Universal prophylaxis with gancyclovir preparation is not necessary in our kidney allograft recipients

Background

Cytomegalovirus (CMV) infection is a common cause of morbidity, graft loss, and mortality among kidney recipients due to its direct and indirect influences on organs and systems. In this study, we evaluated CMV infection in transplant recipients in Iran.

Materials and methods

We performed a retrospective study of 104 renal allograft recipients and their donors transplanted between January 2005 and January 2010. We included all patients (recipients and donors) with least one valid laboratory result for CMV immunoglobulin (Ig)G and CMV IgM. We evaluated the occurrence of CMV disease in allograft recipients in at least the first 3 years after renal transplantation.

Results

Fifty-seven renal allograft recipients (54.8%) were males and 47 (45.2%) were females. The overall mean (± standard error) age was 40.32 ± 13.30 years. CMV IgG was positive in 95 cases (91.3%), negative in 9 (8.7%). Serologically, 76.9% patients were D⁺/R⁺ 14.4% D⁻/R⁺, and 8.7% D⁺R⁻. Due to the proccurrence of rejection rendering them high-risk patients for CMV infection about 15% of subjects were treated with anti thymocyte globulin (ATG) followed by prophylactic intravenous gancyclovir for 2 weeks, at doses based on allograft function. Confirmed CMV infection and CMV disease occurred in less than 5% of recipients in the first year after transplantation. About 6% of renal allograft recipients died due to infections during the first 3 years posttransplantation but CMV disease was not confirmed in these patients.

Conclusion

Due to the living donor-based renal transplantation program, the selection of low-risk patients (panel-reactive antibodies 30%), the low percent of D⁺/R⁻ patients (8.7%) and the low use of ATG for induction therapy in the Iranian model, universal prophylaxis with gancyclovir is not routinely recommended for our cases.     

Signs and symptoms of cytomegalovirus disease in kidney transplant recipients

Purpose

To investigate the range of clinical presentations of cytomegalovirus (CMV) disease in kidney transplant recipients.

Materials and methods

We retrospectively reviewed the records of hundred kidney recipients who developed CMV disease between 1984 and December 2002 for demographic characteristics, laboratory findings, and presenting signs and symptoms.

Results

The most common presentations were elevated serum creatinine in 74 patients, fever in 71, thrombocytopenia in 43, nausea in 32, vomiting in 25, elevated alkaline phosphatase in 24, leukocytosis in 22, and leukopenia in 21. Tissue involvement was relatively rare, but six patients had pneumonia, two had conjunctivitis, and one had vascular dermatitis. Four percent of the patients had received intravenous ganciclovir prophylaxis, and 7% had received oral ganciclovir prophylaxis. Fever was associated with number of hospitalizations (P = .006), elevated creatinine (P = .006), nausea (P = .017), vomiting (P = .031), and previous posttransplantation infections (P < .001). All the patients with conjunctivitis, pneumonia, pulmonary symptoms, and abnormal heart sounds and most of those with arthralgia, nausea, and vomiting were febrile during their CMV disease course.

Conclusion

Our findings showed that leukocytosis should be considered as much as leukopenia when CMV disease is suspected. CMV-induced pneumonia is not common in renal transplant recipients compared to other organ transplant recipients. CMV invasion to other tissues is also rare. Finally, fever is a common symptom and important in assessing the severity and prognosis of the disease.     

Lack of cytomegalovirus and polyomavirus coexistence in Iranian kidney transplant recipients

Introduction

Maintenance of kidney graft function is essential, averting infection and coinfection. Cytomegalovirus (CMV) and BK polyomavirus (BKV) coinfection have been reported. There are a few studies of CMV and BKV infection in kidney transplant recipients in Iran, but no studies of their coinfection.

Objective

To assess the coexistence of CMV and BKV infection in renal transplant recipients.

Patients and Methods

The presence of CMV and BKV was assessed using real-time polymerase chain reaction in a cross-sectional study in 91 renal transplant recipients at 1 month posttransplantation. Assessment of CMV was performed only in blood samples, whereas BKV was assessed in both serum and urine samples.

Results

The 91 patients included 57 men (62.6%) and 34 women (37.4%), who ranged in age from 19 to 76 years. Simultaneous evaluation of CMV in plasma and BKV in urine demonstrated no significant association. Of 24 patients positive for BKV in urine, 8 (33.3%) were positive for CMV in plasma. Sixty-seven patients tested negative for BKV in urine, whereas 23 (34.4%) tested positive for CMV, which is unremarkable. Comparison of coinfection with plasma CMV and plasma BKV demonstrated no significant correlation. In 3 patients positive for BKV in plasma only, 1 (33.3%) was positive for CMV, whereas in 88 patients negative for BKV in plasma, 30 were positive for CMV.

