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

BACKGROUND: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. METHODS: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. RESULTS: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR=4.5 and 2.9, p=0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR=3.3 and 2.5, p=0.009 and 0.047, respectively). CONCLUSION: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.

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

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 Pearson's 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.

Preliminary results with early corticosteroid withdrawal in African American renal allograft recipients.

BACKGROUND: There is a paucity of data regarding the use of steroid-avoidance immunosuppression (SAI) in African American (AA) renal allograft recipients, traditionally considered a high-risk subgroup of patients with higher reported rates of acute rejection and graft loss. METHODS: We compared the outcomes of 27 AA renal allograft recipients receiving SAI (SA group; mean follow-up period, 12 +/- 3 mo) with those of 20 patients receiving a steroid taper (ST group; 24 +/- 11 mo). In both groups, thymoglobulin was used for induction, and mycophenolate mofetil and tacrolimus were used for maintenance. Four doses of methylprednisolone were given on days 0 to 3. In the SA group no further steroids were given, whereas in the ST group a prednisone taper was continued thereafter. RESULTS: ST patients were more likely to have current panel reactive antibody titers greater than 10%, undergo retransplantation, and receive more doses of thymoglobulin. There were no significant differences between the SA and ST groups with regard to patient survival (96% vs 95%), graft survival (96% vs 90%), acute rejection (11% vs 14%), cytomegalovirus infection (7% vs 10%), posttransplant diabetes mellitus (11% vs 24%), or mean serum creatinine concentration at 6 months (1.6 vs 1.5 mg/dL), respectively, with a trend toward less percent weight gain in SA patients at 6 months (5% vs 11%, P = .06). CONCLUSIONS: SAI can produce excellent short-term results in AA kidney transplant patients when compared with a conventional ST protocol. Our results will need to be verified in larger numbers of patients with longer follow-up evaluation.

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

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.

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.

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

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.

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.