Comparison of long-term effect of thymoglobulin treatment in patients with a high risk of delayed graft function.

BACKGROUND: T-lymphocyte depletion is a strategy to reverse the impact of ischemia-reperfusion injury (IRI) in progression to chronic allograft dysfunction, especially among patients at high risk for delayed graft function (DGF). METHODS: The present work assessed the effect of thymoglobulin among a population with a high incidence of DGF. We analyzed 209 transplanted patients: 97 in the thymoglobulin and 112 in the control group. RESULTS: The main complication was DGF (59.3%), with a similar incidence in both groups (63.9% vs. 55.3%; P = .36). Acute rejection episodes (ARE) were decreased with thymoglobulin (8.2% vs. 28.5%; P < .001), but cytomegalovirus viremia was 3.4-fold more frequent (58.3% vs. 17.1%; P < .001). One-year graft function was significantly better in the thymoglobulin group (59.2 ± 17.2 vs. 51.8 ± 15.3 mL/min; P = .004), even when censored by ARE (59.7 ± 17.5 vs. 53.3 ± 14.4; P = .023). The same difference was observed at the 2-year follow-up (P = .024), even when censored for ARE (P = .045). A multivariate analysis showed thymoglobulin to be a factor strongly associated with protection of graft function (P = .039). CONCLUSION: Despite not reducing the incidence of DGF, thymoglobulin induction significantly reduced the incidence of ARE and showed a long-term profile of protection of renal graft function, independent of the reduction in ARE.

Effects of ischemia and reperfusion injury on long-term graft function.

BACKGROUND: The clinical manifestation of ischemia/reperfusion injury in renal transplantation is delayed graft function (DGF), which is associated with an increase in acute rejection episodes (ARE), costs, and difficulties in immunosuppressive management. We sought to evaluated the DGF impact after renal transplant. METHODS: We evaluated a group of 628 patients undergoing deceased donor renal transplantation between 2002 and 2005 at 3 Brazilians institutions to define the main DGF characteristics. RESULTS: DGF incidence was 56.8%, being associated with elderly donors (P = .02), longer time on dialysis (P = .001), and greater cold ischemia time (CIT; P = .001). Upon multivariate analysis, time on dialysis >5 years increased DGF risk by 42% (P = .02) and CIT >24 hours increased it by 57% (P = .008). In contrast, DGF was associated with an higher incidence of ARE: 27.7% in DGF versus 18.4% in IGF patients (P = .047). The ARE risk was 46% higher among individuals with DGF (P = .02), 44% among patients >45 years old (P < .001), 50% among those with >5 years of dialysis time (P = .02), and 47% lower among the who were prescribed mycophenolate instead of azathioprine (P < .001). Patients with DGF showed worse 1-year graft function (54.6 ± 20.3 vs 59.6 ± 19.4 mL/min; P = .004), particularly those with ARE (55.5 ± 19.3 vs 60.7 ± 20.4; P = .009). One-year graft survival was 88.5% among DGF versus 94.0% among non-DGF patients. CONCLUSION: The high incidence of DGF was mainly associated with a prolonged CIT. There was a relationship between DGF and ARE, as well as with a negative influence on long-term graft function.

Vimentin expression and myofibroblast infiltration are early markers of renal dysfunction in kidney transplantation: an early stage of chronic allograft dysfunction?

INTRODUCTION: The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up. METHODS: Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function. RESULTS: Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 ± 8.5 months. The mean Cr at biopsy time was 1.44 ± 0.33 mg/dL, and after the follow-up it was 1.29 ± 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively. CONCLUSION: Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

Effect of thymoglobulin in graft survival and function 1 year after kidney transplantation using deceased donors.

UNLABELLED: This study evaluated 1-year graft function and survival among kidney transplantations from deceased donors using thymoglobulin (Thymo) as an induction strategy. PATIENTS AND METHODS: Fifty-seven percent of patients were men and overall mean age was 42 +/- 15 years. Cold ischemia time was 20.1 +/- 4.8 hours. The primary outcome was defined as survival not censored for death after 1 year. The secondary outcome was defined as a comparison of function and survival among patients who received more or less then six doses of Thymo. RESULTS: Four patients experienced acute rejection episodes and the other three died during follow-up. One-year graft survival was 91% with a mean serum creatinine of 1.28 +/- 0.43 mg/dL. Cytomegalovirus infection occurred in 56%. Forty-two (64%) patients displayed acute tubular necrosis of mean duration of 6.89 +/- 7.48 days. Patients who received lower doses showed better serum creatinine values 3 months (1.45 vs 1.86 mg/dL, P = .013) and 12 months (1.05 vs 1.50 mg/dL, P = .04). The difference was probably due to acute tubular necrosis that produced a RR of 1.7 (P = .02; CI 1.04-2.97) when compared with patients with Scr values above 1.30 mg/dL. When censored for death, graft survival was not different between the two groups (< or =6 doses 93% vs >6 doses 97%, P = .43). CONCLUSION: Immunologic induction with Thymo produced excellent graft survival after 1 year with preservation of graft function. Delayed graft function was the most important determinant of graft function after 1 year.