RESUMO
INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.
Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim , Receptor Tipo 1 de Angiotensina/imunologia , Receptor de Endotelina A/imunologia , Adulto , Feminino , Antígenos HLA/imunologia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to determine the prevalence and risk factors responsible for the occurrence and progression of chronic allograft dysfunction (CAD) among patients treated in our transplant center. MATERIAL AND METHODS: Retrospective analysis included 637 kidney allograft recipients transplanted between 1990 and 2003 with functioning graft for at least 1 year. CAD was diagnosed based on increased creatinine concentration ≥ 2 mg/dL, occurrence of proteinuria, and worsening of arterial hypertension. In immunosuppressive treatment, 50% of patients received cyclosporine A (CsA), azathioprine, and prednisone; 25% received CsA, mycophenolate mofetil (MMF), and prednisone; whereas 20% received tacrolimus, MMF, and prednisone. The influence of immune and non-immune factors before and after transplantation on the occurrence and progression of CAD was analyzed. RESULTS: CAD was diagnosed in 43.1% of patients within 10 years after kidney transplantation. CAD development considerably worsened the actual 10-year survival rate of patients (80% versus 92%) and the graft (42% versus 92%). The following factors had the greatest influence (as confirmed with multivariate regression analysis) on CAD progression: proteinuria (odds ratio [OR]: 11.3; P < .0001), serum creatinine concentration > 1.5 mg/dL at 12th month (OR: 3.5; P < .0001) and 24th month (OR: 6.69; P < .0001), cytomegalovirus (CMV) infections (OR: 3.15; P < .0001), and male gender of recipients (OR: 1.48; P < .04). In the CAD patients, acute rejection episodes, delayed graft function, urinary tract infections, and hepatitis C virus (HCV) infections were statistically significantly more often observed compared with the group of patients with stable renal function (reference group). Moreover, in the CAD group, donors were older and recipients younger. The CAD patients had higher arterial pressure and uric acid concentration. CONCLUSIONS: During the 10-year follow-up, chronic renal allograft dysfunction developed in 43.1% of patients. Proteinuria, serum creatinine level >1.5 mg/dL at 12th and 24th month, and CMV infections were identified as the most significant CAD progression factors. CAD had detrimental effects both on graft and patient survival rates.
Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim , Adulto , Doença Crônica , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transplante HomólogoRESUMO
BACKGROUND: Detection of antibody-mediated injury is becoming increasingly important in post-transplant patient care. The role of donor-specific anti-human leukocyte antigen (HLA) antibodies in kidney transplant damage is known, whereas the significance of non-HLA antibodies remains an unresolved concern. The aim of the study was to determine the presence and influence on renal function of non-HLA and anti-HLA antibodies in stable patients at 5 years after kidney transplantation. METHODS: We evaluated the antibodies in 35 consecutive patients with stable renal function at 5 years after transplantation. RESULTS: Pretransplant screening for donor-specific antibodies by CDC cross-matches was negative in all patients. Anti-endothelial cell antibodies (AECA), anti-angiotensin II type 1 receptor antibodies (anti-AT1R), and anti-endothelin receptor antibodies (anti-ETAR) were assayed as non-HLA antibodies. Non-HLA antibodies were observed in 12 (34%) patients, including AECA (n = 5; 14%), anti- AT1R (n = 6; 17%), anti-ETAR (n = 4; 11%), and both anti-AT1R and anti-ETAR (n = 3). Among 13 (37%) patients with anti-HLA antibodies, 7 also had both non-HLA antibodies: AECA (n = 1), anti-AT1R (n = 3), and anti-ETAR (n = 3). The antibody-negative group (n = 13) showed significantly better renal function than the antibody-positive group (non-HLA and/or anti-HLA; n = 22). Biopsy-proven acute rejection had occurred in 2 of 13 (15%) antibody-negative versus 8 of 22 (36%) antibody-positive patients. These preliminary data revealed an high prevalence of autoantibody and alloantibody production among stable patients at 5 years after kidney transplantation. CONCLUSION: Simultaneous production of these antibodies and their association with reduced renal function suggests that active humoral immune responses are poorly controlled by immunosuppression.
