Nonfunctioning renal allograft embolization as an alternative to graft nephrectomy: report on seven years' experience.

PURPOSE: Graft nephrectomy is the treatment of choice in patients with graft intolerance syndrome, but it is associated with high morbidity and mortality rates. Renal vascular embolization has been suggested as a possible alternative. The aim of this study was to evaluate the efficacy and safety of arterial embolization of these nonfunctioning transplanted kidneys. METHODS: Twenty-six transplanted kidneys in 25 patients with irreversible renal graft rejection and graft intolerance who underwent arterial embolization at our center from August 1994 to April 2001 were analyzed for procedural success and long-term outcome. Embolization was performed with absolute alcohol or with polyvinyl alcohol (Ivalon) and coils. RESULTS: Twenty-four of the 26 (92%) procedures were technically successful, but in one patient only partial occlusion of one of two renal arteries was achieved, and in another the renal artery was already completely occluded. There were two major complications: emphysematous pyelonephritis necessitating nephrectomy and groin abscess that was drained. Follow-up ranged from 8 to 84 months. Clinical success was achieved in 24 of the 26 procedures (92%), and only in one patient did embolization fail to relieve the symptoms, and nephrectomy was performed 3 months later. CONCLUSION: Renal vascular embolization is a simple, safe and effective technique for the treatment of nonfunctioning renal allografts associated with graft intolerance syndrome. We suggest that it be considered the treatment of choice.

Replicative senescence in organ transplantation-mechanisms and significance.

In the past two decades, transplantation has become a preferred modality of treatment of end-stage failure of vital organs. Currently, with the significant improvement in short-term graft survival rates, the main effort is concentrated on prolonging the functional life span of transplanted organs. One of the theories which were put forward to explain the progressive deterioration of transplant function was that of replicative senescence. Senescence of an organ or tissue results from age and/or environmental stress-dependant modification of cellular function. With time, the accumulation of cellular alterations may lead to deleterious effects in various organs and tissues and adversely affect transplants. In this article we are reviewing the candidate mechanisms of senescence such as telomere shortening, genetic regulation and environmental-'toxic' factors and are examining the implications of the theory of replicative senescence for organ allograft. We are also presenting our experiments with renal ischemia/reperfusion in rat serving as a model of kidney transplantation, where baseline kidney telomere length and novel marker of cellular senescence--senescence associated beta-Galactosidase (SA-Gal) expression in tissue served as markers. For the first time in vivo, we were able to show that with aging of the animals the amount of senescent cells in kidney tissue was increasing, while the average renal tissue telomere length was decreasing. The degree of tissue senescence, as determined by amount of SA-Gal positively stained cells, was inversely correlated with the recovery of the kidney function after ischemia/reperfusion injury. These results confirm the theory of replicative senescence in organ ischemia for the first time in vivo, and quantitatively validate the direct correlation between the amount of senescent cells in the organ and its susceptibility to ischemic injury. We conclude that recent advances in study of the cellular basis of senescence, in vitro and especially in vivo, may hold clues to the understanding of events which could be implicated in the damage or protection of organ allografts.

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS: Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS: During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS: Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Mucormycosis of the renal allograft: case report and review of the literature.

Fungal infection is an uncommon complication after renal transplantation. We describe a rare form of mucormycosis in the renal graft. Our method was to review chart data and to perform medline searches. The patient was a 42-year-old man who underwent living-unrelated kidney transplantation in Egypt and returned to Israel on POD 8. Within the ensuing 4 weeks he experienced acute rejection which responded to treatment with steroids. Few days after discharge he was readmitted because of fever and graft dysfunction. An infected large perigraft collection was drained, but the patient became anuric and septic. Kidney biopsy showed infarcted necrotic tissue infiltrated by fungi which grew Mucor species. Despite initial improvement following graft nephrectomy and antifungal treatment the patient died of sepsis. Literature review revealed only three additional cases of graft infection due to Mucorales. We conclude that Renal graft infection due to Mucorales is an extremely rare and potentially lethal complication. Living unrelated donation in third world countries might be a possible risk factor. Fungal colonization may occur during transplantation. A high index of suspicion, leading to early diagnosis and initiation of antifungal treatment, in addition to graft nephrectomy, are keys to a more favorable outcome.

Single-bolus high-dose ATG for prophylaxis of rejection in renal transplantation--a prospective, randomized study.

Currently, most centers use antithymocyte globulin (ATG) for induction or treatment of acute rejection. In the literature, postponement of introduction of cyclosporine or delay in acute rejection following ATG induction are well documented [1-4]. In contrast, data are very scant on the reduction of incidence of rejection or improvement of graft survival following ATG prophylaxis [5, 6]. The objective of this study was to compare the efficacy and safety of ATG high-dose single-bolus therapy with that of a standard cyclosporine-based protocol in prophylaxis of acute rejection in renal transplantation in an adult population. Rabbit ATG (Fresenius, Oberursel) was administered intraoperatively (before revascularization) to 19 renal transplant recipients as a single intravenous injection in a dose of 9 mg/kg body weight (high dose, single bolus). Treatment results were compared with those of a control group comprising 19 recipients receiving the same cyclosporin-Neoral-based protocol as the study group. In all patients concomitant medication consisted of steroids and azathioprine. The incidence of acute rejection in the high-dose ATG bolus group was 26%, compared with 58% in controls (P < 0.05). In the ATG treated group no grafts were lost to acute rejection in both high- and low-risk recipients, versus compared with a loss of 37% of rejecting grafts in controls. Though the observed difference in 1-year graft survival between study and control groups (84.2% vs 73.6%) did not reach statistical significance, the same trend was also observed in patients (n = 9 and n = 12 respectively) who, at he time of this report, had completed a 2nd post-transplantation year. The bolus and control groups had a similar incidence of complications and comparable renal function. We conclude that a single-bolus high-ATG protocol is efficient and safe in prophylaxis of renal allograft rejection.