BK Virus Infection in Thai Kidney Transplant Recipients: A Single-Center Experience.

INTRODUCTION: BK virus-associated nephropathy (BKVAN) is a significant cause of allograft dysfunction and failure in kidney transplant recipients. Early detection and proper adjustment of immunosuppression is the best method for treatment of this condition and to improve long-term allograft outcome. Here, we reported the prevalence and risk factors of BK virus (BKV) infection in our population. METHODS: We retrospectively reviewed kidney transplant recipients at Siriraj Hospital between January 2012 and December 2015 who had been investigated using real-time polymerase chain reaction BK viral load. BKV infection including BK viruria, BK viremia, and BKVAN had been reported. RESULTS: In all, 173 patients were enrolled. Fifty-three patients (30.6%) were diagnosed with BKV infection. The median time to diagnosis of BKV infection was 10.9 months after transplantation. There were 11 cases of BKVAN. Mycophenolic acid (MPA) more than 1 g/d was the only significant risk factor for developing BKV infection (odds ratio = 2.35, 95% confidence interval 1.07-5.14). The high level of BK viral load in urine (>1.7 × 107 copies/mL) could predict BK viremia. CONCLUSION: Protocol screening of BKV following with adjusted immunosuppressive regimens should be established for preventing allograft loss in BKVAN especially in the first year after transplantation and in patients who receive more than 1 g of MPA per day. Urinary BK viral load is the early marker for prediction of BK viremia, which leads to BKVAN.

Predictive model for the optimal glomerular filtration rate in living kidney transplant recipients.

BACKGROUND: Recipient glomerular filtration rate (GFR) after living kidney transplantation (KT) is influenced by many factors. Defining the appropriate level of recipient GFR post-KT is helpful. The aim of this study was to establish a predictive model to estimate the optimal recipient GFR at 1 week post-KT. METHODS: We retrospectively analyzed 211 living KTs without delayed or slow graft function. Estimated GFR was calculated using the Cockcroft-Gault (CG) formula. Donor kidney volume was obtained from routine computed tomographic angiography (CTA) by work station GE (AW 4.20) program. Multivariate analysis was carried out with automated backward selection to establish the predictive model. The bias, precision, and accuracy of our model were also determined by application of the model to another 37 living KTs. RESULTS: In multivariate analysis, the significant parameters to predict recipient GFR were donor age (P = .025) and kidney volume (P < .0001) and both were incorporated in the predictive model; predicted CG recipient GFR = 28.325 + (donor kidney volume x 0.282) - (0.297 x donor age). The correlation coefficient (R) is 0.5. Application to another group revealed that our model had high precision (14.45 mL/min), small positive bias (0.24 mL/min), and high percentage (81%) of predicted value, which was within 30% of the observed recipient GFR post-KT. CONCLUSION: Our predictive model included donor age and donor kidney volume and could be used to estimate the optimal recipient GFR post-KT. This could be helpful to identify early graft dysfunction and to make a decision if further invasive investigation such as allograft biopsy is necessary.

Clinicopathologic features and treatment response of early acute antibody-mediated rejection in Thai kidney transplant recipients: a single-center experience.

BACKGROUND: Acute antibody-mediated rejection (AMR) is a major cause of early kidney allograft dysfunction. This study was conducted to examine the clinicopathologic features and long-term outcomes of early AMR in our center. METHODS: We retrospectively reviewed all patients who underwent kidney transplantation between January 2005 and December 2012. Patients who had histopathologic features of AMR within 3 months after transplantation were enrolled. RESULTS: Of 444 patients, early acute AMR was diagnosed in 25 patients (5.36%). Seventeen patients (68%) were highly sensitized. Histological analysis revealed acute vascular rejection and thrombotic microangiopathy in 21 (84%) and 6 (24%) patients, respectively. Staining of C4d in peritubular capillaries was detected in 6/20 patients (12%). All patients received plasma exchange (PE) 1.5 blood volume for 1-5 sessions followed by intravenous immunoglobulin (IVIG) 2 g/kg. Sixteen patients (64%) received 1-2 doses of rituximab 375 mg/m(2). We repeated treatment with PE and IVIG in refractory cases. Allografts could be rescued in 20 patients (80%) whereas 5 patients (20%) lost their grafts. Kaplan-Meier survival analysis revealed lower cumulative graft survival in the early AMR group compared with patients without early AMR (1 year survival rate of 80% vs 96% and 3 survival of 64% vs 80%; P < .001). After median follow-up time of 25 months, 7/20 patients (33%) developed late AMR. CONCLUSION: ABMR is a serious early complication after KT. Early detection and intensive treatment is mandatory for salvaging the graft. After surpassing from early AMR, long-term close monitoring is also necessary.

Clinicopathologic characteristics and outcomes of late acute antibody-mediated rejection in Thai kidney transplant recipients: a single-center experience.

BACKGROUND: Late antibody-mediated rejection (ABMR) has worse prognosis than early ABMR. The objective of this study was to examine the clinical and pathological features of late acute ABMR in our experience. METHOD: We retrospectively reviewed all patients who underwent kidney transplantation (KT) between January 2001 and December 2012. Patients who had glomerulitis and/or peritubular capillaritis on kidney biopsy performed 6 months after KT were enrolled. RESULTS: Of 592 patients, late acute ABMR was diagnosed in 34 cases (5.74%) with a mean onset of 49.2 ± 30.2 months post-KT. Six patients (17.6%) had nonadherence. Allograft histopathology demonstrated concomitant transplant glomerulopathy in 23 patients (67.6%) and positive peritubular C4d staining in 25 patients (73.5%). Donor-specific antibody (DSA) was detected in 25 patients (73.5%). Anti-HLA class II antibody was more prevalent than class I (67.6% vs 20.6%; P = .003) and most of them were anti-HLA DQ. We prescribed intravenous immunoglobulin (IVIG) 1-2 g/kg for 30 patients (88.2%), plasma exchange (PE) for 27 patients (79.4%), and rituximab 375 mg/m(2) for 18 patients (52.9%). We repeated treatment with PE and IVIG in 12 refractory cases. For clinical outcome, 21 patients (61.7%) had deterioration of graft function; 9 of them (26.5%) eventually lost their graft. Thirteen patients (38.2%) had stable graft function. CONCLUSION: Late acute ABMR has unsatisfactory prognosis in spite of aggressive standard antihumoral treatment. Surveillance of late ABMR using DSA monitoring may be helpful in early detection and management.

High prevalence of obesity in Thai renal transplant recipients: a multicenter study.

BACKGROUND: Obesity is a risk factor for cardiovascular disease and cardiovascular mortality in renal transplant recipients (RTRs). There are limited studies of prevalence and associated factors of obesity in Asian RTRs. METHODS: A cross-sectional study was conducted from July to December 2012 in 4 kidney transplant centers in Bangkok, Thailand. Obesity was diagnosed based on the International Obesity Taskforce-proposed classification. At risk of obesity, obese I, and obese II were defined as having a body mass index (BMI) of 23-24.9 kg/m(2), 25-29.9 kg/m(2), and ≥ 30 kg/m(2), respectively. RESULTS: Of 263 recipients studied, 50 (19.0%), 70 (26.6%), and 17 (6.5%) were at risk of obesity, obese I, and obese II, respectively. The prevalence of obesity was 12.6% in the 1st year, was 28.6% in the first 3 years, and rose to 39.7% after 3 years after transplantation. Age (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), systolic blood pressure ≥ 130/85 mm Hg (OR, 2.82; 95% CI, 1.51-5.26), number of antihypertensive medications (OR, 1.99; 95% CI, 1.42-2.79), fasting plasma glucose (OR, 1.03; 95% CI, 1.01-1.04,) and high-density lipoprotein (HDL) cholesterol (OR, 0.96; 95% CI, 0.94-0.98) were associated with obesity. Compared with 100 RTRs with normal BMI, obese patients tended to have higher prevalence of chronic kidney disease (OR, 1.59; 95% CI, 0.89-2.83). CONCLUSIONS: The study demonstrates the high prevalence of obesity in Thai RTRs especially after 3 years after transplantation. Obesity is more prevalent with advanced age and variable components of metabolic syndrome in the RTR population. Obese RTRs had significantly higher blood pressure and required more antihypertensive medication when compared with RTRs with normal BMI.

