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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- Urinary CD80 and Serum suPAR as Biomarkers of Glomerular Disease among Adults in Brazil(2023) ZEN, Renata de Cassia; DOMINGUEZ, Wagner Vasques; BRAGA, Ivone; REIS, Luciene Machado dos; JORGE, Lecticia Barbosa; YU, Luis; WORONIK, Viktoria; DIAS, Cristiane BitencourtIntroduction: Urinary CD80 has been shown to have good specificity for minimal change disease (MCD) in children. However, the investigation of circulating factors such as soluble urokinase plasminogen activator receptor (suPAR) as biomarkers of focal segmental glomerulosclerosis (FSGS) is quite controversial. The objective of this study was to determine whether urinary CD80 and serum suPAR can be used for the diagnosis of MCD and FSGS, respectively, in the adult population of Brazil. We also attempted to determine whether those biomarkers assess the response to immunosuppressive treatment. Methods: This was a prospective study in which urine and blood samples were collected for analysis of CD80 and suPAR, respectively, only in the moment of renal biopsy, from patients undergoing to diagnostic renal biopsy. At and six months after biopsy, we analyzed serum creatinine, serum albumin, and proteinuria in order to evaluate the use of the CD80 and suPAR collected in diagnosis as markers of response to immunosuppressive treatment. In healthy controls were collected urinary CD80 and proteinuria, serum suPAR, and creatinine. Results: The results of 70 renal biopsies were grouped, by diagnosis, as follows: FSGS (n = 18); membranous nephropathy (n = 14); MCD (n = 5); and other glomerulopathies (n = 33). There was no significant difference among the groups in terms of the urinary CD80 levels, and serum suPAR was not significantly higher in the FSGS group, as would have been expected. Urinary CD80 correlated positively with nephrotic syndrome, regardless of the type of glomerular disease. Neither biomarker correlated with proteinuria at six months after biopsy. Conclusion: In adults, urinary CD80 can serve as a marker of nephrotic syndrome but is not specific for MCD, whereas serum suPAR does not appear to be useful as a diagnostic or treatment response marker.
- 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.
- Collapsing glomerulopathy associated with proliferative lupus nephritis: reversible acute kidney injury(2011) MELO, N. C. V.; MALHEIROS, D. M. A. C.; BARROS, R. T.; WORONIK, V.Collapsing glomerulopathy is a rare form of glomerular injury, characterized by segmental or global collapse of the glomerular capillaries, wrinkling and retraction of the glomerular basement membrane, and marked hypertrophy and hyperplasia of podocytes. Prognosis is usually poor, with most cases developing end-stage renal disease, in spite of treatment. The association of collapsing glomerulopathy and systemic lupus erythematosus is very unusual. In this report, we describe the first case of a simultaneous diagnosis of collapsing glomerulopathy and diffuse proliferative lupus nephritis. The case presented with acute kidney injury and nephrotic syndrome and evolved with partial remission of nephrotic syndrome and recovery of renal function after aggressive treatment with intravenous cyclophosphamide and methylprednisolone. Lupus (2011) 20, 98-101.
bookPart Nefrite lúpica(2022) WORONIK, Viktoria; YU, Luis; JORGE, Lecticia BarbosaconferenceObject 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.- Gut-kidney axis in IgA nephropathy: Role on mesangial cell metabolism and inflammation(2022) LUVIZOTTO, Mateus Justi; MENEZES-SILVA, Luisa; WORONIK, Viktoria; MONTEIRO, Renato C.; CAMARA, Niels Olsen SaraivaIgA Nephropathy (IgAN) is the commonest primary glomerular disease around the world and represents a significant cause of end-stage renal disease. IgAN is characterized by mesangial deposition of IgA-immune complexes and mesangial expansion. The pathophysiological process includes an abnormally glycosylated IgA1, which is an antigenic target. Autoantibodies specifically recognize galactose-deficient IgA1 forming immune complexes that are amplified in size by the soluble IgA Fc receptor CD89 leading to deposition in the mesangium through interaction with non-classical IgA receptors. The local production of cytokines promotes local inflammation and complement system activation, besides the stimulation of mesangial proliferation. The spectrum of clinical manifestations is quite variable from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. Despite all the advances, the pathophysiology of the disease is still not fully elucidated. The mucosal immune system is quoted to be a factor in triggering IgAN and a ""gut-kidney axis "" is proposed in its development. Furthermore, many recent studies have demonstrated that food intake interferes directly with disease prognosis. In this review, we will discuss how mucosal immunity, microbiota, and nutritional status could be interfering directly with the activation of intrinsic pathways of the mesangial cells, directly resulting in changes in their function, inflammation and development of IgAN.
- 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.
bookPart Doenças do podócito em lúpus eritematoso sistêmico(2014) DIAS, Cristiane Bitencourt; WORONIK, Viktoria- 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.
- Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes(2016) MONTEIRO, Maria Beatriz; THIEME, Karina; SANTOS-BEZERRA, Daniele Pereira; QUEIROZ, Marcia Silva; WORONIK, Viktoria; PASSARELLI, Marisa; MACHADO, Ubiratan Fabres; GIANNELLA-NETO, Daniel; OLIVEIRA-SOUZA, Maria; CORREA-GIANNELLA, Maria LuciaPurpose. After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. Methods. qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25 mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. Results. No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P = 0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P = 0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r = 0.43; P = 0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r = - 0.57; P = 0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25 mM glucose and to albumin. Conclusions. B2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.