Tsung-Ching Chou

Reappraisal of HLA Antibody Analysis and Crossmatching in Kidney Transplantation

Enzyme-linked immunosorbent assay (ELISA) and flow cytometric techniques have been introduced to overcome the limited sensitivity and specificity of the CDC assay. This retrospective study used lambda antigen tray-mixed screening and Luminex HLA class I and II specificity assays to re-examine: (1) the accuracy with which detection of HLA antibody and specificity by ELISA predicts pretransplantation National Institutes of Health (NIH)/Centers for Disease Control and Prevention (CDC) crossmatch; and (2) a comparison of Luminex and ELISA methods to detect HLA antibodies. Sera from 481 patients awaiting kidney transplantation were tested using the ELISA method lambda antigen tray-mixed and using NIH-CDC to determine how well HLA antibodies detected using ELISA predicted crossmatches using CDC. Pretransplantation sera from 48 patients with follow-up data were retested using both ELISA lambda antigen tray-mixed and Luminex to compare the efficacy of the 2 methods.

Does Immunosuppressive Pharmacotherapy Affect Isoagglutinin Titers

OBJECTIVE Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy. METHODS We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period. RESULTS Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups. CONCLUSION Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.

Kidney grafts with multiple renal arteries is no longer a relative contraindication with advance in surgical techniques of laparoscopic donor nephrectomy

OBJECTIVES Kidney grafts with multiple renal arteries were considered as a relative contraindication. We retrospectively reviewed our experience of kidney grafts with multiple renal arteries to clarify the usefulness of these grafts. METHODS Between September 2002 and June 2011, 100 laparoscopic donor nephrectomies (LDNs) were performed consecutively. Three-dimensional computed tomographic angiography was routinely performed preoperatively. Donor demographics, operative characteristics, donor and recipients perioperative complications, and donor and recipient outcomes were reviewed retrospectively. RESULTS Eighty-nine donors had single (group A1) and 11 donors had multiple renal arteries (group B1). Multiple arteries caused by application of the vascular stapler were found in another six donors. Overall, 17 kidney grafts required bench arterial reconstruction (group B2). The other 83 donors with single renal artery did not require further arterial reconstruction (group A2). There was a significant increase of warm ischemic time in the group of multiple renal arteries. There were no significant difference between groups A1 and B1 in regard to donor demographics, operative characteristics, and donor outcome. Kidney grafts requiring vascular reconstruction experienced equal immediate and long-term allograft outcomes with those of group A2. The actuarial 1-, 3-, and 5-year allograft survival rates were also comparable in both groups (95.4%, 92.6%, 92.6% in group A2 and 100%, 100%, 100% in group B2). CONCLUSION LDN in the presence of multiple renal arteries is feasible and safe. Both immediate and long-term allograft outcomes are comparable between kidney grafts with and without vascular reconstruction. Kidney grafts with multiple renal arteries are no longer a relative contraindication with advanced LDN surgical techniques.

Development of Laparoscopic Donor Nephrectomy: A Strategy to Increase Living Kidney Donation Incentive and Maintain Equivalent Donor/Recipient Outcome

BACKGROUND/PURPOSE Laparoscopic donor nephrectomy (LDN) has emerged as the preferred technique worldwide, and has contributed to a dramatic increase in living kidney donation during the past decade. We adopted LDN in 2002 with the intention of increasing living kidney donation incentive and maintaining equivalent donor/recipient outcome. METHODS Forty-five LDNs were performed between September 2002 and November 2007. Donor demographics, operative characteristics, perioperative complications and donor/recipient outcome were reviewed retrospectively. The LDN series was divided into earlier and later groups for comparison. To confirm the safety and efficacy of LDN, we compared the results with those of previous series and our open donor nephrectomy (ODN) series. RESULTS All 45 LDN kidneys were procured and transplanted successfully. Mean donor operation time was 327.7+/-10.2 minutes, blood loss was 286.0+/-48.3 mL, and warm ischemia time was 233.9+/-19.6 seconds. Two (4.4%) open conversions happened in the earlier group. There was a significant decrease in warm ischemia time and donor intraoperative complications in the later group. There was no donor mortality and there were no repeat surgical procedures. Delayed graft function occurred in 8.9% of cases and three (6.7%) recipients developed ureteral complications. All but one recipient was discharged with adequate renal function. Graft function continued in 41 of the 43 harvested kidneys (95.3%). Compared with ODN, there was a significant decrease in donor postoperative stay in the LDN series (p=0.00). There was no difference between the series with regard to donor safety, donor outcome, and immediate and long-term recipient outcome. CONCLUSION The number of living kidney donations increased significantly after adopting LDN in our series. The equivalent donor/recipient outcome of the LDN series compared with that of previous and ODN series was achieved with increasing experience.

