Comparison of disease activity between tacrolimus and mycophenolate mofetil in lupus nephritis: a randomized controlled trial.

We conducted a prospective multicenter, opened-label, parallel, randomized, controlled trial to compare tacrolimus (TAC) and mycophenolate mofetil (MMF) for induction and maintenance therapy in lupus nephritis (LN). Adult patients with biopsy-proven LN International Society of Nephrology/Renal Pathology Society classes III-V and active nephritis were to receive prednisolone (0.7-1.0 mg/kg/day for four weeks of run-in period and tapered) and randomly assigned to receive TAC (0.1 mg/kg/day) or MMF (1.5-2 g/day) as induction therapy for six months. All patients who had remission received azathioprine (AZA) 1-2 mg/kg/day as standard treatment in the maintenance phase. The primary outcome was Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) at six and 12 months, and the secondary outcomes included renal SLEDAI, non-renal SLEDAI, modified SLEDAI-2K, immunity SLEDAI, and disease activity remission. Eighty-four patients were randomized. One patient who was randomized to the TAC group withdrew from the study immediately after randomization. Therefore, 42 patients received MMF and 41 patients received TAC. Disease activity remission rate and time to disease activity remission were similar in both groups. Twelve patients (28.57%) in the MMF group and 10 patients (24.39%) in the TAC group achieved disease activity remission. For disease activity scores, both regimens significantly improved SLEDAI-2K during induction and maintenance therapy. Overall, SLEDAI-2K score in the MMF group decreased more compared with the TAC group. In the MMF group, mean SLEDAI-2K decreased from 11.6 ± 4.8 to 6.3 ± 3.9 after induction therapy and to 5.4 ± 4.4 after maintenance therapy. In the TAC group, mean SLEDAI-2K decreased from 9.0 ± 3.7 to 6.3 ± 5.1 after induction therapy and to 7.1 ± 5.4 after maintenance therapy. Renal SLEDAI and modified SLEDAI-2K showed a similar pattern with SLEDAI-2K. In non-renal SLEDAI and immunity SLEDAI, both regimens also resulted in decreased disease activity scores during the first two months. After that the scores were slightly increased. In the MMF group, the scores were still lower than baseline but in the TAC group were not. In conclusion, disease activity remission rate was similar in the MMF and TAC groups. For disease activity score as measured by SLEDAI-2K, TAC was comparable with MMF during induction but MMF was more effective on disease activity of active LN classes III and IV at 12 months, especially in the renal system.

Ten-Year Follow-up of Pharmacokinetics-Guided Very Early Cyclosporine Minimization Synchronized With Everolimus Initiation in De Novo Kidney Transplantation.

BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4. The CsA dosage was further reduced to keep a lowest value of serum creatinine and a target EVL level. Primary outcomes were estimated glomerular filtration rate (eGFR) at baseline and last follow-up. RESULTS: Patients' mean age at last follow-up was 60.6 ± 11.7 years. Follow-up duration was 121.6 ± 12.8 months. Pharmacokinetics study found that Cmax of CsA ranged from 309 to 1,896 ng/mL, mean area under the receiver operating characteristic curve (AUC) of CsA was 3,449 ± 1,402 ng·h/mL, C0 of EVL was 5.2 ± 1.5 ng/mL, Cmax of EVL was 15.4 ± 4.6 ng/mL, and AUC of EVL was 99.7 ± 26.1 ng·h/mL. Achieved nadir serum creatinine was 1.03 ± 0.33 mg/dL. Achieved best eGFR (Modification of Diet in Renal Disease formula) was 99.7 ± 26 mL/min. eGFR at 12 months was 82 ± 25 mL/min. Last serum creatinine was 1.32 ± 0.45 mg/dL. Last eGFR was 57.2 ± 13.55 mL/min. Actuarial death-censored 10-year graft survival was 100%. Actuarial 10-year patient survival was 80%. CONCLUSIONS: Our intervention can lead to an average of 75% CsA minimization and a very good eGFR at 10 years.

Outcome of Pretransplantation Therapeutic Plasma Exchange in Highly Sensitized Deceased-donor Kidney Transplant Recipients.

BACKGROUND: Sensitization is associated with a high rate of post-transplantation rejection. A desensitization protocol using therapeutic plasma exchange (TPE) was proposed to reduce anti-HLA antibody before transplantation, but there has been limited data regarding the efficacy of pretransplantation TPE in highly sensitized deceased-donor kidney transplantation (DDKT). METHODS: A retrospective cohort study of 142 patients who received DDKT was conducted and divided into two groups: a high-panel-reactive antibody (PRA) >50% group and a low-PRA ≤50% group. The high-PRA group was sub-divided into those who received and did not receive pretransplantation TPE. Donor-specific anti-HLA antibodies (DSA) were also collected pretransplantation in the high-PRA group. RESULTS: The probability of acute rejection was 26, 4, and 9 cases/1000/person month in the high-PRA group with no TPE, the high-PRA group receiving TPE, and the low-PRA group, respectively (P = .0208). In the multivariable logistic regression analysis, the hazard ratio for graft rejection was 2.37 (95% confidence interval: 0.89 to 6.35) and 2.22 (95% confidence interval: 0.54 to 9.13) in the group of high-PRA who received TPE and high-PRA with no TPE, compared with the low-PRA group, respectively (P value not significant). The incidence of antibody-mediated rejection in 6 months in the DSA-positive subgroup was not different between those who received TPE or no TPE. CONCLUSION: Desensitization with TPE is a reasonable alternative for highly sensitized DDKT. Patients who received pretransplantation TPE had a lower incidence of acute rejection compared to the group that did not receive TPE. However, pretransplantation TPE alone was not effective in the prevention of acute rejection in recipients with DSA.

Significance of HLA Antibody Detected by PRA-Bead Method in Kidney Transplant Outcomes.

BACKGROUND: The impact of specific HLA antibodies on the allograft function in the Luminex era is not clearly known. This study aimed to investigate kidney transplantation outcomes in patients with different anti-HLA antibody status as detected by Luminex PRA. METHODS: This retrospective study included 106 deceased-donor kidney transplantation (DDKT) patients divided into 3 groups by PRA status as detected by PRA-bead: (1) PRA = 0; (2) positive PRA but with negative antibody against donor's HLA antigens; and (3) positive PRA with positive anti-HLA antibody specificity against donor's HLA antigens. RESULTS: There were 65, 23, and 18 patients in groups 1, 2, and 3, respectively. Early allograft rejections were highest in group 3 (22.2%) (P = .02). In multivariate analysis, delayed graft function was the only factor that was associated with allograft rejection (hazard ratio, 8.9; 95% confidence interval, 1.9-39.8; P = .004). Estimated glomerular filtration rates at 1 year of the 3 groups were 54.6, 55.8, and 60.0 mL/min (P = .71). One-year allograft failure and death were not different among the 3 groups. Expanded-criteria deceased donors were associated with both allograft failure (P = .003) and patient death (P = .02). CONCLUSIONS: Anti-HLA antibody as detected by Luminex PRA was associated with early allograft rejection but not graft or patient survival. The effect of newer treatment modalities can improve the outcomes of PRA-positive patients to be similar to nonsensitized patients at 1 year.

Assessment of the Changes in Health-related Quality of Life After Kidney Transplantation in a Cohort of 232 Thai Patients.

