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1.
Am J Transplant ; 17(8): 2092-2102, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28245084

RESUMO

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim , Adulto , Idoso , Aloenxertos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Humanos , Incidência , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos
3.
Pharmacogenomics J ; 17(1): 69-75, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26644205

RESUMO

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, ß=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.


Assuntos
Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Transplante de Órgãos/efeitos adversos , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Dislipidemias/epidemiologia , Dislipidemias/genética , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Incidência , Modelos Lineares , Modelos Logísticos , Síndrome Metabólica/diagnóstico , Análise Multivariada , Obesidade/epidemiologia , Obesidade/genética , Razão de Chances , Fenótipo , Prevalência , Medição de Risco , Fatores de Risco , Suíça/epidemiologia , Fatores de Tempo , Resultado do Tratamento
4.
PLoS One ; 11(11): e0165233, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27855166

RESUMO

BACKGROUND: Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy. METHODS: Immunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids. RESULTS: The per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21-128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22-132) (Thymo-group) (p = 0.69). CONCLUSION: We found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Transplantados , Adulto , Idoso , Animais , Soro Antilinfocitário/efeitos adversos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Imunoglobulinas Intravenosas , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Coelhos , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo
5.
Oncogene ; 35(34): 4529-39, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-26804167

RESUMO

Organ-transplant-recipients exhibit cancerization of the skin from which multiple human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs) arise. However, the molecular basis for HPV-induced invasion of skin keratinocytes is not known. We generated a transgenic mouse model expressing the E7 oncoprotein of HPV8 in the murine epidermis under the control of the keratin-14 promoter and showed that E7 is carcinogenic in mice. We further showed that both, the E7-expressing keratinocyte and mesenchymal components of the extracellular matrix as critical in eliciting the invasive behavior. E7 expression in basal keratinocytes, grown on fibronectin, led to epithelial-mesenchymal transition mediated by a cadherin switch. E7-positive keratinocytes displayed enhanced EDA-fibronectin expression and secretion and stimulated dermal fibroblasts to express EDA-fibronectin. Deposition of fibronectin was also detected in the peritumoral stroma of HPV8-positive skin SCC. When grown on fibronectin, E7-positive keratinocytes, in particular stem cell-like cells, exhibited increased cell surface levels of the α3-integrin chain. Functional blocking confirmed α3 as a critical molecule sufficient to induce E7-mediated invasion. This mechanistic link is further supported by expression of an E7-mutant, impaired in targeting α3 to the cell surface. These findings highlight the importance of epithelial-extracellular matrix interaction required for keratinocyte invasion and provide further mechanistic evidence for a role of HPV in skin carcinogenesis.


Assuntos
Fibronectinas/fisiologia , Integrina alfa3beta1/fisiologia , Queratinócitos/patologia , Proteínas E7 de Papillomavirus/fisiologia , Animais , Células Cultivadas , Transição Epitelial-Mesenquimal , Proteínas da Matriz Extracelular/metabolismo , Camundongos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia
6.
Nephrol. dial. transplant ; 30(11): 1790-1797, nov. 2015.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-965351

RESUMO

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.


Assuntos
Humanos , Doadores de Tecidos , Transplante de Rim , Nefropatias , Nefropatias/cirurgia , Assistência Perioperatória , Transplantados
7.
Transpl Infect Dis ; 17(3): 481-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25704776

RESUMO

INTRODUCTION: In immunosuppressed hosts, rapid identification of microorganisms of bloodstream infections is crucial to ensuring effective antimicrobial therapy. Conventional culture requires up to 72 h from sample collection to pathogen identification. METHODS: We used the SepsiTyper Kit and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF; Microflex, Bruker) directly from positive blood culture (BacT/ALERT 3D, FN/FA vials; bioMérieux) in comparison to standard culture methodology (VITEK 2; bioMérieux) for species identification. RESULTS: A total of 62 consecutive positive blood cultures from immunosuppressed patients (solid organ or hematopoietic transplant recipients, or with febrile neutropenia) were analyzed. Culture yielded gram-negative bacteria (GNB) in 27/62 (43.5%) and gram-positive (GPB) in 35/62 (56.5%) vials. For GNB, the predominant species identified by MALDI-TOF and confirmed by VITEK were Escherichia coli (16/16 correctly identified) and Enterobacter cloacae (4/4), with a sensitivity and specificity of 92.6% and 100%, respectively. For GPB, predominant species were Staphylococcus aureus (3/3), coagulase-negative staphylococci (12/24), and Enterococcus faecium (6/6) with a sensitivity of 100%, 60%, and 100%, respectively. The median time from blood collection to species identification was 27.4 h with MALDI-TOF identification and 46.6 h with conventional methodology. CONCLUSION: Using MALDI-TOF directly from positive blood cultures allowed a shorter time to identification with high sensitivity and specificity in immunosuppressed patients.


Assuntos
Bacteriemia/diagnóstico , Doenças Transmissíveis/diagnóstico , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Estudos de Coortes , Doenças Transmissíveis/microbiologia , Humanos , Hospedeiro Imunocomprometido , Sensibilidade e Especificidade , Fatores de Tempo
8.
Int J Organ Transplant Med ; 5(1): 7-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25013673

RESUMO

BACKGROUND: Literature review suggests that adherence to immunosuppressive drugs may be lower in recipients of living than of deceased donor kidney grafts, possibly because of profile differences. OBJECTIVE: To compare the level of immunosuppressive adherence levels between patients with deceased and living (-related; -unrelated) donor grafts in Switzerland. METHODS: Using data from two similar cross-sectional studies at two transplant centers in Switzerland, the level of adherence between the two groups was compared. Medication adherence was assessed by self-report or electronic monitoring. Possible explanatory factors included age, beliefs regarding immunosuppressive drugs, depressive symptomatology, pre-emptive transplantation, and the number of transplants received, were also considered. Data were analyzed using logistic regression analysis. RESULTS: Unadjusted non-adherence odds were 2 to 3 times higher in living-related than deceased donor transplantation (ORs: 2.09-3.05; p<0.05). Adjustment for confounders showed that these differences were associated most with the younger age of living-related subjects and the belief that immunosuppressive drugs are less important for living-related donations. CONCLUSION: There is a lower immunosuppressive adherence in recipients of living-related donor kidneys, possibly owing to differences in patient profile (ie, health beliefs regarding their immunosuppressive needs), knowledge of which may enhance adherence if addressed.

9.
Transplant Proc ; 44(10): 2961-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23195006

RESUMO

Immunosuppressive maintenance therapy after kidney transplantation leads to various undesired side effects such as calcineurin inhibitor (CNI)-associated nephrotoxicity or elevated cardiovascular risk due to posttransplantation diabetes and hypertension. These effects show negative impacts on long-term allograft function as well as patient morbidity and mortality. Therefore, we used an immunosuppressive regimen with early corticosteroid withdrawal (ESW), maintenance therapy containing tacrolimus, sirolimus (SRL), and mycophenolate sodium for 3 months followed by a prospective randomized trial comparing a CNI free versus a low-dose CNI therapy. The primary endpoint was 6-month graft function. Among 75 patients, ESW was performed after 4 days in 65 patients. Over the following 3 months before randomization to CNI-free maintenance therapy, we experienced a high number (25%) of SRL discontinuations due to adverse events, including leukopenia, anemia, arthritis, and pneumonitis. In addition there were significantly more allograft rejection episodes in the CNI-free group (P = .017) during the study period leading to a switch from SRL to a CNI. Despite the higher rate of rejection episodes in the CNI-free groups, glomerular filtration rates (GFR) at 6 months were comparable between the study groups (P = .25). After 1 year only 9.2% (6/65) of all patients treated with SRL remained on this drug. Conclusion, there was an unacceptably high rate of SRL intolerance using an ESW and CNI-free immunosuppressive regimen combined with a significantly higher rate of rejection episodes.


