Efficacy of risk stratification in tailoring immunosuppression regimens in kidney transplant patients at the national kidney and transplant institute.

OBJECTIVES: To evaluate the efficacy of tailored immunosuppressive regimens prescribed according to a risk stratification scoring system based on the number of HLA mismatches, donor source, panel-reactive antibodies (PRA), and repeat transplant. METHODS: Patients in a retrospective cohort of 329 kidney transplantations performed from October 2004 to December 2005 were assigned scores of 0, 2, 4, or 6 with higher scores for > or =1 HLA mismatches, PRA > 10%, repeat transplant, and unrelated or deceased donor. Added scores of < or =4 comprised the low-risk group who received a Calcineurin inhibitor (CNI)-based regimen without induction, whereas a score > or = 6 denoted high risk including a CNI-based regimen with an interleukin-2 receptor antibody. The efficacy analysis compared the incidences of biopsy-proven acute rejection episodes (BPAR) at 1 year. RESULTS: Only 227 (69%) of 329 patients had a complete data set and 84 were excluded because they did not follow the prescribed protocol, yielding 113 low- and 30 high-risk patients in the final population. Low-risk patients had a mean PRA of 5.4%, living related donors in 68%, and primary transplants. High-risk patients had a mean PRA of 18.8% (range = 10%-97%), living nonrelated donors in 84%, four deceased donors, and four repeat transplants. The overall 1-year incidence of BPAR was 5.7%. No significant difference (P = .081) was observed in 1-year BPAR between the low- (4.5%) and high-risk (9.8%) groups. Likewise, no significant difference in the 1-year mean serum creatinine was observed according to the CNI. The mean creatinine was 1.12 for cyclosporine and 1.38 for tacrolimus treatment (P = .06) in the low-risk group and 1.08 for cyclosporine and 1.2 for tacrolimus (P = .61) in the high-risk cohort. CONCLUSION: There was no significant difference in acute rejection rates between the immunologically low- or high-risk patients using tailored immunosuppression, which was effective to minimize its occurrence with good renal function at 1 year.

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.

Alemtuzumab induction with tacrolimus monotherapy in de novo renal transplantation.

OBJECTIVES: Alemtuzumab is increasingly being used as induction therapy for kidney transplantation, allowing immunosuppression minimization. This study examined the efficacy of alemtuzumab induction followed by low-dose tacrolimus monotherapy in standard risk primary kidney transplant patients. METHODS: This retrospective cohort of primary standard risk renal transplant recipients were given alemtuzumab induction and low-dose tacrolimus maintenance immunosuppression (target trough 7 to 10 ng/mL for the first 6 months and 5 to 7 ng/mL thereafter). Serum creatinine values, acute rejection episodes, and graft survival were noted at week 1 as well as months 3, 6, 12, and 18. RESULTS: At the time of analysis, 47 patients were at 6 months, 28 at 12 months, and 6 patients at 18 months from transplant. Mean follow-up was 12.53 months (range, 6 to 23). Mean serum creatinine was 1.47 +/- 0.65 mg/dL at 3 months, 1.56 +/- 0.84 at 6 months, 1.45 +/- 0.37 at 12 months, and 1.74 +/- 0.35 at 18 months. The 1-year clinical acute rejection rate was 21% (6/28), occurring at 0 to 3 months in 2 (33%), 4 to 6 months in 1 (17%), and >6 months in 3 patients (50%). Biopsy-proven acute rejection was 14% (4/28). The episodes were classified as borderline in one, Banff 2A in two, and Banff 3 in one patients. One patient had both acute cellular and acute humoral rejection; half responded to steroid pulse therapy. The 1-year patient survival rate was 90%. The 1-year death-censored graft survival rate was 98%. CONCLUSION: Alemtuzumab induction with tacrolimus monotherapy is an acceptable option in standard risk patients. BPAR was 14%, but renal function remained satisfactory at 18 months posttransplant.

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.

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.

A survey on the prevalence and management of hepatitis B after renal transplantation in Asian-Pacific countries.

The carrier rate for hepatitis B virus (HBV) varies from 1% to 2% to 10% in Asian-Pacific countries. A survey involving 12 transplant centers from 11 countries in this region showed that 1% to 25% of kidney transplant recipients were infected with HBV, and up to 60% of these subjects showed abnormal liver biochemistry. While nearly all centers tested anti-HBs in potential kidney transplant recipients, HBV vaccination of nonimmune subjects was routine in only 66.7%. One-third of the surveyed units rejected HBsAg-positive subjects as kidney donors, while the others demonstrated differing policies in choosing the respective recipients. Two units (16.7%) excluded HBsAg-positive patients from kidney transplantation, whereas the others only excluded those with severe liver disease. Heterogeneity also applies to the immunosuppressive regimens, the use of HBV DNA in serial monitoring, and the timing of antiviral therapy in HBsAg-positive kidney transplant recipients. The data showed that despite HBV infection being a significant problem in kidney transplantation, there is a lack of uniform management policy, attributable to the clinical complexity and deficiency of research data. Although improvement in clinical outcome is likely with the advent of nucleoside analogue therapy and better monitoring, the financial implications in the adoption of these recent advances remain realistic concerns.