AIM: The aim of this study was to investigate QoL of these patients before and after KT and to determine relationships between basic factors of gender, age, educational background, marital status, income, and QoL of patients after undergoing KT. METHODS: A retrospective study to determine HQoL of 232 ESRD patients who received KT in a single center in Thailand. HQoL was determined by 3 methods: WHO questionnaires, EQ5D questionnaires, and visual analog scale (VAS) questionnaires. Other important demographic information including gender, age, education, marital status, and family income were recorded. Pre- and post-KT HQoL was scored and compared. The Pearson method was used to calculate correlation statistics. RESULTS: WHO QoL is significantly improved in all domains including physical health, psychological health, social health, and environmental health after KT (P < .001). EQ5D QoL is also significantly improved after KT for the categories of self-mobility, self-care, pain, distress, anxiety, and depression. The mean score of VAS before KT was 40.98 and rose to 83.10 after KT (P < .001). Gender and marital status were not significantly correlated with quality of life. The level of education and average income of the family are positively correlated with increased QoL after KT (P < .01 and P < .001). However, age is negatively correlated with increased QoL (P < .05). CONCLUSION: Successful KT leads to a significant increase of HQoL as determined by 3 independent measurements. The improvement is shown by better physical health, psychosocial health, environmental health, and functional abilities of the transplant recipients. Our results confirm that KT should be the treatment of choice for patients with ESRD.

Increased urine transforming growth factor ß1 (TGF-ß1) and serum uric acid are associated with an early decline of glomerular filtration rate in kidney transplant recipients.

BACKGROUND: The renin-angiotensin system (RAS) and transforming growth factor ß1 (TGF-ß1) may play a role in the pathogenesis of fibrosis in kidney allografts. Experimental hyperuricemia shows activation of intrarenal RAS. However, the association between uric acid (UA), RAS, and TGF-ß1 in allograft recipients has not been demonstrated. Therefore we investigated the association between serum UA levels, RAS, and TGF-ß1 in kidney transplant recipients during the 1st year after transplantation. METHODS: Sixty-two transplant recipients were included in the study. Serum UA level, plasma renin activity (PRA), and urine TGF-ß1 concentration were studied at 3, 6, and 12 months after transplantation. Statistical correlation was demonstrated with the use of Spearman rank correlation coefficient. Receiver operating characteristic curve analysis and area under the curve were performed to assess the diagnostic performance to discriminate between estimated glomerular filtration rate (eGFR) <60 and ≥ 60 mL/min/1.73 m(2). RESULTS: For all 62 patients, urine TGF-ß1 and serum UA had a tendency to increase during the 1-year follow-up period, despite no statistically significant change in eGFR. We found that increased urine TGF-ß1 was correlated with rising serum UA levels and a decrease of the eGFR (r = 0.27 [P = .01]; r = -0.38 [P = .0003]). In contrast, there was no significant change in PRA and it was not correlated with eGFR or TGF-ß1 (r = -0.01; P = .93). CONCLUSIONS: Increased urine TGF-ß1 and serum UA level during the 1st year after transplantation correlated with a decline in eGFR. The evaluation of these parameters in the early post-transplantation period may identify patients at risk of allograft dysfunction.

Comparison of the immunogenicity of a monovalent influenza A/H1N1 2009 vaccine between healthy individuals, patients with chronic renal failure, and immunocompromised populations.

BACKGROUND: Data on the immunogenicity (IG) of the influenza vaccine among patients at high risk of influenza-related complication are limited. METHODS: We studied the antibody titer following a single dose of monovalent 2009 influenza A (H1N1) vaccine between groups of adult patients who were healthy, those with chronic renal failure (CRF), kidney transplant (KT) recipients, and human immunodeficiency virus (HIV)-infected patients. The IG (primary endpoints) was accessed at 4 weeks after vaccination. The secondary endpoint was safety of the vaccine. RESULTS: A total of 293 patients were studied. Patients' mean age was 41(standard deviation [SD], 13.3) years old. At baseline, mean age (P < .001), history of vaccination in a prior year (P < .001), and geometric mean titers (GMT; P < .001) significantly differed between each groups and the majority (70%) of participants had the hemagglutination inhibition titer <1:10. The IG of the vaccine was highest in the healthy group (71.4 %). The response rate among CRF, KT, and HIV groups was 42.4% (risk ratios [RR], 0.72; 95% confidence interval [CI], 0.5-1.02), 31.9% (RR, 0.51; 95% CI, 0.34-0.76), and 29.7% (RR, 0.42; 95% CI, 0.3-0.6), respectively. The vaccine was well-tolerated in all studied groups. Thirty (10.2%) patients experienced at least 1 adverse reaction but systemic reaction was uncommon (3.4%). CONCLUSIONS: A single dose of monovalent 2009 influenza A (H1N1) vaccine result in poor IG among high-risk populations, including CRF, KT and HIV patients.

