VIKTORIA WORONIK
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, 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.
- Worse renal outcome of subclass IV-G lupus nephritis patients over IV-S(2018) CARNEIRO FILHO, E. J. Duque de Sa; JORGE, L. B.; TESTAGROSSA, L.; BITENCOURT, C.; YU, L.; WORONIK, V.Background International Society of Nephrology/ Renal Pathology Society (ISN/RPS) consensus on the classification of lupus nephritis (LN) subdivided class IV into diffuse segmental (IV-S) and diffuse global (IV-G). Nephrologists and nephropathologists believe that this subclassification would be clinically relevant based on hypothetical distinct immunopathogenesis of those subclasses guiding therapy as well as judging prognosis. Methods All adult patients with a renal biopsy-confirmed diagnosis of LN class IV undergoing regular follow-up in the Nephrology Division between January 2004 and December 2014 were enrolled excluding those with diabetes, hepatitis B, hepatitis C, HIV as well as those with insufficient clinical and hystopathological data. Biopsies were reviewed and reclassified according to ISN/RPS 2003 classification by two experienced pathologists and were examined by light microscopy and direct immunofluorescence. Results On baseline subclass IV-G compared to IV-S showed higher frequency of males and histologically higher activity (7.52.8 vs 5.1 +/- 2.3, p=0.004) and chronicity index (3.4 +/- 1.6 vs 2.4 +/- 1.8, p=0.016) as well as a higher percentage of epithelial crescents (12.9 vs 5.1, p=0.0001) and vessel abnormalities (72% vs 42%, p=0.017). Although renal function on baseline was not different between subclasses, IV-G showed lower levels, although not significant, of estimated glomerular filtration based on CKD-EPI formula (91.0 +/- 34.8 vs 64.4 +/- 44.5, p=0.059) at the end of follow-up. In addition, we observed a higher rate of patients reaching CKD-EPI under 60mL/min/1.73m(2) in subclass IV-G over IV-S on last follow-up. Conclusion Subclasses IV-S and IV-G patients show some clinical and pathological differences that might represent distinct stages of the same disease and they should thus be treated the same.
conferenceObject 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- 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.
conferenceObject Molecular Expression of Podocytes in the Variants of Focal Segmental Glomerulosclerosis(2012) TESTAGROSSA, L. A.; AZEVEDO NETO, R.; WORONIK, V.; MALHEIROS, D. M. A. C.Background: Focal segmental glomerulosclerosis (FSGS) is the most prevalent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Primary FSGS is characterized clinically by affecting young people and causing severe proteinuria and nephrotic syndrome. The pathogenesis is related to podocyte injury, which may be due to several factors: viruses, drugs, immunological, etc. In 2004, the Columbia classification of FSGS identifiedfive histological variants of the disease: collapsing (COL), usual (NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). Several studies have demonstrated molecular changes in podocytes of FSGS patients, which were observed in molecules involved in the filtering and structural function of these cells like nephrin, podocina, CD2AP,α-actinin-4, synaptopodin, etc. as well as in molecules of podocyte differentiation like CD10, WT-1, and of cell division: Ki-67 and PCNA. The objective of this study was to classify the FSGS biopsies according to the Columbia classification and to analyze the occurrence of molecular changes on these variants. Design: 131 cases of renal biopsies with a diagnosis of primary FSGS in the period 1996 to 2006 were classified in COL, NOS, TIP, PHI and CEL, and then stained with immunohistochemical reactions to the primary antibodies: CD10, WT-1, Vimentin, Synaptopodin, α-actinin-4, GLEPP-1, cytokeratin 8-18, cytokeratin 19, and Ki-67. Results: FSGS classification resulted in 38.2% of NOS variant, 36.6% COL, 14.5% TIP, 6.9% PHI and 3.8% CEL. The podocytes of COL variant biopsies were distinguished from the other variants for having lost the expression of CD10 (p<0,01), WT-1 (p<0,01) and α-actinin-4 (p <0,05) in podocytes. Furthermore, they gained expression of the cytokeratin 8-18 (p <0.05) and 19 (p <0.01). The group of CEL and COL variants differed from the group pf other variants regarding the expression of cell division marker Ki-67 in podocytes (p <0.05). Conclusions: COL variant of FSGS presents molecular changes in podocytes that differs from other variants and can be demonstrated by immunohistochemistry. The differential diagnosis of this variant is important because of the worse clinical outcome in comparison with TIP, NOS, PHI and CEL variants, so the identification of these markers by immunohistochemical may be useful in the diagnosis on the routine practice and also for the better compreention of the disease.- 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.
- Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?(2017) VELOSO, Mariana P.; NEVES, Precil D. M. M.; JORGE, Lecticia B.; DIAS, Cristiane B.; YU, Luis; PINHEIRO, Rafaela B. B.; TESTAGROSSA, Leonardo A.; MALHEIROS, Denise M.; BALBO, Bruno E. P.; LERARIO, Antonio M.; ONUCHIC, Luiz F.; WORONIK, ViktoriaAlport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders. (C) 2017 S. Karger AG, Basel
conferenceObject Molecular Expression of Podocytes in the Variants of Focal Segmental Glomerulosclerosis(2012) TESTAGROSSA, L. A.; AZEVEDO NETO, R.; WORONIK, V.; MALHEIROS, D. M. A. C.Background: Focal segmental glomerulosclerosis (FSGS) is the most prevalent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Primary FSGS is characterized clinically by affecting young people and causing severe proteinuria and nephrotic syndrome. The pathogenesis is related to podocyte injury, which may be due to several factors: viruses, drugs, immunological, etc. In 2004, the Columbia classification of FSGS identified five histological variants of the disease: collapsing (COL), usual (NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). Several studies have demonstrated molecular changes in podocytes of FSGS patients, which were observed in molecules involved in the filtering and structural function of these cells like nephrin, podocina, CD2AP, α-actinin-4, synaptopodin, etc. as well as in molecules of podocyte differentiation like CD10, WT-1, and of cell division: Ki-67 and PCNA. The objective of this study was to classify the FSGS biopsies according to the Columbia classification and to analyze the occurrence of molecular changes on these variants. Design: 131 cases of renal biopsies with a diagnosis of primary FSGS in the period 1996 to 2006 were classified in COL, NOS, TIP, PHI and CEL, and then stained with immunohistochemical reactions to the primary antibodies: CD10, WT-1, Vimentin, Synaptopodin, α-actinin-4, GLEPP-1, cytokeratin 8-18, cytokeratin 19, and Ki-67. Results: FSGS classification resulted in 38.2% of NOS variant, 36.6% COL, 14.5% TIP, 6.9% PHI and 3.8% CEL. The podocytes of COL variant biopsies were distinguished from the other variants for having lost the expression of CD10 (p<0,01), WT-1 (p<0,01) and α-actinin-4 (p <0,05) in podocytes. Furthermore, they gained expression of the cytokeratin 8-18 (p <0.05) and 19 (p <0.01). The group of CEL and COL variants differed from the group pf other variants regarding the expression of cell division marker Ki-67 in podocytes (p <0.05). Conclusions: COL variant of FSGS presents molecular changes in podocytes that differs from other variants and can be demonstrated by immunohistochemistry. The differential diagnosis of this variant is important because of the worse clinical outcome in comparison with TIP, NOS, PHI and CEL variants, so the identification of these markers by immunohistochemical may be useful in the diagnosis on the routine practice and also for the better compreention of the disease.- SEGMENTAL VERSUS GLOBAL SUBCLASSES OF PROLIFERATIVE LUPUS NEPHRITIS: RENAL OUTCOMES(2015) CARNEIRO FILHO, Eduardo Jorge Duque de Sa; PIRES, Alcino Gama; ANDRADE, Mariana Pin de; HOLANDA, Beatriz Seves de; DANTAS, Jonatas Gonzaga; NUNEZ, Claudia Rojas; TESTAGROSSA, Leonardo; YU, Luis; DIAS, Cristiane Bitencourt; JORGE, Lectcia Barbosa; WORONIK, Viktoria
- Clinical and histological features of patients with membranoproliferative glomerulonephritis classified by immunofluorescence findings(2017) DIAS, Cristiane Bitencourt; TESTAGROSSA, Leonardo; JORGE, Lectícia; MALHEIROS, Denise; WORONIK, ViktoriaAbstract Background: New classification for membranoproliferative glomerulonephritis has been proposed in the literature. The aim of this study was to compare the clinical, biochemical, etiology and renal biopsy findings of these patients grouped by immunofluorescence as proposed by the new classification. Methods: Patients with renal biopsy-proven membranoproliferative glomerulonephritis unrelated to systemic lupus erythematosus, diagnosed between 1999 and 2014. The patients were divided according to immunofluorescence: Immunoglobulin positive group, C3 positive only and negative immunofluorescence group. Results: We evaluated 92 patients, the majority of which were in the immunoglobulin positive group. Infectious diseases, hepatitis C virus and schistosomiasis, were the most frequent etiology. A negative immunofluorescence group had more vascular involvement in renal biopsy compare with others groups. Conclusions: The only difference between the groups was higher vascular involvement in renal biopsy in negative immunofluorescence group. These new classification was satisfactory for the finding of etiology in one part of the cases.