S. Jirasiritham

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.

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.

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.

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.

Malignancies in Renal Transplant Patients: 15 Years Experience in Thailand

The increased incidence of malignancies post-renal transplantation is well established. We performed a retrospective review of the 270 renal transplant patients from May 1, 1992 to April 30, 2007, including 18 cases (6.7%) of malignancy. The most common cancer in the study was transitional cell carcinoma of the urinary tract (7/18). The second most common cancer was hepatocellular carcinoma (3/18). In contrast to reports from Caucasian countries, we found only 2/18 patients had posttransplantation lymphoproliferative disease and no report of skin cancer. Among the 18 patients with malignancy, 11 died (mortality rate = 61%). We encourage a more extensive study of malignancy post-renal transplantation at multiple centers with a tumor registry in Thailand.

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.

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.

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.

Vascular calcification in long‐term kidney transplantation

Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD‐related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long‐term.