The 37-year kidney transplantation experience at Siriraj Hospital.

With 37-years of experience, a total of 801 kidney transplantations (59.4% were deceased donors and 40.6% were living donors) performed at Siriraj hospital were reported. The point system parallel to OPTN/UNOS for waitlists was utilized. Most of the recipients of deceased donor kidney transplantations had 3 HLA mismatches. Due to the point allocation system, none of them had 6 HLA mismatches. Extended criteria donor comprised 7.8% of all deceased donors. Mean duration of dialysis prior to deceased donor transplant was 53 +/- 34 months. Delayed graft function (DGF) was found in 54% of deceased donor kidney transplantation and resulted in significantly higher rate of 1 year biopsy-proven acute rejection, longer duration of kidney transplant admission, higher admission cost and lower patient survival compared to those with immediate graft function. Most of living donor kidney transplant recipient had 1 haplotype match. Mean donor age was 35.9 +/- 9.8 years. 95.6% of the recipients were on hemodialysis prior to transplantation. The current standard regimen includes calcineurin inhibitor, Mycophenolic acid and prednisolone. Interleukin-2 receptor monoclonal antibody has been used in the high immunological risk or high risk for DGF recipients that were 50% of the recipients. There was no statistically significant difference in the biopsy-proven acute rejection (BPAR) free survival between deceased and living donor transplantation. Proportion of cases with the diagnosis of acute rejection according to Banff 2007 classification is as follows: 32.4% acute cellular rejection (ACR), 39.4% antibody-mediated rejection (AMR) and 21.1% mixed cellular and antibody-mediated rejection. Seventy two patients, 35 deceased donor and 37 living donor kidney transplant recipients, had biopsy-proven glomerular disease after transplantation which IgA nephropathy is the most common form of glomerulonephritis. Median graft survival was 7.6 and 13.2 years and median patient survival was 12.1 and 15.5 years for recipient of deceased and living donor transplant respectively. The follow up program of living donors was introduced in 2003 and there were not any donors who required renal replacement therapy.

The prevalence of C4d-positive renal allografts in 134 consecutive biopsies in Thai patients.

Antibody-mediated rejection (AMR) has been recognized recently as an important cause of graft failure. Detection of C4d in renal allograft biopsies is a proven ancillary technique in the diagnosis of AMR. The prevalence of C4d staining in Western countries varies from 17% to 60% among indication biopsies. There are only a few C4d prevalence studies in an Asian population. The objective of this study was to identify prevalence of C4d among Thai renal transplant patients. Consecutive renal allograft biopsies from 99 patients from 1999 to 2007 were stained for C4d by an immunoperoxidase technique. The biopsy slides were evaluated for the diagnosis according to the Banff'07 classification and histological scores. The relevant clinical data were obtained from clinical records. The prevalence of C4d in renal allografts was reported as a percentage using a descriptive analysis. Chi-square and unpaired Student t tests were used to evaluate the association between clinicopathologic findings and C4d positivity. P values less than .05 were considered significant. The prevalence of positive C4d staining was 16.4%. Fourteen biopsies (10.4%) showed diffuse staining while 8 (5.9%) revealed focal staining. Transplant glomerulopathy, glomerulitis, and peritubular capillaritis were associated with C4d positivity. Most inflammatory cells in peritubular capillaritis were mononuclear cells. Banff score elements, including tubulitis, intimal arteritis, interstitial infiltrate, interstitial fibrosis, tubular atrophy, mesangial matrix increase, vascular fibrous thickening, and arteriolar hyaline thickening, were not associated with C4d positivity. Many factors contribute to the varied prevalence of C4d positivity, including immunologic risks for AMR, type of allograft biopsy, and technique of C4d staining. Our study showed no difference in C4d prevalence among Thai renal allograft patients compared to the Western population. The suggestion to use C4d staining on all allograft biopsies should applied to Thai patients as well.

