Systematic review: hepatitis C viraemic allografts to hepatitis C-negative recipients in solid organ transplantation.

BACKGROUND: Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. AIM: To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. METHODS: A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. RESULTS: Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. CONCLUSIONS: Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

The Abdominal Transplant Surgery Workforce: Current state and future trends.

Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy-one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5-8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up-to-date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.

Prevention of poor psychosocial outcomes in living organ donors: from description to theory-driven intervention development and initial feasibility testing.

CONTEXT: Although some living donors experience psychological, somatic, and interpersonal difficulties after donation, interventions to prevent such outcomes have not been developed or evaluated. OBJECTIVE: To (1) summarize empirical evidence on psychosocial outcomes after donation, (2) describe a theoretical framework to guide development of an intervention to prevent poor outcomes, and (3) describe development and initial evaluation of feasibility and acceptability of the intervention. METHODS: Based on a narrative literature review suggesting that individuals ambivalent about donation are at risk for poor psychosocial outcomes after donation, the intervention targeted this risk factor. Intervention structure and content drew on motivational interviewing principles in order to assist prospective donors to resolve ambivalence. Data were collected on donors' characteristics at our institution to determine whether they constituted a representative population in which to evaluate the intervention. Study participants were then recruited to assess the feasibility and acceptability of the intervention. They were required to have scores greater than 0 on the Simmons Ambivalence Scale (indicating at least some ambivalence about donation). RESULTS: Our population was similar to the national living donor population on most demographic and donation-related characteristics. Eight individuals who had been approved to donate either a kidney or liver segment were enrolled for pilot testing of the intervention. All successfully completed the 2-session telephone-based intervention before scheduled donation surgery. Participants' ratings of acceptability and satisfaction were high. Open-ended comments indicated that the intervention addressed participants' thoughts and concerns about the decision to donate. CONCLUSIONS: The intervention is feasible, acceptable, and appears relevant to donor concerns. A clinical trial to evaluate the efficacy of the intervention is warranted.

Antibody-mediated rejection in kidney transplantation: a review.

Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

BACKGROUND: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS: Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.

Pediatric living donor kidney transplantation under alemtuzumab pretreatment and tacrolimus monotherapy: 4-year experience.

BACKGROUND: Alemtuzumab has been used in off-label studies of solid organ transplantation. METHODS: We analyzed the first 42 pediatric consecutive living donor kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning. We focused especially on the causes of recipient death and graft loss and the characteristics of rejection. RESULTS: Laparoscopic live-donor nephrectomy was associated with no mortality and no delayed graft function. The actuarial 1, 2, 3, and 4 years patient and graft survivals were 97.6% and 97.6%, 93.5% and 85.4%, 93.5% and 85.4%, and 93.5% and 85.4%, respectively. The incidence of cumulative acute cellular rejection (ACR) at 1, 2, 3, and 4 years was 0%, 2.4%, 4.8%, and 4.8%, respectively. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m) at 1, 2, and 3 years were 0.8+/-0.4 and 94.0+/-36.8, 0.9+/-0.4 and 79.6+/-31.9, and 0.9+/-0.4 and 95.0+/-21.7, respectively. Two (4.7%) recipients had ACR, and both Banff 1a ACRs were steroid sensitive. No patients had antibody-mediated rejection. Weaning to spaced dose (qod or less) tacrolimus monotherapy was attempted in 16 (38%) and was successful in 12 (26%) patients. All patients are currently steroid free. There was no tissue invasive cytomegalovirus disease or infection, no BK/polyoma viral nephropathy, and no posttransplant proliferative disease. CONCLUSION: This experience confirms the 4-year safety and efficacy of this approach in pediatric recipients.

Alemtuzumab preconditioning with tacrolimus monotherapy-the impact of serial monitoring for donor-specific antibody.

BACKGROUND: Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning. METHODS: Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e., reduction of tacrolimus monotherapy dosing to every other day, three times a week, twice a week, or once a week) attempted. Routine monitoring for donor-specific antibody (DSA) was begun in September 2004. Mean follow-up is 34+/-6.5 months after transplantation and 26+/-8.1 months after the initiation of spaced weaning. RESULTS: One hundred and twenty-two (44%) patients remained on spaced weaning. One- and 2-year actual patient/graft survival was 99%/99%, and 97%/96%. Fifty-six (20%) patients experienced acute rejection after initiation of spaced weaning. One- and 2-year actual patient/graft survival was 100%/98%, and 94%/78%. Forty-two (15%) patients with stable renal function had spaced weaning stopped because of the development of DSA, which disappeared in 17 (40%). One- and 2-year actual patient and graft survival was 100% and 100%. CONCLUSION: Adult renal transplant recipients who are able to be maintained on spaced weaning have excellent outcomes. Patients with stable renal function who have reversal of weaning because of the development of DSA also have excellent outcomes. Routine monitoring for DSA may allow patients to avoid late rejection after spaced weaning.

Cold heparinized lactated Ringers with procaine (HeLP) preservation fluid in 266 living donor kidney transplantations.

Since the 1960s simple inexpensive cold lactated Ringers with additives has been used for short-term cold preservation of kidneys from living donors. We performed 266 living donor kidney transplantations from January 22, 2003 to October 30, 2006. Donor allografts were recovered laparoscopically and flushed with cold heparin, lactated Ringer's and procaine (HeLP) solution. Warm and cold ischemic times were typically <45 min and <90 min, respectively. The mean follow up was 21.6+/-12.2 months. There was no delayed graft function. Actuarial 1-year patient and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year was 1.46+/-0.51 mg/dL. The cumulative incidences of acute cellular rejection at 6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no identifiable side effects attributed to the HeLP solution. This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost.

Alemtuzumab pretreatment and tacrolimus monotherapy in living-donor liver and kidney transplantation.

We previously described the use of alemtuzumab as a pretreatment agent in 207 living-donor renal transplants, a trial that represented the largest series to date of live-donor renal and liver transplant recipients undergoing alemtuzumab pretreatment, and confirmed the short-term safety, efficacy and cost-effectiveness of this approach. This paper examines the use of the immunosuppressive combination of alemtuzumab and tacrolimus monotherapy in 47 patients with right-lobe adult living-donor liver transplantation.

Immunosuppressive preconditioning or induction regimens : evidence to date.

The success of solid organ transplantation has been directly related to the development of immunosuppressive drug therapies. Preconditioning or induction therapy was developed to reduce early immunological and nonimmunological renal injury, with the goal of increasing long-term graft survival. However, the routine induction of immunological tolerance to solid organ allograft is currently not achievable because of the morbidity and mortality related to the immunosuppressive regimens themselves. The different therapeutic preconditioning or induction agents and their associated effects on cellular rejection, graft survival outcomes and the need for multiagent post-transplant maintenance therapy are reviewed.

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation.

OBJECTIVE: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. STUDY DESIGN: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. RESULTS: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 +/- 0.35 mg/dL and creatinine clearance was 90.8 +/- 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. CONCLUSION: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.

Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes.

BACKGROUND: Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS: Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS: One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37+/-0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION: A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear.