Outcome of referrals for deceased organ donation to the government organ procurement organization.

BACKGROUND: The Human Organ Preservation Effort is a government organ procurement organization that pioneered the Deceased Organ Donation Program in the Philippines. Deceased organ donation comprises only 20% of kidney transplantation in the Philippines in the last 3 years. Various measures were implemented to improve deceased organ donor referrals and organ retrieval. OBJECTIVE: To compare outcome of deceased organ donor referrals from 2002 to 2008 and 2009 to 2012 in the Philippines. METHODS: This retrospective study reviewed the deceased organ donor referrals from 2002 to 2008 and 2009 to 2012. RESULTS: There were 437 referrals for potential deceased organ donors from 2009 to 2012, compared to 434 referrals from 2002 to 2008. Referrals were mainly trauma victims (76%) followed by those with cerebrovascular accidents (12%). In the recent cohort, 81% were approached and 60% consented for donation, but only 23% were retrieved and transplanted. Among those not retrieved, the majority (19%) were medically unsuitable and 6% retracted their consent. CONCLUSION: Although there was an increasing trend of organ donation referrals in the last 4 years, only 25% were procured. The reasons for nonprocurement should be addressed.

Everolimus with reduced-dose cyclosporine versus full-dose cyclosporine and mycophenolate in de novo renal transplant patients: a 2-year single-center experience.

BACKGROUND: Although calcineurin inhibitors (CNIs) has improved short-term graft survival, long-term function remains a challenge. CNIs have been implicated in the development of chronic allograft failure. Low-dose cyclosporine with everolimus may mitigate CNI nephrotoxicity and prolong graft survival. We compared the efficacy and safety of de novo everolimus with low-dose cyclosporine and prednisone versus cyclosporine, mycophenolate, and prednisone among kidney transplant patients up to 24 months after transplantation. METHODS: Kidney transplant patients given low-dose cyclosporine, everolimus, and prednisone were compared with patients given cyclosporine, mycophenolate, and prednisone from December 2006 to December 2008. All had living donors, panel reactive antibody <15%, and follow-up for 2 years after transplantation. Continuous variables using mean and standard deviation, t test and test for proportions were used to determine significant differences between the baseline characteristics of the 2 treatment groups. Generalized linear regression and logistic regression were used to measure the effect of treatment on outcomes. RESULTS: Demographic characteristics were similar in both groups except for age, length of time awaiting kidney transplantation, type of renal replacement therapy, follow-up time, sex distribution, and number of HLA mismatches. These independent variables were used in the generalized linear regression model. There was no significant difference between the everolimus and mycophenolate groups up to 2 years in mean serum creatinine (1.2 mg/dL vs 1.4 mg/dL-, respectively P ≥ .05), acute rejection (12 months: 20% vs 31%; 24 months: 31% vs 40%; P ≥ .05), patient survival (98%), and graft survival (100%). Likewise, there were no significant differences in surgical, infectious, metabolic, and gastrointestinal side effects between the 2 groups. CONCLUSIONS: Everolimus with low-dose cyclosporine and prednisone in de novo kidney transplant recipients was similar in efficacy and safety to cyclosporine, mycophenolate, and prednisone. Longer follow-up is needed to see whether everolimus with low-dose cyclosporine will result in improved kidney function.

Everolimus with reduced-dose cyclosporine in de novo renal transplant recipients: Philippine experience.

OBJECTIVE: The objective of this study was to describe the appropriate dose of everolimus to achieve target trough concentrations in standard-risk Filipino kidney transplant recipients. METHODOLOGY: We reviewed all kidney transplant recipients from December 1, 2006 to June 15, 2007 who were given everolimus (1.5 mg/d) in combination with low-dose cyclosporine (5 mg/kg/d) and prednisone but without induction therapy for their immunosuppressive doses, trough levels, as well as hematologic and blood chemistry profiles. Target everolimus trough concentration was 3-8 ng/mL and C2 level was 1000-1400 ng/mL for the first 3 months. RESULTS: Among 148 patients who underwent transplantation during the study period, 26 comprised the study population but only 15 patients completed the 3-month follow-up and are the subject of this report. Their mean age was 33 years, average PRA 2%, and mean HLA mismatches 3. All were from living donors. At 7 days posttransplantation, all patients achieved or exceeded the target everolimus trough and cyclosporine C2 level. At 1 and 3 months posttransplantation the mean everolimus dose was 1.17 and 0.78 mg/d, respectively, whereas the cyclosporine dose was 195 and 148 mg/d, respectively. Three patients showed elevated alanine aminotransferase (ALT) and all patients had hypercholesterolemia after 1 month, which improved with everolimus dose reduction (half required statins). One patient experienced a Banff Grade IA acute rejection episode at 2 months posttransplantation with a serum creatinine value of 2 mg/dL after steroid pulsing. CONCLUSIONS: Most standard-risk Filipino kidney transplant recipients required a maintenance everolimus dose of 1 mg/d at 1 month. The cyclosporine dose requirement was also lower. A larger sample size is needed to provide a level of significance compared with other populations.

Rituximab in highly sensitized kidney transplant recipients.

OBJECTIVES: Rituximab, an anti-CD20 monoclonal antibody therapy, depletes B cells and suppresses antibody production. This study sought to describe the efficacy and safety of rituximab among seven highly sensitized kidney transplant patients. METHODOLOGY: A highly sensitized patient was defined as panel-reactive antibody (PRA) >30%, more than three pregnancies, or history of positive tissue crossmatch. Demographics, immunological risk profile, and immunosuppression were collected on all highly sensitized patients transplanted from March to July 2007 and given rituximab. We noted graft function as well as clinical events posttransplantation. RESULTS: The seven patients included in the study showed a mean age of 39 years (range = 17-60) and a mean follow-up of 3 months (range = 1.5-5). Their average PRA was 62% with mean HLA mismatches of three. Five patients (71%) were retransplantations; one had a history of a positive crossmatch, and two had multiple pregnancies. Two had donor-specific antibody, but negative tissue crossmatches. All had living donors. Six patients received a single dose of rituximab (375 mg/m2) 1 day prior to transplantation and one received two doses after 19 sessions of plasmapheresis. All were given tacrolimus, mycophenolate, and steroids combined with induction therapy using 30 mg alemtuzumab in 33%; two doses of 20 mg basiliximab in 33%; and seven doses of 1 mg/kg/dose of daclizumab in 14%. Mean shown creatinine levels were 1.1 and 1.2 mg/dL at 1 and 6 months posttransplantation. Two recipients experienced acute humoral rejections within 1 month after transplantation. Both were given steroid pulsing, one of whom was steroid-resistant necessitating alemtuzumab therapy and plasmapheresis. Graft function of both improved with creatinine values of 1.3 mg/dL on discharge. No episodes of infection were noted. CONCLUSIONS: Rituximab can be safely administered and may be effective to improve outcomes among highly sensitized kidney transplant patients.

Use of alemtuzumab (Campath-1H) as induction therapy in pediatric kidney transplantation.

Alemtuzumab (Campath-1H) is a monoclonal antibody directed against CD52-positive B and T lymphocytes. Initial results of its use as an induction agent in adult renal transplantation have been encouraging. We report a case series of four low-risk pediatric renal transplantation patients who received 20 to 40 mg of alemtuzumab as induction followed by a steroid-free regimen consisting of a calcineurin inhibitor and mycophenolate mofetil. No infusion-related reactions occurred. Patients were aged 9 to 14 years with a mean creatinine of 1.2 mg/dL (range = 0.5-2.3 mg/dL) at a mean follow-up of 10 months (range = 4-16 months). One patient experienced biopsy-proven acute cellular rejections at 4 and 12 months posttransplantation, which were steroid sensitive. Lymphopenia post-alemtuzumab induction started to improve at 3 months posttransplantation. Two patients who received 40 mg of alemtuzumab experienced repeated infections that responded to 7-day courses of antibiotics. There was no cytomegalovirus disease detected. From these preliminary results, alemtuzumab seems to show a promising role to achieve adequate graft function with a steroid-free regimen among low-risk pediatric patients.

Campath-1H (alemtuzumab) as an induction agent for the prevention of graft rejection and preservation of renal function in kidney transplant patients: Philippine 3-year follow-up.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of induction with Campath-1H with low-dose cyclosporine (CsA) monotherapy using outcome measures of acute rejection episodes (ARE), chronic allograft nephropathy (CAN), graft and patient survivals, as well as malignancies and infections. MATERIALS AND METHODS: Fourteen kidney transplant recipients were randomized to receive either Campath 1H induction with CsA monotherapy (9 patients) or immunosuppression with CsA, azathioprine, and steroids (5 patients). Campath (20 mg IV) was administered within 6 hours after the anastomosis and repeated 24 hours later. Cyclosporine was started 72 hours after the first Campath dose (10 mg/kg on the first day, then 4 mg/kg/d), seeking to achieve target trough CsA levels of 90 to 110 ng/mL. This is a 3-year follow-up of the 9 patients who received Campath-1H induction. RESULTS: Six of 9 (67%) patients developed ARE (borderline ARE to Banff IB) in the Campath group compared with 1 of 5 (20%) in the other group (ARE Banff IIA). They all received methylprednisolone for 3 days with good responses. One of the 6 patients in the Campath group with ARE also displayed CAN and was converted to sirolimus; 2 others had mycophenolate mofetil and steroids added to their immunosuppression after the ARE. Creatinine levels ranged from 1 to 1.7 mg/dL at 24 to 36 months posttransplantation in both groups. Among the Campath group, 1 patient died 6 months posttransplantation with sepsis secondary to infectious diarrhea. Upper respiratory tract infections comprised the majority of infections at 24 to 36 months. No malignancies were observed. CONCLUSIONS: Three years posttransplantation, patients given Campath induction with CsA monotherapy showed a greater incidence of ARE, although renal function remained comparable to CsA-azathioprine-prednisone therapy. AREs were easily reversed with steriods. Infections were minor.