Prevalence of previous hepatitis A virus infection in renal transplant patients with hepatitis C: evidence of persistent anti-hepatitis A virus immune response

Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney transplant recipients are scarce. There is little information concerning natural immunity acquired after acute HAV infection. In most renal transplant recipients, anti-HAV antibodies are not detectable after vaccination; it is reasonable to suppose that immunosuppressive therapy interferes with the immunity. The objective of this study was to evaluate, in an endemic area, the prevalence of anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in 40 HCV-positive renal transplant recipients. This group showed a 90% prevalence of previous HAV infection. These findings suggest that in an endemic area, the prevalence of previous HAV infection is high, even among immunosuppressed patients. HAV antibodies acquired after natural infection are detectable even after the onset of immunosuppressive therapy. These data should be considered when renal transplant recipients are considered for HAV vaccination. Prevaccination screening of renal transplant recipients must follow the same guidelines as those for immunocompetent subjects.     

Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine

Influenza vaccination has been strongly recommended for immunosuppressed renal transplant recipients. However, immunosuppression may lead to impaired antibody responses. We studied the antibody response to an inactivated trivalent influenza vaccine in 59 renal transplant recipients with life-sustaining kidney function: 21 were on cyclosporine and prednisone, 38 on azathioprine and prednisone. Healthy volunteers (n = 29) and patients on hemodialysis (n = 28) served as controls. Despite comparable renal allograft function, cyclosporine-treated patients had a significantly lower immune response against influenza A viruses than azathioprine-treated patients, whether mean antibody levels, fourfold titer rise, or seroconversion to protective titers was analyzed. No significant differences in antibody responses were found between healthy controls and patients on azathioprine. The patients on hemodialysis showed an impaired response to vaccination. However, in contrast to the cyclosporine-treated patients, booster immunization proved valuable in this group.     

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients

No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1+/-5.2 years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6+/-1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6 months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1 year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1 year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.     

Effect of basiliximab on renal allograft rejection within 1 year after transplantation

Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.     

Humoral and Cellular Immune Responses after Influenza Vaccination in Kidney Transplant Recipients

It has been speculated that influenza vaccination of renal allograft recipients could be associated with de novo production and/or increased titers of anti-HLA antibodies (HLA-Ab). To directly address this issue, we recruited 66 stable renal transplant recipients and 19 healthy volunteers during the 2005–2006 vaccination campaign. At day 0 and day 30 following vaccination, HLA-Ab were screened and in parallel influenza-specific antibody and T-cell responses were assessed. Humoral postvaccinal responses to A/H1N1 and A/H3N2 strains, but not B strain, were less frequent in transplanted patients than in control subjects. Significant expansion of influenza-specific IFN-γ-producing T cells was observed at similar frequencies in patients and controls. There was no correlation between cellular and humoral postvaccinal responses. No impact of sex, age or immunosuppressive regimen could be evidenced. Vaccination was not associated with any significant change in preexisting or de novo anti-HLA sensitization. No episode of allograft rejection was recorded in any of the patients. Our results suggest that flu vaccination is safe in stable renal transplanted patients. Larger studies are needed for definitive statistical proof of the safety and effectiveness, with regard to the quality of the immune response, of yearly influenza vaccination in immunosuppressed patients.     

肾移植后免疫抑制用药方案与移植肾长期存活的关系

目的 分析肾移植后不同的免疫抑制用药方案对移植肾长期存活的影响。方法 根据不同用药组合将患者分为环孢素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）和泼尼松（Ｐｒｅｄ）三联治疗组、ＣｓＡ和Ｐｒｅｄ二联治疗组、Ａｚａ和Ｐｒｅｄ传统二联治疗组。统计分析免疫抑制用药、排斥反应发生及人、肾存活情况;对发生排斥反应的患者追踪其发生排斥前１２个月内的药物更动情况。结果 采用三联治疗的患者人／肾５年存活率（８８％／７８％）显     

Immunogenicity of hepatitis B vaccine in renal transplant recipients

To evaluate the immunogenicity of hepatitis B vaccine in renal transplant recipients, we administered three 40-microgram doses of vaccine to 17 patients who had previously undergone transplantation and were on immunosuppressive therapy. Life-table analysis revealed a cumulative antibody response rate of only 17.6% at 12 months, and the three responders had low titers of antibody to hepatitis B surface antigen. There were no serious adverse effects and no episodes of graft rejection in responders or nonresponders. In addition, the ratio of helper/inducer (T4) to suppressor/cytotoxic (T8) T cells in vaccinees bore no relationship to the immunogenicity of the vaccine. These data indicate that hepatitis B vaccine is weakly immunogenic in renal transplant recipients and illustrate the need for vaccination prior to transplantation for maximal protection against hepatitis B virus infection.     

Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients

BackgroundThis study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients.MethodsWe measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status.ResultsThe proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer.ConclusionThis study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.     

The effect of Daclizumab in a high-risk renal transplant population

INTRODUCTION: African-American (AA) renal transplant recipients have a higher incidence of acute rejection when compared to Caucasian renal transplant recipients. This higher rejection rate holds true even with the addition of several of the newer immunosuppressive agents (e.g. mycophenolate mofetil (MMF) and Rapamycin). Acute rejection rates among Hispanic (H) renal transplant recipients are higher in some settings, while lower or the same as in Caucasians in other settings. IL-2 receptor antibodies have been shown to decrease rejection rates when added to a regimen of cyclosporine (CsA), azathioprine and prednisone. Limited data are available on these agents in conjunction with triple CsA, MMF and prednisone therapy, particularly in higher risk group patients. We studied the effect of the addition of the IL-2 receptor antibody Daclizumab to a CsA, MMF, prednisone regimen in a group of African American and high-risk Hispanic renal transplant recipients. METHODS: This was a non-randomized, prospective study. A total of 49 renal transplant recipients (29 African American and 20 Hispanic) were studied and followed. A simultaneous cohort of 56 (31 African-American and 25 Hispanic) renal transplant recipients receiving CsA, MMF and prednisone with no standard induction agent served as the control group. The study cohort received the same regimen with the addition of Daclizumab at 1 mg/kg for five doses over 10 wk. Multivariate analysis was performed to isolate independent factors influencing the study's results. RESULTS: A total of 56 patients in the control group and 49 patients in the Daclizumab group received an average follow-up of 17.1 +/- 6.9 and 12.7 +/- 5.1 months, respectively. Acute rejection rates were lower in the Daclizumab group as compared to the control group 26.4% versus 49.3% per patient years, respectively. A total of eight recurrent rejections in 6 patients occurred in the control group and none in the Daclizumab arm. Graft loss at this follow-up was no different between the groups. CONCLUSION: The addition of Daclizumab to a regimen of CsA, MMF and prednisone decreases acute rejection episodes in a high-risk group of African American and Hispanic renal transplant recipients.     

No myelosuppression when mizoribine is combined with allopurinol for the treatment of hyperuricemia in renal transplant patients

Background. In cadaveric renal transplant recipients, a commonly used triple immunosuppression regimen includes azathioprine, cyclosporin, and prednisolone. Azathioprine is a potential bone marrow suppressant. Allopurinol is a commonly used drug to treat hyperuricemia, which frequently occurs in kidney transplant recipients. Azathioprine is metabolized by xanthine oxidase, which is inhibited by allopurinol, leading to accumulation of its active metabolites, which are potential myelosuppressants. Moreover, in certain clinical situations, azathioprine is contraindicated. The immunosuppressive drug mizoribine has been used to prevent rejection of organ allografts in humans. Its effect is mediated through a different pathway in purine metabolism, and allopurinol does not interfere with its metabolism. Therefore, a combination of mizoribine with allopurinol does not cause myelosuppression. Methods. Thirteen cadaveric renal transplant recipients who had hyperuricemia were treated with allopurinol and mizoribine as an alternative to azathioprine, along with steroids and cyclosporin A. They were followed up for 12 months. Results. None of these patients developed bone marrow suppression and all had adequate control of hyperuricemia and had no deterioration in allograft function. Conclusions. Mizoribine can be safely combined with allopurinol in cadaveric renal transplant recipients who have hyperuricemia, without causing bone marrow suppression. Received: October 31, 2000 / Accepted: March 14, 2001     

The uptake of influenza and pneumococcal vaccination among immunocompromised patients attending rheumatology outpatient clinics

Purpose and objectives

The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.

Methods

This was a questionnaire-based study. Patients were eligible to partake in this study if they were using immunosuppressive drugs. During the study period (4 weeks), 337 patients were screened, and 110 patients fulfilled the criteria for inclusion.

