Safety and efficacy of induction treatment with low thymoglobulin doses in kidney transplantation from expanded-criteria donors.

BACKGROUND: Induction treatment has been recommended as part of the initial immunosuppressive regimen in kidney transplantation, and antithymocyte globulin is one of the drugs used for it, but at usual dosage it has been related to an increase of infectious and neoplastic complications. Our aim was to analyze the safety and efficacy of induction treatment with low doses of antithymocyte globulin, compared to basiliximab. METHODS: In this retrospective cohort study of 321 kidney transplant patients with a minimum follow-up of 2 years, 162 were treated with low doses of antithymocyte globulin (1.25 mg/kg, every other day) and 159 with basiliximab. Mean follow-up was 76.6 ± 37.51 months (range, 24-187 mo) and was similar for the 2 groups. RESULTS: Mean number of antithymocyte globulin doses was 1.89 ± 0.32 mg/kg (range, 1-3). The globulin group received a higher proportion of kidneys from donors >70 years old (25.3% vs 13.8%; P = .010) and donors with higher creatinine levels (1.01 ± 0.62 vs 0.86 ± 0.28 mg/dL; P = .006). The basiliximab group presented a higher incidence of acute rejection (22.1% vs 9.1%; P = .010). Cytomegalovirus disease was more frequent in the globulin group (18.6% vs 8.1%; P = .011) without an increase of infectious hospitalizations. Graft (P = .214) and patient (P = .533) survivals were similar. CONCLUSIONS: Induction with low doses of antithymocyte globulin resulted in a lower incidence of acute rejection with graft and patient survivals similar to that obtained with basiliximab induction, in spite of a worse donor profile. CMV disease was more frequent with antithymocyte globulin, without an increase of infectious hospitalizations or cancer development, in long-term follow-up.

Delayed graft function after renal transplantation: an unresolved problem.

Unlike other areas in renal transplantation, delayed graft function (DGF) remains an apparently unavoidable complication owing to the characteristics of current donors. The aim of this study was to analyze risk factors for DGF in relation to graft and patient survivals. We retrospectively analyzed 507 renal transplant recipients with a median follow-up of 74.83 ± 45.06 months. DGF, which occurred among 189 patients (36.8%) was defined as requirement for dialysis within the first week after transplantation. Donor (P = .000) and recipient (P = .000) age were greater in the DGF group without differences in recipient or donor gender, HLA sensitization, or dialysis time before transplantation. Donor factors as the cause of death associated with DGF were secondary cerebrovascular stroke (P = .002) and hypertensive history (P = .000). Recipient characteristics associated therewith were higher body mass index (P = .000), smoking habit (P = .003), ischemic cardiopathy (P = .01), and dyslipidemia (P = .05). Moreover, the DGF group showed longer cold ischemia (P = .01) and vascular anastomosis (P = .02) times. On multivariate analysis, recipient age (P = .00) and smoking habit (P = .01) together with a donor history of hypertension (P = .02) were independent risk factors for DGF. No differences were observed in acute rejection incidence (P = .07) with worse renal function during follow-up (P < .05). Graft (81% vs 88%; P = .00) and patient (89% vs 95%; P = .00) survivals at 5 years were lower among the DGF group. In conclusion, DGF which was associated with factors related to the donor, the recipient, and the surgical times, produced worse graft and patient survivals. Shortening the cold ischemia time seems to be a modifiable variable to reduce DGF.

Very low-grade proteinuria at 3 months posttransplantation is an earlier marker of graft survival.

