Intravenous Immunoglobulins in the Prevention of Rejection of a Second or Third Kidney Graft.

BACKGROUND: Intravenous immunoglobulin (IVIg) reduces acute rejection episodes in kidney transplantation, but adverse events (AEs) are common. The aim of this study was to assess whether human IVIg enhances immunosuppressive effects without increasing AEs in the prevention of acute kidney graft rejection. METHODS: Patients receiving a second or third kidney graft were treated with standard immunosuppressant therapy with (n = 18) or without (n = 10) IVIg. The primary efficacy endpoint was biopsy-proven acute rejection (BPAR) rate at 3 months, and secondary endpoints included acute rejection rate at 12 months, intensity of rejection, and patient survival. RESULTS: Patients in the experimental arm received 3 infusions of IVIg. The BPAR rate decreased with IVIg versus standard immunosuppression alone over 12 months of follow-up. Experimental versus control rates of survival without BPAR were 94% versus 63% and 82% versus 63% at 3 and 12 months. The intensity of the acute rejection episodes (BANFF 97 grade) was similar between groups. One patient from each group died during the 12-month follow-up period. Treatment-emergent AEs were reported in 100% and 94.4% of the control and experimental arms. Most AEs were considered unrelated or unlikely to be related to treatment. CONCLUSIONS: This study supports the efficacy and safety of IVIg in highly sensitized transplant patients for improving transplant rates and reducing graft rejection episodes.

Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases.

STUDY QUESTION: How effective is ovarian tissue cryopreservation (OTC)? SUMMARY ANSWER: In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 and 33%, respectively. WHAT IS KNOWN ALREADY: OTC for fertility purposes has been performed for >20 years now. With over 86 live births reported worldwide and success rates of ~30% after autotransplantation of frozen-thawed ovarian cortex, the procedure should no longer be considered experimental. However, very few publications report the efficacy of this procedure. STUDY DESIGN, SIZE, DURATION: Cases of ovarian tissue cryobanking for fertility preservation performed between 1997 and 2013 in a single institution were reviewed by analysis of the cryobank database and a prospective questionnaire sent out in March 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 545 patients who underwent OTC during this period. The analysis included indications for OTC, survival rates, ovarian function and spontaneous pregnancies after OTC, come-back rates for ovarian tissue transplantation, pregnancy rates after transplantation, and complication and satisfaction rates. MAIN RESULTS AND THE ROLE OF CHANCE: OTC was performed in this cohort at a mean age of 22.3 ± 8.8 years for oncological indications (79%), benign gynecological pathologies (17.5%) and genetic risks of POF (3.5%). Of the 545 patients, 29% were under 18 years of age at the time of OTC and 15% were prepubertal. While 10% of patients died from their disease, 21 patients (3.9%) underwent autotransplantation, 7 of whom delivered a healthy baby, yielding a post-transplantation live birth rate of 33%. Of 451 patients who were sent the questionnaire, 143 agreed to respond (32%). Nevertheless, ovarian function could not be evaluated in 36% of those who answered. Of 92 evaluable patients, 31.5% were menopausal and 68.5% showed persistent ovarian function. Of 52 women who attempted to conceive naturally, 37 were successful (71%). Among 140 patients who answered the questionnaire, 96% were satisfied with the procedure and only 1 major complication (intra-abdominal hemorrhage) was encountered. Among all the patients, 12% have donated their ovarian cortex for research purposes or have had it destroyed. LIMITATIONS, REASONS FOR CAUTION: The questionnaire participation rate (32%), limited follow-up (mean 7.6 ± 3.5 years) and use of only clinical criteria for evaluation of ovarian function made it difficult to accurately assess the risk of POF and efficiency of OTC. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this study and none of the authors have any conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registration ID: CRYOFONOV01.

Impact of the cryopreservation technique and vascular bed on ovarian tissue transplantation in cynomolgus monkeys.