Results

Positive vaccination uptake of our cohort was as follows: common influenza alone (34%, 37 out of 110), pneumonia alone (11%, 12 out of 110), and both pneumococcal and influenza vaccination (11%). The status of influenza A (H1N1) vaccination was not recorded as a part of this audit. The two most common reasons cited by patients for non-uptake of vaccinations were: ‘not offered’ and ‘thought it was unnecessary’. Of 37 patients who had influenza vaccination, 33 patients (89%) had additional risk factors, and there were only four patients who had influenza vaccine solely because they were taking immunosuppressive drugs. All pneumococcal vaccinated patients (n = 12) were noted to have additional risk factors.

Conclusion

There is suboptimal uptake of influenza and pneumococcal vaccinations among immunosuppressed patients attending rheumatology outpatient clinics. These results are a cause of concern given the morbidity and mortality of associated infections.     

Response of renal allograft recipients to pneumococcal vaccine.

Antibody responses to pneumococcal polysaccharide vaccine were compared in a control group of 17 normal adults and in a group of 27 adult patients with stable renal function (serum creatinine 0.8--2.1 mg/dl) seven months to nine years following renal transplantation. Using the indirect hemagglutination technique, antibody titers to 13 of the 14 capsular antigens contained in the vaccine were determined for each patient just prior to and again three weeks following immunization. There was no significant difference between the two groups in the proportion of patients responding with a fourfold rise in titer to 12 of the 13 antigens tested. The response rate to antigen type 3 was reduced in the transplant group (p less than 0.05). Mean fold increase in indirect hemagglutination titers was likewise determined for each antigen, and a reduced response in the transplant group was noted only to antigen type 23 (p = 0.037). Immunosuppressed renal allograft recipients appear capable of mounting a nearly normal antibody response to pneumococcal vaccine.     

Influenza vaccination does not promote cellular or humoral activation among heart transplant recipients

BACKGROUND: The impact of influenza vaccination on in vitro parameters of cellular and humoral immunity, anti-viral titers, and clinical outcome was evaluated among cardiac transplant recipients. METHODS: Blood was collected from 29 patients before and 3-4 weeks after influenza vaccination and tested for phenotypic changes in lymphoid subpopulations and generation of antibodies against the allograft and vaccine. RESULTS: Vaccination did not change the percentage of lymphoid subpopulations and did not induce generation of anti-HLA alloantibodies. Anti-vaccine response was detected in 12 of 29 patients and did not correlate with rejection history, length of graft survival, or immunosuppressive therapy. Vaccination did not change the frequency of rejection. Flu-like symptoms were reported in one patient but not confirmed microbiologically. CONCLUSION: Despite the small number of patients in the study, influenza vaccination did not induce undesirable side effects, such as graft rejection or allo-sensitization. Generation of a positive anti-vaccine response was lower among the transplant recipients than healthy volunteers (41% vs. 80%). Clinical efficacy of the vaccine among the responders was not evaluated.     

Conversion to Everolimus in Kidney Transplant Recipients With Calcineurin Inhibitor-Induced Nephropathy: 3 Case Reports

BackgroundCalcineurin inhibitors (CNIs), which remain the most important immunosuppressants in kidney transplant recipients, are a major cause of renal dysfunction due to CNI-induced nephropathy. However, a safe and effective CNI-sparing protocol is yet to be established. Herein, we report a case series of kidney transplant recipients experiencing CNI nephropathy, whose renal function is improved after conversion from CNIs to everolimus.CasesThe 3 kidney transplant recipients included in this study were diagnosed with CNI arteriolopathy by episode biopsy between 9 months and 11 years after transplantation. All patients received triple immunosuppressive therapy consisting of CNI (tacrolimus or cyclosporine), mycophenolate mofetil, and methylprednisolone. All allografts were transplanted from elderly living donors to ABO-compatible and donor-specific antibody-negative recipients. All allograft biopsy specimens exhibited CNI arteriolopathy with alternative quantitative criteria for hyaline arteriolar thickening (aah score: 2 or 3), according to the Banff classification; however, histopathologic assessment did not show any evidence of allograft rejection. Conversely, total dose and blood concentrations of CNIs were within appropriate ranges. After conversion from CNIs to everolimus (1.5 mg/day, twice daily; trough level, 3–5 ng/mL), serum creatinine levels returned to baseline levels measured before the diagnosis of CNI arteriolopathy. In all patients, renal allograft function remained stable, with no evidence of donor-specific antibodies, 1 year after conversion from CNIs to everolimus.ConclusionConversion from CNIs to everolimus can safely and effectively improve renal function in kidney transplant recipients experiencing CNI-induced nephropathy.     

