Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial.

In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n = 359) or remain on standard calcineurin inhibitor (CNI) therapy (n = 356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.732 versus -1.5(1.5) mL/min/1.732 (p = 0.116). Biopsy-proven acute rejection (BPAR) at month 12 was more frequent under everolimus versus CNI overall (9.7% vs. 4.8%, p = 0.014) and versus tacrolimus-treated patients (2.6%, p < 0.001) but similar to cyclosporine-treated patients (8.8%, p = 0.755). Reporting on de novo donor-specific antibodies (DSA) was limited but suggested more frequent anti-HLA Class I DSA under everolimus. Change in left ventricular mass index was similar. Discontinuation due to adverse events was more frequent with everolimus (23.6%) versus CNI (8.4%). In conclusion, conversion to everolimus at 10-14 weeks posttransplant was associated with renal function similar to that with standard therapy overall. Rates of BPAR were low in all groups, but lower with tacrolimus than everolimus.

Potential impact of Thai Kidney Transplant program on immunosuppressive utilization: an analysis of the national transplant registry.

BACKGROUND: The Thai Kidney Transplant (TKT) program was launched in October 2008 to promote transplantation among previously disadvantaged populations, using fixed-rate provider payment. This study investigated if the introduction of this program could alter the natural practice trends of immunosuppressive drug use. METHODS: Data from the Thai Transplantation Registry were analyzed. The change in trend of immunosuppressive use was assessed using the multivariate adaptive regression splines (MARS) technique. RESULTS: During 1987-2012, 3975 kidney transplantations were done. The average age of patients was 42 years and 62% were male. Chronic glomerulonephritis accounted for one third of those with known causes of end-stage renal disease (ESRD). Eighty-six percent were on hemodialysis before transplantation. Prednisolone was used in 95.87% of all transplant recipients, whereas calcineurin inhibitors (CNIs), mycophenolates (MPAs), azathioprine (AZA), and mammalian target of rapamycin inhibitors (mTORis) were used in 95.67%, 64.22%, 12.25%, and 2.31%, respectively. Overall use after 2008 was decreased for AZA (18.16% to 3.40%) and mTORis (2.86% to 1.5%) but increased for MPAs (50.80% to 84.34%), CNIs (95.43% to 96.04%), and prednisolone (95.60% to 96.29%), as compared with before the program inception. The slopes of use trends of AZA, MPAs, and CNIs did not significantly marginally differ from their natural trends before the program inception (P = .496, .108, and .741, respectively). However, the natural increasing use trend of mTORis significantly changed to a decreasing pattern after the introduction of the TKT program (P = .018). CONCLUSION: Fixed-rate provider payment might interfere with the natural practice trends of immunosuppressive drug use.

Long-term outcome of kidney retransplantation in comparison with first kidney transplantation: a report from the Thai Transplantation Registry.

INTRODUCTION: Kidney retransplantation is a high-risk procedure that is increasingly performed because of previous graft failure. The aim of this study was to determine the long-term outcomes of kidney retransplantations compared with first kidney transplantations under the current era of immunosuppression. METHODS: Since the first retransplantation in Thailand was performed in 1993, this study included all consecutive cases registered in the Thai Transplantation Registry database from January 1993 to December 2011. A total of 3337 kidney transplantations were available for the analysis. Graft loss was defined as a return to dialysis or graft removal. Death with a functioning graft was censored. RESULTS: Of 3337 kidney transplantations during the study period, 113 were second and 3 were third transplantations. Among these 116 retransplantations, the most common identified causes of end-stage renal disease were chronic glomerulonephritis (38.8%), followed by hypertensive nephropathy (13.0%), diabetic nephropathy (6.0%), and lupus nephritis (1.7%). The retransplantation recipients were older (mean age, 46.2 ± 12.8 years) than the first transplantation group (mean age, 42.2 ± 12.8 years). The proportion of living-related kidney transplantations and male sex were similar between first and retransplantation recipients. Fourteen percent of retransplantation recipients showed high immunologic risk as defined by current panel reactive antibodies ≥30% compared with 3% of those in the first transplantation group (P < .001). The percentages of induction therapy with antithymocyte globulin and anti-interleukin-2 antibody in the retransplantation and first transplantation groups were 18.3% versus 4.3% and 60.0% versus 32.6%, respectively. The graft survival rates (95% confidence interval [CI]) at 1, 5, and 10 years were 88.6% (80.7-93.3), 87.3% (79.1-92.5), and 74.4% (53.7-86.9) among retransplantation, versus 95.0% (94.1-95.7), 87.0% (85.5-88.5), and 70.7% (67.4-73.8) among first transplantation groups, respectively (P = .63). Patient survival rates were not different between first and retransplantation groups (P = .42). The leading cause of graft loss in the retransplantation group was chronic allograft nephropathy (22%), whereas infection (57%) was the major cause of death in this group. CONCLUSION: The 10-year patient and graft survival rates of kidney retransplantation were acceptable. The combination of induction therapy with a calcineurin inhibitor and a mycophenolate mofetil/mychophenolic acid-based regimen lead to outcomes comparable to first kidney transplantations among our cohort of 3337 patients.

Different etiologies of graft loss and death in Asian kidney transplant recipients: a report from Thai Transplant Registry.

BACKGROUND: Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade. PATIENTS AND METHODS: The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths. RESULTS: Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%). CONCLUSION: Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations.

Risk factors and outcome of delayed graft function after cadaveric kidney transplantation: a report from the Thai Transplant Registry.

