LUCIENE MACHADO DOS REIS
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
31 resultados
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- Overview of renal osteodystrophy in Brazil: a cross-sectional study(2023) CARBONARA, Cinthia E. M.; ROZA, Noemi A. V.; REIS, Luciene M. dos; CARVALHO, Aluizio B.; JORGETTI, Vanda; OLIVEIRA, Rodrigo Bueno deIntroduction: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. Methods: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. Results: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. Conclusions: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.
- Persistence of Bone and Mineral Disorders 2 Years After Successful Kidney Transplantation(2013) NEVES, Carolina L.; REIS, Luciene M. dos; BATISTA, Daniella G.; CUSTODIO, Melani R.; GRACIOLLI, Fabiana G.; MARTIN, Rita de Cassia T.; NEVES, Katia R.; DOMINGUEZ, Wagner V.; MOYSES, Rosa M.; JORGETTI, VandaBackground. Studies that have conducted bone biopsies after kidney transplantation are scarce, and the results are conflicting. Methods. We evaluate the bone histomorphometry, in vitro proliferation, and alkaline phosphatase expression in osteoblasts isolated from bone biopsies from 27 kidney transplant patients. The patients had preserved renal function and were treated with the same immunosuppressive therapy, receiving a minimum dose of corticosteroids. Results. The biochemical analysis revealed that 41% of the patients presented with hypercalcemia, 26% presented with hypophosphatemia, and hypovitaminosis D was detected in 63%. The histomorphometric analysis showed a reduced trabecular number and increased trabecular separation, mineral apposition rate, and mineralization lag time, as well as higher osteoid surface, osteoblastic surface, resorption surface, and osteoclastic surface and a lower mineralizing surface, compared with the controls. Based on the TMV classification, bone turnover was normal in 48%, high in 26%, and low in 26% of patients. Bone mineralization was delayed in 48% of the patients, and 58% of the patients with hypovitaminosis D presented with delayed bone mineralization. Bone volume was low in 37% of the patients. The osteoblasts from patients exhibited a higher degree of proliferation compared with those from controls. Conclusion. Eight-two percent of our patients presented with alterations in at least one of the TMV parameters. Persistence of hyperparathyroidism, hypovitaminosis D, and immunosuppressive drugs may have influenced osteoblast function, which would explain many of the bone alterations found in these patients.
- Disturbances of Wnt/beta-catenin pathway and energy metabolism in early CKD: effect of phosphate binders(2013) OLIVEIRA, Rodrigo B. de; GRACIOLLI, Fabiana G.; REIS, Luciene M. dos; CANCELA, Ana L. E.; CUPPARI, Lilian; CANZIANI, Maria E.; CARVALHO, Aluizio B.; JORGETTI, Vanda; MOYSES, Rosa M. A.Mineral bone disorder (MBD) is an early complication of chronic kidney disease (CKD), with complex interactions in the bonekidneyenergy axis. These events lead to impaired bone remodelling, which in turn is associated with cardiovascular disease. Recently, we reported on a positive effect of phosphate binder treatment on bone remodelling markers and a reduction in serum FGF-23 levels in predialysis-CKD patients. The goal of the present study of this trial was to examine the effects of phosphate binders on energy-regulating hormones and Wnt pathway. In this present post hoc analysis of the above randomized, open-label, 8-week trial, which compared the effects of increasing doses of sevelamer-HCl or calcium acetate on various CKD-MBD parameters in 40 normophosphatemic CKD Stage 34 patients, we measured serum sclerostin, Dickkopf-1, leptin, adiponectin and serotonin concentrations. Serum sclerostin, Dickkopf-1 and leptin were elevated at baseline despite normal calcium, phosphorus levels and daily urinary phosphorus excretion. There were significant and positive correlations between sclerostin and FGF-23, as well between leptin and Dickkopf-1. Treatment with both phosphate binders led to a significant decrease in phosphate overload. However, sevelamer-HCl, but not with calcium acetate, led to a significant decrease in serum FGF-23, sclerostin and leptin, and to a significant increase in bone alkaline phosphatase levels. Early stages of CKD are associated with an impairment of the Wnt pathway, as reflected by elevated sclerostin, and a dysregulation of energy-regulating hormones. Many of these disturbances can be ameliorated by phosphate binder treatment, more with sevelamer-HCl than with calcium acetate.
- The unexpected presence of iron in bone biopsies of hemodialysis patients(2018) CUSTODIO, Melani R.; ELIAS, Rosilene M.; VELASQUEZ, Wagner D.; REIS, Luciene M. dos; OLIVEIRA, Ivone B.; MOYSES, Rosa M. A.; CARVALHO, Aluizio B.; JORGETTI, VandaPurpose Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics. Methods This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital. Results Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload. Conclusion Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.
- Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system(2012) CUSTODIO, Melani R.; KOIKE, Marcia K.; NEVES, Katia R.; REIS, Luciene M. dos; GRACIOLLI, Fabiana G.; NEVES, Carolina L.; BATISTA, Daniella G.; MAGALHAES, Andrea O.; HAWLITSCHEK, Philippe; OLIVEIRA, Ivone B.; DOMINGUEZ, Wagner V.; MOYSES, Rosa M. A.; JORGETTI, VandaBackground. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V + normal-phosphorus diet (np)) and 'Nx + PTx': G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, alpha-actin, transforming growth factor-beta (TGF-beta) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.
- Serum sclerostin is an independent predictor of mortality in hemodialysis patients(2014) GONCALVES, Flavia Leticia Carvalho; ELIAS, Rosilene M.; REIS, Luciene M. dos; GRACIOLLI, Fabiana G.; ZAMPIERI, Fernando Godinho; OLIVEIRA, Rodrigo B.; JORGETTI, Vanda; MOYSES, Rosa M. A.Background: Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality. Methods: we measured serum Scl in a hemodialysis patients' cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death. Results: Ninety-one patients aged 42.3 +/- 18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR = 2.2), higher age (HR = 1.04) and presence of diabetes (HR = 2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality. Conclusion: Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.
conferenceObject Chronic Kidney Disease-Associated Frailty is characterized by changes in Muscular Expression of RANKL and FNDC5, which are partially reverted after Parathyroidectomy(2023) DUQUE, Eduardo J.; CRISPILHO, Shirley; OLIVEIRA, Ivone B.; REIS, Luciene M. dos; FURUKAWA, Luzia; TAKAYAMA, Liliam; PEREIRA, Rosa M.; SHINJO, Samuel K.; AVESANI, Carla; JORGETTI, Vanda; ELIAS, Rosilene M.; MOYSES, Rosa M.- Transcription factor HNF4 & alpha;2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy(2023) MARTINEZ-CALLE, Marta; COURBON, Guillaume; HUNT-TOBEY, Bridget; FRANCIS, Connor; SPINDLER, Jadeah; WANG, Xueyan; REIS, Luciene M. dos; MARTINS, Carolina S. W.; SALUSKY, Isidro B.; MALLUCHE, Hartmut; NICKOLAS, Thomas L.; MOYSES, Rosa M. A.; DAVID, Valentin; MARTIN, AlineRenal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4 & alpha; (HNF4 & alpha;), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4 & alpha; expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4 & alpha; resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4 & alpha;1 and Hnf4 & alpha;2, we showed that HNF4 & alpha;2 is the main osseous Hnf4 & alpha; isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4 & alpha;2 prevented bone loss in mice with CKD. Our results showed that HNF4 & alpha;2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.
- Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease(2015) OLIVEIRA, Rodrigo A. de; BARRETO, Fellype C.; MENDES, Monique; REIS, Luciene M. dos; CASTRO, Joao Henrique; BRITTO, Zita Maria L.; MARQUES, Igor D. B.; CARVALHO, Aluizio B.; MOYSES, Rosa M.; JORGETTI, VandaChronic kidney disease-mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins, and dialysis modality. Although extensively studied in hemodialysis (HD) patients, only a few studies exist for peritoneal dialysis (PD) patients. Since most of these older studies contain no bone biopsy data, we studied the pattern of renal osteodystrophy in 41 prevalent PD patients. The most common presentation was adynamic bone disease (49%). There was a significant inverse association between serum sclerostin (a Wnt/beta-catenin pathway inhibitor that decreases osteoblast action and bone formation) and the bone formation rate. Bone alkaline phosphatase had the best sensitivity and specificity to detect both high-and low-turnover diseases. The comparison between nondiabetic PD and HD patients, matched by age, gender, parathyroid hormone level, and length of dialysis, revealed low 25-hydroxyvitamin D levels, worse bone mineralization, and low bone turnover in the nondiabetic PD group. Thus, adynamic bone disease was the most frequent type of renal osteodystrophy in PD patients. Sclerostin seems to participate in the pathophysiology of adynamic bone disease and bone alkaline phosphatase was the best serum marker of bone turnover in these patients.
- Ethnic differences in bone and mineral metabolism in healthy people and patients with CKD(2014) JORGETTI, Vanda; REIS, Luciene M. dos; OTT, Susan M.Several studies have shown racial differences in the regulation of mineral metabolism, in the acquisition of bone mass and structure of individuals. In this review, we examine ethnic differences in bone and mineral metabolism in normal individuals and in patients with chronic kidney disease. Black individuals have lower urinary excretion and increased intestinal calcium absorption, reduced levels of 25(OH)D, and high levels of 1.25(OH)(2)D and parathyroid hormone (PTH). Body phosphorus concentration is higher and the levels of FGF-23 are lower than in whites. Mineral density and bone architecture are better in black individuals. These differences translate into advantages for blacks who have stronger bones, less risk of fractures, and less cardiovascular calcification. In the United States of America, the prevalence of kidney disease is similar in different ethnic groups. However, black individuals progress more quickly to advanced stages of kidney disease than whites. This faster progression does not translate into increased mortality, higher in whites, especially in the first year of dialysis. Some ethnicity-related variations in mineral metabolism persist when individuals develop CKD. Therefore, black patients have lower serum calcium concentrations, less hyperphosphatemia, low levels of 25(OH)D, higher levels of PTH, and low levels of FGF-23 compared with white patients. Bone biopsy studies show that blacks have greater bone volume. The rate of fractures and cardiovascular diseases are also less frequent. Further studies are required to better understand the cellular and molecular bases of these racial differences in bone mineral metabolism and thus better treat patients.