Conclusion

No significant association was observed between CMV and BKV infections in kidney transplant recipients.     

Historical comparison of prophylactic ganciclovir for gastrointestinal cytomegalovirus infection in kidney transplant recipients

Background

Cytomegalovirus (CMV) can cause morbidity in kidney transplant recipients. The gastrointestinal (GI) tract is a major target for CMV disease. The aim of this study was to evaluate the benefit of ganciclovir prophylaxis on GI CMV infection in intermediate-risk CMV seropositive transplant recipients.

Methods

Since January 2009, intravenous ganciclovir (5 mg/kg, twice daily) was administered for 14 days after kidney transplantation in 41 patients. The historical control group consisted of 45 patients who received kidney transplantations between January 2007 and December 2008. To evaluate the effects of prophylaxis on GI CMV infection, we performed routine endoscopic examinations with mucosal biopsies at the time of transplantation as well as 1, 3, and 6 months thereafter.

Results

The average age of the 86 studied patients was 43.7 ± 10.6 years (range = 14-63) and the male-to-female ratio 1:1.3. Forty-three (50%) patients underwent deceased donor transplantations and 84 (97.7%) patients were CMV seropositive at that time. The incidence of GI CMV infection was significantly lower among the prophylaxis than the historical control group (24.4% vs 48.9%, P = .026). Patient age, numbers of deceased donors, and tacrolimus trough levels at 1 and 3 months posttransplant were significantly lower in the prophylaxis than the historical control group. Logistic regression analysis revealed ganciclovir prophylaxis to be the only significant risk factor for GI CMV infection.

Conclusion

Prophylactic treatment with ganciclovir decreased the incidence GI CMV infection among seropositive kidney transplant recipients.     

Post-renal transplant cytomegalovirus infection: study of risk factors

Objectives

Cytomegalovirus (CMV) is a common opportunistic infection following renal transplantation (RTx). It responds promptly to antiviral treatment. The mortality rate reaches 90% if untreated. Identification of risk factors helps in the early diagnosis of CMV. We studied demographic features, risk factors, and outcomes associated with CMV infection in RTx recipients despite ganciclovir prophylaxis.

Materials and methods

We reviewed 720 RTx recipients between 2007 and 2009. We examined the serostatus of the donor and recipient before transplantation using an enzyme-linked immunosorbent assay, and diagnosed CMV infections in recipients by CMV DNA detection with a polymerase chain reaction.

Results

A total of 42 of 750 (5.6%) patients were identified to display CMV infection (69.1%) or disease (30.9%). Their mean age was 34 ± 13.5 years, with 80.9% men. CMV serologic status was D+/R− in 21.4% and D+/R+ in 59.5% patients. Fever, malaise (76.2%), and leukopenia (52.3%) were the commonest presenting symptoms; diabetes (30.9%) and hepatitis C virus (28.6%) the commonest comorbid conditions. Risk factors were triple drug immunosuppression (47.6%), antithymocyte globulin ATG induction (54.8%), and a rejection episode (26.1%) and methylprednisolone (76.2%) which were more common in CMV disease than infection. Mean CMV DNA at diagnosis was 78,803; 71.2% patients developed CMV within 6 months posttransplantation, the majority occurring after 3 months. With a mean follow-up of 4 ± 1.9 years, patient and graft survival rates were 85.7% and 81% with a mean serum creatinine value of 1.83 ± 12 mg/dL.

Conclusions

Universal CMV prophylaxis was associated with a low incidence (5.6%) and mild form of CMV disease among our patients.     

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients

Aim

A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease.

Patients and methods

With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 μg/5 μL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored.

Results

Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US $721 while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US $64.

Conclusion

Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.     

The role of the altruistic unbalanced chain in exchange living donor renal transplantation: single-center experience

Background

The exchange donor program in renal transplantation is an efficient solution for recipients with a blood type or crossmatch-incompatible donor. However, this program has some difficulties to define unacceptable human leukocyte antigen matches, deteriorating clinical potential recipient condition, and withdrawal of donor consent. We analyzed the outcomes of exchange donor renal transplantation through the altruistic unbalanced chain.

Methods

Among 152 cases of exchange donor renal transplantation from 1991 to 2010 in our hospital, we performed 58 procedures through altruistic unbalanced chains. We compared their outcomes with the direct and balanced chain group. We analyzed retrospectively whether this program expanded the donor pool, seeking better immunologic, size, and age matching.

