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.

Serial beta-2 microglobulin measurement as an auxilliary method in the early diagnosis of cytomegalovirus infection in renal transplant patients.

Infection by cytomegalovirus is one of the most important causes of morbidity and mortality after renal transplant. During episodes of acute rejection serum levels of beta-2 microglobulin (B2M) are elevated due to decreased excretion and/or increased production from T-cell proliferation. Sequential measurement of B2M in the first months after transplantation may detect patients at increased risk of rejection. This study assesses the usefulness of serum B2M for early detection of patients with increased risk of cytomegalovirus disease. Among 16 of 18 cases of CMV infection, there was an increase in serum B2M levels before CMV diagnosis. In all cases, B2M serum levels increased at an average of 10.8 days before the symptoms or the positive antigenemia. From a mean baseline B2M value of 5.0 mg/L, the mean value at the time of diagnosis was 7.7 mg/L before any clinical or laboratory evidence of CMV infection. These findings suggest that B2M serum levels can be used as a marker for early diagnosis of cytomegalovirus infection.