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1.
Am J Transplant ; 13(6): 1474-83, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23721552

RESUMO

Control of polyomavirus BK (BKV) is achieved by reducing immunosuppression allowing an effective BKV-specific T-cell response. The morphology of resolving BKV-associated nephropathy (PyVAN) has not been systematically investigated. Ninety-nine surveillance biopsies of 35 patients with BKV viremia treated exclusively by immunosuppression reduction were scored according to Banff criteria and grouped relative to BKV viremia as pre-, increasing, decreasing and post-BKV viremia. Thirty-four of 35 patients (97%) cleared BKV viremia after a median of 9 months posttransplantation. The tubulitis score, extent of tubules with intraepithelial lymphocytes, and interstitial inflammation significantly increased from the time of increasing to decreasing viremia. Tubulointerstitial inflammation, to a lower extent, persisted after clearance. The number of SV40+ tubules correlated with the BKV load in plasma, but SV40 immunohistochemistry was frequently negative (60%). During decreasing viremia, 31% of PyVAN cases were plasma cell-rich and 40% showed tubular HLA-DR expression. Compared to baseline 1 month posttransplantation, allograft function remained stable or improved in 29/35 patients (83%) after a median follow-up of 48 months. Within 1 year after clearance of BKV viremia, clinical rejection occurred in 2/35 patients (6%). Our data suggest that resolving PyVAN is typically characterized by a self-limiting acute interstitial nephritis, morphologically indistinguishable from interstitial rejection.


Assuntos
Rejeição de Enxerto/patologia , Nefropatias/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Infecções por Polyomavirus/patologia , Polyomavirus/isolamento & purificação , Infecções Tumorais por Vírus/patologia , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Rejeição de Enxerto/virologia , Humanos , Imuno-Histoquímica , Rim/virologia , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Transplante Homólogo , Infecções Tumorais por Vírus/virologia , Carga Viral , Adulto Jovem
2.
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
3.
Prilozi ; 33(2): 5-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23425866

RESUMO

From 1995 Polyomavirus (PyV) nephropathy (PVN) has played an important role in solid organ transplant recipients. The disease is caused by a DNA virus, usually the BK variant, more rarely JC virus. In immune incompetent patients either latent endogenous virus is reactivated, or donated virus can multiply. The frequency of PVN nephropathy (previously 10% or higher) is declining. The disease follows a stepwise course: viruria, viraemia, nephropathy. Nephropathy usually manifests itself during the first year after transplantation. The disease remains clinically silent for long periods, later progressive loss of renal function and renal failure occur. A major risk factor is therapy with potent immune suppressive agents. Morphologically, viral replication produces nuclear inclusions and necrosis, predominantly in the urothelium and tubular epithelium. Inflammation (T and B lymphocytes, monocytes/macrophages and granulocytes) accompanies necrosis. Progression is marked by tubular atrophy, interstitial fibrosis and transplant loss. The virus can be detected by the electron microscope and, better, by immunohistology (preferentially mAb against SV40 Large T antigen). It is often hard to differentiate PVN from an interstitial cellular rejection reaction (Banff 1 A/B). As no effective drug treatment exists, the disease must be diagnosed as early as possible and immune suppression reduced. Screening for polyomavirus reactivation is best done stepwise: search for urinary "Decoy cells" (PyV infected cells), PCR for PyV in the blood and in the case of reduced renal function, renal biopsy. Compliance with a stringent screening algorithm allows early detection and adequate treatment and prevents organ loss.


Assuntos
Nefropatias/patologia , Nefropatias/virologia , Transplante de Rim , Infecções por Polyomavirus/patologia , Polyomavirus/patogenicidade , Infecções Tumorais por Vírus/patologia , Vírus BK/patogenicidade , Biópsia , Rejeição de Enxerto/virologia , Humanos , Vírus JC/patogenicidade , Fatores de Risco
4.
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
5.
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
6.
Clin Nephrol ; 73(2): 122-30, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20129019

