty-six biopsies were categorized as moderate-severe (MS-TCMR), 77 as negative-mild (NM-TCMR). DSA was positive in 95/103 (92.2%) cases and wasn't associated with MS-TCMR. Anti-AT1R antibodies were elevated in serum paired with MS-TCMR vs. NM-TCMR (18.8[15.2–40.0] vs. 13.0[10.0–21.5] U/ml, p < 0.01). Positive anti-AT1R antibodies were associated with a higher incidence of MS-TCMR (HR = 12.4[1.5–101.6], p = 0.02). A panel of 18 non-HLA Abs was significantly associated with MS-TCMR. The number of panel-18 non-HLA antibodies was higher with MS-TCMR vs. NM-TCMR (3[2–5] vs. 1[0–1], p < 0.001). The incidence of MS-TCMR was higher in cases with panel-18 non-HLA antibodies ≥3 vs. <3 (HR = 19.6[6.0–64.8], p < 0.001). The frequency of MS-TCMR was the highest when DSA, anti-AT1R, and panel-18 non-HLA antibodies were all present.

Conclusions

Non-HLA antibodies to AT1R or the Luminex panel are associated with MS-TCMR in LTx biopsies. The incidence of MS-TCMR is higher when non-HLA antibodies are present concomitantly with DSA, indicating an additive effect. Further studies are warranted to investigate the utility of routinely monitoring DSA and non-HLA antibodies in LTx recipients.

Background

Sarcopenia and obesity are prevalent in end-stage-liver-disease (ESLD) patients undergoing Liver Transplantation (LT), contributing to morbidity and mortality. Although LT restores liver function, sarcopenia and obesity often persist. Body mass index (BMI) is unreliable in ESLD for assessing adiposity, necessitating alternative measures. Visceral-to-subcutaneous adipose tissue (VAT/SAT) ratio affects outcomes, with VAT associated with poorer cardiovascular health and survival. This study investigated long-term changes in body composition post-LT and their associations with survival and hospital/ICU stay.

Methods

A single-center retrospective cohort analyzed 81 adults undergoing LT (2009–2015). Body composition was assessed via CT/MRI at L3 level pre-LT and longitudinally up to 10y post-LT. Sarcopenia was defined using sex-specific skeletal muscle index (L3-SMI) thresholds. VAT and SAT areas quantified fat distribution. Outcomes included ICU/hospital stay and survival. Longitudinal changes were modeled using linear mixed models. Associations resulted from survival analysis and Spearman correlations.

Results

Pre-LT, 61% were sarcopenic, 53% had BMI ≥ 25 kg/m², and 19% had sarcopenic obesity. Post-LT, L3-SMI declined, partially recovered, but remained below baseline. BMI decreased initially, then increased. VAT rose for 2–4y, then declined; SAT increased steadily. VAT/SAT ratio increased modestly early, then declined after ∼4.5y. Pre-LT sarcopenia predicted lower survival; post-LT didn't. Higher pre-LT VAT was associated with prolonged ICU stay. Elevated pre-LT VAT/SAT ratio correlated with longer ICU/hospital stays.

Conclusions

Sarcopenia persists long after LT and is associated with reduced survival. Unfavorable fat distribution was associated with longer hospital/ICU stay. Early diagnosis and targeted management of sarcopenia and visceral adiposity seem promising to improve post-LT outcomes.

Introduction

Donor age is a key determinant of liver transplant (LT) outcomes, but its impact varies across recipient age groups. Specific donor age thresholds associated with excess risk remain undefined.

Methods

Using data from the Scientific Registry of Transplant Recipients (2011–2021; follow-up through 2024), we analyzed first-time, single-organ LT recipients. Donors and recipients were stratified by age. Outcomes included patient, graft, and death-censored graft survival. Multivariable Cox regression models adjusted for liver disease severity, comorbidities, graft type, and transplant year were used to identify donor age thresholds associated with increased risk in each recipient age group.

Results

Among 70 078 recipients (median age, 57 years), mean donor age rose from 39.6 to 40.9 years (p = .004), while recipient age increased from 50.7 to 51.9 years (p = .003). Donor age ≥50 years was associated with a sixfold increase in mortality in pediatric recipients (aHR, 6.48; 95% CI, 1.92–21.83; p = .003). For adults aged 18.1–30 years, excess mortality and graft loss were observed with donors >55 years (aHRs >2.5). In recipients aged 40.1–60 years, risk increased progressively with donor age. Among recipients ≥65 years, donor age was not significantly associated with outcomes. These thresholds were consistent across outcomes and robust in sensitivity analyses.

Conclusions

This is the first national study to define recipient age-specific donor age thresholds associated with post-LT risk. These findings support the development of age-informed allocation strategies and call for a reassessment of organ discard practices as donor and recipient ages continue to rise.

Background

Complement system overactivation contributes to transplanted kidney injury in both ischemia-reperfusion and antibody-mediated rejection, ultimately affecting post-transplant renal function. C1 esterase inhibitor (C1-INH) may reduce complement-mediated injury, yet its effects on renal function and safety outcomes remain uncertain in randomized trials.

