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
6 resultados
Resultados de Busca
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- Chronic environmental hypoxia attenuates innate immunity activation and renal injury in two CKD models(2023) ZAMBOM, Fernanda Florencia Fregnan; ALBINO, Amanda Helen; TESSARO, Helena Mendonca; FORESTO-NETO, Orestes; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; ZATZ, RobertoTissue hypoxia has been pointed out as a major pathogenic factor in chronic kidney disease (CKD). However, epidemiological and experimental evidence inconsistent with this notion has been described. We have previously reported that chronic exposure to low ambient Po-2 promoted no renal injury in normal rats and in rats with 5/6 renal ablation (Nx) unexpectedly attenuated renal injury. In the present study, we investigated whether chronic exposure to low ambient Po-2 would also be renoprotective in two additional models of CKD: adenine (ADE) excess and chronic nitric oxide (NO) inhibition. In both models, normobaric ambient hypoxia attenuated the development of renal injury and inflammation. In addition, renal hypoxia limited the activation of NF-?B and NOD-like receptor family pyrin domain containing 3 inflammasome cascades as well as oxidative stress and intrarenal infiltration by angiotensin II-positive cells. Renal activation of hypoxia-inducible factor (HIF)-2a, along with other adaptive mechanisms to hypoxia, may have contributed to these renoprotective effects. The present findings may contribute to unravel the pathogenesis of CKD and to the development of innovative strategies to arrest its progression.
- KIDNEY TISSUE PROTECTIVE RESPONSE OF LIVING RENAL TRANSPLANTATION: COMPARISON TO OPEN AND LAPAROSCOPIC DONOR NEPHRECTOMY.(2012) MACHADO, Christiano; MALHEIROS, Denise Maria Avancini C.; ANTONOPOULUS, Ioannis; SAITO, Fernando; URBAN, Cero de Andrade; KALIL, Jorge; LEMOS, Francine Brambate Carvalhinho; NAHAS, William Carlos
- Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country(2022) SZOR, Roberta Shcolnik; FERNANDES, Fabio; LINO, Angelina Maria Martins; MENDONCA, Leonardo Oliveira; SEGURO, Fernanda Salles; FEITOSA, Valkercyo Araujo; CASTELLI, Jussara Bianchi; JORGE, Lecticia Barbosa; ALVES, Lucas Bassolli de Oliveira; NEVES, Precil Diego Miranda de Menezes; SOUZA, Evandro de Oliveira; CAVALCANTE, Livia Barreira; MALHEIROS, Denise; KALIL, Jorge; MARTINEZ, Gracia Aparecida; ROCHA, VandersonBackground: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients' medical records were retrospectively reviewed. Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, & GE; 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had & GE; 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG & GE; 2 were identified as independent risk factors for reduced survival. Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.
- Bevacizumab-Associated Thrombotic Microangiopathy Treated with Eculizumab: A Case Report(2023) PADILHA, Wallace Stwart Carvalho; CESAR, Bruno Nogueira; PACHECO, Samara Theodoro; SOUSA, Alessandra Alves De; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; TEIXEIRA, Marcela Crosara AlvesPatient: Female, 64-year-old Final Diagnosis: Bevacizumab-associated thrombotic microangiopathy Symptoms: Microangiopathic hemolytic anemia and acute kidney injury Clinical Procedure: - Specialty: Nephrology Objective: Rare disease Background: Bevacizumab is an approved targeted therapy for metastatic cancer treatment. It can have adverse effects on multiple organs. Despite its low incidence, thrombotic microangiopathy (TMA) is the most severe complication. TMA has been associated with complement dysregulation, and treatment with eculizumab can be effective, despite the paucity of literature on eculizumab therapy for bevacizumab-associated TMA. To date, 10 cases have been reported, with less than half of them including a kidney biopsy. We present a new case of bevacizumab-associated TMA successfully treated with eculizumab, along with kidney biopsy records and an overview of mechanisms underlying TMA development in bevacizumab-treated patients. Case Report: A female patient diagnosed with metastatic breast cancer who was treated with bevacizumab in conjunction with chemotherapy was admitted to the hospital for acute kidney injury requiring hemodialysis, microangiopathic hemolytic anemia, and thrombocytopenia. TMA was diagnosed and was later confirmed by a kidney biopsy. Primary causes for TMA, such as ADAMTS13 deficiency and shiga toxin associated hemolytic-uremic syndrome, were ruled out, and the patient's condition was ultimately found to be triggered by exposure to bevacizumab. After discontinuing bevacizumab and receiving 4 weekly doses of eculizumab, kidney function and hematological parameters improved. Conclusions: Bevacizumab-associated TMA can be reversed or attenuated in some patients with the use of eculizumab (inhibiting complement system overactivation), possibly reducing time to recovery, with fewer long-term sequelae. This additional case encourages future clinical trials to evaluate the safety and efficacy of eculizumab in cases of TMA associated with bevacizumab.
- Determination of Anti-Phospholipase A2 and Anti-Thrombospondin Type 1 Domain-Containing Protein 7A in Latin Patients with Membranous Nephropathy(2023) BATTAINI, Ligia C.; RANZANI, Otavio T.; MARCAL, Lia J.; ANTONANGELO, Leila; JORGE, Lecticia B.; BITENCOURT, Cristiane D.; WORONIK, Victoria; MALHEIROS, Denise M. A.; YU, LuisPrimary membranous nephropathy (MN) is caused by antibodies against podocyte antigens, especially the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A). This study's aim was the determination of anti-PLA2R, anti-THSD7A serum antibodies, and anti-PLA2R renal tissue staining prevalence in a Latin population with MN, as well as evaluating their role as biomarkers for disease activity. The performance of the two anti-PLA2R serum diagnostic methods-ELISA and indirect immunofluorescence (IFI)-was evaluated for the diagnosis of MN. Fifty-nine patients, including 29 with MN, 18 with lupus membranous nephropathy (LMN) and 12 with focal and segmental glomerulosclerosis (FSGS), were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R staining. Twenty-one patients with MN were followed for 1 year. Patients with LMN and FSGS were negative for both antibodies. All 29 MN patients were negative for anti-THSD7A; 16 MN patients were positive for anti-PLA2R by ELISA and/or IFI, and 3 MN patients were positive for anti-PLA2R only by IFI. Thus, the anti-PLA2R ELISA test demonstrated 45% sensitivity and 97% specificity, while the IFI test showed, respectively, 55% and 100% in our MN patients. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, corresponding to a 72% sensitivity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. In conclusion, determination of anti-PLA2R antibodies in the MN Latin population showed similar rates to those reported for other populations. The anti-PLA2R serum levels correlated with MN disease activity.
- Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis(2023) LOPES-GONCALVES, Guilherme; COSTA-PESSOA, Juliana Martins; PIMENTA, Ruan; TOSTES, Ana Flavia; SILVA, Eloisa Martins da; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; ZATZ, Roberto; THIEME, Karina; CAMARA, Niels Olsen Saraiva; OLIVEIRA-SOUZA, MariaFocal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome, which is characterized by podocyte injury. Given that the pathophysiology of nondiabetic glomerulosclerosis is poorly understood and targeted therapies to prevent glomerular disease are lacking, we decided to investigate the tight junction protein claudin-1 and the histone deacetylase sirtuin-1 (SIRT1), which are known to be involved in podocyte injury. For this purpose, we first examined SIRT1, claudin-1 and podocin expression in kidney biopsies from patients diagnosed with nondiabetic FSGS and found that upregulation of glomerular claudin-1 accompanies a significant reduction in glomerular SIRT1 and podocin levels. From this, we investigated whether a small molecule activator of SIRT1, SRT1720, could delay the onset of FSGS in an animal model of adriamycin (ADR)-induced nephropathy; 14 days of treatment with SRT1720 attenuated glomerulosclerosis progression and albuminuria, prevented transcription factor Wilms tumor 1 (WT1) downregulation and increased glomerular claudin-1 in the ADR + SRT1720 group. Thus, we evaluated the effect of ADR and/or SRT1720 in cultured mouse podocytes. The results showed that ADR [1 mu M] triggered an increase in claudin-1 expression after 30 min, and this effect was attenuated by pretreatment of podocytes with SRT1720 [5 mu M]. ADR [1 mu M] also led to changes in the localization of SIRT1 and claudin-1 in these cells, which could be associated with podocyte injury. Although the use of specific agonists such as SRT1720 presents some benefits in glomerular function, their underlying mechanisms still need to be further explored for therapeutic use. Taken together, our data indicate that SIRT1 and claudin-1 are relevant for the pathophysiology of nondiabetic FSGS.