Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients.

INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney transplantation (KT) and, once transplanted, in the incidence of rejections and long-term allograft survival despite aggressive induction and maintenance therapy. METHODS: This study retrospectively evaluates the impact of combining T- and B-cell-depleting agents and intravenous immunoglobulin for induction therapy in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%, positive flow cytometry crossmatch or donor specific antibodies at the time of transplantation). The outcome data included the occurrence of biopsy-proven acute rejection, new-onset proteinuria, development of leukopenia, incidence of poliomavirus infection (BK or JC virus), fungal or bacterial infection after KT, de novo neoplasia, graft function, graft loss, or death with functioning KT. RESULTS: The average panel reactive antibody was 62.5%; 41 patients (91.1%) had ≥3 HLA mismatches with the donor and 91.1% of patients had class I or II anti-HLA antibodies. Fourteen patients (31.1%) presented pre-KT donor-specific antibodies and 6 patients (13.3%) had a positive flow cytometry cross-match at the time of transplantation. The incidence of acute rejection in the first 6 months was 24.4% and the cumulative incidence was 37.8%. Two patients were diagnosed with leukopenia in the first 6 months after KT. Two patients (4.5%) had cytomegalovirus disease, 17 patients (37.8%) were diagnosed with bacterial infections. Cutaneous neoplasms were identified in 5 patients (11.1%) and solid tumors in 4 (8.9%). The death-censored graft survival was 100% in the first 6 months and 93.5% at the last evaluation. Patient survival in the same periods was 97.8% and 93.3%, respectively. CONCLUSIONS: Induction immunosuppressive therapy with intravenous immunoglobulin and rituximab is effective; outcomes demonstrate an excellent patient and allograft survival and allograft function over the follow-up period.

Hepatitis C Virus Eradication in Kidney Transplant Recipients: A Single-Center Experience in Portugal.

INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz. From a total of 32 HCV RNA+ KT recipients on follow-up, we describe the first 23 patients treated with DAA. They were 56.7 ± 9.1 years old; 22 were white, 52.2% were males, they underwent transplantation 18.8 ± 9.0 years ago, and 13 had genotype 1B, 21 were naïve, and 9 had stages F3/F4. All but 2 patients, treated with grazoprevir/elbasvir, received sofosbuvir (18 with ledispasvir, 2 with daclastavir, and 4 with simultaneous ribavirin). Pretreatment, intra-treatment, and post-treatment creatinine clearances were 61.4, 60.6, and 60.7 mL/min/1.73 m2, respectively (not significant [NS]). Cyclosporine A was the basis of immunosuppression in the majority [(n = 14); pretreatment and intra-treatment levels were 79.5 ± 23.0 and 91.8 ± 26.0 ng/mL, respectively (P = .08)]; tacrolimus (n = 8) and mammalian target of rapamycin (mTOR) levels (n = 5) were also similar. One patient interrupted ribavirin after 7 weeks due to anemia; all other patients completed the treatment course without major side effects. Only 3 patients presented positive viral RNA at the fourth week of treatment and SVR was achieved in 100% of the patients 12 weeks after treatment. CONCLUSIONS: DAA therapy was well tolerated and effective in 100% of our treated patients, without significant impact on the renal function or on the immunosuppression.

JC polyomavirus nephropathy confirmed by using an in-house polymerase chain reaction method.

We report the case of an isolated JC virus (JCV) infection, without co-infection by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney transplantation. Clinical suspicion followed the observation of a decrease in estimated glomerular filtration rate (eGFR) and a renal allograft biopsy revealing polyomavirus-associated tubulointerstitial nephritis and positivity for SV40. An in-house real-time polymerase chain reaction assay, targeting the presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis. Thirteen months after diagnosis, and following therapeutic measures, eGFR remains stable.

Renal Transplantation in HIV-Infected Patients: The First Portuguese Review.

INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed. Patients were transplanted following the American and Spanish guideline recommendations that included maintenance on cART, undetectable plasma HIV RNA copies, and absolute CD4 counts of ≥ 200 cells/µL in the last 6 months. RESULTS: Fourteen KT were performed on men and 3 on women. The mean age of patients at the time of transplantation was 49.9 ± 11.7 years. HIV status was known for 12 ± 5 years. Eight patients had AIDS in the past and all patients received grafts from deceased donors. Twelve patients (64.7%) underwent induction therapy with basiliximab and 2 patients experienced early graft loss. In 2 patients, humoral rejection was diagnosed and in 3 patients, cellular rejection. Two patients died and an additional patient had early graft loss. CONCLUSION: KT is a possible, but challenging, renal replacement therapy in selected HIV-positive patients. Even in those with AIDS criteria in the past, when the disease is controlled, and after the reconstitution of the immune system with cART, KT can be performed. Nevertheless, the risk-benefit ratio for each patient needs to be taken in consideration.

Antimicrobial photodynamic therapy: photodynamic antimicrobial effects of malachite green on Staphylococcus, enterobacteriaceae, and Candida.

OBJECTIVE: This study investigated in vitro the photodynamic antimicrobial effects of the photosensitizer malachite green on clinical strains of Staphylococcus, Enterobacteriaceae, and Candida. MATERIALS AND METHODS: Thirty-six microbial strains isolated from the oral cavity of patients undergoing prolonged antibiotic therapy, including 12 Staphylococcus, 12 Enterobacteriaceae, and 12 Candida strains, were studied. The number of cells of each microorganism was standardized to 10(6) cells/mL. Twenty-four assays were carried out for each strain according to the following experimental conditions: gallium-aluminum-arsenide laser and photosensitizer (n = 6, L+P+), laser and physiologic solution (n = 6, L+P-), photosensitizer (n = 6, L-P+), and physiologic solution (n = 6, L-P-). Next, cultures were prepared on brain-heart infusion agar for the growth of Staphylococcus and Enterobacteriaceae, and on Sabouraud dextrose agar for the growth of Candida, and incubated for 48 h at 37 degrees C. The results are reported as the number of colony-forming units (CFU/mL) and were analyzed with analysis of variance and the Tukey test. RESULTS: The Staphylococcus, enterobacterial, and Candida strains were sensitive to photodynamic therapy with malachite green (L+P+). A reduction of approximately 7 log(10) for Staphylococcus, 6 log(10) for enterobacteria, and 0.5 log(10) for the genus Candida. Significant statistical differences were observed between the L+P+ groups and the control groups (L-P-). CONCLUSION: The Staphylococcus, Enterobacteriaceae, and Candida strains studied were sensitive to photodynamic therapy with malachite green.

Frequency of Candida spp. in the oral cavity of Brazilian HIV-positive patients and correlation with CD4 cell counts and viral load.

The aim of this study was to evaluate the prevalence of Candida spp., and particularly C. dubliniensis, among oral isolates from Brazilian HIV-positive patients correlating these results with CD4 cell counts and viral load. Forty-five individuals (23 female and 22 male) diagnosed as HIV-positive by ELISA and Western-blot, under anti-retroviral therapy for at least 1 year and without oral candidosis signals were included in the study. The control group was constituted by 45 healthy individuals, matched to the test group in relation to age, gender, and oral conditions. Oral rinses were collected and the identification was performed by phenotypic tests. The existence of C. dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Candida spp. were detected at significantly higher number in the oral cavity of HIV-positive patients in relation to the controls (P = 0.0008). C. albicans was the most frequently isolated species in both groups. In the HIV group, C. glabrata, C. lipolytica, C. krusei, C. guilliermondii, and C. parapsilosis were also identified. In the control group, we additionally identified C. tropicalis and C. dubliniensis. Two isolates (1.9%, 2/108) from control individuals were identified as C. dubliniensis and this species was not verified in the HIV group. Candida spp. counts were statistically lower (P = 0.0230) in the oral cavity of patients with low viral load (<400 copies/mm(3)). Candida spp. counts did not differ statistically among groups with different levels of CD4 cells counts (P = 0.1068).