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
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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.
- APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses(2021) WATANABE, Andreia; GUARAGNA, Mara Sanches; BELANGERO, Vera Maria Santoro; CASIMIRO, Fernanda Maria Serafim; PESQUERO, Joao Bosco; FELTRAN, Luciana de Santis; PALMA, Lilian Monteiro Pereira; VARELA, Patricia; NEVES, Precil Diego Miranda de Menezes; LERARIO, Antonio Marcondes; SOUZA, Marcela Lopes de; MELLO, Maricilda Palandi de; LUTAIF, Anna Cristina Gervasio de Brito; FERRARI, Cassio Rodrigues; SAMPSON, Matthew Gordon; ONUCHIC, Luiz Fernando; NOGUEIRA, Paulo Cesar KochBackground APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. Methods Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m(2)] and slow/non-progressors (eGFR > 30 mL/min/1.73 m(2) through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. Results Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. Conclusions Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.
- The immunohistological profile of membranous nephropathy associated with chronic Schistosoma mansoni infection reveals a glomerulopathy with primary features(2019) ARAUJO, Stanley de Almeida; NEVES, Precil Diego Miranda de Menezes; WANDERLEY, David Campos; REIS, Marlene Antonia dos; DIAS, Cristiane Bitencourt; MALHEIROS, Denise Maria Avancini Costa; ONUCHIC, Luiz Fernando
- 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.
- Brazilian Network of Pediatric Nephrotic Syndrome (REBRASNI)(2020) FELTRAN, Luciana S.; WATANABE, Andreia; GUARAGNA, Mara S.; MACHADO, Ivan C.; CASIMIRO, Fernanda M. S.; NEVES, Precil D. M. M.; PALMA, Lilian M.; VARELA, Patricia; VAISBICH, Maria H.; MARIE, Suely K. N.; FACINCANI, Inalda; PESQUERO, Joao B.; BELANGERO, Vera M. S.; SAMPSON, Matthew G.; NOGUEIRA, Paulo C. Koch; ONUCHIC, Luiz F.
- Periostin and polycystic kidney disease: more pieces in the puzzle(2019) WATANABE, Elieser H.; AMARAL, Andressa G.; ONUCHIC, Luiz F.
- Post-transplantation Recurrence of Fibrinogen A-alpha Amyloidosis(2021) FEITOSA, Valkercyo A.; FERREIRA, Fernanda T.; NEVES, Precil D. M. M.; WATANABE, Andreia; WATANABE, Elieser H.; PROENCA, Henrique M. S.; AZEVEDO, Vega F. S.; PESTANA, Jose Osmar M.; ONUCHIC, Luiz F.
- 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.
- Renal cyst growth is the main determinant for hypertension and concentrating deficit in Pkd1-deficient mice(2014) FONSECA, Jonathan M.; BASTOS, Ana P.; AMARAL, Andressa G.; SOUSA, Mauri F.; SOUZA, Leandro E.; MALHEIROS, Denise M.; PIONTEK, Klaus; IRIGOYEN, Maria C.; WATNICK, Terry J.; ONUCHIC, Luiz F.We have bred a Pkd1 floxed allele with a nestin-Cre expressing line to generate cystic mice with preserved glomerular filtration rate to address the pathogenesis of complex autosomal dominant polycystic kidney disease (ADPKD) phenotypes. Hypertension affects about 60% of these patients before loss of renal function, leading to significant morbimortality. Cystic mice were hypertensive at 5 and 13 weeks of age, a phenotype not seen in noncystic controls and Pkd1-haploinsufficient animals that do not develop renal cysts. Fractional sodium excretion was reduced in cystic mice at these ages. Angiotensinogen gene expression was higher in cystic than noncystic kidneys at 18 weeks, while ACE and the All receptor were expressed in renal cyst epithelia. Cystic animals displayed increased renal cAMP, cell proliferation, and apoptosis. At 24 weeks, mean arterial pressure and fractional sodium excretion did not significantly differ between the cystic and noncystic groups, whereas cardiac mass increased in cystic mice. Renal concentrating deficit is also an early finding in ADPKD. Maximum urine osmolality and urine nitrite excretion were reduced in 10-13- and 24-week-old cystic mice, deficits not found in haploinsufficient and noncystic controls. A trend of higher plasma vasopressin was observed in cystic mice. Thus, cyst growth most probably plays a central role in early-stage ADPKD-associated hypertension, with activation of the intrarenal renin-angiotensin system as a key mechanism. Cyst expansion is also likely essential for the development of the concentrating deficit in this disease. Our findings are consistent with areas of reduced perfusion in the kidneys of patients with ADPKD.