INTRODUCTION: Kidney transplantation is the best treatment for end-stage renal disease patients. Delayed graft function (DGF) remains one of the major problems after cadaveric kidney transplantation. This study has reported the risk factors and outcomes of DGF using data from Thai Transplant Registry Database. METHODS: The data of all cadaveric kidney transplantations (CD-KT) were retrieved from the database. DGF was defined as a failure to decrease the serum creatinine within 72 hours or a requirement for dialysis within the first week after transplantation. We performed logistic regression analysis to correlate donor features (age, sex, cardio-pulmonary resuscitation (CPR), brain death from a cerebrovascular accident (CVA), best and last serum creatinine) with recipient demographics (age, sex) and clinical outcomes cold ischemic time [CIT] and DGF. RESULTS: We analyzed 756 CD-KT including 320 (42%) patients experiencing DGF. Upon multivariate analysis, factors significantly correlated with DGF were CIT (P < .001), donor last serum creatinine (P < .001), interleukin 2 monoclonal antibody induction (P = .004), donor age (P = .017), donor CVA (P = .012), and prior peritoneal dialysis (PD) (P = .012). There was no significant correlation between DGF and donor height, weight, sex, CPR, brain death from CVA, best serum creatinine, recipient age, or sex in multivariate analysis. Graft survivals at 1 and 5 years after transplantation were significantly lower among the DGF group namely, 91.0% vs. 95.2% and 78.7% vs. 86.0%, respectively (P = .006). Patient survival was also significantly lower 94.1% vs. 96.4% and 82.1% vs. 92.2%, respectively, (P = .001). CONCLUSION: A higher value of the donor's terminal serum creatinine, CIT, IL2mAb induction, PD prior to KT and donor age increased the risk for DGF after CD-KT. DGF significantly lowered kidney allograft and patient survivals at 1 and 5 years after transplantation among the Thai population.

Graft survival analysis in kidney transplantation: a 12-year experience in a Thai medical center.

INTRODUCTION: To analyze graft survival and to find the factors that influence survival in kidney transplantation recipients, we performed an analytic retrospective study. METHODS: A retrospective analysis was undertaken on records of all patients who underwent transplantation from December 25, 1990 to December 24, 2002. Survival studies were calculated using the Kaplan-Meier method. The outcome endpoints were death, redialysis, lost to follow-up, and study termination. RESULTS: One hundred thirty-eight operations (49 living-related kidney transplantations [LRKT] and 89 cadaveric kidney transplantations [CDKT])were recruited. Age of patients was 39.9 +/- 9.8 years (range, 9-57 years). The male to female ratio was 1.9:1. The waiting time was 24.25 +/- 25.2 months. Only 9 recipients had diabetes mellitus. The graft survival rate of the cadaveric group was slightly higher than the living related group: 90.65% vs 87.48%, 88.97% vs 85.05%, 83.04% vs 79.72%, and 76.65% vs 67.78% at 1, 2, 3, and 4 years, respectively (P = .94). Age, sex, waiting time, modality of dialysis, diabetes mellitus, ischemia time, HLA-mismatch, 2 DR-mismatch, delayed graft function (DGF), and body mass index (BMI) had no influence on graft survival. Acute rejection had a negative influence on graft survival in both the LRKT group (P = .09) and the CDKT group (P = .015). Patients who received cyclosporine (CSA), prednisone (Pred), and mycophenolate mofetil (MMF) showed better graft survival than ones on CSA, Pred, and azathioprine (Aza) (P = .18). CONCLUSION: There was no significant difference in graft survival between the LRKT and CDKT groups. In this study, only acute rejection was demonstrated to have negative influence on survival rates in CDKT. The timing of transplantation may play a major confounding factor on the results.

Risk factors between analgesic use and chronic nephropathy in Thailand.

Analgesic abuse is common in Thailand. Heavy use of analgesic may also increase risk of chronic nephropathy. However, the extent of this risk remains unclear. We carried out a case-control study in three referral hospitals. A total of 84 patients with newly diagnosed of chronic tubulointerstitial nephritis were enrolled as cases. Two control groups were randomly selected, 192 from hospitalized patients who had no renal disease and serum creatinine below 1.2 mg/dl and 166 from relatives of friends visiting the hospitals. Both cases and controls were interviewed by a standardized pre-coded questionnaire to obtain histories of analgesic use before diagnosis of renal disease. On multiple logistic regression analysis, patients whose estimated lifetime use of acetaminophen of 1,000 g or more had an increased risk of chronic nephropathy compared with non-users, the odds ratio (OR) was 5.9 (95% confidence interval (CI) 1.3-25.6, hospital controls) and OR = 5.8 (95% CI 1.04-31.9, visitor controls). Also, uses of aspirin showed a similar relationship. Patients who used aspirin 1,000 g or more per lifetime had higher risk of chronic nephropathy when compared to non-users, the odds ratio were 7.1 (95% CI 2.0-25.8, hospital controls) and 20.4 (95% CI 2.4-174.2) for visitor controls. These data indicate that analgesic abuse increased risk of chronic nephropathy in Thailand.

Bilateral facial nerve paresis in eosinophilic meningitis.

A 29-year-old man presented with headache, nuchal rigidity and bilateral facial paralysis. Lumbar puncture revealed eosinophilic CSF pleocytosis. Facial diplegia was improved by supportive treatment. Thus, eosinophilic meningitis is one of the etiologies of bilateral facial nerve paresis.