Assuntos
Corticosteroides/administração & dosagem , Inibidores de Calcineurina , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/imunologia , Sirolimo/administração & dosagem , Adolescente , Corticosteroides/efeitos adversos , Adulto , Idoso , Distribuição de Qui-Quadrado , Esquema de Medicação , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Estudos Prospectivos , Sirolimo/efeitos adversos , Suíça/epidemiologia , Tacrolimo/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Am J Transplant ; 12(7): 1811-23, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22390571

RESUMO

Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.


Assuntos
Biomarcadores/urina , Quimiocina CXCL10/urina , Transplante de Rim , Nefrite Intersticial/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/urina , Transplante Homólogo
11.
Transpl Infect Dis ; 14(1): 57-63, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22093165

RESUMO

Ureteral stent insertion at the time of renal transplantation significantly decreases complications of urine leakage and obstruction, but bears an intrinsic risk of microbial colonization. Associated urinary tract infection (UTI) may pose a significant risk for graft infection and subsequent graft failure, in particular, during high-level immunosuppression in the early phase after transplantation. The aims of this prospective study were (i) to assess the frequency of microbial ureteral stent colonization (MUSC) in renal transplant recipients by sonication, (ii) to compare the diagnostic value of sonication with that of conventional urine culture (CUC), (iii) to determine biofilm forming organisms, and (iv) to investigate the influence of MUSC on the short-time functional outcome. A total of 80 ureteral stents from 78 renal transplant recipients (deceased donors n = 50, living donors n = 28) were prospectively included in the study. CUC was obtained prior to renal transplantation and at ureteral stent removal. In addition, a new stent sonication technique was performed to dislodge adherent microorganisms. CUCs were positive in 4% of patients. Sonicate-fluid culture significantly increased the yield of microbial growth to 27% (P < 0.001). Most commonly isolated microorganisms by sonication were Enterococcus species (31%), coagulase-negative staphylococci (19%), and Lactobacillus species (19%), microorganisms not commonly observed in UTIs after renal transplantation. The median glomerular filtraton rate (GFR) of the study population increases from 39 mL/min immediately after transplantation (time point A) to 50 mL/min 6 month post transplantation (time point B). In patients without MUSC, the GFR improves from 39 mL/min (A) to 48 mL/min (B) and in patients with MUSC from 39 mL/min (A) to 50 mL/min (B), respectively. In summary, MUSC in renal transplant recipients is common and remains frequently undetected by routine CUC, but colonization had no measurable effect on renal function.


Assuntos
Transplante de Rim/efeitos adversos , Sonicação/métodos , Stents/microbiologia , Ureter/cirurgia , Infecções Urinárias/microbiologia , Adulto , Biofilmes/crescimento & desenvolvimento , Meios de Cultura , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Urina/microbiologia
12.
Am J Transplant ; 11(6): 1302-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21486386

RESUMO

Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer-cell immunoglobulin-like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44-0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60-1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.


Assuntos
Centrômero , Infecções por Citomegalovirus/prevenção & controle , Transplante de Rim/efeitos adversos , Receptores KIR/genética , Telômero , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Am J Transplant ; 10(12): 2615-23, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21114642

RESUMO

Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus-associated nephropathy (PyVAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for decoy cells and, if positive, measure plasma BKV-loads. In a cohort of 203 consecutive renal transplantations performed from 2005-2008, 38 patients (19%) developed BKV-viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV-viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV-loads of ≥ 4 log(10) copies/ml (n = 17) and (iii) low BKV-viremia (n = 8). Clearance of BKV-viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV-loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow-up at 34 months (range 18-60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV-replication and reduction of immunosuppression is an effective strategy to preserve medium-term allograft function even in patients developing definitive PyVAN.


Assuntos
Vírus BK/isolamento & purificação , Terapia de Imunossupressão , Nefropatias/virologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adulto , Idoso , Vírus BK/genética , Creatinina , Feminino , Rejeição de Enxerto , Humanos , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade
14.
Am J Transplant ; 10(5): 1254-62, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20353473

RESUMO

Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.


Assuntos
Anticorpos/imunologia , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Doadores de Tecidos/estatística & dados numéricos , Protocolos Clínicos , Feminino , Humanos , Imunoglobulinas Intravenosas/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia
15.
Transpl Infect Dis ; 12(1): 54-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19804583

RESUMO

The growing need for organs and the scarcity of donors has resulted in an increased use of extended criteria donors. We report a case where a recipient of a cardiac graft was used as an organ donor. Death of the recipient occurred 9 days after transplantation and was attributed to presumed cerebral hemorrhage, which post mortem was diagnosed as invasive aspergillosis of the brain. One recipient of a kidney transplant lost the graft due to infection with Aspergillus fumigatus, whereas prompt initiation of therapy successfully prevented disseminated aspergillosis in the other recipients. Despite the pressure to extend the use of organs by lowering the acceptance criteria, organs should only be accepted if the cause of death of the donors is unequivocally explained.


Assuntos
Aspergilose/transmissão , Aspergillus fumigatus/isolamento & purificação , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Adulto , Idoso , Aspergilose/diagnóstico , Aspergilose/microbiologia , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Am J Transplant ; 8(6): 1312-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18444913

RESUMO

Viral infection is a common complication after kidney transplantation. The role of natural killer cells (NK cells) in this setting remains unknown. NK cells express activating and inhibitory killer cell immunoglobulin-like receptors (KIR). We analyzed whether activating KIR genes carried by kidney transplant-recipients influence the rate of viral infection during the first year after transplantation. In patients with a KIR A/A genotype (n = 40, KIR2DS4 only activating KIR) the rate of cytomegalovirus (CMV) infection and reactivation was 36%, as compared to 20% in transplant recipients with more than one activating KIR gene (KIR B/X genotype, n = 82, p = 0.04). Adjusting for other risk factors in Cox regression, the relative risk of B versus A genotype patients was 0.34 (95% CI 0.15-0.76, p = 0.009). The degree of protection increased with the number of activating KIR genes. Symptomatic CMV disease was only observed in four individuals, all carrying a KIR A/A genotype. As for viral infections other than CMV, and for bacterial infections, no KIR-linked protective effect could be detected. Also, graft function and the rate-rejection episodes were similar in KIR A/A and KIR B/X genotype individuals. This study supports a role for activating KIR in the control of CMV infection after kidney transplantation.


Assuntos
Infecções por Citomegalovirus/genética , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Proteínas Monoméricas de Ligação ao GTP/genética , Adulto , Idoso , Vírus BK , Infecções por Citomegalovirus/etiologia , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Polyomavirus/etiologia , Infecções por Polyomavirus/genética , Recidiva , Risco , Infecções Tumorais por Vírus/etiologia , Infecções Tumorais por Vírus/genética
18.
Am J Transplant ; 8(3): 616-26, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18294158

RESUMO

Valid assessment of immunosuppressive therapy non-adherence (NAH) is vital: NAH is associated with negative transplantation outcomes. We studied the diagnostic accuracy of assay, patient self-reports and clinicians' collateral reports and composite adherence scores using electronic monitoring (EM) as a reference standard. This cross-sectional study included a convenience sample of 249 adult kidney transplant recipients (Ktx) (female: 43.4%; mean age 53.6 [SD: 12.7], median 7 years [IQR: 9 years] post-Ktx). NAH was assessed using EM over 3 months (i.e. reference standard), assays of cyclosporine, tacrolimus, mycophenolat-mofetil, patients' self-reports and clinicians' collateral reports. The constructed composite adherence score included assay, self-reports and collateral reports. NAH's prevalence across the measurement methods was EM: 17.3%; assay: 33% (cyclosporine: 25.8%; tacrolimus: 35.1%; mycophenolat-mofetil: 40.2%); self-report: 12.4%; collateral reports: 24.9% and composite adherence score: 38.9%, respectively. The composite adherence score and collateral reports showed the highest and lowest sensitivities to NAH (72.1% and 15.8%, respectively). Specificity was highest for collateral reports of at least three clinicians (93.1%). Likelihood ratio of a positive test was 2.74 for composite adherence score. No measures showed high sensitivity alongside high specificity. Combining measures increased diagnostic accuracy, indicating the relevance of combined measures for clinical and research purposes.


