The morbidity related to long-term steroid therapy has led to continued interest in withdrawal of steroids from immunosuppressant regimens after renal transplantation. A number of recent trials have provided long-term information regarding the risks and benefits of steroid avoidance or withdrawal (SAW). A literature search was performed using Ovid Medline, Embase, the Cochrane Library, and the Transplant Library. Randomized controlled trials comparing a maintenance steroid group with complete avoidance or withdrawal of steroids were selected. All studies were assessed for methodological quality. Trials were pooled by meta-analysis to provide summary effects (relative risk [RR] or weighted mean difference) with 95% confidence intervals (CI). Thirty-four studies including 5,637 patients met the inclusion criteria. SAW regimens significantly increased the risk of acute rejection (AR) over maintenance steroids (RR 1.56, CI 1.31-1.87, P<0.0001). No significant differences in corticosteroid resistant AR, patient survival, or graft survival were observed. Serum creatinine was increased and creatinine clearance was reduced with SAW. Cardiovascular risk factors including incidence of hypertension (RR 0.90, CI 0.85-0.94, P<0.0001), new onset diabetes (RR 0.64, CI 0.50-0.83, P=0.0006), and hypercholesterolemia (RR 0.76, CI 0.67-0.87, P<0.0001) were reduced significantly by SAW. Despite an increase in the risk of AR with SAW protocols, there is only a small effect on graft function with no measurable effect on graft or patient survival. There are significant benefits in cardiovascular risk profiles after SAW. SAW protocols would seem justified with current immunosuppressive protocols in low-risk recipients.

Mycophenolate mofetil (MMF) has increasingly replaced azathioprine (AZA) as the antimetabolite of choice in immunosuppressive protocols. Initial trials comparing MMF with AZA in patients receiving cyclosporine A sandimmune showed a clinical benefit in reducing the incidence of acute rejections. It has been questioned whether this benefit remains significant when using newer formulations of cyclosporine A (neoral) and tacrolimus. Literature searches were performed using the Transplant Library, Cochrane library, Medline, and Embase for all randomized controlled trials directly comparing MMF with AZA in renal transplant recipients. Trials were assessed for quality using the Jadad scoring system. Trials were pooled using meta-analysis software. Confidence intervals were set at 95%. Nineteen relevant studies were identified, including a total of 3143 patients. MMF significantly reduces the risk of acute rejection when used in combination with any calcineurin inhibitor (relative risk 0.62, 0.55–0.87, P<0.00001). The hazard for graft loss, including death with a functioning graft, is also significantly reduced in patients treated with MMF (hazard ratio 0.76, 0.59–0.98, P=0.037). There is no significant difference in patient survival or renal transplant function between groups. Risk of adverse events, including cytomegalovirus infection, anemia, leukopenia or rates of malignancy, does not differ significantly. A greater risk of diarrhea is seen in MMF-treated patients. We have shown that MMF used with a calcineurin inhibitor does indeed confer a clinical benefit over AZA by reducing the risk of acute rejection and also possibly reducing graft loss. This effect is independent of whether MMF is used in combination with sandimmune, neoral or tacrolimus.

Background.: The use of mycophenolate mofetil (MMF) as a primary immunosuppressant after transplantation is increasing. A number of factors interact to result in variability in blood levels of mycophenolic acid (MPA) increasing the risk of toxicity. This has led to interest in the application of therapeutic drug monitoring to optimize its use. Methods.: A systematic literature search was performed using Medline, Embase, the Cochrane Central Registry of Clinical Trials, the Transplant Library, and clinical trial registries for studies investigating the clinical role of MMF pharmacokinetic drug monitoring. Studies relating monitoring regimens to clinical outcomes were included. Results.: The majority of studies are retrospective in nature, demonstrating good correlation between the full total MPA area-under-the-curve and the risk of acute rejection, but not toxicity. Free MPA levels may better predict toxicity. Single-point parameters, in particular trough levels, show poor correlation with the risk of acute rejection and toxicity, and in prospective studies do not improve clinical outcomes. Limited sampling strategies using samples from the first few hours postdose allow good prediction of the full area-under-the-curve, and monitoring using these strategies may improve clinical outcomes. Conclusions.: The current data regarding therapeutic monitoring of MMF is of limited quality. The most promising results to date come from limited sampling strategies, with benefit seen in one prospective randomized trial. Further prospective trials and longer follow-up are required to investigate the optimum sampling strategy and subsets of patients who may benefit from monitoring, but the current evidence in favor of monitoring is weak.

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions. We performed a systematic literature search using MEDLINE, EMBASE, the Cochrane Library, the Transplant Library and trial registries. Inclusion criteria specified any comparative, prospective study for deceased donor renal allografts. Studies were assessed for methodological quality. The primary outcome was delayed graft function (DGF). Fifteen trials with a total of 3584 kidneys were included. Eurocollins was associated with a higher risk of DGF than University of Wisconsin solution (UW) in two randomized controlled trials (RCTs) and histidine–tryptophan–ketoglutarate (HTK) in two RCTs. UW was associated with an equal risk of DGF compared with Celsior in three RCTs and HTK in two RCTs. There was limited data regarding other comparisons and outcomes. The choice of preservation solution has an effect on the incidence of DGF, which might, in turn, affect long‐term outcomes. Both UW and HTK have lower rates of DGF than Eurocollins. There is no difference in the incidence of DGF with the use of Celsior, HTK and UW. These findings are supported by registry data.

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilisation were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20°C, studies were grouped as hypothermic (HRP, ≤20°C) or normothermic (NRP, >20°C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared to ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilisation needs further research.