Assuntos
Autoanticorpos/sangue , Antígenos HLA/imunologia , Transplante de Rim , Adulto , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Extracorporeal photopheresis (ECP) is considered a promising immunomodulatory therapy of acute allograft rejection in organ transplantation and graft-versus-host disease. Our aim was to investigate the biological responses of 10 patients who underwent kidney transplantation with ECP as prophylactic treatment. They received conventional immunosuppressive therapy plus ECP immediately after transplantation: 12 to 16 applications over the course of 2.5 months. ECP procedures were performed using an automated system for leukocyte separation and photoactivation with methoxsalen. All recipients were followed by estimated glomerular filtration rate (eGFR) and peripheral T, B, natural killer, T-regulatory (Treg) and dendritic cells (DC) counts and phenotypes. An acute rejection episode appeared in one control group recipient. The ECP group showed a positive trend to an higher GFR at months 3 (53±11 vs 47.1±9; P=.17) and 6 (67.5±10 vs 53.6±3; P=.03, Wilcoxon test). An increased percentage of Treg (CD3+ CD4+ CD25+) among the total CD3 cell count (4.9%±1% to 9.4%±15%) as well as inducible Treg (CD3+ CD8+ CD28-) was observed among CD3 cells (3.3%±3% to 11.8%±8%, P=.025) within 3 months of ECP treatment. A significant difference in the percentage of Treg was noted at month 3 (completed ECP) between the ECP and the control groups (9.4%±15% vs 3%±1%; P=.01). Addition of ECP to standard immunosuppression was associated with a significantly higher GFR at 6 months and with a significant increase in natural Treg among CD3 cells.
Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Rim/imunologia , Fotoferese , Adulto , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Humanos , Imunomodulação , Transplante de Rim/fisiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Fatores de TempoRESUMO
Due to its anatomical location the popliteal artery is exposed to injury during surgical procedures in the region of the knee joint, in particular during high-level corrective osteotomies of the proximal tibial epiphysis. Nevertheless, posttraumatic (iatrogenic) pseudoaneurysm constitutes a very rare complication of the procedure. Only few reports of such complication have been published and they were usually connected with lateral tibial osteotomy - the accidents after medial osteotomy are seldom. The complication we report was observed in a 52-year-old female patient after corrective osteotomy of the medial portion of the proximal tibial epiphysis. The complication was diagnosed 7 days after surgery on US-examination and subsequently confirmed by emergently performed angio-CT. The patient was referred for urgent reconstructive surgery. No significant complications were observed, neither postoperatively nor during follow-up visits.
Assuntos
Falso Aneurisma/etiologia , Doença Iatrogênica , Osteotomia/efeitos adversos , Artéria Poplítea/lesões , Tíbia/cirurgia , Lesões do Sistema Vascular/etiologia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Epífises/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Reoperação , Veia Safena/transplante , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/cirurgiaRESUMO
Chemokines induced during an acute immune alloresponse cause cellular infiltration of the allograft. These chemokines and cells are excreted with urine. The aim of the study was to assess the diagnostic utility of urinary excretion of monocyte chemotactic peptide-1 and certain cells involved in infiltration i.e. CD3+, CD64+ and HLA-DR+ cells. The study entailed 35 patients with acute renal rejection and 65 with a stable graft function. Urinary sediments were prepared by means of cytospin and stained with anti-CD3, anti-CD64, anti-HLA-DR labeled monoclonal antibodies. Urinary expression of MCP-1 was assayed by ELISA. In the patients with acute rejection MCP-1 level was ten-fold higher than in the patients with a stable graft function (6.1+/-3.4 vs 0.6+/-0.4 ng/mg creatinine). The number of CD3+ cells was over 5 times higher than in the non-rejection patients (13.4+/-4.6 vs 2.5+/-2.2). The number of HLA-DR+ cells was 6 times higher in the acute rejection patients (15.7+/-5.9 vs 2.5+/-2.7). The number of CD64+ cells was significantly increased in the patients during an acute rejection episode (p<0.0001). CD3+, HLA-DR+ and CD64+ cell counts strongly correlated with urine excretion of MCP-1. The counts of CD3+ and HLA-DR+ cells correlated with Banff score. The assessment of MCP-1 as well as CD3+, CD64+ and HLA-DR+ cells can provide a useful non-invasive device for the diagnosis of acute rejection. A sole assay of HLA-DR+ cell excretion provides enough specificity and sensitivity for the routine monitoring of patients after kidney transplantation, saving costs and time.