Assuntos
Monitoramento de Medicamentos/métodos , Imunossupressores/sangue , Transplante de Rim , Recusa do Paciente ao Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Sensibilidade e Especificidade
19.
J Endourol ; 21(11): 1357-60, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18042030

RESUMO

BACKGROUND AND PURPOSE: Secondary vesicoureteral reflux (SVUR) after renal transplantation may cause recurrent urinary-tract infections (UTI) and loss of renal function. There are only a few reports on the endoscopic treatment of SVUR by transurethral injection therapy. This is the first report of transurethral injection of dextranomer/hyaluronic acid copolymer (Deflux; Q-Med Scandinavia, Uppsala, Sweden) to relieve SVUR after renal transplantation. PATIENTS AND METHODS: Between November 2003 and October 2005, four women were treated for SVUR with transurethral injections of dextranomer/hyaluronic acid copolymer. All patients had deterioration of renal function attributable to SVUR, recurrent UTI, or both. The mean follow-up was 29 months (range 16-38 months). RESULTS: Initially, SVUR was corrected in all patients. Recurrent SVUR made a second treatment necessary in two patients. Three patients had no signs of SVUR 15, 27, and 36 months after the treatment. Renal function remained stable in these patients, and two were free of UTI. One of the patients who received two Deflux injections developed a filiform stenosis of the distal ureter, which was corrected by ureteropyeloplasty with the native ureter. CONCLUSION: Transurethral injection therapy with Deflux is a minimally invasive treatment option for patients with SVUR after renal transplantation. A second treatment seems to be necessary in some cases. Complications such as ureteral obstruction may occur.


Assuntos
Dextranos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Transplante de Rim/efeitos adversos , Refluxo Vesicoureteral/tratamento farmacológico , Adulto , Cistoscopia , Dextranos/efeitos adversos , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Injeções , Pessoa de Meia-Idade , Recidiva , Uretra
20.
Transplant Proc ; 39(5): 1381-5, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17580144

RESUMO

UNLABELLED: We retrospectively compared perioperative donor outcomes and early complication rate of right- and left-sided retroperitoneoscopic living donor nephrectomy (RLDN). METHODS: From November 2001 to April 2006, we performed 118 RLDN. Including 24% (n = 28) right-sided RLDN and 76% (n = 90) left-sided RLDN. Perioperative results and the rate of adverse events were compared for both sides. RESULTS: We observed no significant difference in operation time, blood loss, warm ischemia time, or postoperative creatinine levels between right- and left-sided kidney donors. RLDN was successfully performed in 116 of 118 donors. One donor in each group had to be converted to an open approach. We observed one graft loss due to renal artery kinking in one recipient after left-sided RLDN. Two right donations needed a saphenous venous patch due to a short right renal vein (<2 cm). Overall, intraoperative and postoperative complications were comparable between the two donor groups. CONCLUSION: Right-sided RLDN provides comparable perioperative and postoperative results to those of left-sided RLDN. Our results demonstrated that groups with significant experience in RLDN can perform right living donor nephrectomy safely and efficiently with minimal invasiveness.


Assuntos
Doadores Vivos , Nefrectomia/métodos , Espaço Retroperitoneal/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/psicologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/efeitos adversos , Coleta de Tecidos e Órgãos/métodos
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