Prevalence of anemia in renal transplant patients: results from MOST, an observational trial

INTRODUCTION: Anemia is one of the most common complications of chronic renal disease. However, the incidence or prevalence of anemia in kidney transplant recipients has not been well studied. The aim of this study was to assess the prevalence of anemia in renal transplant in early and late posttransplant period and the influence of drugs (immunosuppressive and antihypertensive). METHODS: MOST is an observational, prospective trial of renal transplant receiving cyclosporine-based immunosuppressive regimen under condition of normal practice in de novo or maintenance recipients. We analyzed the Spanish data from 397 de novo recipients and 2102 maintenance recipients. RESULTS: In maintenance recipients mean hemoglobin levels were 12.8 +/- 1.6 g/dL (13.2 +/- 1.7 in men and 12 +/- 1.4 in women); 22.73% of men and 20.19% of women were found to be anemic. There was a significant correlation between hemoglobin and graft function (r = .14, P < .0001). The percentage of patients with anemia increased with the severity of chronic renal disease according to the KDOQI classification. Therapy with mycophenolate mofetil was also associated with a higher likehood of anemia as compared with other immunosuppressive therapies (azathioprine or sirolimus). There were no differences with angiotensin-converting enzyme inhibitors or ARB II. In de novo patients postransplant anemia was a frequent complication during the first 3 to 6 months. In patients with delayed graft function the recovery of anemia was slower. CONCLUSION: The prevalence of anemia in transplant recipients was remarkably high, especially in the early postransplant period, and appeared associated with impaired renal function and with immunosuppressive treatment.     

Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression.

BACKGROUND: Impaired phosphate handling of the renal allograft is a common problem and of multifactorial origin. The aim of the study was to elucidate whether a rapamycin- or a mycophenolate-based immunosuppressive therapy aggravates the renal phosphate leak in kidney transplant recipients. METHODS: Renal phosphate handling was determined in thirty-eight cadaveric allograft recipients, with good renal function at 8, 12, 20 and 28 weeks after transplantation. Nineteen patients (group 1) received triple immunosuppression with rapamycin, cyclosporine and prednisolone, nineteen other transplant recipients received mycophenolate mofetil, cyclosporine and prednisolone immunosuppression (group 2), and six healthy subjects (group 3) served as controls. After 12 weeks of stable graft function, group 1 patients were divided further into two subgroups. Ten patients were kept on their immunosuppressive regimen (group 1A), whereas the remaining nine randomly chosen subjects had their cyclosporine withdrawn; they were thus maintained on a dual immunosuppression regimen with prednisolone and a higher dosage of rapamycin (group 1B). RESULTS: Renal phosphate reabsorption was significantly lower in group 1 at 8 and 12 weeks after transplantation as compared with groups 2 and 3. At 20 weeks after transplantation, patients with rapamycin-based immunosuppression (groups 1A and 1B) continued to exhibit hypophosphataemia and impaired renal phosphate handling. Group 1B had the lowest TmP/ GFR compared with all groups. At 28 weeks, renal phosphate reabsorption and plasma phosphate levels were no longer different between patient groups and controls. CONCLUSION: These data suggest that rapamycin-based immunosuppression prolongs the phosphate leak of the allografted kidney, leading to low serum phosphate levels during the first weeks after transplantation.     

Efficacy of pneumococcal immunization in patients with renal disease--what is the data?

BACKGROUND/AIMS: There is an increased incidence of invasive pneumococcal disease in patients with renal allografts, chronic renal insufficiency (CRI), or nephrotic syndrome (NS). Routine pneumococcal immunization (PI) has been recommended for these patients, but the efficacy of PI in this population is not well established. METHODS: A review was done of studies that reported the immunologic response, efficacy, or safety of PI in patients with renal allografts, CRI, or NS. RESULTS: On review of 26 published studies of PI in this population, all studies demonstrated a serologic response by the majority of patients to at least some pneumococcal serotypes. Use of steroids did not alter this response. In the studies with a greater than 6-month follow-up, declining antibody titers were consistently reported, and this decline was usually more rapid than in healthy controls. However, because the studies of the efficacy of PI in this population involve small numbers of patients and are not controlled, the significance of this decline in titers is not known. The incidence of serious adverse reactions to PI is very low. CONCLUSION: Pending more data, patients with renal transplants, CRI, or NS should continue to be offered PI.     