Assuntos
Quimiocina CCL2/urina , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/urina , Transplante de Rim/imunologia , Urina/citologia , Adulto , Idoso , Biomarcadores/urina , Complexo CD3/análise , Creatinina/urina , Feminino , Antígenos HLA-DR/análise , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de IgG/imunologia , Receptores de IgG/metabolismoRESUMO
Fabry disease, an X-linked recessive glycolipid storage disease, is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A), which cleaves a fatty substance called globotriaosylceramide (GL3). The abnormal storage of GL3 in blood vessel walls leads to ischemia and necrosis, particularly in blood vessels of the skin, kidneys, heart, brain, and nervous system. The aim of our study was to present the results of cadaveric kidney transplantation with enzyme alpha-Gal A therapy in a patient with Fabry disease. The patient was diagnosed with Fabry disease at the age of 33 years, based on enzymatic tests. Renal manifestations occurred a year later as proteinuria. At the age of 35 years, the glomerular filtration rate (GFR) was within the normal range. The patient received supplemental enzyme treatment with alpha-Gal (1 mg/kg every 2 weeks). At 3 months after starting supplementation, renal function worsened with serum creatinine levels at 1.7 to 1.8 mg/dL. The following months of supplementation (alpha-Gal 1 mg/kg) concurred with progressive renal dysfunction. After 27 months of supplementation at 37 years, with a creatinine value of 5.5 mg/dL, hemodialysis began and months later the patient received a cadaveric kidney graft. The patient no longer required dialysis. On postoperative day 5 the serum creatinine was 3.9 mg/dL; on day 7, 2.2 mg/dL; on day 14, 1.5 mg/dL. Enzyme supplementation began on posttransplant day 13. Renal graft function has been good during 5 months of observation with creatinine levels at 1.2 to 1.3 mg/dL. The treatment does not interfere with tacrolimus metabolism. Simultaneous chronic enzyme supplementation is the optimal treatment in the fifth stage of end-stage renal disease in Fabry disease.
Assuntos
Doença de Fabry/cirurgia , Transplante de Rim , Rim/enzimologia , alfa-Galactosidase/metabolismo , Adulto , Creatinina/sangue , Humanos , Rim/patologia , Nefropatias/etiologia , Nefropatias/cirurgia , MasculinoRESUMO
Portal vein thrombosis (PVT) after orthotopic liver transplantation (OLT) is a life-threatening complication associated with a high rate of graft loss and patient death, with reported incidence of 1% to 2% in adults. We report a case of an early PVT after OLT complicated by hepatic infarctions in the liver graft. After surgical thrombectomy and restoration of the portal inflow, hepatic infarctions resolved spontaneously within 6 months, which was confirmed by computed tomography.
Assuntos
Infarto/cirurgia , Transplante de Fígado/efeitos adversos , Veia Porta , Complicações Pós-Operatórias/cirurgia , Humanos , Infarto/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Trombectomia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Antiproliferative and non-nephrotoxic properties of sirolimus have been exploited for treatment of patients with chronic graft dysfunction. In this paper we point to the possible association of nephrotic syndrome and renal impairment with rapid conversion from cyclosporine (CsA) to sirolimus in patients with chronic nephropathy. Five male patients, ages 34 to 56 years, with chronic renal failure in the course of glomerulonephritis, were transplanted between 1997 and 1999. For the first 49 to 65 months, the immunosuppressive regimen consisted of CsA, azathioprine (AZA), and prednisone. Thereafter, due to chronic nephropathy evidenced by biopsy, conversion to sirolimus was performed with sharp withdrawal of CsA. The serum creatinine level prior to conversion was 1.9 +/- 0.3 mg/dL. Trace to 86 mg/dL proteinuria was found in 3 patients, while 2 patients had about 200 mg/dL. After 2 to 4 months of sirolimus treatment the proteinuria progressed (558 +/- 183 mg/dL); edema, hypoproteinemia, hypoalbuminemia, and hyperlipidemia developed; and the serum creatinine increased to 3.5 +/- 0.8 mg/dL. Biopsies performed in three patients revealed new pathologic changes. After 4 to 5 months, we performed reconversion to calcineurin inhibitor. Proteinuria decreased to 0 to 150 mg/dL; nevertheless the serum creatinine was continuously rising. Six to 15 months after the conversion, 3 patients returned to dialysis. The fourth patient, who was earlier reconverted, has a serum creatinine level of 2.0 mg/dL after 15 months. In conclusion, conversion from CsA to sirolimus may induce nephrotic syndrome with progressive deterioration of renal function. Converted patients require careful monitoring of proteinuria and renal function. Early reconversion to calcineurin inhibitor may prevent progressive deterioration of graft function.