Results

The graft survival and acute rejection rates did not differ significantly in the two groups. Of 152 cases, 58 (38.2%) renal transplantations were performed through an unbalanced chain. Seventeen waiting list recipients were transplanted through an altruistic unbalanced chain. In blood type O recipients (n = 32), the causes of registration in the exchange program were ABO incompatibility (93.3%), and positive crossmatch (6.7%). Nine altruistic blood type O donors and 9 (28.1%) type O recipients underwent transplantations through this chain.

Conclusions

We suggest the altruistic unbalanced chain may expand the donor pool with advantages for difficult-to-match pairs. The disadvantages of type O recipients may be overcome through the use of an unbalanced chain. The altruistic unbalanced exchange transplantation program can help easy-to-match subjects, shortening the waiting periods.     

Autosomal-Dominant Polycystic Kidney Disease and Kidney Transplantation: Experience of a Single Center

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease that frequently leads to end-stage renal disease and is a common indication for kidney transplantation. We sought to evaluate the demographic characteristics, graft and patient survival, and some posttransplantation complications among ADPKD recipients.

Methods

This retrospective study included 445 renal transplant recipients, among whom 48 had ADPKD. We excluded patients with pretransplantation diabetes mellitus. We evaluated patient and graft survivals as well as posttransplantation complications.

Results

There was no difference between the 2 groups with respect to demographic or transplant characteristics, except for older age among the ADPKD group (51.2 ± 8.6 years vs 44 ± 13.1 years; P < .001). We also observed no significant difference with regard to immediate graft function, immunological graft, or patient survival. Although not significant, there was a lower incidence of proteinuria and a greater number of acute rejections among ADPKD patients. As for posttransplantation complications, there was no difference regarding the prevalence of hypertension, but there was more erythrocytosis among the ADPKD group. The incidence of posttransplantation diabetes mellitus was significantly greater in ADPKD patients (33.3% vs 17.1%; P = .009), and remained significant after adjusting for confounding variables by multivariate analysis with an adjusted odds ratio of 2.3 (95% confidence interval, 1.008-5.136; P = .048).

Conclusion

Our results suggested that ADPKD patients display a greater incidence of diabetes mellitus posttransplantation; ADPKD emerged as an independent predictor for this complication.     

Cytomegalovirus Infection and Disease Following Renal Transplantation: Preliminary Report of Incidence and Potential Risk Factors

Background

Cytomegalovirus (CMV) infection and disease are major causes of morbidity and mortality after renal transplantation. However, the incidence and potential risk factors are different in developing countries. We sought to determine the incidence and potential risk factors for CMV infection and disease in our center. We also sought to identify groups of recipients who may benefit from preemptive therapy.

Materials and methods

Forty renal transplant recipients were monitored regularly for CMV infection within 6 months after transplantation using CMV immunoglobulin (Ig) M and IgG titers, pp65 antigenemia, and CMV DNA by polymerase chain reaction (PCR). Thorough laboratory and physical examinations were performed to detect CMV disease. We evaluated the role of various factors in CMV infection and disease development using Cox regression and Kaplan-Meier statistical models.

Results

CMV infection and disease were detected in 33 (82.5%) and 10 (25%) subjects, respectively. Average time to infection and disease development was 4.7 and 11 weeks, respectively. PCR was the most accurate method of diagnosis in 22 (67%) cases. By comparison to other recipients, patients who received antithymocyte globulin (ATG) showed a significant decrease in time to disease development (P = .009). Upon multivariate survival analysis, ATG therapy remained an independent risk factor for CMV disease (odds ratio: 6.8; P = .02).

Conclusion

Due to the low rate of progression from CMV infection to disease, it does not seem reasonable to perform preemptive therapy in all infected cases. ATG therapy was an independent risk factor for CMV disease. Recipients of this treatment would be proper candidates to receive preemptive therapy.     

Cause of Death in Multiorgan Donors and Its Relation to the Function of Transplanted Kidneys

Background

Brain death is an important variable contributing to donor-specific kidney damage. Poor kidney performance posttransplantation may be related to the cause of death of the donor.

Objective

To assess the influence of cause of death in multiorgan donors on the function of transplanted kidneys.

Material and Methods

Standard criteria for the brain stem death protocol were applied in 146 potential heart donors included in the study. Conventional supportive management consisted of mechanical ventilation to achieve normocapnia, rewarming, and fluid and electrolyte replacement. Dopamine infusion not exceeding 10 μg/kg/min and desaminovasopressin were titrated to predetermined mean arterial pressure (MAP). In renal allograft recipients (n = 232), kidney function was monitored using serial serum creatinine concentrations on days 1, 2, 3, 7, 14, 30, and 90 posttransplantation. The relation between donor cause of death (injury, bleeding, or other cause) and recipient serum creatinine concentration was analyzed in the postoperative period.

