Po-Chang Lee

All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies

Background. Recent studies show that almost all patients who have rejected a kidney transplant had human leukocyte antigen (HLA) antibodies. In this study, we sought to determine whether patients develop HLA antibodies before chronic rejection. Methods. For the past 8 years, 139 patients who had undergone kidney transplantation were systematically examined, using an enzyme-linked immunosorbent assay–based method, for the development of class-I and class-II HLA antibodies 3 months, 6 months, and yearly after transplantation. Chronic rejection was diagnosed by biopsy. Results. Among 29 patients with chronic rejection, 100% of the patients had HLA antibodies before rejection. Of these patients, 14 patients developed antibodies de novo. In contrast, among 110 patients with stable function, 27% of the patients developed HLA antibodies posttransplant (P <0.001). Conclusions. HLA antibodies were found in 29 consecutive cases of chronic rejection failures as much as one year before the loss of grafts. We conclude that HLA antibodies may be a prerequisite for chronic immunologic rejection.

HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss.

Background. Evidence shows posttransplant antibodies lead to renal allograft failure, but does the time elapsed between transplantation and antibody development impact allograft survival? This is the first study showing importance of when antibodies appear. Methods. Serial sera were collected during 17 years (1991–2008) from two groups of patients, one whose allograft failed due to chronic rejection containing 25 patients (230 sera) and a control group consisting of 25 graft functioning patients (305 sera) who were matched by transplant date to a patient whose graft failed. Results. The median follow-up for failure patients was 7.1±4.8 years and 11.8±4.4 years for controls. Human leukocyte antigens alloantibodies appeared in 24 of 25 (96%) of the failed patients and 48% of the controls (P<0.0001). Time to antibodies also differed between groups. Fifteen (60%) patients from the failure group developed antibodies by 1 year compared with none in the control group. Hazard ratio of antibodies present in 1-year posttransplant from multivariate analysis for allograft loss was 7.77 (P<0.001).Ten-year renal allograft survival in early antibody developers (<1 year) was 27% vs. 80% in the late antibody developers. Conclusions. Overall, human leukocyte antigens antibody development within 1-year posttransplantation markedly lowers allograft survival compared with later antibody development. Therefore, monitoring early antibodies is useful.

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.

A Simple, Secure and Universal Pancreaticojejunostomy following Pancreaticoduodenectomy

Although the operative mortality of pancreaticoduodenal resection has decreased recently, the operative morbidity resulting from a leaking pancreatic anastomosis remains high. We described our experience in 50 consecutive cases with a simple, secure end to side pancreaticojejunostomy. We used a paediatric nasogastric tube in the pancreatic remnant duct as a temporary external pancreatic drain. There were 29 men and 21 women ranging from 12 to 84 years with a median age of 61 years. Forty-two patients underwent a standard Whipple procedure and eight a pylorus preserving pancreaticoduodenectomy. Average operating time was 270 minutes with a range of 170 to 480 minutes. The pancreaticojejunostomy could be constructed in a mean of 8 minutes. Intraoperative blood loss ranged from 150 to 3500 mL with a mean of 910mL. Twenty-five patients (50 %) received no blood transfusion. The consistency of the pancreatic remnant was hard in 12 patients (24 %) and normal in 38 patients (76 %). The pancreatic duct was dilated (>4mm) in 15 patients (30 %). There was no operative mortality and only three (6.0 %) minor leaks from the pancreatic anastomosis which healed spontaneously. It was difficult to determine if the leaks were related to the consistency of the pancreatic remnant, the size of the pancreatic duct, the amount of intraoperative blood loss, operating time, sex of the patient or experience of the surgeon, as there were only three leaks. We concluded that our technique for pancreaticojejunal anastomosis following pancreaticoduodenectomy was safe and applicable to, standard Whipple or pylorus preserving pancreaticoduodenectomy, small or dilated pancreatic ducts, normal or fibrotic pancreas.

Does Immunosuppressive Pharmacotherapy Affect Isoagglutinin Titers

OBJECTIVEnPreoperative 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.nnnMETHODSnWe 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.nnnRESULTSnOur 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.nnnCONCLUSIONnMaintenance 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.

A role for chronic parvovirus B19 infection in liver dysfunction in renal transplant recipients

Background. Clinically, liver dysfunction in renal transplant recipients is related to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The contribution of parvovirus B19 (B19) to liver disease in renal transplant recipients has not been studied. Here we present the association of liver dysfunction with or without the coinfection of B19, HBV, and HCV after renal transplantation. Methods. We used enzyme-linked immunosorbent assay to identify B19, HBV, and HCV infections in serum samples taken from 144 renal transplant recipients before transplantation and at 12 and 24 months after transplantation. After each patient had fasted for 12 hr, blood was taken for measurement of aspartate aminotransferase and alanine aminotransferase monthly for at least 6 months. Results. Liver dysfunction developed at the significantly higher incidence of 47% in the anti-HCV(+) patients compared with 6% in the noninfected group (P <0.0001). HBV infection had no impact on the incidence of liver dysfunction in renal transplant recipients. A higher incidence of liver dysfunction was found in 42% of B19 IgG(+)IgM(−) group patients compared with 13% of the B19 IgG(+)IgM(+) group (P =0.0051) and 9.5% of the B19 IgG(−)IgM(−) group (P =0.0003). A B19 polymerase chain reaction (PCR) assay revealed significantly higher liver dysfunction in 29% of B19 PCR(+) group patients compared with 13.6% of B19 PCR(−) patients (P =0.0419). Patients who were anti-HCV(+) and B19 PCR(+) had a significantly higher incidence of liver dysfunction than B19 PCR(−) patients (P =0.002). Conclusions. Chronic B19 infection and HCV infection, both separately and in combination, increase the incidence of liver dysfunction in renal transplant recipients. HBV infection does not seem to be independently or synergistically associated with liver dysfunction.

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

OBJECTIVESnKidney 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.nnnMETHODSnBetween 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.nnnRESULTSnEighty-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).nnnCONCLUSIONnLDN 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/PURPOSEnLaparoscopic 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.nnnMETHODSnForty-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.nnnRESULTSnAll 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.nnnCONCLUSIONnThe 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.