Assuntos
Ciclosporina/uso terapêutico , Transplante de Rim/patologia , Nefrose/induzido quimicamente , Proteinúria/induzido quimicamente , Sirolimo/efeitos adversos , Adulto , Albuminúria/induzido quimicamente , Azatioprina/uso terapêutico , Colesterol/sangue , Creatinina/sangue , Quimioterapia Combinada , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Testes de Função Renal , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Nefrose/urina , Transplante Homólogo/imunologia , Transplante Homólogo/patologia , Triglicerídeos/sangueRESUMO
Since the incidence of transplant renal artery stenosis (TRAS) in renal allografts varies from 1% to 23%, we sought to examine its incidence, to analyze treatment options, and to ascertain its outcomes. Retrospective analysis of 793 kidney allograft recipients transplanted between 1996 and 2004 revealed an incidence of 0.9% (n = 7). Time from kidney transplantation to the first symptoms varied from 1 week to 3 years (median, 4 months). Three patients experiences refractory hypertension and six patients developed allograft dysfunction. Screening color Doppler ultrasonography showed hemodynamic changes in six patients with the definitive diagnosis confirmed by angiography in all patients. One patient with an anastomotic stenosis was treated with a surgical operation and six patients, percutaneous transluminal angioplasty (PTA), with stenting in three cases. Both surgical as well as PTA treatment were successful in all but one patient, who underwent PTA alone, developed chronic renal insufficiency necessitating hemodialysis and finally lost his allograft. In the other patients all symptoms resolved after treatment and the patients are doing well with functioning allografts. Although TRAS was an uncommon complication, if recognized promptly it could be treated by surgery or PTA with a high success rate.
Assuntos
Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Obstrução da Artéria Renal/epidemiologia , Adulto , Angioplastia com Balão , Humanos , Incidência , Pessoa de Meia-Idade , Polônia/epidemiologia , Obstrução da Artéria Renal/cirurgia , Obstrução da Artéria Renal/terapia , Estudos RetrospectivosRESUMO
The aim of the study was to assess impaired tubular phosphate reabsorption and renal function among patients on cyclosporine- or tacrolimus-based immunosuppression for 2 years after kidney transplantation. Among 60 cadaveric kidney allograft recipients observed for 48 months, 40 received cyclosporine, azathioprine, and prednisone (group A and B). Group C consisted of 20 patients receiving tacrolimus with steroid withdrawal at 3 months after transplantation. Renal function and calcium-phosphate metabolism-iPTH, 25-OHD, 1,25(OH)(2)D concentration, phosphate reabsorption (TRP; mmol/L), and tubular maximum phosphate reabsorption per glomerular filtration rate (TmPO(4)/GFR; mmol/L)-were assessed at 1, 6, 12, 18, and 24 months (groups A and C) or 24, 30, 36, 42, and 48 months (group B). Renal function after 24 months of observation was significantly better among tacrolimus-treated patients (serum creatinine concentration mumol/L; C: 94.6 +/- 16.8 vs A: 110.5 +/- 22.1 vs B: 121.1 +/- 30.9; P < .05). Among tacrolimus-treated recipients, TRP and TmPO(4)/GFR remained within normal values during the whole observation period. In groups A and B, TRP improved during the first year of observation; after 2 years it reached values observed in group C (TRP: A: 0.67 +/- 0.1; B: 0.72 +/- 0.13; C: 0.76 +/- 0.07; P = NS), whereas TmPO(4)/GFR remained low in group A after 2 years (A: 0.78 +/- 0.19; B: 0.91 +/- 0.25; C: 0.94 +/- 0.15; P < .05). Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared with cyclosporine-treated recipients. Tacrolimus-based immunosuppression led to better kidney allograft function during 2-year observation.