Results

Significantly greater serum creatinine concentrations were observed up to 14 days posttransplantation in recipients of a kidney from a donor who died of any cause other than injury. Recipients of a kidney from a donor who died of bleeding exhibited significantly greater serum creatinine concentrations at 30 days posttransplantation.

Conclusions

A cause of death other than injury or bleeding in a multiorgan donor is predictive of worse kidney graft function in the first 14 days posttransplantation. Intracranial bleeding in a multiorgan donor is predictive of worse kidney graft function in the early period posttransplantation.     

Use of simulect can reduce the incidence of acute rejection and demonstrates with superior 3-year patient and graft survival rates in renal transplantation

Background

Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation.

Objectives

We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated.

Method

Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid.

Results

There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%.

Conclusions

Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.     

Health-Related Quality of Life Before and After a Solid Organ Transplantation (Kidney, Liver, and Lung) of Four Catalonia Hospitals

Introduction and Aims

It has been described that patients who receive a transplant display a better Health Related Quality of Life (HRQoL). Our objective was to describe the HRQoL before and after a solid organ transplantation, comparing results among various transplantations.

Methods

This HRQoL study using the SF-36 was implemented before as well as at 3 and 12 months posttransplantation. Posttransplantation were compared with pretransplantation scores as well as with the general population.

Results

One hundred sixty-two renal, 159 liver, and 58 lung candidates were included before transplantation, among whom there were 126 renal, 108 liver, and 22 lung recipients. The median age of all transplant recipients was 53 years with 68% men. The various transplant types began with different HRQoL: lung showed the worst, followed by the liver, and then renal. The scores of the SF-36 before and 3 months posttransplantation showed significant improvements, except for “Pair.” At 12 versus 3 months, mental health was somewhat better for renal, and almost all dimensions showed significant improvement for liver and lung patients. All subjects showed clear improvements after transplantation.

Conclusion

All patients showed clear improvements after transplantation when mental health was compared with the general population, particularly lung transplant recipients who expressed the greatest improvement. However, they still showed deficits in physical health.     

Early and Delayed Onset Cytomegalovirus Infection of Liver Transplant Recipients in Endemic Areas

Background

The delayed onset of cytomegalovirus (CMV) infection after liver transplantation can place patients at risk for graft failure and mortality.

Methods

We compared early versus delayed onset of CMV infection to identify risk factors for mortality among liver transplant recipients in an endemic area.

Results

Among 710 consecutive adult liver transplant recipients, incidence of CMV infection was 47.5% (337/710). Male gender, biliary complications, acute rejection episodes, antilymphocyte antibodies high hemoglobin, and high total bilirubin were significantly different among patients with delayed versus early onset CMV infections. The overall incidence of early versus delayed CMV infections was 43.1% (306/710) versus 4.4% (31/710). Among them, 11.1% (34/306) and 25.8% (8/31) of patients developed CMV disease.

Conclusion

These results showed that a higher proportion of patients developed disease among delayed CMV infected patients (P = .039). The overall and graft survival curves for patients with early onset CMV infections were better than those of patients who had delayed onset CMV infections (P = .026 and P = .014). Recurrence of hepatitis B virus, hepatic dysfunction, and retransplantation were associated with increased mortality among patients who had a delayed CMV infection.     

The value of pre-emptive therapy for cytomegalovirus after liver transplantation

Background

Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R−) casses. We investigated whether this strategy was safe and effective to prevent CMV disease.

Methods

One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL.

Results

Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R−) developed CMV infections significantly more often than D−/R− serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349).

Conclusion

Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.     

Anemia after kidney transplantation in adult recipients: prevalence and risk factors

Objective

To evaluate the prevalence of anemia and appraise its risk factors at 6 months after renal transplantation.

Materials and Methods

This retrospective study was performed between 2008 and 2010 in 2713 adult kidney transplant recipients to determine the prevalence of posttransplantation anemia. Anemia was defined as hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men.

Results

The prevalence of posttransplantation anemia was 52.7%, with severe anemia (hemoglobin ≤11 g/dL) detected in 24.4% of patients. Impaired renal function was the only risk factor associated with anemia (odds ratio, 3.6; P = .047). However, severe anemia after kidney transplantation was correlated with female sex (P = .001), renal allograft dysfunction (P = .00), and cytomegalovirus infection (P = .002).

