Should heart,lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?

Ranney DN, Englesbe MJ, Muhammad W, Al‐Holou SN, Park JM, Pelletier SJ, Punch JD, Lynch RJ. Should heart, lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?
Clin Transplant 2010: 24: 67–72. © 2009 John Wiley & Sons A/S. Abstract: As the outcomes of heart, liver, and lung transplantation continue to improve, more patients will present for subsequent renal transplantation. It remains unclear whether these patients benefit from induction immunosuppression. We retrospectively reviewed induction on solid organ graft recipients who underwent renal transplant at our center from January 1, 1995 to March 30, 2007. Induction and the non‐induction groups were compared by univariate and Kaplan–Meier analyses. There were 21 patients in each group, with mean follow‐up of 4.5–6.0 years. Forty‐seven percent of patients receiving induction had a severe post‐operative infection, compared with 28.6% in the non‐induction group (p = NS). The one yr rejection rate in the induction group was 9.5% compared with 14.3% for non‐induction (p = NS). One‐yr graft survival was 81.0% and 95.2% in the induction and non‐induction group (p = NS). In summary, there is a trend toward lower patient and graft survival among patients undergoing induction. These trends could relate to selection bias in the decision to prescribe induction immunosuppression, but further study is needed to better define the risks and benefits of antibody‐induction regimens in this population.     

Partial left ventriculectomy for dilated cardiomyopathy: is this an alternative to transplantation?

OBJECTIVE: To determine the late effectiveness of partial left ventriculectomy and risk factors for failure. METHODS: Between May 1996 and December 1998, partial left ventriculectomy and concomitant mitral valve surgery were performed in 62 patients (95% transplant candidates) with a mean age of 54 years (range 17-72 years). All patients were in New York Heart Association functional class III (38%) or IV (62%) because of idiopathic dilated cardiomyopathy (59 patients) or ischemic, valvular, or familial cardiomyopathy (1 patient each). Outcomes considered for multivariable analysis included implantation of left ventricular assist device, return to class IV heart failure, relisting for transplantation, and death. RESULTS: Partial left ventriculectomy reduced the left ventricular end-diastolic diameter immediately preoperatively to immediately postoperatively (from 8.4 +/- 1.1 cm to 5.92 +/- 0.8 cm; P =.01), reduced the left ventricular end-diastolic volume index (from 133 +/- 48.6 mL to 64.1 +/- 26 mL; P <.0001), and increased the left ventricular ejection fraction (from 16 +/- 7.6 to 31.5 +/- 10.9; P <.0001). Survival was 80% and 60% at 1 and 3 years after surgery and freedom from failure was 49% and 26%, respectively. Increased systolic pulmonary artery pressure, decreased maximum exercise oxygen consumption, and increased left atrial pressure were associated with failure and/or death. The degree of preoperative mitral regurgitation did not correlate with clinical outcome. CONCLUSIONS: Early and late failures preclude the widespread use of partial left ventriculectomy. However, in view of its sometimes beneficial effect, use in situations that do not allow for transplantation or as a biologic bridge to transplantation may be appropriate.     

Does donor kidney to recipient body weight ratio influence long-term outcomes of living-donor kidney transplantation?

This study evaluated the effect of the donor kidney to recipient body weight (Kw/Rw) ratio on long-term graft function and survival. We investigated retrospectively whether there was any association between Kw/Rw ratio and long-term graft survival and function after a follow-up of >10 years. We studied a consecutive series of 123 adult-to-adult living kidney transplants. According to the Kw/Rw ratio, patients were divided into 3 groups: “low” (Kw/Rw <2.85; n = 29), “medium” (2.85 ≤ Kw/Rw < 4.04; n = 63), and “high” (≥4.04; n = 31). Among the 3 groups, the mean serum creatinine levels at 1 and 6 months as well as 1 year after transplantation were significantly lower among patients with a high Kw/Rw ratio than in those with a medium or low ratio, but serum creatinine levels at 3 and 5 years did not differ significantly (P = .394 and 0.620, respectively). Graft survival rates at 5 and 10 years after transplantation were significantly lower in the “low” group. We observed a significant association between Kw/Rw ratio and graft survival (P = .018). The Kw/Rw ratio is an important factor for long-term graft survival and early graft function. However, it did not significantly affect subsequent renal function.     

