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
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
conferenceObject N-ACETYLCYSTEINE IMPROVES SURVIVAL, RENAL AND CARDIAC PHENOTYPES IN Pkd1-DEFICIENT CYSTIC MICE(2016) MOYSES, Zenaide P.; BASTOS, Ana P.; BALBO, Bruno E.; GARNICA, Margoth R.; CURI-SALEMI, Vera M.; ONUCHIC, Luiz F.- Giant Renal Angiomyolipoma Following Ovarian Stimulation Therapy(2018) WATANABE, Elieser H.; NEVES, Precil D.; BALBO, Bruno E.; SAMPAIO, Carlos A.; ONUCHIC, Luiz F.Renal angiomyolipomas (AMLs) are benign tumors with higher prevalence in women. Female hormones have been shown to induce AML enlargement. This case refers to a 40-year-old woman with 4 left kidney AMLs, the larger ones with 1.0 and 1.3 cm. Ten months after ovarian stimulation for egg harvesting, a computed tomography revealed an 18-cm AML with large-caliber vessels. Given her high risk of AML bleeding, the patient was submitted to selective arterial embolization, which turned out unsuccessful, supporting a plan of nephron-sparing surgery. Our case highlights the pro-growth effects of female hormones on AML, with particular emphasis to ovarian stimulation. (C) 2017 Elsevier Inc.
- Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout(2016) BALBO, Bruno E.; AMARAL, Andressa G.; FONSECA, Jonathan M.; CASTRO, Isac de; SALEMI, Vera M.; SOUZA, Leandro E.; SANTOS, Fernando dos; IRIGOYEN, Maria C.; QIAN, Feng; CHAMMAS, Roger; ONUCHIC, Luiz F.Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond) Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1(cond/cond):Nestin(cre);Lgals(3-/-) (CYG-) and Pkd1(+/-);Lgals(3-/-) (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single -mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1(v/v); VVG+) showed that Pkd1(v/v);Lgals(3-/-) (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkdl-deficient models and suppression of galectin-3 expression rescues this phenotype.
- Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice(2021) SOUSA, Marciana V.; AMARAL, Andressa G.; FREITAS, Jessica A.; MURATA, Gilson M.; WATANABE, Elieser H.; BALBO, Bruno E.; TAVARES, Marcelo D.; HORTEGAL, Renato A.; ROCON, Camila; SOUZA, Leandro E.; IRIGOYEN, Maria C.; SALEMI, Vera M.; ONUCHIC, Luiz F.Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13-18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
- 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.
- Abdominal pain, arthritis, and nephrotic syndrome in a Syrian patient(2012) BALBO, Bruno Eduardo P.; SILVA, Andre Albuquerque; AMARAL, Andressa Godoy; MALHEIROS, Denise M. A. C.; ONUCHIC, Luiz Fernando; BARROS, Rui Toledo
- Secondary Hypertension Caused by Massive Renal Lymphangiomatosis(2013) BALBO, Bruno E. P.; VICENTINI, Fabio C.; WATANABE, Elieser H.; HISANO, Marcelo; SROUGI, Miguel; ONUCHIC, Luiz F.
- 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.
- Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume(2014) BALBO, B. E. P.; SAPIENZA, M. T.; ONO, C. R.; JAYANTHI, S. K.; DETTONI, J. B.; CASTRO, I.; ONUCHIC, L. F.Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.
- Dialysis as a Treatment Option for a Patient With Normal Kidney Function and Familial Tumoral Calcinosis Due to a Compound Heterozygous FGF23 Mutation(2018) GOLDENSTEIN, Patricia T.; NEVES, Precil D.; BALBO, Bruno E.; ELIAS, Rosilene M.; PEREIRA, Alexandre C.; ONUCHIC, Luiz F.; JUPPNER, Harald; JORGETTI, Vanda; ABENSUR, Hugo; MOYSES, Rosa MariaPrimary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c. 201G>C (p. Gln67His) and c. 466C>T (p. Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.