Discrepant serological assays for Pneumococcus in renal transplant recipients – a prospective study

Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype‐specific capsular polysaccharides. Quantitative antibody levels enzyme‐linked immunosorbent assay (ELISA) and antibody‐mediated opsonophagocytic assays (OPA) measure vaccine‐induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein‐conjugate vaccines (PCV) and polysaccharide vaccines (PSV). Antibodies to 19A in serial sera from 30 vaccinated renal transplant recipients were compared using ELISA and OPA assays. Subject titers were classified as protected or not by ELISA (>0.35 μg/ml) and OPA titer (>1:8). Antibody titers analyzed using McNemar's test indicate that protection measured by the two assays are not the same (P = 0.0078); simple linear regression of within‐subject geometric means of 19A enzyme‐linked immunosorbent assay (ELISA) antibody levels versus 19A opsonophagocytic assays (OPA) titers demonstrates significant correlation between the two assays (P < 0.001). Vaccination is increasingly important given increasing antimicrobial resistance worldwide. OPA and ELISA antibody assays do not correlate well using current values for protective immunity against the Pneumococcus in immunosuppressed transplant recipients. Future studies of vaccination in transplant recipients should evaluate protective antibody levels using both functional antibody assays and standard ELISA antibody titers. (ClinicalTrials.gov: NCT00307125).     

Influenza Vaccination in Orthotopic Liver Transplant Recipients: Absence of Post Administration ALT Elevation

Influenza vaccination has reduced life-threatening complications from influenza virus infection in adult liver transplant recipients. We evaluated changes in aminotransferase level and immunogenicity of influenza vaccination in liver transplant recipients. Fifty-one liver transplant recipients were administered a standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT values were measured at baseline, 1 week and 4-6 weeks postvaccination. Antibody responses to each component of the vaccine were measured at baseline and after 4-6 weeks by a hemagglutination inhibition (HAI) assay. Response was defined as an HAI titer > or = 1: 40 and/or a 4-fold increase in antibody titers from baseline. An ALT elevation was defined as a rise of > or = 50% from baseline. There was no difference in the median rise in ALT value between seroconverters and nonseroconverters. A significant number of recipients developed potentially protective antibody titers (p-value < 0.0001). At less than 4 months post transplantation, 1/7 (14%), at 4-12 months, 6/9 (67%), and after 12 months, 30/35 (86%) subjects responded to the H1 strain. Of 51 recipients, one HCV (-) recipients vaccinated within 3 months of transplantation developed acute cellular rejection. Influenza virus vaccination is not associated with allograft rejection or ALT flares in liver transplant recipients.     

A randomized trial comparing triple-drug and double-drug therapy in renal transplantation

A controlled trial was carried out in 86 cadaveric and 14 living haploidentical renal transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (Aza) and steroids with those of higher doses of CsA plus steroids. Patients were followed for 12-26 months after transplantation. The actuarial 2-year patient and graft survival rate was 100% for living-donor transplants. In cadaver renal transplants the 2-year patient survival rate was 100% for patients assigned to the triple regimen and 93% for those allocated to the double regimen. The actuarial 2-year cadaver graft survival rates were 86% and 90.6%, respectively. There were significantly more patients who had severe infections (P less than 0.05), particularly interstitial pneumonia (P less than 0.005), in the double-therapy group. On the other hand, there were more patients who rejected and more patients with severe rejections; more pulses of steroids were also required for patients on the triple regimen, although these differences were not significant. The mean trough blood levels of cyclosporine at the various times were about half as high in patients on triple therapy. There were no differences between the two groups in creatinine clearance at any time. A control renal biopsy, taken from patients with stable renal function after 6-12 months, showed only mild abnormalities. The lesions were semiquantitatively assessed. There was a higher score for interstitial infiltrate in patients on triple therapy (P less than 0.05). On the other hand, the incidence and the mean score of interstitial fibrosis were greater in patients on double therapy, although these differences were not significant. Thus, although similar results were obtained with both regimens, at the doses we used double therapy seems to have more powerful immunosuppressive effects and may prevent rejection, either acute or chronic, better. However, it might expose the patient to a greater risk of infection and of cyclosporine-related nephrotoxicity than triple therapy.