Calcineurin inhibitor-free immunosuppression based on antithymocyte globulin and mycophenolate mofetil in cadaveric kidney transplantation: results after 5 years

Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA) <50% receiving a first renal transplant from a suboptimal donor (age 50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 mol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common and led to overimmunosuppression in the long-term. Starting MMF at low dose, MPA monitoring and probably CMV prophylaxis may improve the results of this regimen.     

Is sirolimus a safe alternative to reduce or eliminate calcineurin inhibitors in chronic allograft nephropathy in kidney transplantation?

PURPOSE: We evaluate whether cyclosporine (CsA) or tacrolimus (FK) could be reduced or eliminated after sirolimus was added in chronic allograft nephropathy (CAN). By reducing doses of CsA or FK, we expected that renal function would improve. METHOD AND MATERIAL: Twenty-one patients with CAN had sirolimus added as an immunosuppressive agent. We evaluated the creatinine (Cr) level 3 months after addition. The doses of CsA and FK were decreased gradually and then eliminated over a course of 4 to 6 weeks. If the Cr level rose rapidly or other prominent signs of rejection occurred; low-dose CsA or FK would be added per protocol. We evaluated the duration of engraftment before sirolimus and the Cr level when it was added. RESULTS: Renal function improved in 13 of 21 cases. The improvement in Cr ranged from 12.5% maximally to 1.84% minimally. Seven of 13 cases still required low-dose CsA. The average duration of engraftment before sirolimus was 13.66 +/- 10.80 months. The average Cr level before sirolimus was 1.65 +/- 0.56 mg/dL. In the other eight cases, the Cr level kept rising from 5.1% to 20.4%. The average duration of engraftment was 88.38 +/- 42.21 months. The average Cr level before sirolimus was 2.85 +/- 0.54 mg/dL. Hyperuricemia was noted in 31.3% and hyperlipidemia in 68.8%. CONCLUSION: Sirolimus is a safe alternative to reduce or eliminate CsA or FK in CAN. In cases with a long duration of engraftment and high Cr level, sirolimus might have some effect as a substitute for CNI and thus prevent further nephrotoxicity.     

Is carotid revascularization worthwhile in patients waiting for kidney transplantation?

Renal failure and haemodialysis are associated with an increased risk of cardiovascular disease. Patients undergoing renal transplantation undergo rigorous pre-operative vascular assessment, including optimisation of risk factors for stroke. The indication for carotid intervention and the threshold for carotid endarterectomy in asymptomatic patients with incidental carotid disease has not been clarified in the context chronic kidney disease (CKD). This review aims to analyse outcomes following carotid endarterectomy in patients with CKD, in order to ascertain whether general guidelines for carotid artery revascularisation apply to this specific cohort. The current literature suggests that outcomes following internal carotid artery (ICA) revascularisation are worse in symptomatic and asymptomatic CKD patients compared to the non-CKD population. Consequently, asymptomatic patients with renal failure should be managed conservatively prior to renal transplantation, whilst those with symptomatic disease should be treated according to general guidelines but be informed of higher associated risk of stroke and death. Multidisciplinary optimisation remains essential in all patients waiting for potential renal transplantation.     

Pharmacogenetics of mycophenolate mofetil: a promising different approach to tailoring immunosuppression?

Since the Human Genome Project, the evaluation of the effectiveness and safety of some medications has become partially connected to innate metabolic patterns. Thus, genes that encode receptors and enzymes could play different roles in metabolism, according to their polymorphisms. Especially in organ transplantation, some of the available medications used in immunosuppressive therapy have a narrow therapeutic index, affecting the individual response to these drugs. This review focuses on the polymorphism of genes that encode enzymes of the uridino-glucuronosyltransferase (UGT) family, responsible for the bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), used as an immunosuppressant in solid organ transplantation. The increasing literature data regarding the pharmacogenetics of UGT and MMF suggest that enzyme polymorphism can explain the factors which influence the occurrence of side effects in patients receiving MMF as drug transplant therapy.     

The so-called medical team system in surgery, an alternative to hierarchy?

Since some years representatives of the "Bundes?rztekammer" (German Board of physicians)--induced too by the German parliament of physicians--demanded the establishment of "team-work-models" as a new form of administration of our clinical departments. There are many reasons argueing against a reformation of the present structures like economical considerations, a well-organized education and especially patient-care-management. Only scientifically-based evidence could justify a change of the well-approved head-physician-system in Germany.