PURPOSE: The aim of this study was to determine the best combination in terms of cryopreservation techniques and vascular bed preparation before grafting in order to obtain functional ovarian tissue after transplantation. METHODS: Five cynomolgus monkeys were used. Strips from 10 ovaries were cryopreserved, 5 by vitrification (V), and 5 by slow-freezing (SF). Pieces of fresh ovarian tissue were used for controls. After 1 month, the strips were autografted to two different vascular beds, healed (HB) or freshly decorticated (FDB), constituting four study groups: SF-HB, SF-FDB, V-HB, and V-FDB. These were compared to fresh tissue. After 6 months, the ovaries were removed and several parameters analyzed: follicle quality, stage, density, proliferation, apoptosis, functionality, vascularization, and fibrosis. Mixed effect linear regression models were built to assess the impact of cryopreservation and vascular bed preparation on ovarian tissue viability and functionality. p values were adjusted for multiple testing using the Benjamini-Hochberg method, and q values < 0.20 were considered significant in order to achieve a 20% false discovery rate. RESULTS: Compared to fresh tissue, no difference was observed in the percentage of morphologically normal follicles, while a significant increase was noted in the follicle proliferation rate (41%, q = 0.19), percentage of antral follicles (12%, q = 0.14), and number of vessels per area (3.3 times, q = 0.07) in the V-FDB group. CONCLUSIONS: Vitrification associated with FDB vascular bed preparation is the best combination to obtain functional autografted ovarian tissue. Further studies are nevertheless required, with confirmed pregnancies and live births before introducing the procedure into clinical practice.

Successful treatment of gynaecological involvement of granulomatosis with polyangiitis (Wegener's granulomatosis) by rituximab.

Granulomatosis with polyangiitis, formerly called Wegener's granulomatosis, is a disease for which the treatment options are increasing, with the recent publication of several studies concerning the use of rituximab. The disease typically involves the upper airways, lungs and kidneys, but other far less frequent localisations are possible. Here, we describe a case of isolated relapse of granulomatosis with polyangiitis affecting the uterine cervix and upper vagina which dramatically responded to rituximab therapy, after failure of methotrexate treatment. This is the first documented response to rituximab of gynaecological involvement in granulomatosis with polyangiitis.

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

A more than 20% increase in deceased-donor organ procurement and transplantation activity after the use of donation after circulatory death.

BACKGROUND: Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS: Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS: There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors ≥60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS: This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source.

[The use of intrauterine device in nulliparous over 18 years: a Belgian consensus]. / La contraception intra-utérine chez la nultlipare de plus de 18 ans: vers un consensus belge.

Under the presidency of prof. H. Depypere (UZ Ghent) and Prof. P. Simon (ULB Erasme) a Belgian panel of thirteen experts (gynecologists, representatives of universities and scientific associations for gynecology-obstetrics) reached a consensus on the use of intrauterine systems, both copper IUDs as hormone IUDs, in nultiparous women.

A comparative, randomized trial of concentration-controlled sirolimus combined with reduced-dose tacrolimus or standard-dose tacrolimus in renal allograft recipients.

BACKGROUND: The clinical safety and efficacy of sirolimus plus reduced-dose tacrolimus was evaluated in de novo renal allograft recipients enrolled in a comparative, open-label study. METHODS: One hundred twenty-eight renal allograft recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months. The primary efficacy endpoint was calculated creatinine clearance values at 6 months. RESULTS: Demographic variables were similar between groups. At 6 months, mean (± standard deviation) calculated creatinine clearance was significantly improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum creatinine values were not significantly different. Patient survival (95.2% and 96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7% with sTAC (P = .095). CONCLUSIONS: The rTAC regimen provided effective immunosuppression and was associated with improved creatinine clearance. Adequate immunosuppressant exposure must be achieved in the early postoperative period to minimize the risk of acute rejection.

Delayed graft function does not harm the future of donation-after-cardiac death in kidney transplantation.

INTRODUCTION: Delayed graft function (DGF) occurs more frequently in kidney transplants from donation after cardiac death (DCD) than from donation after brain death (DBD). We investigated the effect of DGF on posttransplantation outcomes among grafts from controlled DCD kidneys. PATIENTS AND METHODS: This single-center retrospective study recruited 80 controlled DCD kidneys transplanted from January 2005 to December 2011. Mean patient follow-up was 28.5 months. RESULTS: There were no primary nonfunction grafts; the DGF rate was 35.5%. Overall graft survival rates between groups with versus without DGF were 92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5 years, respectively (P = not significant (NS)). Patients with versus without DGF showed the same survival rates at the corresponding time 92.4% vs 97.2%, 92.4% vs 93.9%, and 84.7% vs 93.9% (P = NS). Estimated glomerular filtration rate was significantly lower in the DGF compared with the non-DGF group at hospital discharge (29 vs 42 mL/min; P = .00) and at 6 months posttransplantation (46 vs 52 mL/min; P = .04), but the difference disappeared thereafter: 47 vs 52 mL/min at 1 year, 50 vs 48 mL/min at 3 years, and 54 vs 53 mL/min at 5 years (P = NS). DGF did not increase the risk of an acute rejection episode (29.6% vs 30.6%; P = NS) or rate of surgical complications (33.3% vs 26.5%; P = NS). However, DGF prolonged significantly the length of hospitalization in the DGF versus the non- DGF group (18.9 vs 13 days; P = .00). Donor body mass index (BMI) ≥ 30 kg/m(2), recipient BMI ≥30 kg/m(2), and pretransplantation dialysis duration increased the risk of DGF upon multivariate logistic regression analysis. CONCLUSIONS: Apart from the longer hospital stay, DGF had no deleterious impact on the future of kidney allografts from controlled DCD, which showed comparable graft and patient survivals, renal function, rejection rates, and surgical complications as a group without DGF. Therefore, DGF should no longer be considered to be a medical barrier to the use of kidney grafts from controlled DCD.

Evolution of native kidney function after pancreas transplantation alone.

INTRODUCTION: This study investigated changes in kidney function over time among a cohort of patients undergoing pancreas transplantation alone (PTA) from January 2002 to December 2011. PATIENTS AND METHODS: Ten of eighteen PTA patients bearing functioning grafts for at least 1 year were recruited for the analysis. Primary endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation (mL/min/1.73 m(2)) comparing baseline (pretransplantation) to 6-month, 1-year, 3-year, and 5-year posttransplantation values. Mean follow-up time was 75.7 ± 20.5 months (range, 46-106.5). RESULTS: Baseline eGFR was 89.3 ± 27.9 (range, 58-145). eGFR decreased to 75.7 ± 26.2, 71 ± 20.6, 66.5 ± 14.8, and 62.1 ± 11.2 at 6 months, 1, 3, and 5 years representing -15.2%, -20.5%, -15.8%, and -22.6% percentage decreases respectively (P < .05 for all pairwise comparisons). The Baseline SCr was 8.6 ± 2.3 mg/L (range, 5-13). SCr progressively increased to 10.1 ± 3, 10.5 ± 3.1, 10.9 ± 3.1, and 11.3 ± 1.7 at 6 months, 1, 3, and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P < .05 for all pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR <60 at transplantation versus 3 and 5 years thereafter, respectively. No patient developed a SCr > 25 mg/L or eGFR <30 or needed dialysis or kidney transplantation. Five of ten patients had micro-albuminuria or proteinuria before transplantation. Tacrolimus levels were within recommended therapeutic ranges over time. CONCLUSION: Kidney function deteriorated significantly after PTA. Understanding of risk factors for the development of renal impairment is important to preserve kidney function and to select appropriate candidates for PTA.

Categories of donation after cardiocirculatory death.

The interest in donation after cardiocirculatory death (DCD) was renewed in the early 1990s, as a means to partially overcome the shortage of donations after brain death. In some European countries and in the United States, DCD has become an increasingly frequent procedure over the last decade. To improve the results of DCD transplantation, it is important to compare practices, experiences, and results of various teams involved in this field. It is therefore crucial to accurately define the different types of DCD. However, in the literature, various DCD terminologies and classifications have been used, rendering it difficult to compare reported experiences. The authors have presented herein an overview of the various DCD descriptions in the literature, and have proposed an adapted DCD classification to better define the DCD processes, seeking to provide a better tool to compare the results of published reports and to improve current practices. This modified classification may be modified in the future according to ongoing experiences in this field.

Current practices of organ donation and transplantation among different French-speaking countries and regions.

The aim of the "Transplantation Sans Frontières" (TSF) questionnaire, which was sent to French-speaking centers in 6 different countries and regions, was to establish the current status of organ donation and transplantation in their environments. It was also to examine ways to collaborate and exchange scientific information, teaching, and training in the field of organ transplantation. The French Society of Transplantation and the Agency of Biomedicine already offer specific programs to expand local activities, and the World Health Organization (WHO) regulates them. Therefore, TSF could be a coordinating platform in the near future.

Donor advocacy with special reference to Belgium.

Before any published Belgian law, EU Directive, and/or EU Action Plan, the donor advocate was naturally a member of the transplantation team performing living kidney donation. The need of donor advocacy appeared obvious with liver living donation, which was and is still a risky procedure. Today, it is clear that the donor advocacy must not be limited to living donation but extended to brain-dead and cardiac-dead donation. Nevertheless, its complexity will need experienced persons in the field of organ donation as well as transplantation, while remembering that patients' first right is the right to donate.

Pancreas preservation for pancreas and islet transplantation: a minireview.

Pancreas preservation by cold storage using University of Wisconsin solution was the mainstay method used for pancreas transplantation during the past 2 decades. Other solutions, such as HTK, Celsior, and SCOT 15, could not demonstrate any advantage for short preservation periods. But the advent of clinical islet transplantation and the larger use of controlled non-heart-beating donors have prompted the transplantation community to develop methods for increasing pancreas graft quality while preventing ischemic reperfusion damages. Oxygenation by 1- or 2-layer methods during pancreas preservation, as well as the use of perfluorocarbons, might increase the islet yield. Based on the former methods, there is a renewed interest in machine perfusion and oxygenation in pancreas preservation for pancreas transplantation and islet preparation.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys.

Vascular renal resistance (RR) during hypothermic machine perfusion (HMP) is frequently used in kidney graft quality assessment. However, the association between RR and outcome has never been prospectively validated. Prospectively collected RR values of 302 machine-perfused deceased donor kidneys of all types (standard and extended criteria donor kidneys and kidneys donated after cardiac death), transplanted without prior knowledge of these RR values, were studied. In this cohort, we determined the association between RR and delayed graft function (DGF) and 1-year graft survival. The RR (mmHg/mL/min) at the end of HMP was an independent risk factor for DGF (odds ratio 38.1 [1.56-934]; p = 0.026) [corrected] but the predictive value of RR was low, reflected by a c-statistic of the receiver operator characteristic curve of 0.58. The RR was also found to be an independent risk factor for 1-year graft failure (hazard ratio 12.33 [1.11-136.85]; p = 0.004). Determinants of transplant outcome are multifactorial in nature and this study identifies RR as an additional parameter to take into account when evaluating graft quality and estimating the likelihood of successful outcome. However, RR as a stand-alone quality assessment tool cannot be used to predict outcome with sufficient precision.

Contribution of donors after cardiac death to the deceased donor pool: 2002 to 2009 University of Liege experience.

OBJECTIVE: In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS: We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS: We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION: The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

Renal transplantation from living related donors: a single center experience in Viet Nam.

INTRODUCTION: End-stage renal disease is a major public health problem in Viet Nam. A cooperative project between the University of Liège, Belgium, and the University of Medicine Pham Ngoc Thach, Ho Chi Minh City, Viet Nam, has permitted the establishment of an autonomous program of renal transplantation from living-related donors at the Peoples' Hospital No 115. The aim of this paper was to report the primary results of the project and to draw conclusions for the future. PATIENTS AND METHODS: From January 2004 to July 2008, we performed 33 living-related renal transplantations. Mean ages of donors and recipients were 31.8 ± 9.5 and 41.6 ± 13.5 years, respectively. Laparoscopic nephrectomy was performed in 6 donors. The immunosuppressive regimen consisted of three drugs associated with induction therapy using anti-interleukin-2 receptor monoclonal antibody. RESULTS: The 33 donors are in good health at follow-up. Four developed major intra- or postoperative hemorrhage necessitating transfusion, with a surgical re-exploration in 1 donor. Wound infection occurred in 2 donors. Posttransplant recipient and graft survivals at 1 versus 3 years were 82% and 73% versus 82% and 65%, respectively. Eight recipients presented 13 biopsy-proven acute rejection episodes that were reversible in 7, but 1 patient lost his graft due to an irreversible rejection. Two recipients developed cancer. CONCLUSIONS: These initial results have encouraged us to continue the program of renal transplantation from living-related donors. However, they also pointed out the need to develop other donor sources.

Results of kidney transplantation from donors after cardiac death.

Confronting the organ donor shortage, many transplant centers around the world increasingly use donors after cardiac death (DCD). Over the past 20 years, follow-up studies in kidney recipients comparing DCD and donors after brain death (DBD) have shown comparable long-term graft function and survival. As a consequence, DCD programs should be continued and expanded, for these donors constitute a potential solution to the imbalance between the numbers of end-stage kidney disease patients on waiting lists versus available kidney grafts. DCD kidneys do not necessarily signify suboptimal grafts; they may merit to be allocated the same as DBD grafts.