Effects of donor age and cell senescence on kidney allograft survival.

The biological processes responsible for somatic cell senescence contribute to organ aging and progression of chronic diseases, and this may contribute to kidney transplant outcomes. We examined the effect of pre-existing donor aging on the performance of kidney transplants, comparing mouse kidney isografts and allografts from old versus young donors. Before transplantation, old kidneys were histologically normal, but displayed an increased expression of senescence marker p16(INK4a). Old allografts at day 7 showed a more rapid emergence of epithelial changes and a further increase in the expression of p16(INK4a). Similar but much milder changes occurred in old isografts. These changes were absent in young allografts at day 7, but emerged by day 21. The expression of p16(INK4a) remained low in young kidney allografts at day 7, but increased with severe rejection at day 21. Isografts from young donors showed no epithelial changes and no increase in p16(INK4a). The measurements of the alloimmune response-infiltrate, cytology, expression of perforin, granzyme B, IFN-gamma and MHC-were not increased in old allografts. Thus, old donor kidneys display abnormal parenchymal susceptibility to transplant stresses and enhanced induction of senescence marker p16(INK4a), but were not more immunogenic. These data are compatible with a key role of somatic cell senescence mechanisms in kidney transplant outcomes by contributing to donor aging, being accelerated by transplant stresses, and imposing limits on the capacity of the tissue to proliferate.

The effect of peak and current serum panel-reactive antibody on graft survival.

BACKGROUND: Preformed antibodies against HLA antigens are known risk factors for early graft loss. Pretransplantation panel-reactive antibody (PRA) is often used to estimate the degree of sensitization. This study was conducted to determine the risk of early graft loss among subjects with a PRA cutoff value of 10%. OBJECTIVES: To evaluate the influence on 1-year graft survival of pretransplant recipient sensitization using 10% peak and current PRA cutoff values. METHODS: From January 1988 to July 2007, T-cell and B-cell PRA data were available for 247 (41%) and 241 (40%) patients, respectively. Medical records were reviewed for graft survival, current PRA value, and peak PRA value (both T and B cell). Complement-dependent cytotoxicity (CDC) is the only method of PRA identification in this study. We analyzed the correlation between PRA level and graft survival. RESULTS: Current T-cell PRA > 10% was significantly associated with poorer 1-year graft survival when compared with those with PRA < or = 10% in kidney transplantation from both donor sources: 48.6% versus 86.3% (P = .007) for living donor 94.7% versus 70.0% (P = .029) for deceased donor. Most of the graft losses in recipients with a high PRA occurred within the first 3 months posttransplantation. CONCLUSION: In our experience, current serum T-cell CDC PRA value > 10% was significantly associated with a decreased 1-year graft survival; interventions will be required to preserved graft function in these high-risk individuals.

Anti-CD20 monoclonal antibody (rituximab) for the treatment of membranous nephropathy after living-unrelated kidney transplantation: a case report.

A 41-year-old Thai male with end-stage renal disease of uncertain etiology started chronic hemodialysis in November 2001. Two years later, he underwent a living unrelated, four HLA mismatched, kidney transplantation from his wife. Pretransplant class I panel reactive antibody was 80% and the cross-match was positive for immunoglobulin (Ig)M. There was no complication until 30 months after transplantation, when he developed frank nephrotic syndrome with 12.9 g/day of proteinuria. Serum creatinine was 1.5 mg/dL. Allograft biopsy showed membranous nephropathy and mild acute cellular rejection with plasma cell infiltration. In addition to enalapril, valsartan, and simvastatin, a single dose of rituximab (375 mg/m2) and a 3-day course of pulse methylprednisolone were prescribe for the acute rejection episode. The patient was maintained on the same immunosuppressive regimen: cyclosporine, azathioprine, and prednisolone. Five months after the therapy, proteinuria was reduced to 0.5 g/day with a normalized serum albumin level. At 4 years post transplantation, his renal function remains stable. His serum albumin is 4.5 g/dL and urine protein-to-creatinine ratio 0.2.