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.

Early posttransplant nephrotic range proteinuria as a presenting feature of minimal change disease and acute T cell-mediated rejection.

Early-onset nephrotic range proteinuria is an extremely rare presentation of an acute rejection episode. Herein, we have reported a patient who developed nephrotic range proteinuria 7 days after receiving a renal allograft from his sister despite minor changes in serum creatinine levels. A kidney biopsy spcimen revealed a T cell-mediated acute rejection process concomitant with minimal change disease (MCD). Proteinuria and renal dysfunction improved dramatically in response to corticosteroids. The possibility of acute cellular rejection and coexisting MCD should be considered in patients with early posttransplantation nephrosis and normal serum creatinine levels. The coexistence of these entities provides support for the role of T cells in the pathogenesis of MCD.

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.

Cytomegalovirus viremia after kidney transplantation in Thailand: predictors of symptomatic infection and outcome.

BACKGROUND: While prevention of cytomegalovirus (CMV) infection after kidney transplantation (KT) has become a standard practice in Western countries, this approach is not always feasible in Thailand. In order to argue for the need for CMV prevention, the knowledge on the incidence and impact of the CMV infection following KT is highly desirable. METHODS: We retrospectively reviewed medical records of adult patients who underwent KT at our transplant center between January 2006 and December 2010. Patients who developed CMV viremia within 1 year after transplantation were studied for the incidence, risk factors, and outcome of symptomatic infection. The threshold value of blood CMV DNA load indicating symptomatic infection was also analyzed. RESULTS: Symptomatic CMV infection occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3-30) weeks after KT. At initial presentation, coexisting opportunistic infection was common (44%) and gastrointestinal tract was the major type of organ involvement (44%). Between groups of patients with symptomatic and asymptomatic CMV infection, the mean (± standard deviation) level of blood viral load were significantly higher in the first group [4.2 (± 0.5) vs 3.3 (± 0.4) log copies/mL]. From multivariate analysis, associated factors of symptomatic infection included acute rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44, P = .019). Death (13%) and graft failure (13%) were significantly higher among the symptomatic infection group than those in the no-infection group (P = .005 and .03, respectively). CONCLUSION: Despite a low incidence rate, symptomatic CMV infection clearly resulted in significant morbidity following KT. In Thailand, the prevention of CMV infection should be prioritized among high-risk KT populations.

High incidence of bacteriuria in early post-kidney transplantation; results from a randomized controlled study.

Since the incidence of bacteriuria in kidney transplant recipients varyes according to the study, we examined it among our cases. Our post hoc analysis of data from a single-center, parallel, randomized, controlled, open label study included 90 patients who underwent kidney transplantation at our hospital from April 2010 to January 2011. Patients were randomized to early ureteric stent removal at 8 days versus routine ureteric stent removal at 15 days after kidney transplantation. We identified the incidence of and causative organism for bacteriuria in the early posttransplant period. Seventy-Four patients (58% living donors) participated in this study. The overall incidence of bacteriuria was 56.7% during the first month after kidney transplantation. In patients who had bacteriuria, 48% showed symptomatic urinary tract infection, 40% asymptomatic bacteriuria and 12% urosepsis. The most common organism was Escherichia coli (40%) follow by Klebsiella pneumoniae (19%). The incidence of an ESBL producing organism was 34%. The incidence of bacteriuria was high during the early post-kidney transplant period, requiring increased awareness and surveillance.

Impact of early ureteric stent removal and cost-benefit analysis in kidney transplant recipients: results of a randomized controlled study.

