Monitoring of CD38high expression in peripheral blood CD8+ lymphocytes in patients after kidney transplantation as a marker of cytomegalovirus infection.

BACKGROUND: Cytomegalovirus (CMV) infection is a life-threatening complication after solid organ transplantation. It usually appears in the first months after transplantation as a consequence of immunosuppression. The goal of this study was to evaluate the clinical significance of CD38(high)/CD3(+)8(+) percentages in the detection of CMV infection in patients after kidney transplantation. METHODS: In this retrospective study, 269 patients were monitored 2-3 months after renal transplantation for the percentage of CD38(high)/CD3(+)8(+) lymphocytes estimated by flow cytometry and for the number of CMV DNA copies in peripheral blood using a real-time polymerase chain reaction. RESULTS: CMV infection was diagnosed in 12 (4.5%) patients between the 31st and 63rd days after transplantation, and all of them had percentages of CD38(high)/CD3(+)8(+) T lymphocytes above 20%. In 4 of them, CMV DNAemia in peripheral blood was not detected, and 2 of these suffered from tissue-invasive CMV disease. In 7 patients with CMV DNAemia, the CD38(high)/CD3(+)8(+) T lymphocyte percentage did not exceed 20%, and these patients did not develop CMV infection requiring antiviral treatment. In 23 additional patients, a CD38(high)/CD3(+)CD8(+) percentage above 20% was recorded without CMV DNAemia. All of the remaining 234 patients never exceeded the arbitrary limit of 20%. The estimated sensitivity and specificity were 100% and 91% using clinical decision on the presence of CMV infection as a reference value, respectively. The estimated negative predictive value was 100%; however, the estimated positive predictive value was quite low (34%). CONCLUSIONS: The CD38(high)/CD3(+)8(+) lymphocyte percentage seems to be a useful additional diagnostic marker for CMV infection in patients after kidney transplantation, especially when patients are in the risk of a tissue-invasive disease when CMV DNA copies may not be detectable in peripheral blood.

Discontinuation of mycophenolate mofetil from a tacrolimus-based triple regimen 2 months after renal transplantation: a comparative randomized, multicentre study.

Previous clinical data suggested that with a tacrolimus-based regimen adjunctive immunosuppressives may be withdrawn after an initial treatment period. This study investigated the early discontinuation of mycophenolate mofetil (MMF) from a standard triple regimen. Patients were randomized either to receive a continued tacrolimus/MMF/steroids triple regimen (control group) or to reduce and then stop the MMF dose (MMF stop group). Both groups received identical daily tacrolimus and corticosteroid doses. The initial MMF dose was 1 g/day in both arms, but in the MMF stop group the dose was reduced to 0.5 g/day from week 7 to week 12 and then stopped. The intent-to-treat population consisted of 74 (control) and 78 (MMF stop) patients. MMF was tapered off as planned in 82.9% of the patients in the MMF stop arm. The 6-month incidence of biopsy-proven acute rejection was similar in both arms (21.6% control, 16.7% MMF stop). Graft loss occurred in 5.4% (control) and 3.8% (MMF stop) of the patients. MMF could be safely discontinued from a tacrolimus-based triple therapy early after transplantation without any rebound in efficacy during the 6-month follow-up period. (Name of registry: ClinicalStudyResults.org, number: FG-02-CEE-01, date: 9 June 2006).

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens.

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.

Daclizumab in the induction phase of immunosuppression in heart transplant recipients.

OBJECTIVES: Acute rejection episodes negatively effect both short-term survival and development of graft vasculopathy. METHODS: We assessed the incidence and severity of acute rejection episodes under a new protocol using a monoclonal antibody daclizumab in the induction phase of immunosuppressive therapy. The study group B (26 patients) was given daclizumab (1 mg/kg), the control group A (25 patients) was treated without daclizumab. There was no significant difference between the two groups in the important data. A total of first 10 EMB in every patient was classified according to the ISHLT recommendation. We also analysed the incidence of infections. RESULTS: During the first two months there was a significant lower incidence and/or severity of rejection episodes in the daclizumab group with p < or = 0.0016, 0.001 and 0.005 respectively. CONCLUSIONS: Induction therapy with daclizumab significantly reduces the incidence of acute rejection episodes during the first two posttransplant months in heart transplant recipients. It does not increase the risk of infection.

Modality of brain death and serum troponin T levels in donors and their heart transplant recipients.

Cardiac troponin T levels and inotropic requirements were assessed in the sera of 39 heart donors immediately before heart harvesting and, in their recipients, during the first two days after transplantation. In the donors who died of cranial trauma (n=21), serum troponin T levels as well as inotropic support were lower (P<0.05 and P<0.025, respectively) than in the donors (n= 18) in whom death was caused by spontaneous intracranial haemorrhage. In the recipients, no differences in troponin T or inotropic support levels were found in relation to the modality of their donors' brain death.

Perioperative and postoperative course of cytokines and the metabolic activity of neutrophils in human cardiac operations and heart transplantation.

OBJECTIVES: The purpose of this study was to compare systemic inflammatory responses after heart transplantation and nontransplant cardiac operations, both involving cardiopulmonary bypass with a focus on the role of polymorphonuclear leukocytes. METHODS: Lipid peroxidation, blood phagocyte radical production, and interleukin 6, 8, and 10 plasma concentrations during surgical intervention and on the first and seventh postoperative days were evaluated in patients undergoing heart transplantation (n = 24) and in patients not undergoing transplantation (n = 30). RESULTS: Levels of interleukin 6, 8, and 10 increased in both groups of patients during early reperfusion. They normalized within the first postoperative day in the transplant group, whereas the nontransplant group's interleukin 6 and 8 levels remained increased on the seventh day after the operation. Interleukin 10 plasma levels were higher in the heart transplant group during reperfusion. Lipid peroxidation was increased after the operation in both groups of patients. Phagocyte activity was enhanced at reperfusion and at all other sampling times only in the nontransplant group. On the other hand, phagocyte activity oscillated around the preoperative level during heart transplantation, or it was even decreased. CONCLUSION: Both cardiac operations involving heart transplantation and those without transplantation are associated with increased oxidative stress and an enhanced production of proinflammatory and anti-inflammatory cytokines. Differences in interleukin 10 production and phagocyte activity could be caused mainly by the immunosuppressive therapy in heart transplant operations.