Dale H. Sillix

Infectious complications after kidney transplantation: current epidemiology and associated risk factors

Abstract:  Background:  The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied.

Induction therapy with basiliximab versus thymoglobulin in african-american kidney transplant recipients

Background. It has been suggested that the use of antilymphocyte induction therapy in African-American (AA) renal transplant recipients reduces the risk of acute rejection (AR) and improves graft survival. It is not clear whether the efficacy of basiliximab (BSX) is different from that of Thymoglobulin (ATG) in this regard. Methods. We retrospectively assessed the effect of induction therapy with BSX versus ATG in 88 AA renal allograft recipients receiving transplants at our center between July 2001 and June 2003 and followed for 19±7 months. All patients were maintained on mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus. Study endpoints included patient and graft survival, graft function, and incidence of AR and cytomegalovirus infection. Regression models were used to evaluate the independent effect of each induction agent on these endpoints. Results. Thirty-six patients received ATG, and 52 received BSX. The groups were comparable with regard to donor race and age, and recipient sex, body mass index, human leukocyte antigen (HLA) matching, and hepatitis C virus serostatus. The ATG group was younger, more likely to receive retransplant, had longer duration of end-stage renal disease and higher panel reactive antibody, and was less likely to receive live-donor organs. However, after adjusting for all these variables, graft outcomes, as well as renal function, were comparable between the two induction groups. We found that the degree of HLA mismatch, delayed graft function, and AR were the only significant predictors of graft loss. Conclusion. The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.

Short‐Term Experience with Early Steroid Withdrawal in African‐American Renal Transplant Recipients

There are limited data on the results of early steroid withdrawal (ESW) in African‐American (AA) renal allograft recipients. We examined short‐term transplant outcomes in a retrospective, non‐concurrent cohort study of 40 AAs who did not (ESW group), and 33 who did [steroid maintenance (SM) group] receive maintenance steroids after day 4 post‐transplant. Patients received thymoglobulin (ATG) induction, mycophenolate mofetil, and tacrolimus or sirolimus. Data were analyzed using survival analysis methods and regression models. Patients in the ESW group were older, had lower current panel reactive antibody and fewer re‐transplants, and received fewer doses of ATG. One‐year graft survival and acute rejection (AR) rates were 100% and 13% in the ESW group and 97% and 15% in the SM group. After controlling for confounders, at 1 year, ESW was not associated with higher risk of graft loss, AR, or worse graft function, but was associated with less weight gain. The SM group had higher cholesterol levels at 3 months and higher risk of post‐transplant diabetes mellitus. We did not observe any cases of subclinical rejection. This study suggests that ESW under modern immunosuppression is safe over the short term in at least a subset of AA recipients with risk profiles similar to those studied herein, and could be associated with improved outcomes.

Sirolimus‐Induced Angioedema

Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use in organ transplantation. Its full spectrum of side‐effects is yet to be defined. We describe herein three cases of SRL‐induced angioedema (AE) in African‐American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow‐up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side‐effect, especially in AA patients, is warranted.

West Nile virus encephalitis: an emerging disease in renal transplant recipients.

Abstract:  West Nile virus (WNV) has emerged as an important cause of several outbreaks of febrile illness and encephalitis in North America over the past few years. The most common manifestation in symptomatic patients is a transient febrile illness. Neuroinvasive disease, that can be fatal, occurs most often in elderly and immunocompromised hosts. The role of this virus as a cause of meninoencephalitis in organ transplant recipients is becoming better recognized. We describe herein the clinical course of two renal allograft recipients who developed WNV encephalitis. One patient developed status epilepticus and eventually died, while the other had a full recovery. In both cases, the diagnosis was confirmed by detection of WNV‐specific IgM in CSF or serum, with a delayed antibody response in one patient. This viral infection should be considered in all renal transplant recipients who present with a febrile illness associated with neurological symptoms.

Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker for graft outcomes in a predominantly African-American renal transplant cohort.

Abstract: The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino‐acid sequences of the antibody‐accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African‐American (AA) cohort (N=101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearsons correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan–Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA‐DQ (r=0.88). The association between triplet matching at HLA‐A, ‐B, ‐DR and ‐DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p=0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio=0.2, confidence interval=0.04–1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

Cytomegalovirus prophylaxis with valganciclovir in African-American renal allograft recipients based on donor/recipient serostatus.

Abstract:  There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk‐stratified dosing regimen. Eighty adult African–American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post‐transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R−) received 900 mg (n = 12); moderate risk (D+/R+, D−/R+) received 450 mg (n = 60); and low risk (D−/R−) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high‐risk (25%) and three in the moderate‐risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue‐invasive disease, resistance to treatment, or recurrence. D+/R− serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients.

Racial perspectives on kidney transplant donors and recipients

Prior to undertaking a campaign to increase organ donation, demographic patterns of kidney recipients and donors were examined for our transplant center--the city and state in which it is located (Detroit and Michigan respectively). From 1984 to 1986 there were 964 kidney recipients in Michigan; 28% were black and 69% were white, whereas only 13% of the population in Michigan is black. As has been shown elsewhere in the United States, blacks have more end-stage renal disease than whites and thus require renal transplantation more often. There were 413 kidney donors from Michigan during the same period, 13% were black and 85% were white. In contrast to studies from other parts of the United States, our data show that blacks and whites in Michigan donate kidneys at a similar rate--i.e., 1.5 per 100,000 population. Data such as these should be obtained for areas where campaigns are to be conducted to increase organ donation. This information can be used to educate the public about the needs of the community.