Safety and efficacy of generic cyclosporine arpimune in Filipino low-risk primary kidney transplant recipients.

BACKGROUND: In the Philippines, maintenance of immunosuppression may not always be affordable, leading to acute rejection and graft loss. The availability of the generic cyclosporine Arpimune could be economically beneficial, but its safety and efficacy should be established. METHODS: This prospective cohort study enrolled 30 renal transplant patients who received Arpimune with mycophenolate/prednisone. Their results were compared up to 6 months with 30 matched control patients who received Neoral during the same period. Areas under the receiver operating characteristic curves (AUC) after intake of Arpimune and therapeutic drug monitoring using cyclosporine levels 2 hours after each dose were done. Pearson correlation was performed to determine linearity of relationship between the generic cyclosporine concentrations and AUC 0-4. Chi-square test was used in obtaining cyclosporine Arpimune concentrations. RESULTS: The abbreviated concentration AUC of Arpimune was similar to that of Neoral, and the 2-hour sampling point (r = 0.813; P < .001) showed the best correlation. Calculated creatinine clearance (mL/min) versus Neoral was 71.36 ± 13 versus 68.03 ± 16.6 (P = .61) at 1 month, 70.4 ± 14.8 versus 64.2 ± 11.4 (P = .12) at 3 months, and 74.02 ± 15.8 versus 62.03 ± 12.1 (P = .002) at 6 months. Two Arpimune versus 4 Neoral patients (P = .67) developed biopsy-proven acute rejection. One septic death occurred in the Arpimune group. Graft survival was 100% in both groups. Hyperlipidemia was the most frequent side effect for both. CONCLUSIONS: The AUC of Arpimune was similar to that of Neoral. Use of the generic cyclosporine Arpimune provided effective immunosuppression in the 6 months after transplantation. Renal allograft function was similar to that of Neoral, with minimal rates of acute rejection and adverse events.

National survey of Filipinos on acceptance of incentivized organ donation.

BACKGROUND: The increasing number of patients requiring transplantation has brought about a shortage of donor kidneys. Incentives can potentially improve organ donation. There is a need to know if the public can accept incentivized organ donation. OBJECTIVES: To evaluate knowledge and opinions on organ donation and compensating the donor/donor family and to determine factors affecting consent. METHODS: The third survey in 2009 covered 15 regions, 29 provinces, and 14 cities in the National Capital Region. There were 1500 respondents interviewed using a structured questionnaire. Analysis used Statistical Package for Social Science and chi-square. RESULTS: Of the respondents, 63% were females and 74% were married. Nearly half were between 26 and 45 years old. Fewer than 5% were unschooled. Monthly household income was less than USD $222.00 in 70% of respondents. A majority knew about donation from 2001 to 2009. Fewer than 20% knew about deceased donors. Those who wanted to become donors decreased. Sixty-five percent were willing to donate a brain-dead relative's organs. Respondents felt that kidney donors deserve a token of gratitude. Options included livelihood (32%), cash (31%), and educational assistance (26%). Sixty percent wanted the donor assistance termed a "token of gratitude." Consent for donation was positively correlated (P < .05) with higher education and monthly income. CONCLUSION: Awareness on organ transplantation and donation increased. Factors that promote organ donation are higher education and monthly income. A majority of Filipinos felt that the donor deserves a token of gratitude. Public acceptance of incentivized organ donation may be pursued. Strategies to improve the national advocacy campaign for deceased donation are needed.

A national program toward improving renal health: advancing organ donation awareness.

BACKGROUND: Despite the national advocacy campaign for kidney transplantation from deceased donors in the Philippines 96% of kidneys transplanted into 721 kidney transplants from 1999 to 2001 came from living donors. A national survey on the knowledge, attitudes and perceptions of Filipinos on organ donation in 2001 showed factors that disadvantaged deceased organ donation to be poor understanding of "brain death," religion, and fear of the operation. These concerns were addressed and another survey was conducted in 2005. OBJECTIVES: To compare knowledge, attitudes, and perceptions of Filipinos on organ donation between 2001 and 2005, and compare the number of kidney transplants from deceased donors between 2001 until 2008. METHODS: Two surveys in 15 regions of the Philippines were conducted using multistage sampling. Using a structured questionnaire there were 2000 respondents in 2001, and 2140 in 2005. Analysis was performed using chi-square analysis. RESULTS: The majority of respondents knew about kidney donation. Between 2001 and 2005, there was increased awareness that transplants came from both living and deceased donors (37% to 41%) and a decline in those believing transplants came only from deceased donors (14% to 9%). Willingness to become a living (59% to 87%) or a deceased donor (35% to 49%) increased. The increase in transplantation from deceased donors from an average of 10 per year from 1999 to 2001 to 31 per year from 2006 to 2008. CONCLUSION: Increased awareness about kidney donation among Filipinos, improved consent to become an organ donor, and an increase in kidney transplantation from deceased donors occurred from 2001 to 2008.