Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in renal transplantation between 1990 and 2002 in Spain.

Background. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) decrease cardiovascular mortality and slow the progression of renal disease in non-transplant patients, but their impact on kidney transplant outcome has not been well established.Methods. Patients receiving a renal allograft in Spain in 1990, 1994, 1998 and 2002 were considered for the present study. Only adult (>/=18 years) recipients of a single kidney transplant functioning at the end of the first year were considered. A total of 4842 patients with clinical data about ACEI/ARB therapy were included.Results. During the initial 2 years after transplant, ACEI/ARB were less frequently used in the 1990 and 1994 cohorts than in 1998 and 2002 (15.1%, 24.6%, 33.5% and 45.1%, respectively; P < 0.001). During the first year, a total of 1063 patients (22.8%) received ACEI/ARB treatment, and graft survival (50.0% for treated patients and 51.4% for untreated, P = ns), death-censored graft survival (60.6% versus 63.5%, P = ns) and patient survival (68.8% versus 66.6%, P = ns) were not different. During the initial 2 years, 1472 patients (31.4%) received treatment with ACEI/ARB, and graft survival tended to be higher in treated patients (54.4% and 50.9%, P = 0.063). Since there was an interaction between ACEI/ARB treatment and year of transplant, graft survival was analysed in each cohort. Cox regression analysis including the propensity score for ACEI/ARB treatment showed an association between ACEI/ARB treatment and graft survival in the 2002 cohort (relative risk 0.36 and 95% confidence interval 0.17-0.75, P = 0.007). Death-censored graft survival (63.8% versus 63.1%, P = ns) and patient survival (68.1% and 66.5%, P = ns) were not significantly different.Conclusions. The use of ACEI/ARB during the initial 2 years after transplantation was associated with a better graft survival, but this effect was only observed in the 2002 cohort.

CD127(low) expression in CD4+CD25(high) T cells as immune biomarker of renal function in transplant patients.

BACKGROUND: Noninvasive tests measuring cellular immunity could help predict immunologic risk and subsequent allograft dysfunction in transplant patients. CD25 is a promising marker of activation. Recent descriptions of CD127 expression as a discriminating factor between regulatory and activated T cells suggest its potential utility. METHODS: Expression of CD127 in CD4+CD25 T cells was analyzed by flow cytometry in peripheral blood from 62 renal transplanted patients and 30 healthy controls. Forty patients presented stable graft function and 22 suffered renal failure. RESULTS: Renal transplant patients showed higher levels of CD127(high) and a lower frequency of CD127(low) than healthy controls (0.63% vs. 0.29% [P<0.001] and 1.4% vs. 2.4% [P<0.001], respectively). However, high frequencies of not only CD127(high) but also CD127(low) showed a significant correlation with serum creatinine levels (P=0.012 and P=0.003, respectively). Allogenic stimulation in vitro increased the frequency of CD127(low) subset in a dose dependent manner. Furthermore, in patients with a high frequency of CD127(low) subset, this consisted mostly of FoxP3 negative cells, discarding their regulatory origin. Median frequency of CD127(low), but not CD127(high), cells showed significant differences between patients with stable function and with renal failure (P<0.005), with 16.7% and 53.1% of individuals above the median CD127(low) value (1.4%), respectively. CONCLUSION: Quantification of CD127(low) subset through staining of CD4+ T cells with the combined markers CD127/CD25/CD45RO has been demonstrated to be a significant tool for monitoring the outcome course of renal transplant patients.

Fluvastatin in the prevention of renal transplant vasculopathy: results of a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Statins prevent the progression of transplant vasculopathy in heart transplants, but its beneficial effect on the transplanted kidney is controversial. METHODS: The aim is to evaluate the utility of fluvastatin 80 mg/day to reduce the progression of 6-month renal transplant vasculopathy in a multicenter, prospective, randomized, placebo-controlled trial stratified according to donor age. All patients received cyclosporine, mycophenolate mofetil, and prednisone. The progression of transplant vasculopathy was evaluated in paired donor and 6-month protocol biopsies. The primary efficacy variable was the progression of mean arterial intimal volume fraction (deltaVvintima/artery) evaluated with histomorphometry. The minimum sample size to detect a 50% reduction in the progression of deltaVvintima/artery was 62 patients per group. The secondary efficacy variable included the incidence of transplant vasculopathy evaluated according to Banff criteria. RESULTS: A total of 89 patients were included, 74 completed the 6-month study and 57 have paired biopsies with sufficient tissue for histological evaluation. The deltaVvintima/artery was not different between treatment and placebo groups (6.9+/-8.2% vs. 6.9+/-7.4%, P=ns), whereas the incidence of transplant vasculopathy was lower in the fluvastatin group (7% vs. 33%; P=0.02). Because there was a discrepancy between the primary and secondary efficacy variables, post hoc analysis was performed to evaluate the reproducibility of both variables in a subset of 50 biopsies. The reproducibility of transplant vasculopathy was higher than the reproducibility of Vvintima/artery (kappa 0.86 vs. 0.33). CONCLUSIONS: In summary, there were no differences in deltaVvintima/artery between groups, but fluvastatin treatment was associated with a reduced incidence of transplant vasculopathy.

The effects of hyperlipidaemia on graft and patient outcome in renal transplantation.

Hyperlipidaemia is a frequent complication after renal transplantation. As to whether total cholesterol (TC) and triglyceride levels are risk factors for cardiovascular disease and graft survival is controversial. The prevalence of hypercholesterolaemia in the transplanted population in Spain has increased over the years, going from 38.8% in 1990 to 48% in 1998. In contrast, the prevalence of hypertriglyceridaemia being approximately 20%, has not shown any significant variation. Transplant recipients with high cholesterol were characterized by increased age, lower proportion of males, higher mean body mass index, lower proportion of HCV antibodies, reduced time on dialysis and diabetes. Patients with high cholesterol were more frequently treated with cyclosporine + MMF + prednisone and less frequently treated with tacrolimus + MMF + prednisone. Hypertriglyceridaemia was more frequent in patients treated with cyclosporine + MMF + prednisone, and these patients showed significantly higher creatinine plasma levels at 1 year and were more frequently treated with lipid-lowering agents. Hypertriglyceridaemia at 3 months after transplantation is associated with worse graft survival (RR 1.078; CI 1.07-1.143; P = 0.011) and greater cardiovascular mortality (RR 1.265; CI 1.20-1.428; P = 0.0002), while treatment with statins has a protective effect on the graft survival (RR 0.64; CI 0.512-0.888; P = 0.0051). In conclusion, in the renal transplant population in Spain, hypertriglyceridaemia rather than hypercholesterolaemia, may exert a deleterious effect on graft and patient survival.