ROBERTO ZATZ
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 - Líder
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
Resultados de Busca
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- Influence of low free thyroxine on progression of chronic kidney disease(2020) SOUZA, Alexandre Barbosa Camara de; ARANTES, Marcia Fernanda; ZATZ, Roberto; ELIAS, Rosilene Motta; LOPES, Roberto Iglesias; MACEDO, EtienneBackgroundHypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism.MethodsWe assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels..ResultsOne thousand six hundred ten patients (6415years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30-45 and 15-30ml/min/1.73m(2) in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT, p=0.032). Median follow-up time was of 21months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was -0.05(-0.26, 0.23) ml/min/1.73m(2), reaching 1.7(1.3, 2.4) ml/min/1.73m(2) by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT.Conclusions We confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.
- NF-kappa B System Is Chronically Activated and Promotes Glomerular Injury in Experimental Type 1 Diabetic Kidney Disease(2020) FORESTO-NETO, Orestes; ALBINO, Amanda Helen; ARIAS, Simone Costa Alarcon; FAUSTINO, Viviane Dias; ZAMBOM, Fernanda Florencia Fregnan; CENEDEZE, Marcos Antonio; ELIAS, Rosilene Motta; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; FUJIHARA, Clarice Kazue; ZATZ, RobertoHigh glucose concentration can activate TLR4 and NF-kappa B, triggering the production of proinflammatory mediators. We investigated whether the NF-kappa B pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups - progressors and non-progressors - could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-kappa B and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-kappa B or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-kappa B p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-kappa B pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD.
- Poikilodermatous Mycosis Fungoides: Comparative Study of Clinical, Histopathological and Immunohistochemical Features(2020) BERG, Roberta Vasconcelos; VALENTE, Neusa Yuriko Sakai; FANELLI, Camilla; WU, Isabelle; PEREIRA, Juliana; ZATZ, Roberto; SANCHES, Jose AntonioBackground: Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma. Objectives: Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation. Methods: Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF). Results: Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mix-pMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mix-pMF). Discussion: This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.
- NF-kappa B blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease(2020) OLIVEIRA, Karin Carneiro; ZAMBOM, Fernanda Florencia Fregnan; ALBINO, Amanda Helen; ARIAS, Simone Costa Alarcon; AVILA, Victor Ferreira; FAUSTINO, Viviane Dias; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; FUJIHARA, Clarice Kazue; ZATZ, RobertoNitric oxide synthase inhibition by N-omega-nitro-L-arginine methyl ester (L-NAME) plus a high-salt diet (HS) is a model of chronic kidney disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but progressive renal injury develops, associated with persistent low-grade renal inflammation. We investigated whether innate immunity. and in particular the NF-kappa B system, is involved in this process. Male Munich-Wistar rats received HS + L-NAME (32 mg.kg(-1).day(-1)), whereas control rats received HS only. Treatment was ceased after week 4 when 30 rats were studied. Additional rats were studied at week 8 (n = 30) and week 28 (n = 30). As expected, HS + L-NAME promoted severe hypertension, albuminuria, and renal injury after 4 wk of treatment, whereas innate immunity activation was evident. After discontinuation of treatments, partial regression of renal injury and inflammation occurred, along with persistence of innate immunity activation at week 8. At week 28, glomerular injury worsened, while renal inflammation persisted and renal innate immunity remained activated. Temporary administration of the NF-kappa B inhibitor pyrrolidine dithiocarbamate, in concomitancy with the early 4-wk HS + L-NAME treatment, prevented the development of late renal injury and inflammation, an effect that lasted until the end of the study. Early activation of innate immunity may be crucial to the initiation of renal injury in the HS + L-NAME model and to the autonomous progression of chronic nephropathy even after cessation of the original insult. This behavior may be common to other conditions leading to CKD.
- Design and methodology of the Aging Nephropathy Study (AGNES): a prospective cohort study of elderly patients with chronic kidney disease(2020) COELHO, Venceslau A.; SANTOS, Giovani GN.; AVESANI, Carla M.; BEZERRA, Cicero Italo L.; SILVA, Luana Cristina A.; LAUAR, Julia C.; LINDHOLM, Bengt; STENVINKEL, Peter; JACOB-FILHO, Wilson; NORONHA, Irene L.; ZATZ, Roberto; MOYSES, Rosa M. A.; ELIAS, Rosilene M.Background: Renal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m(2). However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology. Methods: AGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at the Hospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho. Discussion: The AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis.