Can we direct organ allocation based on predicted outcome? Hepatocellular carcinoma outside of UCSF criteria or retransplant?

Background

In this study, we ask between patients with graft failure listed for retransplant and patients with hepatocellular carcinoma (HCC) outside of UCSF criteria, who has the greater survival benefit with transplantation?

Methods

This is a retrospective analysis, of liver transplant (LT) patients, done between February 2002 and December 2009 at our center. Patients were included in the “extended HCC” group if their tumor was pathologically beyond UCSF criteria at LT and in the “redo” group if they underwent LT for graft failure occurring more than 3?months after the initial LT. Extended criteria donors (ECDs) were defined as donors above 70?years old, DCD, serology positive for HCV, and split grafts.

Results

There were 25 redos and 37 extended HCC patients. Use of ECDs or high donor risk index organs was associated with poor outcome in both groups (P?=?0.005). Overall, the extended HCC population had a much better survival than redos, both at 1 and 3?years.

Conclusion

These two very different but high risk patient populations have very different survival rates. At a time where regulatory agencies demand more and more with regards to transplant outcomes, we think the transplant community has to reflect on whether allocation justice and fair access to transplant are respected if we start allocating organs based on outcomes.     

A Significant Expansion of CD8 CD28 T-Suppressor Cells in Adult-to-Adult Living Donor Liver Transplant Recipients

Background

The appearance of human regulatory CD8⁺ CD28⁻ T-suppressor (Ts) cells has been associated with a reduced need for maintenance immunosuppression in cadaveric heart- kidney transplant recipients and pediatric liver-intestine transplant recipients. However, few data are available in adult-to-adult living donor liver transplantation (A-A LDLT).

Materials and Methods

To study the population of CD8⁺ CD28⁻ Ts cells in A-A LDLT, we performed flow cytometry on whole blood specimens obtained from 20 transplant recipients, 18 end-stage liver disease patients, and 20 normal controls. Meanwhile, we measured the trough levels of immunosuppressants and monitored graft function in transplant recipients. We retrospectively reviewed the clinical data of the 20 recipients.

Results

A significant expansion of CD8⁺ CD28⁻ Ts cells was observed among recipients of A-A LDLT as compared with a disease control group (P = .000) or healthy individuals (P = .000). All recipients were free of acute cellular rejection episodes. During the follow-up period, no grafts were lost due to acute or chronic rejection.

Conclusion

Expansion of CD8⁺ CD28⁻ Ts cells in A-A LDLT seemed to be associated with a decreased occurrence of acute or chronic rejection and sustained good graft function. Based on our low dosages of immunosuppressants for recipients of A-A LDLT, we suggest that this strategy may promote expansion of CD8⁺ CD28⁻ Ts cells, which can conversely maintain the low immunosuppressant dosages.     

Advanced donor age alone is not a risk factor for graft survival in kidney transplantation

Background

The use of kidneys from elderly deceased donors has substantially increased organ supply, although it is associated with worse graft function and survival rates. The risk of kidneys from elderly donors as well as expanded criteria donors (ECDs) on kidney transplant outcome was investigated.

Patients and methods

Seventy-five kidney transplants from ECDs over a 5-year period were reviewed retrospectively. Old age and increased donor risk variables were analyzed separately in relation to graft function and survival.

Results

Sixty-four of 75 (85.3%) recipients had functioning grafts 5 years posttransplant. The overall actuarial graft survivals from 1 to 5 years were 87.5%, 68.1%, 57.3%, 55.4%, and 47.3%, respectively. Early graft function gave 47 (62.7%) kidneys remarkable actuarial survivals of 100.0%, 88.3%, 75.8%, 75.8%, and 68.4% at 1 to 5 years posttransplant, and 28 (37.3%) kidneys had delayed graft function with substantially decreased actuarial survival rates, ranging from 66.7% to 23.2%. Kidneys from elderly donors had considerable actuarial graft survival rates of 100.0%, 83.3%, 76.9%, 76.9%, and 67.0% from 1 to 5 years, respectively; these were the best graft survival rates compared with kidneys from the other donor categories. The other donor risk variables when associated with advanced age of any had an adverse effect on recipient graft function and survival, but no single risk variable alone, or a combination of any two, showed any statistically significant variability.

Conclusion

Elderly kidney donors provided a substantial organ pool expansion without affecting patient and graft survival in many patients. ECDs can be utilized safely if adequate measures are taken.     

Early and Delayed Onset Cytomegalovirus Infection of Liver Transplant Recipients in Endemic Areas

Background

The delayed onset of cytomegalovirus (CMV) infection after liver transplantation can place patients at risk for graft failure and mortality.

Methods

We compared early versus delayed onset of CMV infection to identify risk factors for mortality among liver transplant recipients in an endemic area.

Results

Among 710 consecutive adult liver transplant recipients, incidence of CMV infection was 47.5% (337/710). Male gender, biliary complications, acute rejection episodes, antilymphocyte antibodies high hemoglobin, and high total bilirubin were significantly different among patients with delayed versus early onset CMV infections. The overall incidence of early versus delayed CMV infections was 43.1% (306/710) versus 4.4% (31/710). Among them, 11.1% (34/306) and 25.8% (8/31) of patients developed CMV disease.

Conclusion

These results showed that a higher proportion of patients developed disease among delayed CMV infected patients (P = .039). The overall and graft survival curves for patients with early onset CMV infections were better than those of patients who had delayed onset CMV infections (P = .026 and P = .014). Recurrence of hepatitis B virus, hepatic dysfunction, and retransplantation were associated with increased mortality among patients who had a delayed CMV infection.     

Long-Term Outcomes of Kidney Transplantation From Expanded-Criteria Deceased Donors: A Single-Center Experience

Background

Organ shortage has prompted the use of expanded-criteria donors (ECDs). Our objective was to compare long-term outcomes of kidney transplants from ECDs with those from concurrent standard-criteria donors (SCDs). In addition, we evaluated variables associated with graft survival in both groups.

Creatinine clearance and proteinuria as early markers of kidney graft survival

Introduction

In patients who receive a kidney transplant from expanded criteria donors (ECDs), few studies are available concerning the relation between the clinical characteristics, pretransplant biopsies, and graft outcomes.

Aim

To identify early clinical markers predicting worse graft survival in recipients of kidneys from ECDs.

Materials and methods

Between 1999 and 2006, we performed a prospective, observational study in 180 recipients of kidney grafts from ECDs that had undergone a preoperative biopsy to evaluate viability. The patients received immunosuppression with basiliximab, late introduction of tacrolimus, mycophenolate mofetil, and steroids. Data were gathered on demographic and posttransplantation clinical characteristics at 1, 3, 6, and 9 months, including estimates of proteinuria and of the glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) formula.

Results

The mean age of the donors was 63.54 years and of the recipients, 58.38 years. A creatinine clearance below the median (40 mL/min, interquartile range 32-50 mL/min) in the first posttransplant year was significantly associated with worse death-censored graft survival (log-rank 14.22, P < .0001). A proteinuria value above the median (100 mg/24 h, interquartile range 40-275 mg/24 h) at 1 year posttransplant significantly reduced the death-censored graft survival (log-rank 14.3, P < .0001). Multivariate Cox analysis showed that a creatinine clearance < 40 mL/min in the first year (hazardsratio [HR] 5.7, 95% Confidence Interval [CI] 1.62-20.37; P = .007) and proteinuria at 1 year greater tan 100 mg/24 h (HR 8.3, 95% CI 2.15-32.06; P = .002) were independent risk factors for death-censored graft loss after adjusting for donor age and acute rejection episodes.

Conclusions

Limited renal function and/or low proteinuria at 1 year posttransplant were associated with worse kidney graft survival among recipients of kidneys from ECDS.     

Opportunistic posttransplantation virus infections in renal transplant recipients

Background

Opportunistic virus infection is one of the most common complications in renal transplant (RT) recipients. Cytomegalovirus (CMV) and BK virus (BKV) are important pathogens and each of these infections affects the other. In contrast, there is only limited information on JC virus (JCV) infection and its relation to CMV infection in RT recipients. This prospective study investigated the rates of JCV and CMV infections and their risk factors and correlations.

Methods

We studied 52 RT recipients. JCV and CMV were detected using nested qualitative polymerase chain reaction assays of urine. The clinical characteristics of JCV and CMV infection were compared and risk factors analyzed with the use of binary logistic regression.

Results

JCV and CMV were detected in 40.4% and 34.6% of the RT recipients, respectively. Cyclosporine (CsA) was a risk factor for both JCV and CMV infection (odds ratio [OR] 7.187; P = .002; OR 4.182; P = .021); CMV infection was a risk factor for JCV infection (OR 3.900; P = .039).

Conclusions

JCV and CMV infections are common in RT recipients. CsA is a risk factor for both JCV and CMV infection. JCV infection is related to CMV infection.     

Kidney Transplantation Using Expanded-Criteria Deceased Donors: A Comparison With Ideal Deceased Donors and Non–Expanded-Criteria Deceased Donors

Purpose

The use of expanded-criteria deceased-donor (ECD) kidneys must be evaluated within the objective perspective of critical organ shortage and graft function and survival. In this study, we aimed to compare the clinical outcomes of ECD reliance with concurrent use of ideal-criteria deceased donors (IDDs) and non-ECDs in adult renal transplantation.

Race and gender are not independent risk factors of allograft loss after kidney transplantation

Background

Little is known about the impact of gender on kidney allograft survival in black recipients.

Methods

A total of 805 kidney transplant recipients were reviewed retrospectively.

Results

All blacks compared with all whites had significantly reduced graft survival at 1, 2, and 3 years (89%, 84%, 82% vs 93%, 89%, 87%, respectively, log-rank P = .03). After stratification by race and gender, black females showed the worst graft survival. When black females were excluded, allograft survival between black males and all whites were similar. Black females carried more risk factors for graft loss. Compared with all others, the unadjusted hazard ratio of graft loss for black females was 1.67 (P < .01; 95% confidence interval, 1.15–2.43), but the adjusted hazard ratio was 1.47 (P = .07, 95% confidence interval, .98–2.23).

Conclusions

Race and gender in a multivariate analysis are not statistically significant independent risk factors for poor allograft outcomes.     

Outcomes of organ transplants when the donor is a prior recipient

Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donation After Transplant (ODAT) donors. We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From October 1, 1987 to June 30, 2015, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately 4 years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period June 1, 2005 to December 31, 2014, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non‐ODAT liver transplants (P = .008). Kidney grafts donated by ODAT donors whose initial transplant occurred >1 year prior were associated with significantly increased graft failure (P = .012). Despite increased risk of graft failure amongst certain ODAT grafts, 5‐year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances.     

ARTIFICIAL URETERAL REPLACEMENT FOR URETERAL NECROSIS AFTER RENAL TRANSPLANTATION: REPORT OF 3 CASES

Purpose

We applied a new minimally invasive technique of artificial ureteral replacement for renal transplant ureteral necrosis.

Materials and Methods

Artificial ureteral replacement was performed in 3 renal transplant recipients with ureteral necrosis (complete in 1 and distal in 2) after failure of primary endoscopic treatment. Under fluoroscopic guidance a percutaneous tract is created and progressively dilated. The ureteral silicone polytetrafluoroethylene bonded tube is introduced into the pyelocaliceal renal graft cavities, tracked subcutaneously down to the suprapubic area and introduced into the bladder via a short incision.

Results

There were no immediate postoperative complications except for transient postoperative acute prostatitis in 1 patient. No secondary complications were observed with a mean followup of 2.5 years. All grafts have good late function and all tubes are patent with no evidence of encrustation or obstruction. The tubes are well tolerated underneath the skin. Reflux was present in all 3 cases with no clinical manifestation. An asymptomatic episode of lower urinary tract infection was observed in the female patient.

Conclusions

In select cases of ureteral necrosis after renal transplantation artificial ureteral replacement by subcutaneous pyelovesical bypass offers a possible alternative to open ureteral reconstruction.     

Clinical research and social status investigation for donor and recipient of living-related kidney transplant

Objective

Renal transplantation is the best options for treating end-stage renal disease. Better patient and allograft survival rates are provided by living donation, which has been safe, with minimal immediate and long-term risk for the donor. This study aims to investigate the life status and summarize the clinical experience in living-related kidney transplant (LRKT) before and after renal transplantation.

Methods

A total of 310 cases of LRKT have been performed in our center since 1998. Tissue matching and risk factors assessment in donors and recipients were performed before donation. Small lumbar incision was used in all cases for unilateral nephrectomy. Donors and recipients were followed up regularly after renal transplantation.

Results

All living donors were healthy, with normal renal function after unilateral nephrectomy. The 1- and 5-year patient/graft survival rates of LRKT were 98.3 %/97.6 % and 91.3 %/86.9 %, respectively. The cumulative incidence of delayed graft function (DGF) and acute rejection (AR) was 2.9 % (9 cases). Thirteen cases developed pulmonary infection (4.2 %) and eight cases were cured. The graft function in most cases returned to normal range soon after kidney transplant. Moreover, the creatinine and BUN levels of grafts donated by children or siblings of recipients were markedly lower than those donated by parents, at 1 month after transplant.

Conclusion

Adequate pretransplant assessment, better tissue matching, and reduced ischemia time may result in lower incidence of DGF, AR and higher patient/graft survival rates for LRKT. It is important to improve selection criteria and health assessment of donors. Long-term follow-up is essential to ensure a healthy life for donors and recipients after kidney transplant.     

The outcome of heart transplantation in hepatitis C-positive recipients

Background

Clinical outcomes of heart transplantation (HTx) among recipients with chronic hepatitis C virus (HCV) infection are poorly understood especially in Asia. Therefore, this study evaluated these clinical outcomes.