INTRODUCTION: Duration of retaining ureteric stent in kidney transplantation is still controversial. Our study aimed to compare healthcare expenditures in kidney transplant recipients with early or routine ureteric stent removal. METHODS: This study was a post hoc analysis of data from a single-center parallel randomized controlled open-label study. Ninety patients who underwent kidney transplantation at a university-based hospital in Thailand from April 2010 to January 2011 were enrolled. Patients were randomized to early ureteric stent removal (8 days) or routine ureteric stent removal (15 days) after kidney transplantation. The costs of direct health care associated with kidney transplantation, urologic complication, and urinary tract infection (UTI) within the postoperative period among the 2 groups were compared. RESULTS: Seventy-four patients (58% living donor) fulfilled the randomized criteria (early removal, n = 37; routine removal, n = 37). By intention-to-treat analysis, incidence of UTI in early stent removal was less than the routine stent removal group (15/37, 40.5% vs 27/37, 72.9%; P = .004). Urologic complication showed no significant difference between the early and routine groups (4/37 vs 2/37; P = .39). The cost-benefit analysis of early over routine stent removal was 2390 United States dollars (USD) per patient (11,182 vs 8792 USD). Presence of UTI significantly increase the hospitalization cost of 5131 USD per patient (mean cost = 12,209 vs 7078 USD; P < .001). CONCLUSION: UTI in the early post-kidney transplantation period increases healthcare cost. Early ureteric stent removal can reduce UTI and reduce hospitalization cost. This approach shows cost-benefit in the early management of kidney transplant recipients.

Severe nonfebrile dengue infection in an adolescent after postoperative kidney transplantation: a case report.

We herein have reported a case of severe nonfebrile dengue infection complicated with refractory pancytopenia and a large perinephric hematoma with shock in a 16-year-old adolescent during the early postoperative period after kidney transplantation. After the diagnosis of end-stage renal disease she underwent living-related kidney transplantation. Thirteen days after successful transplantation, she exhibited a notable amount of ascites, bilateral pleural effusions, thrombocytopenia, and increased hemoglobin without pre-existent fever. Further investigation revealed positive dengue nonstructural protein 1 antigen (dengue NS1 Ag) and dengue virus serotype 1 by a reverse transcriptase-polymerase chain reaction (RT-PCR) in the patient's serum. She exhibited hemophagocytic syndrome, manifested by refractory pancytopenia and refractory anemia resulting in hypovolemic shock and acute graft failure on day 28 posttransplantation. The anemia was attributed to a large hematoma around the transplanted kidney requiring surgical evacuation of clotted blood. Postoperatively, she gradually recovered with resolution of thrombocytopenia and excellent graft function. Persistent dengue antigenemia and viremia was shown by dengue NS1 Ag and RT-PCR of dengue serotype-1. The viremia was present longer than the dengue antigenemia. Dengue-specific immunoglobulin M (IgM) and IgG by enzyme-linked immunosorbent assay confirmed the primary dengue infection and evidence of a recent donor dengue infection.

Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery.

Information on the clinical spectrum and management of adenovirus infection after kidney transplantation is limited. From April 2007 to April 2010, 17 kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2-300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6-month follow-up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection.

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.

Long-term outcome of very early cyclosporine minimization and de novo everolimus therapy in kidney transplant recipients: a pharmacokinetic guided approach.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity is an important cause of chronic allograft dysfunction. Clinical information concerning the impact of very early CsA dose reduction in kidney transplant recipients is limited. We have examined the long-term outcomes of very early CsA dose reduction. This is synchronized with de novo everolimus and steroid therapy. METHODS: We enrolled 10 de novo kidney transplant recipients to receive CsA (target C(0) 250-350 ng/mL) and prednisolone as initial therapy. CsA dosage was reduced by 50% at posttransplant day 7. Everolimus (target trough level, 3-8 ng/mL) was concomitantly started at the day of CsA reduction. Full pharmacokinetic studies of everolimus and CsA were studied at the period of 4-8 weeks after CsA reduction. CsA was then gradually reduced to maintain a trough level of 50-100 ng/mL and/or C(max) <600 ng/mL. RESULTS: The mean follow-up was 51.2 ± 3.45 months. The nadir serum creatinine was 1.03 ± 0.33 mg/dL. The mean initial estimated glomerular filtration rate (eGFR) was 97.97 ± 23.36 mL/min. The mean initial trough everolimus was 5.2 ± 1.5 ng/mL. The eGFR at 1 year, 3 years, and last follow-up was 82 ± 25, 80 ± 21, and 80 ± 25 mL/min, respectively. Patient and graft survival was 100%. CONCLUSION: Very early CsA dose reduction synchronized with de novo everolimus therapy was associated with good long-term patient and graft survival in kidney transplant recipients. This intervention can lead to 75% CsA minimization and is associated with very good GFR by the modification of Diet in Renal Disease Formula at year 4.