Assuntos
Ciclosporina/uso terapêutico , Testes de Função Renal , Transplante de Rim/fisiologia , Túbulos Renais/metabolismo , Fosfatos/metabolismo , Tacrolimo/uso terapêutico , Adulto , Cadáver , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Creatinina/sangue , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão/métodos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Estudos Retrospectivos , Doadores de TecidosRESUMO
The role of cytomegalovirus (CMV) disease to induce chronic nephropathy using new immunosuppressive regimens is debated. This study sought to assess the influence of CMV disease on early and late graft function in relation to immunosuppressive therapy. Among 456 renal recipients transplanted from 1997 to 2003, 95 were diagnosed with CMV disease on the basis of clinical symptoms and the presence of pp65 protein. The patients were divided into 2 groups according to their immunosuppressive regimen: group I included 43 patients treated with cyclosporine (CsA), azathioprine (AZA), and prednisone (P); group II, 52 patients treated with calcineurin inhibitor (CI), mycophenolate mofetil (MMF), and P. A control group of 90 CMV disease-free renal recipients were transplanted in 2001. CMV disease occurred in 20.8% of renal recipients: 14.8% from group I and 25.5% from group II. CMV disease was diagnosed in 73 patients (76.8%) before the third month after transplantation. An acute rejection episode (ARE) appeared in 42 patients, of whom 31 had CMV disease diagnosed within 1 month after ARE, while 5 before an ARE. In six patients ARE was not time related to CMV disease. The serum creatinine values at 6 months after transplantation were significantly higher among the CMV versus control groups: 1.69 and 1.76 vs 1.49 (P < .05). In patients with ARE and CMV disease, the serum creatinine value was also higher at 6 and 12 months after transplantation compared with patients without an ARE (P < .03). One- and 3-year graft survival rates were 95.1% and 83.7% in group I versus 93.4% and 86.5% in group II versus 95.4% and 90.2% in the control group. In conclusion, CMV disease showed a negative impact on early graft function independent of the immunosuppressive regimen, an effect that was emphasized by an ARE.
Assuntos
Infecções por Citomegalovirus/etiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/virologia , Adulto , Feminino , Rejeição de Enxerto/epidemiologia , Teste de Histocompatibilidade , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
In some patients polyomavirus replication induces chronic tubulointerstitial inflammation in the transplanted kidney. The aim of this study was to investigate whether immunocytological urinalysis and monocyte chemoattractant protein-1 (MCP-1) assays could be used for an early diagnosis of nephropathy for patients with polyomavirus replication. We analyzed 1189 urine sediments from 174 renal allograft recipients who were transplanted between 2000 and 2005. Decoy cells were identified by an immunofluorescence method using specific antibodies (JC/BK monoclonal antibody). A similar method was used to detect CD3(+), CD14(+), and HLA-DR(+) cells with appropriate antibodies. The urinary excretion of MCP-1 was assayed by enzyme-linked immunosorbent assay. The results of urine sediment analysis and MCP-1 concentrations were compared with those of patients with stable graft function (control group n = 65). In 17 patients (10%) decoy cells were identified in urine. In 12 patients polyomavirus DNA was detected in plasma or urine by a polymerase chain reaction method. Polyomavirus nephropathy was diagnosed in eight patients by the presence of intranuclear viral inclusions or immunohistochemical staining with SV40 large T-antigen specimens from a renal biopsy, as well as by clinical and histopathological evidence (group I). Polyomavirus replication was diagnosed in four patients by urinary excretion of decoy cells and polyomavirus DNA detection (group III). In five patients only decoy cells were found. The patients of groups I and II showed an increased number of CD3, CD14, HLA-DR surface antigen-positive cells and greater excretion of MCP-1 compared with the control group (P < .02). The number of excreted cells was higher among patients with more severe infiltration. The results of patients from group III were similar to the control group. In conclusion, increased excretion of cells with CD3, CD14, and HLA-DR surface antigens and of MCP-1 were associated with intragraft tubulointerstitial inflammation in patients with polyomavirus nephropathy. Asymptomatic polyomavirus replication was associated with hidden tubulointerstitial inflammation. Monitoring cell excretion and chemokine content may be utilized for early detection of polyomavirus-induced nephropathy.