Eighteen-Year Follow-Up of a Retrospective Study of HLA Antibody on Kidney Graft Survival

An increasing number of studies have demonstrated adverse graft survival in patients who have anti-HLA antibodies, whether preformed or developed posttransplantation. This retrospective study used Lambda antigen tray-mixed (LAT-M) screening and Luminex HLA class I and II specificity assay to re-examine the impact of pretransplantation HLA antibody on long-term graft survival. In this study, pretransplantation sera from 288 renal patients were tested using the enzyme-linked immunosorbent assay (ELISA) method, LAT-M. Among the 234 of the patients who did not have pretransplantation antibodies, 85% enjoyed 5-year functional graft survival, 76% 10-year functional graft survival, and 56% 15-year functional graft survival. The corresponding functional graft survival for the 54 patients who tested HLA antibody-positive was 65%, 53%, and 28%, respectively (P = .0021).

Peliosis Hepatis in a Kidney Transplant Recipient With Manifestation as Massive Ascites and Liver Dysfunction: Case Report

We report a case of 59-year-old woman who received a kidney transplant 7 years earlier without evidence of viral hepatitis history. She was asymptomatic initially and a newly developed nodule, ∼2.3 cm in size, was discovered in the right liver during routine sonographic examination. Computerized tomography-guided biopsy was inconclusive at that time. However, the lesion grew to 6.8 cm and bilobular multiple nodules developed with concomitant massive ascites and hyperbilirubinemia months later. Laparoscopy showed typical bluish-reddish-blackish nodules. Needle-biopsy histology showed severe sinusoid dilation and dropout of centrilobular hepatocytes consistent with peliosis hepatis. Reticulin staining also demonstrated disruption of sinusoidal reticulin fibers. We tried to withdraw possible offending drugs to anticipate regression of peliosis, but it failed and liver dysfunction progressed, leaving liver transplant as the last resort in such rare circumstances.

Cyclosporine or tacrolimus: Which is the better partner for Myfortic or CellCept?

BACKGROUND Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (CellCept) formulation are known to differ between patients receiving tacrolimus (FK) or cyclosporine (CyA), but only limited data exist concerning concomitant use of FK or CyA with enteric-coated mycophenolate sodium (EC-MPS; Myfortic). This retrospective study compared the drug interactions with the mycophenolic acid blood levels using different immunosuppressants and their relation to graft survival. PATIENTS AND METHODS We studied MPA levels in posttransplant sera from 298 renal transplant recipients. RESULTS Patients receiving immunosuppression with CyA + Myfortic showed 94% at 5- and 10-year graft survivals, which were better than CyA + CellCept (75%, 63%). This combination suppressed posttransplant human leukocyte antigen (HLA) antibody development significantly (P = .03) with higher MPA levels. CONCLUSION Patients immunosuppressed with CyA + Myfortic showed higher MPA levels and lower posttransplant HLA antibody development as well as the best graft survival. CyA + Myfortic or FK + Cellcept may be better combinations.