Methods

Four RCTs were included, all focusing on the use of C1-INH in kidney transplant recipients, comparing it with control groups receiving saline. The studies were evaluated for methodological quality using the Jadad scoring system and the Cochrane Risk of Bias tool. Meta-analysis was performed using RevMan software, assessing outcomes such as renal function (eGFR), AMR incidence, and SAE occurrences.

Results

This study included four randomized controlled trials encompassing 148 kidney transplant recipients. The findings suggest that treatment with C1-INH may be associated with an improvement in renal function, as reflected by eGFR. No statistically significant difference was observed in the incidence of delayed graft function or antibody-mediated rejection between the treatment and control groups. The overall incidence of serious adverse events was comparable between groups, with no significant differences detected in infection-related, renal, cardiovascular, or gastrointestinal events.

Conclusion

The use of C1-INH may be associated with improved graft renal function following kidney transplantation. However, no significant benefit was observed with respect to delayed graft function or antibody-mediated rejection. The available evidence suggests an acceptable safety profile for C1-INH in this setting. Nevertheless, given the clinical heterogeneity of the included studies and the limited cumulative sample size, these findings should be interpreted as preliminary. Larger, well-designed randomized controlled trials are required to further clarify the therapeutic role of C1-INH in kidney transplantation.

Introduction

Dual kidney transplantation (DKT), an uncommonly performed procedure, provides a unique opportunity to transplant nonstandard kidneys that might otherwise not be utilized. We compared perioperative and five-year posttransplant outcomes between DKT, and single kidney transplants (SKT) performed at our institution.

Methods

We analyzed all adult deceased donor kidney-alone transplant recipients at our center between 2001 and 2020. Recipients of pediatric en bloc kidney transplants were excluded. Perioperative outcomes of interest included delayed graft function (DGF), posttransplant length of stay (LOS), rehospitalization, and reoperation. Five-year outcomes included biopsy-proven acute rejection (AR), death-censored graft failure (DCGF), uncensored graft failure (UCGF), and death with functioning graft (DWFG).

Results

A total of 100 DKT and 3125 SKT recipients were included. DKT recipients were older (p < 0.001), more often male (68%), and more often underwent early steroid withdrawal (p = 0.04). In comparison to SKT, after adjustment for multiple variables, DKT was not independently associated with DGF (aOR: 1.25; 95% CI 0.76–2.08); prolonged LOS (linear coefficient 0.42; −0.9–1.7); reoperation (aOR: 0.73; 95% CI: 0.21–2.51) or rehospitalization (aOR 0.98; 95% CI: 0.55–1.74). However, within five years, DKT had a lower adjusted incidence rate ratio (aIRR) for AR (aIRR: 0.28; CI 0.12–0.64); DCGF (aIRR: 0.30; 95% CI 0.13–0.68), and UCGF (aIRR: 0.53; 95% CI: 0.33–0.86), without statistically significant differences in DWFG (aIRR: 0.83; 95% CI: 0.46–1.53).

Conclusion

In selected recipients, DKT offered superior medium-term outcomes compared to SKT without compromising perioperative outcomes. DKT can mitigate concerns associated with medically complex donor kidneys, increase organ utilization, and increase access to transplantation.

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can potentially cure various hematologic disorders. However, transplant-related complications, including hemorrhagic cystitis (HC), remain major causes of adverse outcomes and decreased survival. This study examines the associations of HC with pharmacogenetic single nucleotide polymorphisms (SNPs) and clinical characteristics.

Methods

This retrospective study included 259 pediatric patients who underwent allo-HSCT. HC was predefined as the primary endpoint, and other major complications were analyzed as secondary exploratory outcomes. Bone marrow samples were collected at initial diagnosis for genomic DNA extraction. SNP genotyping was performed by targeted next-generation sequencing via a customized 30-gene panel.

Results

Among the 30 SNPs analyzed, all except CYP2C19 (c.99T > C) were in Hardy-Weinberg equilibrium (all p > 0.05). In univariate Cox regression, CYP2C19 (c.681G > A) GA/AA genotype, older age, higher body weight, haploidentical transplantation, use of cord blood in the graft, peri-engraftment syndrome (peri-ES), severe acute graft-versus-host disease, and cytomegalovirus infection were significantly associated with an increased risk of HC, whereas HLA 9/10-10/10 match appeared protective (all p < 0.05). Multivariate Cox analysis identified CYP2C19 (c.681G > A) GA/AA (hazard ratio (HR) = 1.90, p = 0.021), older age (HR = 2.14, p = 0.036), and peri-ES (HR = 1.86, p = 0.034) as independent risk factors for HC.

Conclusion

This study demonstrates that CYP2C19 (c.681G > A) GA/AA genotype, older age, and peri-ES are each independent risk factors for HC after allo-HSCT. These findings highlight the value of pharmacogenetic and clinical profiling in predicting susceptibility to HC and guiding personalized preventive strategies, contributing to a deeper understanding of the interplay among genetic predisposition, immune responses, and chemotherapy-related toxicity in HC pathogenesis.