Proteinuria is an early finding that appears in the first 3 months after transplantation in half of patients. Frequently, it is very low grade (VLP; <0.5 g/24 h). The aim of this study was to analyze the risk factors and prognostic significance of VLP at 3 months posttransplantation, which was maintained for the first year among our renal recipients. We compared 141 patients (39.7%) who showed VLP with 214 patients (60.3%) without proteinuria. VLP was associated with older recipients (P = .002), HLA incompatibilities (P = .001), older donors (P = .000), nontraumatic cause of brain death (P = .033) and previous hypertension (P = .030), tacrolimus (P = .000) and induction treatment with Thymoglobulin (P = .018) or anti-CD25 monoclonal antibodies (P = .000), as well as delayed graft function (DGF; P = .000). VLP patients showed worse renal function (P < .05) and greater requirement for antihypertensive drugs (P = .001). Multivariate analysis confirmed the impact of donor age, HLA incompatibilities, DGF, and tacrolimus treatment to predict the presence of VLP. Graft (P = .0019) and patient (P = .0146) survivals were lower among the VLP group. Cox analysis showed that VLP (RR: 2.047; P = .018) and DGF (RR: 2.062; P = .0017) were independently associated with reduced graft survival. The positive predictive value of VLP on graft survival was low. In conclusion, VLP was related to increasing acceptance of marginal donors, DGF, and worse renal function. Proteinuria was a noninvasive, readily determined parameter which was related to reduced graft and patient survivals, so renoprotective measures are mandatory from the early stages after transplantation.

Use of basiliximab induction in low-immunological risk renal transplant recipients receiving tacrolimus-based immunosuppression.

Basiliximab induction treatment has been shown to reduce the incidence of acute rejection episodes without the secondary side effects observed with antilymphocyte polyclonal antibodies. We analyzed our experience with basiliximab induction associated with tacrolimus-based immunosuppression among low-immunological risk renal transplant recipients. We retrospectively analyzed 55 renal transplantation patients of low inmunological risk who received organs from donors younger than 55 years. We compared a group of 21 patients (38.9%; group 1) treated with basiliximab (Simulect, Novartis, Basel, Switzerland) with 33 patients (61.1%; group 2) without induction. The patient groups did not differ in recipient age (46.39 +/- 11.1 in group 1 vs 41.82 +/- 11.02 years in group 2; P = .25), donor age (36.71 +/- 14.72 vs 35.09 +/- 14.63 years; P = .69), or recipient and donor gender. No differences were observed in dose or tacrolimus levels during follow-up. The incidences of delayed graft function (DGF; 28.6% vs 28.1%; P = .97) and of acute rejection episodes (9.5% vs 15.6%; P = .52) were similar in both groups. Serum creatinine and proteinuria levels (P > .05) and hospital admissions due to infections (36.4 vs 35.7%; P = .97) were also similar in both groups. At 1 year graft survival rates were 92% and 96% (P = .97) in groups 1 and 2, respectively. Considering our findings and the costs of basiliximab treatment, we conclude that routine administration of basiliximab cannot be justified in young, low-immunological risk transplant recipients undergoing tacrolimus-based immunosuppression.

Induction treatment with low-dose thymoglobulin or basiliximab in renal transplants from older donors.

Transplantation of kidneys from older donors is followed by an increase in delayed graft function (DGF) and acute rejection episodes (ARE). In these circumstances, induction treatment, whether with antithymocyte globulin or with interleukin-2 receptor blockers, may delay the introduction of calcineurin inhibitors (CNI) with effective prevention of ARE. We examined the efficacy and safety of induction treatment with 2 low doses of thymoglobulin compared with 2 doses of basiliximab. A group of 27 patients were treated with thymoglobulin and another 36 with basiliximab. CNI introduction was delayed until day 3 posttransplantation. The thymoglobulin group received 2 doses of 1.25 mg/kg on alternate days and the basiliximab group 2 doses of 20 mg. A trend to a lower incidence of DGF was observed in the thymoglobulin group (33% vs 55.6%; P = .08), with lower levels of serum creatinine on days 7 (P = .02) and 14 (P = .02) posttransplantation. No patient in the thymoglobulin group experienced ARE, but 11 patients (30.6%) in the basiliximab group did (P < .001), and 5 needed rescue treatment with thymoglobulin. We found no differences in the incidence of cytomegalovirus (CMV) disease (P = .945), admission due to infections (P = .274), or neoplasia (P = .340), or differences in graft (P = .69) and patient (P = .21) survivals at 1 and 3 years. Low-dose thymoglobulin was more effective at preventing DGF and ARE in renal transplant recipients of organs from older donors, with no differences in infectious complications or graft and patient survivals.