Five-Year Experience of Adoption and Evolution of Laparoscopic Living Donor Nephrectomy: Results From a Center Without Large Volume of Patients

OBJECTIVES Despite the advantages of laparoscopic living donor nephrectomy (LDN), this technique is known to have a steep learning curve that makes worldwide adoption challenging, especially in institutions without a large patients volume. Herein, we have reviewed our 5-year experience of adoption and evolution of this surgical technique, examining the donor and recipient outcomes. METHODS Between September 2002 and June 2007, 40 LDNs were performed consecutively. Our surgical technique was mainly derived from the University of California San Francisco method. We retrospectively reviewed the donor demographics, operative characteristics, perioperative complication of donors/recipients, and outcomes of donors and recipients. RESULTS Among the 40 cases, 36 (90.0%) were left-sided LDNs. Mean operative time was 335.1 +/- 66.9 minutes, blood loss was 303.9 +/- 333.2 mL, and warm ischemia time was 243.2 +/- 127.0 seconds. Multiple renal arteries required bench arterial reconstruction in 7 (17.5%) donor kidneys. Three renovascular injuries occurred intraoperatively, and 2 (5.0%) required open conversion. The overall postoperative complication rate was 20.0%. Postoperative donor serum creatinine was 1.5 times higher than preoperative serum creatinine. All but one recipient was discharged with adequate renal function. Graft function continues in 36 of the 38 harvested kidneys (94.7%) during the follow-up period. One (2.5%) recipient developed ureteral necrosis, and no recipients developed vascular thrombosis. CONCLUSIONS LDNs can be performed with careful adoption and evolution in institutions without a large patient volume. The intraoperative complication rate of LDN can be reduced with experience.

Association between preoperative allograft function (effective renal plasma flow) and the change in glomerular filtration rate among living-donor kidney transplant recipients.

BACKGROUND Predonation kidney function may be an important factor affecting graft outcome. Increased baseline allograft function may be more effective than strategies to slow the decline in glomerular filtration rate (GFR). However, the role of donor effective renal plasma flow (ERPF) on long-term outcome is less well understood. The purpose of this study was to examine the relationship between preoperative allograft function as measured by ERPF and the decline of allograft function as defined by the annualized change in GFR among living-donor kidney transplant recipients. METHODS We performed a retrospective analysis of 83 patients who underwent living donor renal transplantation at our institution from March 2001 to October 2010. A time series analysis of autoregressive integrated moving average (ARIMA) model was applied to determine the annualized change in GFR after transplantation. Univariate and stepwise multivariate analyses were performed using linear regression between preoperative ERPF and annualized change in GFR after transplantation. We also investigated the influence on annualized change in GFR of other donor or recipient variables. RESULTS The ARIMA model revealed that the annualized change in GFR was -1.344 ± 12.476 mL/min/1.73 m(2) per year. Pearson correlation coefficient for the association between predonation ERPF of the transplanted kidney and the annualized change in GFR was 0.033 (P = .777). CONCLUSIONS Poor predonation kidney function was not associated with an increased rate of decline of allograft function. Neither donor age nor renal function (preoperative ERPF value) was a valid predictor of change in GFR among living-donor kidney transplant recipients.

The Clinical Significance of Human Leukocyte Antigen Antibody Development in Kidney Transplantation

BACKGROUND This retrospective study uses the LAT-M (One Lambda Inc., Calif) screen assay to reexamine the impacts (a), of pretransplant human leukocyte antigen (HLA) antibody on long-term graft survival; (b) posttransplant HLA antibody on long-term graft survival and (c) immunosuppressive regimen on posttransplant HLA antibody development. PATIENTS AND METHODS Pretransplant sera from 222 renal transplant recipients and posttransplant sera from 216 renal transplant recipients were studied for the impact of HLA antibody on long-term graft survival. RESULTS Among the patients who did not display pretransplant HLA antibodies, 85% enjoyed 5-year and 59% 10-year graft survival, whereas the patients who tested positive were 83% and 83% (P = .5596). Among the patients who did not show posttransplant HLA antibodies, 99% enjoyed 5-, 91% 10-, and 65% 15-year graft survival, whereas for the 44 patients who tested positive they were 59%, 44%, and 30%, respectively (P < .0001). Patients prescribed cyclosporine + myfortic (odds ratio 0.17, P = .05) or FK + Cellcept (odds ratio 0.36, P = .04) showed the lowest posttransplant HLA antibody development. CONCLUSION Both regimens improve graft survival.