Assuntos
Quimiocina CCL2/urina , Transplante de Rim/fisiologia , Polyomavirus/fisiologia , Adulto , Antígenos CD/urina , Feminino , Antígenos HLA-D/urina , Antígenos HLA-DR/urina , Humanos , Imuno-Histoquímica/métodos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Polyomavirus/isolamento & purificação , Estudos Retrospectivos , Replicação ViralRESUMO
The aim of this study was to evaluate the impact of sirolimus and cyclosporine (CsA) combined therapy on the incidence and duration of delayed graft function (DGF), and the impact of the latter on 1-year graft function. The study entailed 23 cadaveric renal recipients treated with sirolimus-CsA-prednisone regimen (sirolimus group). The reference group entailed 23 patients treated with CsA-azathioprine-prednisone. In the sirolimus group the frequency of DGF was 39% and was essentially the same as in reference group (34.8%). The duration of DGF was significantly longer in SRL group and lasted 21.2 +/- 12.2 days versus 6.8 +/- 2.5 in reference group (P = .004). Serum creatinine level decreased below 3.0 mg/dL after 36 +/- 22 days in sirolimus group versus 16.8 +/- 6 days in reference group (P < .04). Cold ischemia was slightly longer and donors were older in DGF patients in both groups. Sirolimus dose during first month was higher in DGF patients (3.5 versus 2.6 mg), whereas level of CsA was lower (230 versus 310 ng/mL). Biopsy-proven acute rejection (AR) occurred in most of DGF patients and during the DGF period. Serum creatinine level at the 12th month posttransplant was higher in DGF versus non-DGF patients (2.0 +/- 0.5 versus 1.5 +/- 0.4 mg/dL). One-year patient and graft survival was 100% in sirolimus group and 100% and 95% in reference group. In conclusion, sirolimus significantly retards the recovery from posttransplant renal failure; however, it does not increase the incidence of DGF. Patients who suffered from posttransplant acute renal failure had worse renal function at 1 year after transplantation, independent of the treatment protocol.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , Sirolimo/efeitos adversos , Adulto , Cadáver , Creatinina/sangue , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Doadores de Tecidos , Falha de Tratamento , Cicatrização/efeitos dos fármacosRESUMO
The aim of our study was to correlate intragraft mRNA expression of cytokines and growth factors with histopathologic features in renal allograft biopsies. Fifty-six core biopsies performed in 51 kidney transplant recipients were assessed by the Banff '97 classification. Tubular and glomerular expressions of IFN-gamma, TGF-beta1, and PDGF-B as well as IL-2, IL-6, and IL-10 mRNA were assessed using semiquantitative RT-PCR in situ. No significant differences were noted between acute cellular and vascular rejection with regard to the glomerular and tubular mRNA expression of cytokines examined. We observed a positive correlation between tubular and glomerular IL-10 and IFN-gamma mRNAs during acute rejection. In chronic rejection the mRNA expression levels of IFN-gamma and IL-2, IL-6, and IL-10 did not differ from those of acute rejection; moreover, the glomerular expression of mRNA for TGF-beta1 (P < .05) and PDGF-B (P < .1) was even lower than during acute rejection episodes. Both tubular and glomerular IL-2, TGF-beta1, and PDGF-B mRNA expression levels in biopsies with acute rejection were significantly higher than in acute tubular necrosis (ATN). Biopsy samples with borderline changes exhibited the lowest levels of cytokine gene expression and were close to the intensity of control specimens obtained from living donor kidney biopsies taken during organ harvest. Our data failed to show a dichotomy between Th1 and Th2 cytokine activation in biopsy specimens from kidney allograft recipients; both Th1- and Th2-derived cytokines were involved to similar extents in rejection processes.
