L. Mjörnstedt

A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation

We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depletion of CD19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66±22 mL/min in the study group and 67±23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.

Successful Combined Partial Auxiliary Liver and Kidney Transplantation in Highly Sensitized Cross-Match Positive Recipients

Combined liver and renal transplantations can be performed against a positive cross‐match, indicating that the liver protects the kidney from the harmful HLA antibodies. This led us to the hypothesis that a partial auxiliary liver graft may have a similar protective effect when performed together with the kidney in highly sensitized patients. Seven patients, with broadly reacting HLA antibodies and positive crossmatches, were transplanted with a partial liver and a kidney from the same donor. In one of the cases a living donor was used. We performed lymphocytotoxic and flow cross‐matches before and after the transplantation. Cross‐matches turned negative after grafting in five of seven cases. The kidney function was excellent, without rejections, during the follow‐up (24–60 months) in these patients. In two cases the cross‐match remained positive after transplantation, one with a never‐functioning renal graft and the other with an early graft failure, probably due to humoral rejection. A simultaneous transplantation of a partial auxiliary liver graft from the same donor, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, can be performed successfully despite a positive cross‐match and may thus be a new option of treatment for highly sensitized patients waiting for a kidney transplant.

Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study

BACKGROUND Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.

Improved renal function after early conversion from a calcineurin inhibitor to everolimus: a randomized trial in kidney transplantation.

In an open‐label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric‐coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12‐month incidence of biopsy‐proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI‐treated controls but discontinuations and BPAR were more frequent.

ABO‐incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti‐CD20 antibody treatment

Abstract: Background: Blood group ABO‐incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO‐incompatible LD renal transplantation using specific anti‐A/B antibody (Ab) immunoadsorption (IA) and anti‐CD20 monoclonal Ab (mAb) treatment.

Liver transplantation for metastatic neuroendocrine tumor disease.

METASTASES from neuroendocrine tumors (NET) of the gastrointestinal tract, carcinoids, and endocrine pancreatic tumors (EPT) can be limited to the liver for long periods and may have slow growth. The symptoms are often related to hormone overproduction and debulking surgery, for example, liver resection, is recommended to achieve tumor remission or symptom palliation. If liver resection is not feasable, hepatectomy and orthotopic liver transplantation (OLT) have been proposed. For EPT where the primary tumor is located in the head of the pancrea it may be advantageous to resect the primary tumor and the liver metastases en bloc and perform a multivisceral transplantation (MVTx).

Liver transplantation for polycystic liver disease-indications and outcome

OLYCYSTIC liver disease (PLD), often associated with autosomal dominant polycystic kidney disease, may lead to considerable hepatomegaly with discomfort, pain, anorexia, dyspnea, and a severely reduced quality of life. Liver function per se is usually normal. Different therapeutic procedures from percutaneous drainage and sclerosing treatment to fenestration and liver resection may alleviate symptoms but with substantial mortality and morbidity in view of the only short-term palliation. 1,2 Liver transplantation (LT) usually leads to excellent symptomatic relief but is a high-risk procedure. 1–7 The aim of the present study was to review all the patients with PLD who have undergone LT on our unit. PATIENTS AND METHODS

A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation : a 3-year follow-up

A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation : a 3-year follow-up

Adult ABO‐incompatible liver transplantation, using A2 and B donors

Abstract: Background: The longer waiting time for a liver graft in patients with blood group O makes it necessary to expand the donor pool for these patients. This applies in both urgent situations and for elective patients. We report on our experience with ABO‐incompatible liver transplantation using A2 and B non‐secretor donors here.

Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation

In a 36‐month, open‐label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post‐transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus −1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12–36, death‐censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy‐proven acute rejection (BPAR). Protocol biopsies in a limited number of on‐treatment patients showed similar interstitial fibrosis progression. Donor‐specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on‐treatment everolimus and control patients with available data (P = 0.281). During months 12‐36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post‐transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.