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
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- Schistosoma mansoni and membranous nephropathy(2016) NEVES, Precil D. M. M.; BEZERRA, Kalyanna S.; SILVEIRA, Marcelo A. D.; YU, Luis; WORONIK, Viktoria; JORGE, Lecticia B.; TESTAGROSSA, Leonardo A.; MALHEIROS, Denise M. A. Costa; DIAS, Cristiane B.
conferenceObject KIDNEY BIOPSIES IN HIV PATIENTS: A FIFTEEN-YEAR SINGLE CENTER EXPERIENCE IN BRAZIL(2012) CALDIN, Bruno; HUNG, James; REPIZO, Liliany; MALHEIROS, Denise M.; BARROS, Rui; WORONIK, ViktoriaIntroduction and Aims: Human Immunodeficiency Virus (HIV) is associated to many kidney pathologies, like glomerular, vascular and tubule-interstitial alterations. Few data on renal biopsies in HIV patients are available in Brazil. Our objective is to reveal the prevalence and outcomes related to the different diagnosis concerning kidney pathology in a single brazilian reference center. Methods: From 1985 to 2010, we performed 69 kidney biopsies in HIV-positive patients at the Hospital das Clínicas, University of São Paulo. We correlated clinical and laboratorial data to the results of kidney biopsies from these patients and established clinical outcomes depending on the kind of glomerular lesion. Eight biopsies were excluded from analysis due to incomplete data. Results: Mean age of this population was 39,6 ± 11,3 years (range: 15 to 65 years) and 66% were men. Only 3 patients were not under antiretroviral therapy. Main indications for biopsy were: nephrotic syndrome (47%), loss of renal function (37%) and hematuria (31%). The most prevalent glomerulopathy (GP) was focal and segmental glomerulosclerosis (FSGS), which was found in 24 patients (39%), followed by membranoproliferative glomerulonephritis (MPGN) (10 patients, 16% of the total). Six patients (10%) were diagnosed as membranous glomerulonephritis. Vascular disease (atherosclerosis, nephrosclerosis) and acute tubular necrosis were found in three patients each, representing 10% of the population. IgA nephropathy and diabetic GP were diagnosed in two patients each. Other diagnosis, like chronic and acute interstitial nephritis and mesangial glomerulonephritis were made, but represented only 5% of the population. In three patients, diagnosis was not conclusive. To evaluate whether the pattern of glomerular injury has somehow impact under renal prognosis, we divided the patients into two subgroups: FSGS and non-FSGS GP (24 vs 22 biopsies). Clinical and laboratorial aspects are depicted in table 1. Table 1 Clinical and laboratorial characteristics of the study populaton Follow-up between these two groups was slightly different: 22,8 ± 17 months for FSGS group vs 40,7 ± 31,6 months for non-FSGS GP group (p = 0,047). Only hematuria was more prevalent in the non-FSGS GP group. Composite outcome defined as hemodialysis or duplication of serum creatinine resulted in no differences between these groups (p = 0,71) during the follow up (7 patients out of 21 in FSGS group vs 5 patients out of 18 in non-FSGS GP group), as shown in figure 1. Figure 1. Composite outcome in FSGS group vs non-FGSG group FSGS was also compared to a combined group of MPGN and crioglobulinemia (12 patients). Again, only hematuria was different between these groups (22% vs 75%, p = 0,01). Nevertheless, coinfection with HCV was more prevalent in the latter group (50% of the patients, against 16% in the FSGS group, p = 0,027). Conclusions: The main indication for kidney biopsy in HIV-positive patients in our center is nephrotic syndrome and FSGS was the single most prevalent GP. MPGN was the second most prevalent diagnosis and is strongly associated to coinfection with HCV. Our composite outcome showed that the kind of GP found in kidney biopsy does not correlate to renal prognosis.- Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis(2017) DIAS, Cristiane B.; MALAFRONTE, Patricia; LEE, Jin; RESENDE, Aline; JORGE, Lecticia; PINHEIRO, Cilene C.; MALHEIROS, Denise; WORONIK, ViktoriaIntroduction Renal histology of proliferative lupus nephritis (LN) shows increased macrophage infiltration, but its association with renal outcome is a matter of debate. Here, we investigate the potential relationship that macrophage expression has with renal prognosis in patients with proliferative LN. Methods Fifty patients newly diagnosed with proliferative LN were followed for a median of 8 years. Laboratory testing was conducted at diagnosis, after induction therapy and at the final follow-up evaluation. Renal biopsies were obtained at diagnosis and underwent immunohistochemical analysis with anti-CD68 and monocyte chemoattractant protein 1 monoclonal antibodies. Patients were stratified at final follow-up evaluation into glomerular filtration rate (GFR) > 60 ml/min/1.73 m(2) (non-progressor group; n = 24) and GFR <= 60 ml/min/1.73 m(2) (progressor group; n = 26). All patients were treated with prednisone and six pulses of cyclophosphamide on induction therapy. Conventional maintenance therapy was administered in both groups. Results Compared to progressors, the non-progressor group showed a lower chronicity index (p = 0.01) and fewer CD68-positive cells in the renal tubules (p = 0.01) and particularly in the renal interstitium (p = 0.0003). Baseline and final serum creatinine correlated positively with the chronicity index (r = 0.3, p = 0.01 and r = 0.3, p = 0.04, respectively), and final serum creatinine correlated positively with interstitial expression of CD68 (r = 0.4, p = 0.0006). Conclusion Renal expression of CD68 and the chronicity index are associated with progression to chronic kidney disease in patients with proliferative LN.
bookPart Nefropatia por IgA(2022) WORONIK, Viktoria; MALHEIROS, Denise Maria Avancini CostaconferenceObject IMMUNOGLOBULIN DEPOSITS IN GLOMERULI OF LUPUS MEMBRANOUS NEPHROPATHIES(2015) CARNEIRO FILHO, Eduardo Jorge Duque de Sa; PIRES, Alcino Gama; TESTAGROSSA, Leonardo; MALHEIROS, Denise Mac; YU, Luis; DIAS, Cristiane Bitencourt; JORGE, Lectcia Barbosa; WORONIK, Viktoria- Methimazole-Induced ANCA Vasculitis: A Case Report(2021) NEVES, Precil Diego Miranda de Menezes; MOTA, Lucas Braga; DIAS, Cristiane Bitencourt; YU, Luis; WORONIK, Viktoria; CAVALCANTE, Livia Barreira; MALHEIROS, Denise Maria Avancini Costa; JORGE, Lecticia BarbosaRapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m(2)), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm(3), platelets 238,000/mm(3), complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m(2)) and negative p-ANCA.
- Atypical presentation of acute post-infectious glomerulonephritis in patients with sickle cell disease: report of two cases(2020) NEVES, Precil Diego Miranda de Menezes; REICHERT, Bernardo Vergara; BRIDI, Ramaiane Aparecida; YU, Luis; DIAS, Cristiane Bitencourt; PINHEIRO, Rafaela Brito Bezerra; TESTAGROSSA, Leonardo de Abreu; CAVALCANTE, Livia Barreira; MALHEIROS, Denise Maria Avancini Costa; JORGE, Lecticia Barbosa; WORONIK, ViktoriaBackgroundSickle cell disease (SCD) is a highly prevalent genetic disease worldwide. In the natural evolution of SCD, glomerular lesions can develop, presenting histopathological patterns of segmental or focal membranoproliferative glomerulosclerosis, with or without thrombotic microangiopathy. We report two cases of acute post-infectious glomerulonephritis (APIGN), with atypical presentations, in patients with SCD.Case presentationCase 1: An 18-year-old female with SCD presented with a 21-day history of progressive oedema, accompanied by dyspnoea, productive cough, fever, and chest pain. Blood tests showed the following: haemoglobin 6.1g/dl; leucocytes 18,820 cells/mm(3); and creatinine 0.49mg/dl. A urine sample evidenced leucocyturia and haematuria. The 24-h proteinuria was 8.99g, serum albumin level was 1.2g/dl, low serum C3 levels and high levels of anti-streptolysin O. Renal biopsy was consistent with APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving to reversal of the renal alterations. Case 2: A 12-year-old male with SCD presented with a 20-day history of a non-productive cough and progressive oedema, together with hypertension. The serum creatinine concentration was 0.48mg/dl. A urine sample evidenced leukocyturia and haematuria. The 24-h proteinuria was 12.5g, and the serum albumin level was 2.6g/dl. The levels of C3 and C4 were normal. Renal biopsy revealed APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving reversal of the renal alterations.ConclusionsThe presentation of the two cases reported here are not typical of SCD-related kidney injury. Analysis of the renal biopsy specimens elucidated the diagnosis, affecting the prognosis, because that of APIGN is highly favourable, unlike that of nephrotic syndrome associated with SCD glomerulopathy.
- Glomeruloesclerose segmentar e focal (GESF) colapsante associada ao parvovírus B19: relato de caso(2015) FREITAS, Geraldo Rubens Ramos de; PRAXEDES, Marcel Rodrigues Gurgel; MALHEIROS, Denise; TESTAGROSSA, Leonardo; DIAS, Cristiane Bitencourt; WORONIK, ViktoriaObjective: To describe the clinical and laboratory profile of focal segmental glomerulosclerosis (FSGS) of the collapsing subtype in association with infection by parvovirus B19 (PVB19). Case report: Female patient, 37 years old, mulatto, developed pharyngalgia and fever with partial improvement after penicillin. After one week we observed reduced urinary output and lower limb edema. Smoker, family and personal history negative for hypertension, diabetes or kidney disease. Patient presented with olyguria, hypertension and edema, also hypochromic microcytic hypoproliferative anemia, nephritic range proteinuria, microscopic hematuria and renal dysfunction. All rheumatologic investigation, HIV and hepatitis serology were negative. Unremarkable renal ultrasound. PCR positive for PVB19 in bone marrow aspirate and blood and renal biopsy conclusive of collapsing FSGS subtype. Spontaneous remission occurred within two weeks of the profile. The blood PVB19 PCR was repeated within a month and resulted negative. This finding demonstrated PVB19 acute infection or viral reactivation in association with collapsing FSGS. Conclusion: There is demonstrated the temporal association of PVB19 viremia and collapsing FSGS, due primary infection or viral reactivation. The association of collapsing FSGS and PVB19 is described in the literature, demonstrating virus presence in kidney tissue, but the real relationship of virus in the pathogenesis of this glomerulopathy remains unclear.
- Schistosoma mansoni infection as a trigger to collapsing glomerulopathy in a patient with high-risk APOL1 genotype(2020) NEVES, Precil D.; BRIDI, Ramaiane A.; RAMALHO, Janaina A.; JORGE, Lecticia B.; WATANABE, Elieser H.; WATANABE, Andreia; YU, Luis; WORONIK, Viktoria; PINHEIRO, Rafaela B.; TESTAGROSSA, Leonardo A.; CAVALCANTE, Livia B.; MALHEIROS, Denise M.; DIAS, Cristiane B.; ONUCHIC, Luiz F.Author summary Schistosomiasis mansoni is still a public health problem in Brazil and renal involvement is described. In such cases, a glomerulopathy is the typical manifestation, most often membranoproliferative glomerulonephritis. In the current article, we report a patient with a recent diagnosis of hepatosplenic SM who was admitted for nephrotic syndrome associated with reduced renal function and hypertension. Kidney biopsy established the diagnosis of collapsing glomerulopathy (CG) and molecular genetics investigation identified a high-risk APOL1 genotype (HRG). Of note, HRG has been associated with increased risk to develop CG, and a two-hit model has been proposed for the genesis of this glomerulopathy. According to this model, a HRG represents the increased-susceptibility component, while an infection or other environmental factors could act as triggers for the development of CG. Based on those data and model, our case raises SM infection as a new trigger for this severe form of glomerulopathy. This is the first description of a case of CG associated with SM in a patient with an HRG. This case corroborates the interactive role between genetic and environmental factors in the pathogenesis of CG but also identifies SM infection as an additional trigger for its development. Background Schistosoma mansoni schistosomiasis (SM) remains a public health problem in Brazil. Renal involvement is classically manifested as a glomerulopathy, most often membranoproliferative glomerulonephritis or focal and segmental glomerulosclerosis. We report a case of collapsing glomerulopathy (CG) associated with SM and high-risk APOL1 genotype (HRG). Case report A 35-year-old male was admitted for hypertension and an eight-month history of lower-limb edema, foamy urine, and increased abdominal girth. He had a recent diagnosis of hepatosplenic SM, treated with praziquantel, without clinical improvement. Laboratory tests revealed serum creatinine 1.89mg/dL, blood urea nitrogen (BUN) 24mg/dL, albumin 1.9g/dL, cholesterol 531mg/dL, low-density lipoprotein 426mg/dL, platelets 115000/mm(3), normal C3/C4, antinuclear antibody (ANA), rheumatoid factor (RF), and antineutrophil cytoplasmic antibodies (ANCA), negative serologies for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HBsAg negative and AntiHBc IgG positive, no hematuria or leukocyturia, 24 hour proteinuria 6.56g and negative serum and urinary immunofixation. Kidney biopsy established the diagnosis of CG. A treatment with prednisone was started without therapeutic response, progressing to end-stage kidney disease 19 months later. Molecular genetics investigation revealed an HRG. Conclusions This is the first report of CG associated with SM in the setting of an HRG. This case highlights the two-hit model as a mechanism for CG pathogenesis, where the high-risk APOL1 genotype exerts a susceptibility role and SM infection serves as a trigger to CG.
- 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.