Influence of cytotoxic T-lymphocyte antigen-4 polymorphisms on acute rejection onset of cadaveric renal transplants.

We retrospectively examined in cadaveric renal transplants the association between acute rejection episodes (ARE) and single nucleotide polymorphisms (SNPs) localized in the cytotoxic T-lymphocyte antigen (CTLA)-4 promoter, -1147T/C and -318C/T, in exon 1 +49A/G and within the 3' untranslated region (UTR) CT60G/A. Each one of these SNPs may influence the cell surface expression of the CTLA-4 molecule. Seventy-two cadaveric renal transplant recipients with at least 6 month's follow-up were genotyped for CTLA-4 dimorphisms using direct sequencing of specific polymerase chain reaction products. Allele frequencies in both groups of patients with or without acute rejection (ARE and non-ARE) did not show significant differences in various nucleotide positions. At the level of genotype frequency we first noted a positive association to acute rejection of G/G genotypes (ARE af = 14.7%, non-ARE af = 5.9%) for the +49 (cod. 17), which was associated with decreased expression of the CTLA-4 full-length molecule. In contrast, the AG genotype seemed to be protective (61.8% vs 32.4%, P = .028; odds ratio [OR] = 0.2961). Regarding the CT60G/A dimorphism, noteworthy was the identification of a significantly higher incidence of CT60 A/A genotype in ARE compared with non-ARE group (29.7% vs 8.6%; Yates P = .035; OR = 4.51). Such association of protective AA genotype with ARE, as observed also in autoimmunity, was associated with an increased level of sCTLA-4 induced by the polymorphism, which blocks B7-flCTLA-4 interactions, enhancing T-cell reactivity by preventing transduction of inhibitory signals. Considering the various polymorphic sites in the haplotype, we observed a significant increase in ARE among patients of the CTLA4 +49A/CT60A (HF = 51.5% vs 29.5%; P = .014; OR = 2.545) and a reduction among the +49A/CT60G (17.6% vs 33.8%; P = .04; OR = 0.4193) 2-loci haplotype, As regards the -1147/-318/+49/CT60 CTLA-4 4-loci haplotypes, we observed a significantly higher frequency of the CCAA haplotype in ARE patients comparison with those free of rejection (HF = 51.8% vs 31.1%, P = .046 OR = 2.363). These findings are consistent with those observed in allogeneic stem cell transplantation, wherein patients with CT60 AA showed a major incidence of graft-versus-host disease. An association of protective AA genotype with ARE, as observed also in autoimmunity was associated with an increased level of sCTLA-4 induced by this polymorphism, which blocking the B7-flCTLA-4 interaction, would enhance T-cell reactivity by preventing transduction of inhibitory signals.

A rare case of herpes simplex type 1 bronchopneumonia associated with cardiomegaly in renal transplantation.

INTRODUCTION: We report a rare case of herpes simplex virus (HSV) type 1B in patient with kidney transplant as a possible cause of patient death. CASE REPORT: A 32-year-old renal transplanted Caucasian man was referred for asthenia, fever, anemia, chest pain, cough, dyspnea, myalgias, peripheral edema, acute renal failure, diffuse cutaneus and mucous vesicles, and acute weight gain. The home therapy consisted of tacrolimus, sodic mycophenolate, and steroids. Laboratory data, bronchoscopy, and bronchial mucosal biopsy revealed HSV1B. We administered antiviral and antibiotic agents and reduced tacrolimus with clinical resolution. But after 10 days from discharge, the patient was admitted for acute cardiomegaly. So using ex adiuvantibus criteria we administered antiviral therapy with complete clinical improvement. CONCLUSION: According to the literature, posttransplant HSV1B infection is a rare but severe complication of kidney transplantation associated with poor graft survival and a high mortality. Only an early, accurate diagnosis with efficient treatment permitted resolution of the problem. Our report stresses the difficulty of HSV2B clinical diagnosis and treatment.

Prospective clinical trial comparing two immunosuppressive regimens, tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine, in de novo renal transplant recipients: results at 6 months follow-up.

OBJECTIVE: The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus. PATIENTS AND METHODS: Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids. RESULTS: At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 +/- 38 vs EVL 250 +/- 55 mg/dL; P < .003). CONCLUSIONS: This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.

Cardiovascular risk profile in kidney transplant recipients treated with two immunosuppressive regimens: tacrolimus and mycophenolate mofetil versus everolimus and low-dose cyclosporine.

OBJECTIVE: The aim of this prospective study was to compare the cardiovascular risk (CVR) profile in patients treated with 2 different immunosuppressive regimens: tacrolimus and mycophenolate mofetil (TAC) compared with everolimus and low-dose cyclosporine (EVL). PATIENTS AND METHODS: Sixty consecutive renal transplant recipients prospectively assigned to TAC (n = 30) or to EVL (n = 30) were followed for 6 months. TAC group immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroid. EVL group immunosuppression consisted of basiliximab, everolimus, and low doses of cyclosporine and steroid. Main CVR factors analyzed were: hypertension, dyslipidemia, posttransplant diabetes mellitus, and weight gain. RESULTS: Six months posttransplantation, patients in the EVL group showed significantly higher mean serum cholesterol (P < .003) and serum triglyceride levels (P < .027), as well as a greater number of patients were receiving statin treatment (P < .05). Mean systolic blood pressure, mean diastolic blood pressure, number of patients treated for hypertension, number of antihypertensive medications prescribed per patient, posttransplant weight gain, and posttransplant diabetes mellitus were not significantly different among the EVL and TAC groups after 1, 3, and 6 months posttransplantation. CONCLUSIONS: This study showed that at 6 months posttransplantation, patients on EVL displayed significantly greater dyslipidemia with respect to the TAC group. A longer follow-up will be necessary to discover whether the presence of everolimus in the immunosuppressive regimen provides significant benefits for the CVR of renal transplant recipients.