DENISE MARIA AVANCINI COSTA MALHEIROS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- Regression of Albuminuria and Hypertension and Arrest of Severe Renal Injury by a Losartan-Hydrochlorothiazide Association in a Model of Very Advanced Nephropathy(2013) ARIAS, Simone Costa Alarcon; VALENTE, Carla Perez; MACHADO, Flavia Gomes; FANELLI, Camilla; ORIGASSA, Clarice Silvia Taemi; BRITO, Thales de; CAMARA, Niels Olsen Saraiva; MALHEIROS, Denise Maria Avancini Costa; ZATZ, Roberto; FUJIHARA, Clarice KazueTreatments that effectively prevent chronic kidney disease (CKD) when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx) and the effect of an association between an AT-1 receptor blocker, losartan (L), and hydrochlorothiazide (H), shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH), and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP). Rats undergoing sham nephrectomy (S) were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization.
- Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy(2013) MACHADO, Christiano; MALHEIROS, Denise Maria Avancini Costa; ADAMY, Ari; SANTOS, Luiz Sergio; SILVA FILHO, Agenor Ferreira da; NAHAS, William Carlos; LEMOS, Francine Brambate CarvalhinhoOBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic donor nephrectomy utilization in renal transplantation.
- Immunohistochemical expression of podocyte markers in the variants of focal segmental glomerulosclerosis(2013) TESTAGROSSA, Leonardo; AZEVEDO NETO, Raymundo; RESENDE, Aline; WORONIK, Viktoria; MALHEIROS, DeniseBackground. Focal segmental glomerulosclerosis (FSGS) is the most prevalent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Pathogenesis is related to podocyte injury, which may be due to several factors including viruses, drugs, immunology. In 2004, the Columbia classification of FSGS identified five histologic variants of the disease: collapsing (COL), usual (not otherwise specified, NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). Several studies have demonstrated molecular changes in podocytes of FSGS patients. This study sought to classify a large series of FSGS biopsies according to the Columbia classification and analyze the occurrence of immunohistochemical differences among the five variants. Methods. Approximately 131 cases of renal biopsies with a diagnosis of primary FSGS during the period from 1996-2006 were classified according to the criteria of Columbia and were then submitted to immunohistochemical staining to the following antibodies: CD10, WT-1, Vimentin, Synaptopoclin, alpha-actinin-4, GLEPP-1, cytokeratin (CK) 8-18, CK19 and Ki-67. Results. The FSGS classification resulted in 38.2% of NOS variant, in 36.6% COL, in 14.5% TIP, in 6.9% PHI and in 3.8% CEL. COL variant distinguished themselves among the others for having loss of expression of CD10, WT1 and alpha-actinin-4 (P < 0.05). Furthermore, COL gained expression of the CK8-18 and CK19 diverging from the other variants (P < 0.05). Conclusions. COL variant of FSGS presented immunohistochemical characteristics that distinguished it from others pointing to additional studies in this area. The distinct immunohistochemical properties of COL might be of help in the comprehension of this aggressive form of FSGS.
conferenceObject CD68 POSITIVE CELLS IN RENAL BIOPSY PREDICT LONG TERM PROGNOSIS IN PROLIFERATIVE LUPUS NEPHRITIS(2013) DIAS, Cristiane Bitencourt; LEE, Jin; JORGE, Leticia; MALHEIRO, Denise; BARROS, Rui Toledo; WORONIK, ViktoriaIntroduction and Aims:Studies in proliferative lupus nephritis (LN) showed that in more severe clinical forms the renal histology showed increase macrophages detected by immunohistochemistry. However no long-term assessment of this data is known. The aim of this study was to describe any relations of renal outcomes with tecidual macrophages (CD68+) expressed in renal biopsy specimens obtained on the diagnosis. Methods:Forty six newly diagnosed patients with proliferative LN were prospectively followed-up during 3.5 (3.2 - 4.0) years. Conventional laboratory tests were collected on diagnosis and on last follow-up. Renal biopsy was done on diagnosis and immunohistochemical study was performed with monoclonal antibody anti-CD68 (DAKO) and macrophages MCP-1 (R&D), and results expressed as cells/microscopic fields. Patients were stratified in two groups according to renal outcome: GFR ≤ 60 mL/min/1.73m2at the end of follow-up (n=24) and GFR > 60mL/min/1.73m2(n=22). Considering treatment, all patients received prednisone and 6 pulses of cyclophosphamide (CYA) on induction. Maintenance treatment was conventional and applied in both groups. Results: Considering all patients (n=46) tubule and interstitial CD68+cells showed negative correlation with final MDRD (r= - 0.3, p=0.01 and r= -0.45, p=0.001). Macrophages MCP-1 interstitial had positive correlation with chronicity index (r=0.4, p=0.0031). Conclusions:Tubule and interstitial CD68+cells expression on renal biopsies may predict long term GFR in proliferative lupus nephritis.conferenceObject ALPHA-MELANOCYTE STIMULATING HORMONE ANALOGUE: BENEFICIAL EFFECT IN MURINE LUPUS ACTIVITY(2013) BOTTE, D.; NORONHA, I.; MALHEIROS, D.; MELLO, S.- NF-kappa B activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy(2013) OKABE, Cristiene; BORGES, Raquel Lerner; ALMEIDA, Danilo Candido de; FANELLI, Camilla; BARLETTE, Grasiela Pedreira; MACHADO, Flavia Gomes; ARIAS, Simone Costa Alarcon; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; ZATZ, Roberto; FUJIHARA, Clarice KazueAdenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-kappa B activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard chow; ADE (n = 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n = 14), receiving adenine as above and the NF-kappa B inhibitor PDTC (120 mg.kg(-1).day(-1) in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-alpha increased abundance indicated activation of the NF-kappa B system. PDTC treatment prevented p65 migration and normalized IKK-alpha, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-kappa B activation, and suggest that the NF-kappa B system may become a therapeutic target in the treatment of chronic kidney disease.
- Uso do eculizumab na síndrome hemolítica urêmica atípica: relato de caso e revisão da literatura(2013) VAISBICH, Maria Helena; HENRIQUES, Luciana dos Santos; WATANABE, Andréia; PEREIRA, Lilian Monteiro; METRAN, Camila Cardoso; MALHEIROS, Denise Avancini; MODANEZ, Flávia; SILVA, João Domingos Montoni da; VIEIRA, Simone; MACEDO, Ana Catarina Lunz; MASSAROPE, Bianca; FURUSAWA, Érika Arai; SCHVARTSMAN, Benita Galassi SoaresSHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.