Ten-year follow-up of kidney transplantation from hepatitis B surface antigen-positive donors.

Hepatitis B surface antigen positivity (HBsAg(+)) was believed to be an exclusion for kidney donation. However, in the presence of an organ shortage, allocation of kidneys from HBsAg(+) donors to recipients with anti-HBsAb(+) might be allowed. We examined the 10-year outcomes of kidney transplants (KT) from HBsAg(+) donors to natural or vaccine-induced anti-HBsAb(+) recipients (Group 1). Hepatitis B hyperimmune globulin (HBIG) and lamivudine were not used at any time. We compared the 10-year outcomes of patients who had HBsAg(+) prior to KT and received kidneys from HBsAg(-) donors (Group 2). The endpoint was patient survival determined by Kaplan-Meier and Cox proportional hazard methods. A total of 41 patients were transplanted from 1991-1997. There were 14 Group 1 patients and 27 Group 2 patients. Anti-HBsAb titer ranged from 10 to >1000 mIU/mL. Actuarial 10-year patient survivals were 92.8% and 62.5% for Group 1 and Group 2. Only 1 patient in Group 1 died; this case was due to an acute myocardial infarction. Eleven deaths occurred among Group 2; they were due to chronic active hepatitis (n = 5), hepatoma (n = 3), acute fibrosing cholestatic hepatitis (n = 1), and stroke (n = 2). More than 2 times elevated ALT occurred among 45% of Group 2 but none in Group 1. No patients in Group 1 had positive HBsAg and HBV DNA at last follow-up. Four patients in Group 2 displayed seroconversion to positive HBeAg after KT. Secondary analysis examining the impact of KT on patient life expectancy (from the start of dialysis until last follow-up) used Cox regression, revealing that KT was significantly associated with an increased risk for death within 12 months after transplantation (RR = 30, P = .005) but a decreased risk for death thereafter (RR = .03, P = .005) for Group 2. However, KT did not have significant impact on the risk for death within the first year for Group 1 (P = .61). Our results showed that the 10-year survival of KT from HBsAg(+) donors to recipients with anti-HBsAb(+) was good. This was not associated with evidence of active liver disease. The presence of HBsAg(+) in donors thus should not be considered an exclusion for kidney donation for anti-HBsAb(+) recipients.

Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium.

AIMS: Mycophenolate mofetil is an effective therapy for lupus nephritis (LN) and other glomerulonephritis (GN). However, gastrointestinal (GI) complications can limit its use. Enteric-coated mycophenolate sodium (EC-MPS) has been designed to reduce GI adverse events, but it has not been fully investigated in the treatment of GN. METHODS: Patients with LN and primary GN who had received EC-MPS were studied for effects on renal function. RESULTS: 30 subjects (17 LN, 13 primary GN) were studied. EC-MPS decreased proteinuria in both LN and GN. In LN, 16 patients had EC-MPS as induction therapy. Of these, 8 patients achieved complete remission (CR), 4 had partial remission (PR) and 1 improved renal function. In primary GN, CR was achieved in 4 out of 5 with minimal change disease, but only 1 did not relapse. PR was achieved in 1 of 4 patients with membranous glomerulopathy, 2 out of 2 patients with focal segmental glomerulosclerosis and 1 out of 2 patients with IgA nephropathy. Infections, anemia and alopecia were observed, but no patient had GI side effects. CONCLUSIONS: EC-MPS is effective in LN, but not as effective in primary GN. The risk of GI side effects appears to be low, but other side effects can still occur.