Assuntos
Citocinas/genética , Substâncias de Crescimento/genética , Transplante de Rim/imunologia , RNA Mensageiro/genética , Biópsia , Humanos , Interleucinas/genética , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Transplante de Rim/patologia , Túbulos Renais/imunologia , Túbulos Renais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transcrição GênicaRESUMO
The aim of the study was to assess the molecular background of the alloimmune response by the detection of low-abundance mRNA of cytokines in 34 core needle biopsies from kidney allografts with histopathological findings of acute rejection (AR). Recipients were immunosuppressed with a calcineurin inhibitor (CNI), cyclosporine or tacrolimus, and prednisone and azathioprine or mycophenolate mofetil (MMF). Tubular and glomerular expression of IL-2, IL-6, IL-10, IFN-gamma, TGF-beta1, and PDGF-B mRNA were assessed using semiquantitative evaluations of RT-PCR in situ on paraffin tissue sections. This procedure resulted in light microscopy visualization of granular precipitates at the sites of the corresponding mRNA chains. The tubular expression of mRNA for IL-6 and TGF-beta1 was significantly lower in biopsies with AR (n = 34) obtained from patients treated with MMF (n = 12) than in biopsies obtained from patients treated with azathioprine (n = 22) (P < .02). Responsiveness to corticosteroids tended to be more frequent among the MMF group (11 of 12 recipients vs 15 of 22 recipients, P = ns). Moreover, 8 of 12 recipients in the MMF-treated group displayed serum creatinine levels equal or less than 167 mmol/L 1 year after biopsy compared to 7 of 22 recipients in the azathioprine-treated group. There was no significant difference between the groups that had or had not received corticosteroids or between those treated with each type of CNI. These results suggest stronger inhibition of humoral responses and down-regulation of fibrosis by MMF among recipients with AR.
Assuntos
Ciclosporina/uso terapêutico , Citocinas/genética , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Tacrolimo/uso terapêutico , Transcrição Gênica/imunologia , Biópsia , Inibidores de Calcineurina , Quimioterapia Combinada , Substâncias de Crescimento/genética , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/patologia , Túbulos Renais/imunologia , Túbulos Renais/patologia , Doadores Vivos , Ácido Micofenólico/uso terapêutico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
Sixty patients underwent surgery due to abdominal aortic aneurysms; the group included 30 patients with asymptomatic aneurysm and 30 with ruptured aneurysm. A control group comprised 30 organ donors. Surgical specimens derived from aneurysm or aorta fragments were investigated for Chlamydia pneumoniae DNA using PCR. In asymptomatic aneurysms, DNA was found in 9 cases (29%), and in ruptured aneurysms in 14 cases (49%). In the control group, C. pneumoniae DNA was not detected in an aortic wall. These results suggest that healthy aortic wall is not susceptible to chlamydial infection. A large number of aneurysm infections implies C. pneumoniae role in proteolysis and degradation of the aneurysm wall. The biological effect of this process may cause an enlargement of the aneurysm.
Assuntos
Aorta Abdominal/microbiologia , Aneurisma da Aorta Abdominal/microbiologia , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/isolamento & purificação , Adulto , Idoso , Aneurisma da Aorta Abdominal/fisiopatologia , Doenças da Aorta/microbiologia , Chlamydophila pneumoniae/genética , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
It was previously reported that ischemia-reperfusion injury initiates an inflammatory response and may significantly affect the transplanted organ function. The aim of this study was to assess changes of intragraft cytokine mRNA expression in kidneys after cold ischemia (CI) and following reperfusion. We examined mRNA of a product of activated T lymphocytes (IFN-gamma) and a monocyte product (IL-6). Eleven kidneys were transplanted after CI time ranging from 16 to 39 hours. Renal needle core biopsies were obtained from donors after cold ischemia and approximately after 20 minutes of reperfusion. Tubular and glomerular expression of IFN-gamma and IL-6 mRNA were assessed using semiquantitative evaluation of the RT-PCR in situ. After reperfusion an intense increase of IL-6 mRNA expression was observed in four specimens, a slight increase was noticed in five specimens, and a very slight decrease in two specimens. Changes in IL-6 mRNA expression were limited only to tubules. In contrast, the glomerular and tubular mRNA expression of IFN-gamma and glomerular of IL-6 remained stable. Mean CI time for patients with an intense increase was higher than for patients with a slight increase and with the decrease of IL-6 mRNA expression (32.0 +/- 6.8 vs 25.2 +/- 7.3 and 26.0 +/- 5.7 hours). Our results suggest that early inflammatory changes at the time of implantation of renal allografts depends mainly on monocyte/macrophage-associated products. The observed intensity of their expression in tubules was connected to longer CI time.
Assuntos
Citocinas/genética , Transplante de Rim/imunologia , Adolescente , Adulto , Idoso , Biópsia por Agulha , Feminino , Humanos , Interleucina-6/genética , Isquemia , Rim , Transplante de Rim/métodos , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , RNA Mensageiro/genética , Reperfusão , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
AIM: The aim of this research was to assess the impact of eosinophilia in renal biopsy specimens obtained during an acute rejection (AR) episode on the severity and reversibility of rejection and on long-term graft function. MATERIAL: Among 165 renal graft recipients who underwent transplantation (Tx) in 2001 and 2002 whose biopsy specimens revealed AR, 49 with tissue eosinophilia were compared with control group of 48 without this feature. The average biopsy time was 60.6 and 95.8 days, respectively. Biopsies during delayed graft function were performed in 46.9% of patients with eosinophilia and 29% in the control group. The immunosuppressive regimen was based on tacrolimus or cyclosporine. RESULTS: Tissue eosinophilia was observed in 49 of 165 patients (29.6%): 5 patients had eosinophilia <10/mm(2), 31 patients 10-100/mm(2), 13 patients >100mm(2) (3 patients >300/mm(2)). Severity of AR according to Banff score was statistically lower in the control group (P <.002). Patients with tissue eosinophilia who initially received steroid-free treatment presented with significantly higher (P =.02) biopsy/patients index (2.3 vs 1.81) than the total eosinophilic group. Serum creatinine values at 6 and 12 months after transplantation (Tx) were higher among eosinophilic when compared with the control group (2.41 vs 1.82 mg/dL, P <.002; 2.10 vs 1.98 mg/dL, P =.006, respectively). Chronic rejection within the first year occurred in 25% of patients with tissue eosinophilia, and 8.3% of patients in the control group. One-year graft survival rate among patients with tissue eosinophilia was lower compared with the control group (89.8% and 93.7%, respectively). CONCLUSIONS: Biopsy eosinophilia is a negative predictor that indicates a more severe course of AR and a worse response to treatment with the threat of chronic graft dysfunction.
Assuntos
Eosinofilia/patologia , Rejeição de Enxerto/patologia , Transplante de Rim/patologia , Biópsia/métodos , Creatinina/sangue , Eosinofilia/epidemiologia , Rejeição de Enxerto/epidemiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de TempoRESUMO
Estimation of anti-CMV-IgG and anti-CMV-IgM is considered a relatively inexpensive screening tool of CMV status. The aim of study was to estimate how the immunosuppressive protocol influence serum anti-CMV IgG and IgM concentration in renal graft recipients and to estimate the adequacy of anti-CMV-IgG concentration and anti-CMV-IgM index as screening parameters of active CMV disease in patients receiving different immunosuppression. The study group consisted of 33 patients with clinical signs of CMV disease who received one of three types of immunosuppression: (1) azathioprine (Aza) + cyclosporine (CyA) + prednisone (Pr), 20 patients; (2) mycophenolate mofetil (MMF) + CyA + Pr, eight patients; tacrolimus (Tac) + MMF, five patients. Patients were enrolled when the pp65-antigen (pp65) of PBL was positive within 1 to 5 months after transplant (75 patients tested). The IgM-i in the Aza + CyA + Pr group was higher than in MMF + CyA + Pr group (2.73 + 1.8 vs 1.08 +/- 1.07, P =.021). The IgM-i in the Aza + CyA + Pr group was higher than in Tac + MMF (2.73 +/- 1.8 vs 0.78 +/- 0.69; P =.014). There was no difference in IgM-i between MMF + CyA + Pr and Tac + MMF. There was no difference in relative increase of IgG-c among all groups but there was a difference in relative increase of IgM-i between Aza + CyA + Pr and MMF + CyA + Pr groups (6.7 +/- 9.4 vs 2.3 +/- 5.9; P =.007) and between Aza + CyA + Pr and MMF + Tac groups (6.7 +/- 9.4 vs 0.6 +/- 0.54; P =.003). Immunosuppressive protocols including MMF exert an inhibitory influence on B-cell response and synthesis of anti-CMV-IgM. It makes the anti-CMV-IgM index an inadequate rough screening diagnostic parameter of active CMV disease.