RESUMO

BACKGROUND: The impact of different therapy modalities on the outcome of Immunoglobulin A glomerulonephritis (IgAGN) in individual patient is not clear. We present preliminary results from the sequential application of renin-angiotensin system (RAS) inhibition and corticosteroids to discriminate the individual effect of both therapies. METHODS: Regardless of the degree of proteinuria, renal function and histological grading, patients with biopsy-proven IgAGN were treated with a standardized protocol. RAS inhibition was performed for 3 months. Thereafter, immunosuppressive therapy with prednisone (0.5 mg/kg body weight) on alternate days for 6 months was started. The primary endpoint was a maximal reduction of proteinuria (spot urine protein/ creatinine ratio (uPCR)), by RAS inhibition and by the combination of RAS inhibition and steroids. RESULTS: 10 patients were treated according to the protocol. During a median follow-up of 18 months, uPCR decreased from initial 230 mg/mmol (2 g/g) (median, interquartile range (IQR) 146 - 396) to 154 mg/mmol (1.4 g/g) (IQR 88 - 190) at 3 months during the RAS inhibition period (33% reduction, p = 0.01) and further to 31 mg/mmol (0.3 g/g) (IQR 21 - 71) until end of the steroid period at 9 months (80% reduction compared to uPCR at 3 month, p < 0.001). At the last F/U, uPCR (median) remained stable at 41 mg/mmol (0.4 g/g). The estimated glomerular filtration rate was stable during the whole observation period. CONCLUSIONS: Sequential RAS inhibition and steroid treatment leads to a continuous decrease in proteinuria, beyond the decrease produced by isolated RAS inhibition. Our data suggest independent effects of both, RAS inhibition and steroids, on the reduction of proteinuria in a small, non selected group of patients with IgAGN. The hypothesis that patients with IgAGN, regardless of the degree of proteinuria, renal function and histological grading, may benefit from combination therapy with maximal RAS inhibition and low dose corticosteroids now has to be confirmed in a randomized study.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Biópsia , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
7.
Transplant Proc ; 41(5): 1536-40, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19545674

RESUMO

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on various cell types and mediates homophilic cell adhesion. CEACAM1 plays an important role in cell morphogenesis and angiogenesis. Furthermore, CEACAM1 regulates adhesive activity of immune-competent cells, suggesting an additional role in inflammatory processes. METHODS: Therefore, in the present study the expression of CEACAM1 was analysed retrospectively in renal biopsies from kidney transplant recipients (stable graft [Ctr; n = 18], acute vascular rejection [AVR; n = 14], acute tubulointerstitial rejection [AIR; n = 9], and combined vascular and interstitial rejection [AVIR; n = 7]). Expression patterns of CEACAM1 were determined using immunohistochemistry and quantitative morphometry. RESULTS: All biopsy specimens from patients with stable grafts showed low CEACAM1 levels, suggesting a constitutive expression in renal transplants. In patients with acute rejection, CEACAM1 was markedly up-regulated. AVR revealed the highest tubular CEACAM1 levels (4.9 +/- 0.5% [AVR] vs 2.2 +/- 0.3% [Ctr] of tubular area; P < .05), whereas interstitial rejections showed the highest glomerular expressions (4.5 +/- 0.5% [AIR] vs 0.9 +/- 0.1% [Ctr] of glomerular area; P < .05). CONCLUSIONS: An up-regulated expression of CEACAM1 in tubular and/or glomerular cells is an indicator of acute inflammatory processes in biopsy specimens from patients with acute renal allograft rejections and, therefore, might be used as a new clinical marker.


Assuntos
Antígenos CD/genética , Moléculas de Adesão Celular/genética , Rejeição de Enxerto/genética , Adulto , Biópsia , Pressão Sanguínea , Cadáver , Feminino , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Imuno-Histoquímica , Glomérulos Renais/patologia , Transplante de Rim/imunologia , Transplante de Rim/patologia , Túbulos Renais/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos
8.
J Neurol ; 255(1): 77-88, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18204807

RESUMO

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.


Assuntos
Doenças Arteriais Cerebrais/patologia , Nefropatias/patologia , Hepatopatias/patologia , Doenças Retinianas/patologia , Doenças Vasculares/patologia , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Calcinose/patologia , Calcinose/fisiopatologia , Doenças Arteriais Cerebrais/fisiopatologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Imunossupressores/uso terapêutico , Nefropatias/fisiopatologia , Hepatopatias/fisiopatologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Masculino , Microcirculação/patologia , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Artéria Retiniana/patologia , Artéria Retiniana/fisiopatologia , Doenças Retinianas/fisiopatologia , Síndrome , Resultado do Tratamento , Doenças Vasculares/fisiopatologia , Vasculite/patologia , Vasculite/fisiopatologia , Vísceras/irrigação sanguínea , Vísceras/patologia , Vísceras/fisiopatologia
9.
Am J Transplant ; 7(3): 518-26, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17352710

RESUMO

The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15-21 July 2005. Major outcomes included the elimination of the non-specific term "chronic allograft nephropathy" (CAN) from the Banff classification for kidney allograft pathology, and the recognition of the entity of chronic antibody-mediated rejection. Participation of B cells in allograft rejection and genomics markers of rejection were also major subjects addressed by the conference.


Assuntos
Rejeição de Enxerto/diagnóstico , Falência Renal Crônica/diagnóstico , Transplante de Rim , Anticorpos/imunologia , Linfócitos B/imunologia , Doença Crônica , Diagnóstico Diferencial , Fibrose , Marcadores Genéticos , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Humanos , Rim/imunologia , Rim/patologia , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Transplante de Órgãos
10.
Am J Transplant ; 7(3): 626-32, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17352712

RESUMO

Preformed donor-specific HLA-antibodies antibodies (DSA) are a major risk for early antibody-mediated rejection (AMR). This prospective study evaluated the accuracy of pretransplant risk assessment using virtual crossmatching (virtualXM) (i.e. comparing HLA-typing of the donor with the recipient's HLA-antibody specificities determined by flow-beads). Sixty-five consecutive patients were stratified according to virtualXM results: patients without DSA (n= 56) were considered low risk and received standard immunosuppression; patients with DSA (n= 9) were considered high risk and received additional induction with anti-T-lymphocyte-globulin (ATG) and intravenous immunoglobulins. Despite induction therapy 4 of 9 patients with DSA (44%) had clinical/subclinical AMR, whereas only 2 of 56 patients without DSA (4%) (p = 0.002). Notably, one of these two patients had early AMR likely induced by non-HLA-antibodies; the other had subclinical AMR at month 6 consistent with de novo DSA. The results of virtualXM and retrospectively obtained flow-cytometric crossmatches (FCXM) (n= 59) were concordant in 51 patients (86%), four patients (7%) were virtualXM-/FCXM+ and none had AMR, four patients (7%) were virtualXM+/FCXM- and one had AMR. VirtualXM can accurately define absence or presence of DSA and may become an invaluable tool for organ allocation and pretransplant risk assessment. However, further studies need to address whether all HLA-antibodies detected by flow-beads are clinically relevant.


Assuntos
Anticorpos/análise , Citometria de Fluxo/métodos , Rejeição de Enxerto/diagnóstico , Teste de Histocompatibilidade/métodos , Transplante de Rim/imunologia , Adolescente , Adulto , Idoso , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Antígenos HLA-A/imunologia , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Sensibilidade e Especificidade , Doadores de Tecidos
12.
Am J Transplant ; 7(3): 512-7, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17250556

RESUMO

A 1-day symposium on the application of protocol biopsies in renal transplantation was held in Boston, 21 July 2006. Representatives from centers with extensive experience in the use of protocol biopsies for routine patient care and research reported results on the pathological findings and their value in patient management. The consensus was that protocol biopsies, in experienced hands, are a safe and valuable means of detecting subclinical disease that can benefit from modification of therapy. Furthermore, molecular studies reveal evidence of activity or progression not readily appreciated by histological techniques. Wider application is expected in multicenter clinical trials to predict and validate outcomes. The principal barrier to wider use of protocol biopsies is knowledge of the benefits of intervention.


Assuntos
Biópsia/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Complicações Pós-Operatórias/diagnóstico , Biomarcadores/análise , Ensaios Clínicos como Assunto , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Assistência ao Paciente/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia
13.
Oncogene ; 26(17): 2525-34, 2007 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-17146446

RESUMO

Molecular mechanisms of prostate cancer progression are poorly understood. Here, we studied gene amplification of the large conductance calcium-activated potassium channel alpha subunit (KCNMA1), which is located at the chromosomal region 10q22. Fluorescence in situ hybridization (FISH) revealed KCNMA1 amplification in 16% of 119 late-stage human prostate cancers and in the hormone-insensitive prostate cancer cell line PC-3. In contrast, KCNMA1 amplification was absent in 33 benign controls, 32 precursor lesions and in 105 clinically organ-confined prostate cancers. Amplification was associated with mRNA and protein overexpression as well as increased density of BK channel protein and beta-estradiol-insensitive BK currents in PC-3 cells as compared to non-amplified control cell lines. Specific blockade of BK channels by iberiotoxin or RNA(i) significantly inhibited K(+) currents and growth of PC-3 cells. The data demonstrate that 10q22 amplification drives KCNMA1 expression and cell proliferation. Thus, KCNMA1 qualifies as a promising diagnostic and therapeutic target in patients with prostate cancer.


Assuntos
Proliferação de Células , Amplificação de Genes/fisiologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Cromossomos Humanos Par 10 , Humanos , Masculino
14.
Ther Umsch ; 63(9): 609-14, 2006 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-17048177

RESUMO

BK polyomavirusnephropathy (BKN) is a serious complication of the potent immunosuppressive therapies in renal allograft recipients. BKN occurs in 5% of the patients and leads to allograft loss in approximately 50% of those affected. Early detection of BKN improves the chances to retain the allograft by allowing immediate intervention. Urine cytology is a simple, cheap and reliable method for early identification of patients at risk for BKN, together with BK DNA analysis in the serum. BK virus causes a spectrum of morphologic changes of tubular and urothelial cells that can be viewed online at http://vmic.unibas.ch/patho/seminar/index.html. These BK infected cells are called "decoy cells" as they can mimic the features of bladder carcinoma cells. In addition, certain morphologic features of the urinary sediment including tubular cells and lymphocytes can anticipate renal rejection. Historically, urinary cytology was important to screen patients with allograft for analgetic nephropathy for malignant cells, since they were at greatly increased risk of urothelial carcinoma.


Assuntos
Rejeição de Enxerto/patologia , Rejeição de Enxerto/urina , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/urina , Urina/citologia , Humanos , Infecções por Polyomavirus/etiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica
15.
Am J Transplant ; 6(8): 1963-7, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16889550

RESUMO

Renal calcineurin inhibitor (CNI) toxicity is a frequent side effect of immunosuppression with CNIs in solid organ transplantation, leading to acute and chronic renal failure. Acute CNI toxicity is due to vasoconstriction of the vasa afferens and efferens and vacuolization of smooth muscle cells with medial hyalinosis, leading to vessel lumen narrowing. Our case had an acute renal failure 8 months after deceased donor kidney transplantation under treatment with tacrolimus, sirolimus and prednisolone. In Doppler sonography, we observed reverse diastolic intrarenal blood flow, reflecting intense vessel narrowing. There were histological signs of acute CNI toxicity. Within days of reducing the tacrolimus trough level, renal function improved markedly and Doppler sonography showed orthograde intrarenal blood flow. This is the first case of functional, Doppler sonographic evidence for CNI-induced, rapidly reversible narrowing of intrarenal vessels. This case illustrates the potential role of tacrolimus and sirolimus dosing in combination therapy to produce severe intrarenal vasoconstriction.


Assuntos
Inibidores de Calcineurina , Nefropatias/induzido quimicamente , Transplante de Rim , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos , Biópsia , Feminino , Humanos , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Pessoa de Meia-Idade , Sirolimo/farmacologia , Tacrolimo/farmacologia , Ultrassonografia Doppler
16.
Am J Transplant ; 6(6): 1285-96, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16686753

RESUMO

A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days post-transplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals. In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Doenças Vasculares/imunologia , Doença Aguda , Animais , Biomarcadores/sangue , Doença Crônica , Modelos Animais de Doenças , Endarterite/imunologia , Endarterite/patologia , Feminino , Transplante de Rim/mortalidade , Transplante de Rim/patologia , Macaca fascicularis , Masculino , Período Pós-Operatório , Primatas , Análise de Sobrevida , Doenças Vasculares/etiologia
17.
Am J Transplant ; 6(6): 1444-50, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16686769

RESUMO

Arteriolar hyaline thickening (AH) is the most characteristic lesion of chronic calcineurin inhibitor nephrotoxicity. This study was performed to compare the inter-observer reproducibility of AH scoring using Banff criteria and a newly proposed criterion. Forty-five nonprotocol post-transplant biopsies from 38 patients immunosuppressed with tacrolimus or cyclosporine A (CsA) were included. The severity of AH was blindly scored by three observers. According to the new criteria, AH is graded based on circular vs. noncircular involvement and the number of arterioles involved. The kappa statistics were used to assess the inter-observer reproducibility. Twenty-seven (60%) biopsies showed AH. The AH grades by both criteria were correlated with serum creatinine at biopsy and inversely correlated with estimated glomerular filtration rate (GFR) (p < 0.05). The recent AH criteria improved the mean pairwise agreement (79.4% vs. 68%) and the overall kappa value (0.67 vs. 0.52) (p = 0.02) compared to Banff criteria. The mean inter-slide variation using Banff and the new criterion were 23% and 27.6%, respectively (p > 0.05). The new AH criterion results in better inter-observer reproducibility, and is clinically validated against serum creatinine and estimated GFR. There is substantial intra-biopsy variation, therefore, evaluation of more than one section is crucial to determine severity of arteriolar damage more accurately.


Assuntos
Arteríolas/patologia , Ciclosporina/efeitos adversos , Transplante de Rim/patologia , Tacrolimo/efeitos adversos , Adolescente , Adulto , Idoso , Arteríolas/efeitos dos fármacos , Biópsia , Criança , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Transplante Homólogo
18.
Clin Nephrol ; 65(5): 324-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16724652

RESUMO

AIM: Reactivation of latent BK virus in kidney-transplanted patients results in severe graft dysfunction. The role of retroviruses infecting also latently target cells is not investigated so far in this setting. We determined the presence or induction of retroviruses in sera of immunosuppressed patients with renal allografts at the timepoint of organ rejection or ongoing polyomavirus nephropathy. PATIENTS AND METHODS: Sera of patients with acute kidney rejection or polyomavirus nephropathy (n=25) and controls (n=8) were tested for reverse transcriptase activity by the ultrasensitive product enhanced reverse transcriptase (PERT) assay. In parallel, kidney biopsies were investigated for histological signs of kidney rejection or polyomavirus nephropathy confirmed by either immunofluorescence or immunohistochemistry. RESULTS: None of the investigated sera, specifically those of patients with ongoing BK virus nephropathy, indicated reverse transcriptase activity. CONCLUSION: Our results do not support the idea of the induction of known or unknown retroviruses in patients with kidney transplantation, even under highly immunosuppressive therapies.


Assuntos
Rejeição de Enxerto/etiologia , Rejeição de Enxerto/virologia , Transplante de Rim/efeitos adversos , Retroviridae/isolamento & purificação , Retroviridae/fisiologia , Adulto , Vírus BK/isolamento & purificação , Vírus BK/patogenicidade , Vírus BK/fisiologia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Infecções por Polyomavirus/etiologia , DNA Polimerase Dirigida por RNA/sangue , Retroviridae/patogenicidade , Transplante Homólogo , Ativação Viral
19.
Kidney Int ; 69(11): 1961-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16598195

RESUMO

Complement C2 receptor inhibitor trispanning (CRIT) is a novel human complement regulatory cell surface receptor. It binds the human complement protein C2 and blocks the classical pathway of complement activation, thus protecting the cell against complement attack. CRIT expression in the kidney was analyzed by immunohistochemistry and in situ hybridization. Normal kidney and renal biopsies of patients with different nephropathies were studied. In glomeruli, CRIT protein was expressed only in podocytes. CRIT was also detected in endothelial cells of arterioles and arteries, but not of veins and peritubular and glomerular capillaries. A homogeneous and marked upregulation of CRIT was observed in podocytes in membranous nephropathy (MN). In focal and segmental glomerulosclerosis (FSGS) and minimal change disease, CRIT was downregulated in glomeruli with a loss of the staining in sclerotic lesions of FSGS. No specific changes were observed in the other nephropathies studied. However, podocytes showed in all pathologies a redistribution of CRIT in the cell bodies of 'activated' podocytes. The intensity of mRNA transcription correlated directly with the protein staining in the normal kidney and in MN. These data indicate that CRIT is expressed in the normal human kidney essentially by glomerular podocytes and arterial endothelial cells. The podocyte CRIT expression is upregulated in MN, which is in strong contrast with the known loss of podocyte complement receptor 1. CRIT might represent the last line of defense against complement aggression in MN, and the upregulation of CRIT in 'activated' podocytes might represent a similar self-defense mechanism.


Assuntos
Proteínas de Transporte/biossíntese , Glomerulonefrite Membranosa/imunologia , Rim/imunologia , Podócitos/metabolismo , Regulação para Cima , Humanos
20.
Pathologe ; 27(6): 469-76, 2006 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-16096757

RESUMO

Only recently fast-paced developments in computer technology allowed for the digitization of complete histologic slides. The resulting virtual slides may be viewed via webbrowser by any number of pathologists or students independent of time and location. Usage of a virtual microscope simply requires a computer workstation with a fast internet connection, which opens this technology to a broad public. A virtual microscopy system consists of three components: acquisition, server and client. Such systems are under development by different commercial and academic bodies worldwide. We have developed a virtual microscope system called vMic (http://www.vmic.unibas.ch) which provides virtual slides of very high image quality. Several successfully held online slide seminars and a histology course for students in dentistry are freely accessible in the internet. With the commercial availability of ultra rapid and easy-to-use slide scanners and the fast improvements of technology virtual microscopy will offer many applications in teaching, research and diagnostics. Thanks to additional functionalities, real microscopes will most likely be replaced by computer workstations in a couple of years.


Assuntos
Microscopia/métodos , Interface Usuário-Computador , Bases de Dados Factuais , Humanos , Internet , Microscopia/normas , Patologia
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