Conclusion

The present study demonstrated a quite high prevalence of posttransplantation anemia, in particular associated with impaired renal allograft function. Severe anemia was correlated with female sex, degree of kidney graft dysfunction, and cytomegalovirus infection.     

Erectile Dysfunction in Living Donor Kidney Transplant Recipients Associated With Chronic Hepatitis B Infection

Objectives

The objectives of this study were to investigate the prevalence of erectile dysfunction (ED) among living donor kidney transplant (LDKT) recipients associated with chronic hepatitis B infection in China and to assess the effect of successful LDKT to improve ED.

Materials and Methods

From January 2006 to May 2009, erectile function of 26 LDKT recipients associated with chronic hepatitis B infection (Group 1) was evaluated predialysis, during dialysis, and at 6 months posttransplantation using the International Index of Erectile Function, version 5 (IIEF-5). We enrolled 61 age-matched LDKT recipients without hepatitis B/C infection as a control group (Group 2).

Results

The prevalences of ED in Group 1 at predialysis, on dialysis, and 6 months posttransplantation were 23.1%, 80.7%, and 65.3%, respectively. Among Group 2, it was 4.9%, 72.1%, and 41.0%, respectively. The difference in ED between groups was significant at predialysis (P = .031) and 6 months posttransplantation (P = .037). Compared with the dialysis stage, the prevalence of ED at 6 months posttransplantation was significantly decreased in Group 2 (72.1% vs 41.0%; P = .001), but it was not significantly difference from Group 1 (80.7% vs 65.3%; P = .211).

Conclusions

The incidence of ED among hepatitis B recipients was higher than among hepatitis B/C-negative patients at the predialysis and posttransplantation stages. Kidney transplantation is a key treatment to reduce the prevalence of ED among hepatitis B/C-negative recipients, but not those with hepatitis B.     

Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study

Background

Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients.

Methods

We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids.

Results

There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups.

Conclusions

ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation.     

A 39-month follow-up study to evaluate the safety and efficacy in kidney transplant recipients treated with modified-release tacrolimus (FK506E)-based immunosuppression regimen

Background

We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E.

Methods

Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation.

Results

In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment.

Conclusion

This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective.     

Does donor race still make a difference in deceased-donor African-American renal allograft recipients?

Background

Prior studies have demonstrated that African-American (AA) donor kidneys are independently associated with an increased risk for graft loss.

Methods

We examined outcomes in comparable groups of AA deceased-donor (DD) kidney transplant patients receiving an AA donor (n = 35) versus a Caucasian donor (C group; n = 150) organ.

Results

There were no differences between AA and C groups in patient survival, new-onset diabetes, or BK nephropathy. The AA group demonstrated a significantly higher 6-month and overall incidence of acute rejection (AR), increased cytomegalovirus (CMV) infection, and decreased graft survival. Recurrent or de novo focal segmental glomerulosclerosis (FSGS) accounted for a significantly higher fraction of graft losses in the AA versus C group.

Conclusions

AA DD renal allograft recipients have equivalent patient but decreased graft survival when transplanted with an AA versus C kidney using current immunosuppression. This may be the result of increased AR, CMV infection, and recurrence/development of FSGS.     

Prophylactic therapy with valganciclovir in high-risk (cytomegalovirus D+/R-) kidney transplant recipients: a single-center experience

Background

A prospective study was performed in kidney transplant patients at risk of developing cytomegalovirus (CMV) infection (CMV D⁺/R⁻). They were treated with valganciclovir (VGC) for 3 months as prophylactic therapy. The aim was to determine the safety and efficacy of prophylactic therapy with VGC.

Methods

Antigenemia and/or polymerase chain reaction CMV was routinely performed every 2 weeks up to month 3, monthly to month 6, and every other month until the end of the first year posttranplantation, as well as when clinically indicated.

Results

From July 2007 to April 2010, 366 renal transplantations were performed at our center, including 34 (9%) high-risk patients for CMV infection. The median age was 47 years; 19 were males and 15 females. Twelve (35%) patients developed CMV infections: 10 (34%) gastrointestinal disease and 3 viral syndromes. The timing of the clinical manifestations was 16% (3/12) between months 1 and 3, 75% (8/12) between months 4 and 6, and 8% (1/12) in month 9 posttransplantation.

Conclusion

Treatment with intravenous ganciclovir followed by oral VGC was successful in all patients. No opportunistic infections or allograft rejection were observed; only 1 patient developed thrombocytopenia as an adverse event to VGC.