Methods

Using retrospective chart review we collected data on 385 patients including 20 HCV-positive recipients at the time of transplantation. We obtained information on demographics features, serial transaminases, graft function, patient survival as well as the incidences of acute hepatitis and transplant coronary artery disease.

Results

Between 1987 and 2010, the 20 HCV-positive patients had a median age at transplantation of 52 years (range, 30-63). Seventeen were men and three women. All the patients were classified as Child-Pugh class A; two had cirrhosis prior to HTx. Over a mean follow-up of 63 months (range, 2 days to 187 months), there were 11 deaths, including two hospital mortalities and nine subsequent deaths. Only one mortality (5%) was related to Child-Pugh class C cirrhosis, despite liver transplantation. Among the other 19 deceased or surviving recipients, there was no evidence of hepatic dysfunction or hepatocellular carcinoma. Transplant coronary artery disease was detected in six patients (30%). There was no significant difference in Kaplan-Meier actuarial survival between the HCV-positive and HCV-negative recipients (P = .59).

Conclusions

There was no significant difference in patient survival or graft function between HCV-positive and HCV-negative HTx recipients. Additionally, HCV-positive recipients were not at an increased risk of hepatic failure or accelerated transplant coronary artery disease.     

Risk Factors for Development of New-Onset Diabetes Mellitus and Progressive Impairment of Glucose Metabolism After Living-Donor Liver Transplantation

Background

New-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients.

Methods

We collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined.

Results

Pre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes.

Conclusions

Older age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.     

Tipping the Scales: Liver Transplant Outcomes of the Super Obese

Objective

We aim to study outcomes in liver transplant recipients with body mass index (BMI) ≥50 using the United Network for Organ Sharing (UNOS) database.

Methods

We reviewed patients undergoing liver transplantation recorded in the UNOS database from 1988 to 2013. Of 104,250 liver transplant procedures, 123 were performed on super obese patients.

Results

Sixty-four percent of the super obese patients are female (64 %) and had a mean age 47 years (20–71). The mean BMI was 53.5 (50–72.86) and 16 % had diabetes. The mean Model for End-Stage Disease (MELD) score at transplant was 29.1 (6–53). It was found that BMI ≥50 increased 1.6-fold the risk of death within 30 days after liver transplantation. Graft failure was increased by 52 % and overall mortality was by 62 %. A 1:1 propensity score-matched analysis demonstrated that patients with BMI <50 have significantly better graft and overall patient survival than the super obese.

Conclusions

Overall, our data shows that BMI ≥50 is an independent predictor of perioperative mortality and graft and overall patient survival. Further studies are necessary to better understand predictors of outcomes in super obese patients.

     

Comparison between thymoglobulin and ATGAM as an induction agent in adult kidney transplantation: a single-center experience

Objective

The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received Thymoglobulin or ATGAM as an induction agent.

Methods

We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation.

Results

One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving Thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in Thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008).

Conclusion

The efficacy of Thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure.     

Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

Background

The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD.

Effect of Donor-Recipient Age Match in Expanded Criteria Deceased Donor Kidney Transplantation

Purpose

Our objective was to investigate the effects of age on patient and graft survival in expanded criteria donor (ECD) renal transplantation.

Long-term experience with everolimus in kidney transplantation in the United States

Background

Limited long-term data exist on US kidney transplant patients who have received everolimus at time of transplantation.

Methods

Using data from the United Network for Organ Sharing/Organ Procurement Transplant Network database, we described patient characteristics and outcomes among adult patients who received a kidney transplant between 1998 and 2007 and received everolimus maintenance immunosuppression (n = 392) at time of discharge. Outcomes included acute rejection, new-onset diabetes posttransplant, primary graft failure, and serum creatinine. We included single-organ, first-time transplants between 1998 and 2007 as a reference group.

Results

Primary graft survival at 3 and 5 years posttransplantation was 87.2% ± 2.1% (95% confidence interval [CI]: 82.5%–90.7%) and 77.4% ± 3.0% (95% CI: 70.8%–82.7%), respectively, in the everolimus-treated group. Improved graft survival with everolimus seemed to be more pronounced in recipients of deceased donor transplants despite the fact that everolimus-treated patients quantitatively had a higher rate of acute rejection at 3 years posttransplant versus the reference group.

Conclusion

Although the incidence of acute rejection was slightly higher in the everolimus-treated patients, graft survival at 3 and 5 years posttransplantation favored everolimus, with the effect being particularly notable in the recipients who received deceased donor renal transplants.     

Hepatitis C Virus Recurrence Occurs Earlier in Patients Receiving Donation After Circulatory Death Liver Transplant Grafts Compared With Those Receiving Donation After Brainstem Death Grafts

Introduction

Hepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist.