LUCIENE MACHADO DOS REIS
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
18 resultados
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Agora exibindo 1 - 10 de 18
- Urinary CD80 and Serum suPAR as Biomarkers of Glomerular Disease among Adults in Brazil(2023) ZEN, Renata de Cassia; DOMINGUEZ, Wagner Vasques; BRAGA, Ivone; REIS, Luciene Machado dos; JORGE, Lecticia Barbosa; YU, Luis; WORONIK, Viktoria; DIAS, Cristiane BitencourtIntroduction: Urinary CD80 has been shown to have good specificity for minimal change disease (MCD) in children. However, the investigation of circulating factors such as soluble urokinase plasminogen activator receptor (suPAR) as biomarkers of focal segmental glomerulosclerosis (FSGS) is quite controversial. The objective of this study was to determine whether urinary CD80 and serum suPAR can be used for the diagnosis of MCD and FSGS, respectively, in the adult population of Brazil. We also attempted to determine whether those biomarkers assess the response to immunosuppressive treatment. Methods: This was a prospective study in which urine and blood samples were collected for analysis of CD80 and suPAR, respectively, only in the moment of renal biopsy, from patients undergoing to diagnostic renal biopsy. At and six months after biopsy, we analyzed serum creatinine, serum albumin, and proteinuria in order to evaluate the use of the CD80 and suPAR collected in diagnosis as markers of response to immunosuppressive treatment. In healthy controls were collected urinary CD80 and proteinuria, serum suPAR, and creatinine. Results: The results of 70 renal biopsies were grouped, by diagnosis, as follows: FSGS (n = 18); membranous nephropathy (n = 14); MCD (n = 5); and other glomerulopathies (n = 33). There was no significant difference among the groups in terms of the urinary CD80 levels, and serum suPAR was not significantly higher in the FSGS group, as would have been expected. Urinary CD80 correlated positively with nephrotic syndrome, regardless of the type of glomerular disease. Neither biomarker correlated with proteinuria at six months after biopsy. Conclusion: In adults, urinary CD80 can serve as a marker of nephrotic syndrome but is not specific for MCD, whereas serum suPAR does not appear to be useful as a diagnostic or treatment response marker.
- Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function(2012) CANCELA, Ana Ludimila; SANTOS, Raul Dias; TITAN, Silvia Maria; GOLDENSTEIN, Patricia Taschner; ROCHITTE, Carlos Eduardo; LEMOS, Pedro Alves; REIS, Luciene Machado dos; GRACIOLLI, Fabiana Giorgetti; JORGETTI, Vanda; MOYSES, Rosa MariaHigh serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m(2). Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score <= 10 (3.63 +/- 0.55 versus 3.49 +/- 0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6 +/- 0.5 versus 3.5 +/- 0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score ( p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function.
- A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation(2019) MARQUES, Igor Denizarde Bacelar; ARAUJO, Maria Julia Correia Lima Nepomuceno; GRACIOLLI, Fabiana Giorgetti; REIS, Luciene Machado dos; PEREIRA, Rosa Maria R.; ALVARENGA, Jackeline C.; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; ELIAS, Rosilene Motta; MOYSES, Rosa Maria Affonso; DAVID-NETO, EliasBackground Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). Methods In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Results Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Conclusions Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.
- Prefabricated Bone Flap: An Experimental Study Comparing Deep-Frozen and Lyophilized-Demineralized Allogenic Bones and Tissue Expression of Transforming Growth Factor beta(2013) RODRIGUES, Leandro; REIS, Luciene Machado dos; DENADAI, Rafael; RAPOSO-AMARAL, Cassio Eduardo; ALONSO, Nivaldo; FERREIRA, Marcus Castro; JORGETTI, VandaBackground: Extensive bone defects are still a challenge for reconstructive surgery. Allogenic bones can be an alternative with no donor area morbidity and unlimited amount of tissue. Better results can be achieved after allogenic bone preparation and adding a vascular supply, which can be done along with flap prefabrication. The purpose of this study was to evaluate demineralized/lyophilized and deep-frozen allogenic bones used for flap prefabrication and the tissue expression of transforming growth factor beta (TGF-beta) in these bone fragments. Methods: Fifty-six Wistar rat bone diaphyses were prepared and distributed in 4 groups: demineralized/lyophilized (experimental group 1 and control group 2) and deep freezing (experimental group 3 and control group 4). Two bone segments (one of each group) were implanted in rats to prefabricate flaps using superficial epigastric vessels (experimental groups) or only transferred as grafts (control groups). These fragments remained in their respective inguinal regions until the death that occurred at 2, 4, and 6 weeks after the operation. Semiquantitative histologic (tetracycline marking, cortical resorption, number of giant cells, and vascularization) and histomorphometrical quantitative (osteoid thickness, cortical thickness, and fibrosis thickness) analyses were performed. Transforming growth factor beta immunohistochemistry staining was also performed. Results: Group 1 fragments presented an osteoid matrix on their external surface in all periods. Cartilage formation and mineralization areas were also noticed. These findings were not observed in group 3 fragments. Group 1 had more mineralization and double tetracycline marks, which were almost not seen in group 3. Cortical resorption and the number of giant cells were greater in group 3 in all periods. Vascularization and fibrosis thickness were similar in both experimental groups. Group 1 had more intense TGF-beta staining within 2 weeks of study. Nevertheless, from 4 weeks onward, group 3 presented statistically significant stronger staining. Conclusions: Although there are some differences between the preparation methods of allogenic bone, it is possible to prefabricate flaps with demineralized/lyophilized and deep-frozen bones.
- Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO(2020) CARBONARA, Cinthia Esbrile Moraes; REIS, Luciene Machado dos; QUADROS, Kélcia Rosana da Silva; ROZA, Noemi Angelica Vieira; SANO, Rafael; CARVALHO, Aluizio Barbosa; JORGETTI, Vanda; OLIVEIRA, Rodrigo Bueno deABSTRACT Introduction: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. Methods: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. Results: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. Conclusion: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.
- Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE)(2018) ANITELI, Tatiana Martins; SIQUEIRA, Flavia Ramos de; REIS, Luciene Machado dos; DOMINGUEZ, Wagner Vasques; OLIVEIRA, Elizabeth Maria Costa de; CASTELUCCI, Patricia; MOYSES, Rosa Maria Affonso; JORGETTI, VandaHyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (P-i) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent P-i absorption is modulated by dietary P-i. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary P-i concentration over 2 days would alter hormones involved in P-i metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of P-i concentration in the diet affected the apoptosis of enterocytes, particularly with P-i overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of P-i in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.
- Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy(2012) SABBAGH, Yves; GRACIOLLI, Fabiana Giorgeti; O'BRIEN, Stephen; TANG, Wen; REIS, Luciene Machado dos; RYAN, Susan; PHILLIPS, Lucy; BOULANGER, Joseph; SONG, Wenping; BRACKEN, Christina; LIU, Shiguang; LEDBETTER, Steven; DECHOW, Paul; CANZIANI, Maria Eugenia F.; CARVALHO, Aluizio B.; JORGETTI, Vanda; MOYSES, Rosa M. A.; SCHIAVI, Susan C.Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.
- The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease(2021) DUAYER, Irene Faria; DUQUE, Eduardo Jorge; FUJIHARA, Clarice Kazue; OLIVEIRA, Ivone Braga de; REIS, Luciene Machado dos; MACHADO, Flavia Gomes; GRACIOLLI, Fabiana Giorgetti; JORGETTI, Vanda; ZATZ, Roberto; ELIAS, Rosilene Motta; MOYSES, Rosa Maria AffonsoSeveral factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of alpha-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.
- A prospective study of the influence of the skeleton on calcium mass transfer during hemodialysis(2018) GOLDENSTEIN, Patricia Taschner; GRACIOLLI, Fabiana Giorgeti; ANTUNES, Gisele Lins; DOMINGUEZ, Wagner Vasques; REIS, Luciene Machado dos; MOE, Sharon; ELIAS, Rosilene Motta; JORGETTI, Vanda; MOYSES, Rosa Maria AffonsoBackground Calcium gradient, the difference between serum calcium and dialysate calcium d[Ca], is the main contributor factor influencing calcium transfer during hemodialysis. The impact, however, of bone turnover, on calcium mass transfer during hemodialysis is still uncertain. Methods This prospective cross-sectional study included 10 patients on hemodialysis for a 57.6 +/- 16.8 months, with severe hyperparathyroidism. Patients were submitted to 3 hemodialysis sessions using d[Ca] of 1.25, 1.5 and 1.75 mmol/l in three situations: pre-parathyroidectomy (pre-PTX), during hungry bone (early post-PTX), and after stabilization of clinical status (late post-PTX). Biochemical analysis and calcium mass transfer were evaluated and serum bone-related proteins were quantified. Results Calcium mass transfer varied widely among patients in each study phase with a median of -89.5, -76.8 and -3 mmol using d[Ca] 1.25 mmol/L, -106, -26.8 and 29.7 mmol using d[Ca] 1.50 mmol/L, and 12.8, -14.5 and 38 mmol using d[Ca] 1.75 mmol/L during pre-PTX, early post-PTX and late post-PTX, respectively, which was significantly different among d[Ca] (p = 0.0001) and among phases (p = 0.040). Ca gradient and delta of Ca also differed among d [Ca] and phases (p<0.05 for all comparisons), whether ultrafiltration was similar. Serum Osteocalcin decreased significantly in late post-PTX, whereas Sclerostin increased earlier, in early post-PTX. Conclusions The skeleton plays a key role in Ca mass transfer during dialysis, either by determining pre-dialysis serum Ca or by controlling the exchangeable Ca pool. Knowing that could help us to decide which d[Ca] should be chosen in a given patient.
- Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin(2019) ARAUJO, Maria Julia Correia Lima Nepomuceno; MARQUES, Igor Denizarde Bacelar; GRACIOLLI, Fabiana Giorgetti; FUKUHARA, Luzia; REIS, Luciene Machado dos; CUSTODIO, Melani; JORGETTI, Vanda; ELIAS, Rosilene Mota; DAVID-NETO, Elias; MOYSES, Rosa M. A.In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-B ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.