Cristina Silvestre

Technical Aspects of Unilateral Dual Kidney Transplantation from Expanded Criteria Donors: Experience of 100 Patients

One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety‐five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end‐to‐side. Surgical complications were comparable in both groups. At 3‐year follow‐up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3‐years follow‐up.

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

ABSTRACT Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R+) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D+/R−). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.05). During the antiviral prophylaxis, all 20 D+/R− KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.

Calcineurin inhibitor‐free immunosuppression in dual kidney transplantation from elderly donors

Abstract:  Background:  Kidneys from expanded‐criteria donors may be particularly susceptible to calcineurin inhibitor (CI)‐mediated vasoconstriction and nephrotoxicity. In the early post‐transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI‐free protocols have been introduced for maintenance immunosuppressive therapy. A CI‐free protocol of anti‐thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs).

A single-center experience with 200 dual kidney transplantations

This study reports on a large series of 200 dual kidney transplantations (DKTs) from expanded criteria donors (ECDs) and proposes specific ways to optimize outcomes. Data concerning 200 DKTs performed in the last 14 yr were retrospectively analyzed. Kidneys from high‐risk ECD were allocated for use in DKTs on an old‐for‐old basis after histological assessment. Different surgical techniques and immunosuppressant regimens were used over time, and the outcomes are discussed. Donors and recipients were a median 73 (70–77) and a 62 (58–67) yr old, respectively. Delayed graft function occurred in 31.5% of cases, and acute rejection in 13.5%. Patient and graft survival at five yr were 90.4% and 85.8%, respectively. Unilateral kidney placement was preferred for 75% of patients, and was associated with a low rate of surgical complications. Our current standard therapy comprising low‐dose calcineurin inhibitors (CNIs) associated with mammalian target of rapamycin inhibitors (mTOR) and steroids appears to offer the best risk/benefit profile for elderly patients undergoing DKT. In our experience, outcomes after DKT can be improved by: (i) kidney clinical–histological assessment; (ii) unilateral kidney placement; (iii) minimal use of CNI associated with mTOR.

Long-term outcome of renal transplantation from octogenarian donors: A multicenter controlled study

To assess whether biopsy‐guided selection of kidneys from very old brain‐dead donors enables more successful transplantations, the authors of this multicenter, observational study compared graft survival between 37 recipients of 1 or 2 histologically evaluated kidneys from donors older than 80 years and 198 reference‐recipients of non–histologically evaluated single grafts from donors aged 60 years and younger (transplantation period: 2006‐2013 at 3 Italian centers). During a median (interquartile range) of 25 (13‐42) months, 2 recipients (5.4%) and 10 reference‐recipients (5.1%) required dialysis (crude and donor age‐ and sex‐adjusted hazard ratio [95% confidence interval] 1.55 [0.34‐7.12], P = .576 and 1.41 [0.10‐19.54], P = .798, respectively). Shared frailty analyses confirmed similar outcomes in a 1:2 propensity score study comparing recipients with 74 reference‐recipients matched by center, year, donor, and recipient sex and age. Serum creatinine was similar across groups during 84‐month follow‐up. Recipients had remarkably shorter waiting times than did reference‐recipients and matched reference‐recipients (7.5 [4.0‐19.5] vs 36 [19‐56] and 40 [24‐56] months, respectively, P < .0001 for both comparisons). Mean (± SD) kidney donor risk index was 2.57 ± 0.32 in recipients vs 1.09 ± 0.24 and 1.14 ± 0.24 in reference‐recipients and matched reference‐recipients (P < .0001 for both comparisons). Adverse events were similar across groups. Biopsy‐guided allocation of kidneys from octogenarian donors permits further expansion of the donor organ pool and faster access to a kidney transplant, without increasing the risk of premature graft failure.

How does age affect the outcome of kidney transplantation in elderly recipients

The aging of the on‐dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aimed to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased‐donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient age with grafts and patients survival, delayed graft function, acute cellular rejection (ACR), surgical complications, infections, and glomerular filtration rate. Four hundred and fifty‐two patients with a median age of 65 years were included in the study. One‐, 3‐, and 5‐year patients and grafts survival were, respectively, of 98.7%, 93%, 89% and 94.4%, 87.9%, 81.4%. The increasing recipient age was an independent risk factor only for the patients (P=.008) and grafts survival (P=.002). ACR and neoplasia were also associated to a worse graft survival. The reduced graft survival in elderly kidney recipients seems to be related more to the increasing recipients age than to the donors features. In this population, the optimization of organ allocation and immunosuppression may be the key factors to endorse improvements.

Correction: Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

At the time of publication, the html version of this paper contained an error; the authors Imerio Angriman and Lucrezia Furian were not tagged as equally contributing authors. This has now been fixed in the html version of the paper, the PDF was correct at the time of publication.

Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

BackgroundUlcerative colitis patients and transplant recipients are at risk for colorectal cancer. Here, we show that immunosuppressive regimens for kidney transplants are associated with the progression of ulcerative colitis-related carcinogenesis.MethodsWe describe the case of a patient diagnosed with colorectal cancer in ulcerative colitis while on immunosuppressive therapy for a kidney transplant. The immunological microenvironment of the cancer and its mutational status were analyzed, and a mouse colon cancer model was created to replicate the unique clinical conditions. AOM/DSS mice were randomized into seven experimental groups that received different immunosuppressants and an untreated control group to assess the frequencies of adenocarcinoma and high-grade dysplasia. Histopathology, immunohistochemistry, and flow cytometry were also performed on the harvested mouse colons.ResultsAll mice treated with an immunosuppressive regimen developed at least an adenoma, and several of those receiving anti-CD3, anti-CD8, and mycophenolate mofetil also developed adenocarcinomas. In contrast, mice receiving rapamycin did not develop adenocarcinomas, and the extent of high-grade dysplasia in those mice was similar to that in control mice.ConclusionsPatients with pre-neoplastic conditions, such as ulcerative colitis, who are undergoing a solid organ transplant might benefit from the use of mTOR inhibitors given their intrinsic anti-tumor properties.Among transplant recipients, colorectal cancer is more aggressive. This report highlights the association between immunosuppression and the disruption of the immune surveillance mechanisms against colorectal cancer.

Therapeutic apheresis in kidney AB0 incompatible transplantation

Desensitization strategies to safely perform ABO incompatible living donor kidney transplantations are various and still evolving. Given the successful outcome of the majority of the approaches, the current trend is focused on a minimization of treatments. Based on this consideration, the evolution at a single Center of the desensitization protocol is herein described. Starting from 2010, 58 AB0 incompatible living donor kidney transplantations were performed at the University-Hospital of Padua. Over the years, the initial desensitization strategy with rituximab single-dose induction, pre-and post-transplant plasmapheresis and CMV-specific immunoglobulin administration has been shifted to a minimized approach, omitting post-transplant antibody removal in 25 cases. The results of such reduction in post-transplant antibody removal did not affect the outcome of AB0-incompatible kidney transplants, with a reduction in costs and hospitalization.

Combined liver-dual kidney transplant: Role in expanded donors: Letters to the Editor

There is no doubt that kidney transplantation using extended criteria donor (ECD) kidneys has similar outcomes as standard criteria kidney transplantation after a careful selection. The limit could even be pushed with the use of ECD from “very” old donors (>70 years). Selection criteria and technical advancement enabled the use of ECD kidneys in dual kidney transplantation (DKT), which otherwise would be discarded. We read with interest the article from Di Laudo et al. on the use of ECD kidneys as DKT in combined liver-kidney transplantation (CLKT). The authors reported a retrospective analysis of 4 patients with combined liver and dual kidney transplantation (LDKT). They mentioned that high Model for EndStage Liver Disease score priority given to patients listed for CLKT not necessarily translated into an advantage in terms of time on waiting list. However, a table of outcomes indicated that their median waiting time was 89 days (range, 48-191 days) and 118 days (range, 2-1063 days). An interesting point of their practice was the “warm” phase donor kidney biopsies before cross-clamping, although almost all centers in the world perform donor kidney biopsies in the “cold” phase after perfusion. Most importantly, no information was given on the duration of pretransplant hemodialysis or pretransplant chronic kidney disease (CKD) stage 5 (glomerular filtration rate< 30mL/ minute) in order to consider them preemptive. Despite several unknowns about the residual kidney function in the study by Di Laudo et al., we regret to see that the authors did not acknowledge what we performed almost a decade ago. We performed 2 DKTs (ipsilateral placement) using ECD kidneys in recipients of liver transplantation in 2006 and 2007 and published their 1-year follow-up in 2009. In the same article, we also reported the use of ECD kidneys as DKT after heart transplantation. In our patients, both recipients of liver transplantation were on hemodialysis for >2 years prior to DKT. Therefore, there was no doubt about their CKD. After a decade of follow-up, we are pleased to confirm that both recipients of DKT after liver transplantation are still alive with functioning grafts. With the current knowledge in CLKT, we would like to underline the importance of delayed graft function (DGF) of renal grafts on the impact of patient and graft survival. We have recently published longterm outcomes of 130 CLKT. On multivariate analysis, we found that DGF is the most significant independent negative risk factor (hazard ratio, 165; 95% confidence interval, 9-2926) on patient and graft survival in the short and long term. Di Laudo et al. reported a DGF rate of 25% in LDKT and 36% in CLKT (using donors in their thirties). In order to optimally use ECD as DKT in CLKT, the strategy should be reconsidered as follows: