LUIZ FERNANDO ONUCHIC
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
11 resultados
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bookPart Nefropatias hereditárias não císticas(2022) NEVES, Precil Diego Miranda de Menezes; WATANABE, Elieser Hitoshi; ONUCHIC, Luiz Fernando- Two cases of fungal cyst infection in ADPKD: is this really a rare complication?(2019) ONUCHIC, Laura; SATO, Victor Augusto Hamamoto; NEVES, Precil Diego Miranda de Menezes; BALBO, Bruno Eduardo Pedroso; PORTELA-NETO, Antonio Abel; FERREIRA, Fernanda Trani; WATANABE, Elieser Hitoshi; WATANABE, Andreia; ALMEIDA, Maria Claudia Stockler de; TESTAGROSSA, Leonardo de Abreu; CHOCAIR, Pedro Renato; ONUCHIC, Luiz FernandoBackground: Cyst infection is a prevalent complication in autosomal dominant polycystic kidney disease (ADPKD) patients, however therapeutic and diagnostic approaches towards this condition remain unclear. The confirmation of a likely episode of cyst infection by isolating the pathogenic microorganism in a clinical scenario is possible only in the minority of cases. The available antimicrobial treatment guidelines, therefore, might not be appropriate to some patients. Case presentation: We describe two unique cases of kidney cyst infection by Candida albicans, a condition that has not been previously described in literature. Both cases presented clear risk factors for Candida spp. infection. However, since there was no initial indication of cyst aspiration and culture, antifungal therapy was not immediately started and empirical treatment was initiated as recommended by the current guidelines. Antifungal treatment was instituted in both cases along the clinical course, according to their specificities. Conclusion: Our report highlights the possibility of Candida spp. cyst infection. Failure of clinical improvement with antibiotics should raise the suspicion of a fungal infection. Identification of infected cysts should be pursued in such cases, particularly with PET-CT, and when technically possible followed by cyst aspiration and culture to guide treatment. Risk factors for this condition, such as Candida spp. colonization, previous antimicrobial therapy, hemodialysis, necrotizing pancreatitis, gastrointestinal/hepatobiliary surgical procedure, central venous catheter, total parenteral nutrition, diabetes mellitus and immunodeficiency (neutropenia < 500 neutrophils/mL, hematologic malignancy, chemotherapy, immunosuppressant drugs), should be also considered accepted criteria for empirical antifungal therapy.
bookPart Doenças císticas e tumores renais(2022) WATANABE, Elieser Hitoshi; ONUCHIC, Luiz Fernando- Functional Budd-Chiari Syndrome Associated With Severe Polycystic Liver Disease(2017) NEVES, Precil Diego Miranda de Menezes; BALBO, Bruno Eduardo Pedroso; WATANABE, Elieser Hitoshi; ROCHA-SANTOS, Vinicius; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz Augusto Carneiro; ONUCHIC, Luiz FernandoA 50-year-old woman with end-stage renal disease secondary to autosomal dominant polycystic kidney disease was referred to a quaternary care center due to significantly increased abdominal girth. Her physical examination revealed tense ascites and abdominal collateral veins. A 10-L paracentesis improved abdominal discomfort and disclosed a transudate, suggestive of portal hypertension. A computed tomographic scan revealed massive hepatomegaly caused by multiple cysts of variable sizes, distributed throughout all hepatic segments. Contrast-enhanced imaging uncovered extrinsic compression of hepatic and portal veins, resulting in functional Budd-Chiari syndrome and portal hypertension. Although image-guided drainage followed by sclerosis of dominant cysts could potentially lead to alleviation of the extrinsic compression, the associated significant risk of cyst hemorrhage and infection precluded this procedure. In this scenario, the decision was to submit the patient to a liver-kidney transplantation. After 1 year of this procedure, the patient maintains normal liver and kidney function and refers significant improvement in quality of life.
- Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America(2021) SILVEIRA-NETO, Joaquim Nelito Da; AHN, Guilherme Jinson de Oliveira; NEVES, Precil Diego Miranda de Menezes; BAPTISTA, Vinicius Augusto Ferreira; ARAUJO, Stanley de Almeida; WANDERLEY, David Campos; WATANABE, Andreia; WATANABE, Elieser Hitoshi; MURAI, Neide Missae; BERTOLLO, Eny Maria Goloni; VIEIRA-NETO, Osvaldo Merege; DANTAS, Marcio; ANTONIO, Sergio Ricardo de; COSTA, Roberto Silva; BAPTISTA, Maria Alice Sperto Ferreira; MOYSES-NETO, Miguel; ONUCHIC, Luiz FernandoBackground Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. Case presentation - case 1 A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. Case 2 A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. Conclusion We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.
- The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures(2021) WATANABE, Elieser Hitoshi; COELHO, Fernando Morbeck Almeida; LEAO FILHO, Hilton; BALBO, Bruno Eduardo Pedroso; NEVES, Precil Diego Miranda de Menezes; FRANZIN, Fernanda Maria; YAMAUCHI, Fernando Ide; ONUCHIC, Luiz FernandoRenal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.
- Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center(2019) AMARAL, Alexandre Franco; OLIVEIRA, Martina Rodrigues de; DIAS, Olivia Meira; ARIMURA, Fabio Eiji; FREITAS, Carolina Salim Goncalves; ACENCIO, Milena Marques Pagliarelli; ALVARENGA, Vanessa Adelia de; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro; BALDI, Bruno Guedes; SCLEROSIS, Tuberous; BALBO, Bruno Eduardo Pedroso; WATANABE, Elieser Hitoshi; SAMORANO, Luciana Paula; ONUCHIC, Luiz Fernando; RIVITTI-MACHADO, Maria Cecilia da Matta; MANREZA, Maria Luiza Giraldes de; CORDEIRO, Mauricio Dener; TAKAHASHI, Patricia; OLIVEIRA, Zilda Najjar Prado deIntroductionSerum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement.MethodsWe conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels.ResultsOne hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404-1588) versus 162 (117-232)pg/mL, respectively (p<0.001). Patients with tuberous sclerosis complex-LAM, TSC-LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641-2732) vs. 772 (370-1383), p=0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r=-0.26, p=0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800pg/mL (35% vs. 13%, p=0.02).ConclusionsIn LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.
- A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18, IL17A, and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease(2020) SANTOS, Alexandra Gomes dos; WATANABE, Elieser Hitoshi; FERREIRA, Daiane Tomomi; OLIVEIRA, Jamille; NAKANISHI, Erika Shimoda; OLIVEIRA, Claudia Silva; BOCCHI, Edimar; NOVAES, Cristina Terra Gallafrio; CRUZ, Fatima; CARVALHO, Noemia Barbosa; SATO, Paula Keiko; YAMASHIRO-KANASHIRO, Edite Hatsumi; PONTILLO, Alessandra; FREITAS, Vera Lucia Teixeira de; ONUCHIC, Luiz Fernando; SHIKANAI-YASUDA, Maria AparecidaBackground Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism profiles and cardiomyopathy or T. cruzi parasitemia, as well as the impact of HIV infection on cardiopathy. Methods Two hundred twenty-six patients and 90 control individuals were analyzed. IL1B rs1143627 T>C, IL6 rs1800795 C>G, IL17A rs2275913 G>A, IL18 rs187238 C>G, and IL18 rs1946518 C>A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by PCR. Results Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The IL6 rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between IL17A rs2275913 AA and IL18 s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). IL18 rs1946518 AA and IL1B rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class >= 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for IL18 rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class >= 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA >= 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively). Conclusions Our data support a protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the IL6 CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.
- Photobiomodulation for Preventive Therapy of Recurrent Herpes Labialis: A 2-Year In Vivo Randomized Controlled Study(2022) ZANELLA, Paola Aragon; ONUCHIC, Luiz Fernando; WATANABE, Elieser Hitoshi; AZEVEDO, Luciane Hiramatsu; ARANHA, Ana Cecilia Correa; RAMALHO, Karen Mueller; EDUARDO, Carlos de PaulaObjective: The present study aimed to evaluate the effectiveness of the application of photobiomodulation therapy (PBMT) in the prevention of recurrent herpes labialis (RHL) through a randomized controlled clinical trial.Background data: RHL is a lifelong infection that effects patients' quality of life. In the literature PBMT has shown positive results preventing RHL, decreasing recurrences and severity of lesions. Despite the good results reported, there are still few controlled clinical studies published on the subject.Methods: For this study, 158 volunteers were recruited and were randomly divided into three study groups: Laser 1-1 J/point (L1J): n = 61, Laser 2-2 J/point (L2J): n = 50, and placebo-0 J/point: n = 47. The treatment consisted of a protocol of 15 sessions throughout 6 months and 2 years of follow-up posttreatment.Results: The results showed that L1J presented the most satisfactory results concerning the reduction of the number of lesions per year and less severity of recurrences in the long-term evaluation when compared with L2J. Both Laser Groups (L1J and L2J) were statistically more efficient than placebo in all aspects analyzed. All patients who received laser treatment (L1J and L2J) and presented recurrences had significant improvement in frequency and/or severity of lesions. No patient had side effects from treatment.Conclusions: PBMT can be effective in the reduction of the frequency of recurrences of RHL and in the severity of postirradiation lesions that may appear.
- Brazilian Consortium for the Study on Renal Diseases Associated With COVID-19: A Multicentric Effort to Understand SARS-CoV-2-Related Nephropathy(2020) TEIXEIRA JUNIOR, Antonio Augusto Lima; NEVES, Precil Diego Miranda de Menezes; LAGES, Joyce Santos; CUNHA, Kaile de Araujo; MUNIZ, Monique Pereira Rego; BRITO, Dyego Jose de Araujo; WATANABE, Andreia; WATANABE, Elieser Hitoshi; ONUCHIC, Luiz Fernando; NUNES, Lucas Lobato Acatauassu; COUTINHO FILHO, Antonio Fernando; BARCELOS, Flavia Lara; GATTO, Giuseppe Cesare; MONTEIRO, Antonio; POLIDO, Diego do Amaral; MOTTA, Douglas Rafanelle Moura de Santana; LEITE, Thaisa de Oliveira; GUEDES, Felipe Leite; GOMES, Orlando Vieira; VALENTE, Lucila Maria; ISRAEL, Karla Cristina Silva Petruccelli; LADCHUMANANANDASIVAM, Francisco Rasiah; FARIAS, Ligia Cristina Lopes de; MARQUES, Igor Denizarde Bacelar; ULIANO, Gustavo Lemos; MARAMALDO, Carlos Eduardo Campos; NETO, Lidio Goncalves Lima; LUCHI, Weverton Machado; WANDERLEY, David Campos; ARAUJO, Stanley de Almeida; SALGADO FILHO, Natalino; SILVA, Gyl Eanes BarrosKidney involvement appears to be frequent in coronavirus disease 2019 (COVID-19). Despite this, information concerning renal involvement in COVID-19 is still scarce. Several mechanisms appear to be involved in the complex relationship between the virus and the kidney. Also, different morphological patterns have been described in the kidneys of patients with COVID-19. For some authors, however, this association may be just a coincidence. To investigate this issue, we propose assessing renal morphology associated with COVID-19 at the renal pathology reference center of federal university hospitals in Brazil. Data will come from a consortium involving 17 federal university hospitals belonging to Empresa Brasileira de Servicos Hospitalares (EBSERH) network, as well as some state hospitals and an autopsy center. All biopsies will be sent to the referral center for renal pathology of the EBSERH network. The data will include patients who had coronavirus disease, both alive and deceased, with or without pre-existing kidney disease. Kidney biopsies will be analyzed by light, fluorescence, and electron microscopy. Furthermore, immunohistochemical (IHC) staining for various inflammatory cells (i.e., cells expressing CD3, CD20, CD4, CD8, CD138, CD68, and CD57) as well as angiotensin-converting enzyme 2 (ACE2) will be performed on paraffinized tissue sections. In addition to ultrastructural assays, in situ hybridization (ISH), IHC and reverse transcription-polymerase chain reaction (RT-PCR) will be used to detect Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in renal tissue. For the patients diagnosed with Collapsing Glomerulopathy, peripheral blood will be collected for apolipoprotein L-1 (APOL1) genotyping. For patients with thrombotic microangiopathy, thrombospondin type 1 motif, member 13 (ADAMTS13), antiphospholipid, and complement panel will be performed. The setting of this study is Brazil, which is second behind the United States in highest confirmed cases and deaths. With this complete approach, we hope to help define the spectrum and impact, whether immediate or long-term, of kidney injury caused by SARS-CoV-2.