Fabiana G. Graciolli

Universidade de São Paulo

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Rosa Maria Affonso Moysés

Universidade de São Paulo

Vanda Jorgetti

Universidade de São Paulo

Luciene M. dos Reis

Universidade de São Paulo

Rosilene Motta Elias

Universidade Nove de Julho

Kátia R. Neves

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Melani Ribeiro Custódio

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Wagner V. Dominguez

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Daniella Guimarães Batista

Universidade de São Paulo

Aluízio Barbosa Carvalho

Universidade Federal de São Paulo

María Eugênia Fernandes Canziani

Universidade Federal de São Paulo

Cooperative Institutions

Universidade de São Paulo

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Pediatric Nephrology of Alabama

RELX Group (United States)

Universidade Brasil

Universidade Federal de São Paulo

Sapienza University of Rome

Universidade Nove de Julho

Abbott Fund

Renal Association

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

The complexity of chronic kidney disease–mineral and bone disorder across stages of chronic kidney disease

Kidney International (2017)

Fabiana G. Graciolli Kátia R. Neves Fellype Carvalho Barreto Daniela V. Barreto Luciene M. dos Reis

Sclerostin

Bone remodeling

Bone disease

Klotho

Osteopontin

10.1016/j.kint.2016.12.029

Cite

Citations (165)

Predictive Factors of One-Year Mortality in a Cohort of Patients Undergoing Urgent-Start Hemodialysis

PLoS ONE (2017)

Luciene Pereira Magalhães Luciene M. dos Reis Fabiana G. Graciolli Benedito Jorge Pereira Rodrigo Cardoso de Oliveira

Chronic kidney disease (CKD) affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality.We studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD) and mineral and bone disease associated with CKD (CKD-MBD), and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis.The patient mean age was 50 ± 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%). Major risk factors were smoking (19.6%), dyslipidemia (48.8%), and CVD (41%). Upon admission, most patients had no vascular access for hemodialysis (89.4%). Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%). These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D.The combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population.

Nephrology

Dyslipidemia

10.1371/journal.pone.0167895

Cite

Citations (15)

Effect of Mineral and Bone Metabolism on Restless Legs Syndrome in Hemodialysis Patients

Journal of Clinical Sleep Medicine (2017)

Precil Diego Miranda de Menezes Neves Fabiana G. Graciolli Ivone B. Oliveira Ramaiane Aparecida Bridi Rosa Maria Affonso Moysés

Restless legs syndrome (RLS) is a highly prevalent sleep disease among patients on hemodialysis. The physiopathology is still unclear, and may be multifactorial. Because of the association between iron metabolism and chronic kidney disease-mineral and bone disorders (CKD-MBD), we hypothesized that both factors would be associated with RLS.We have evaluated hemodialysis patients, in a face-to-face interview for the diagnosis and severity of RLS, as measured by the International Restless Legs Syndrome Study Group. Clinical, demographic, and biochemical characteristics were measured.Out of 101 adult patients included, RLS was found in 29 (28.7%). Adjusted multinomial regression analysis revealed that age older than 35 years, transferrin saturation less than 47%, serum ferritin level less than 700 ng/mL, hemoglobin level less than 9.8 g/dL, serum phosphate level higher than 5.2 mg/dL, FGF-23 higher than 2,000 RU/mL, and C-reactive protein less than 1.24 mg/dL were independently associated with RLS. RLS was classified as mild, moderate, severe, and very severe in 3.4%, 41.7%, 44.8%, and 10.1% of patients, respectively. Scores of severity correlated significantly with erythropoietin dose/kg/w (p = 0.046), phosphate (p = 0.003), and inversely with serum albumin (p = 0.003) and calcium (p = 0.008). Phosphate and 25(OH)-vitamin D correlated with transferrin saturation. Patients with severe/very severe symptoms were mostly women, presented with lower serum iron, ionic calcium, and serum albumin levels and higher levels of serum phosphate, and higher percentage of 25(OH)-vitamin D deficiency and levels of FGF-23 higher than 2,000 RU/mL than did those with mild/moderate symptoms.CKD-MBD factors besides iron metabolism are associated with RLS in patients on hemodialysis, providing new insights into the understanding of RLS in this population.

Restless Legs Syndrome

Transferrin saturation

10.5664/jcsm.6396

Cite

Citations (24)

Analysis of bone histomorphormometry and osteoblast culture from proteinuric patients

Nephrology Dialysis Transplantation (2003)

Cristiane Bitencourt Dias Rosa Maria Affonso Moysés J. E. B. Gueiros Rui Toledo Barros Viktória Woronik

Source

Cite

Citations (0)

[Oncogenic osteomalacia. Report of two cases].

PubMed (2015)

Fernando Jerkovich Daniel Moncet Silvia Babini Jorge Zoppi Fabiana G. Graciolli

Oncogenic osteomalacia is a rare disease. It is caused by a tumor that produces fibroblast growth factor 23, a hormone that decreases the tubular phosphate reabsorption and impairs renal hydroxylation of vitamin D. This leads to hyperphosphaturia with hypophosphatemia and low calcitriol levels. About 337 cases have been reported and we studied two cases; 44 and 70 year-old men who sought medical attention complaining of suffering diffuse bone pain over a period of approximately one year. In both cases, a laboratory test showed biochemical alterations compatible with a hypophosphatemic osteomalacia. In the first case, a soft tissue tumor of the right foot was removed, one year after the diagnosis. The patient was allowed to diminish the phosphate intake, but symptoms reappeared at this time. Eight years later, a local recurrence of the tumor was noted. A complete excision was now performed. The patient was able to finally interrupt the phosphate intake. In the second case, an F-18 fluorodeoxyglucose positron emission tomography, with computed tomography revealed a 2.26 cm diameter hypermetabolic nodule in the soft tissue of the right forefoot. After its removal, the patient discontinued the phosphate intake. Both patients are asymptomatic and show a regular phosphocalcic laboratory evaluation. The histopathological diagnosis was, in both cases, a phosphaturic mesenchymal tumor, a mixed connective tissue variant. This is the prototypical variant of these tumors.

Osteomalacia

Hypophosphatemia

Bone pain

Source

Cite

Citations (8)

Factors associated with subendocardial ischemia risk in patients on hemodialysis

Figshare (2022)

Bruno Caldin da Silva Adriano Sanjuan Valéria Costa‐Hong Luciene dos Reis Fabiana G. Graciolli

Abstract Introduction: Bone metabolism disorder (BMD) and vascular dysfunction contribute to excess cardiovascular mortality observed in hemodialysis patients. Vascular dysfunction, a new marker of atherosclerosis, can play a role in this risk. Even though associated with higher mortality in the general population, such vascular evaluation in patients on hemodialysis has not been extensively studied. Methods: In this cross-sectional study, hemodialysis patients were submitted to flow-mediated dilation, subendocardial viability ratio (SEVR) and ejection duration index assessment, in order to estimate the impact of BMD markers on vascular dysfunction. Results: A matched cohort of patients with (n = 16) and without (n = 11) severe secondary hyperparathyroidism (SHPT) was studied. Additionally, time spent under severe SHPT was also evaluated. Patients with severe SHPT had lower SEVR and higher ejection duration index, indicating higher cardiovascular risk. Lower SEVR was also associated to diastolic blood pressure (r = 0.435, p = 0.049), serum 25-Vitamin-D levels (r = 0.479, p = 0.028) and to more time spent under severe secondary hyperparathyroidism (SHPT), defined as time from PTH > 500pg/ml until parathyroidectomy surgery or end of the study (r = -0.642, p = 0.027). In stepwise multiple regression analysis between SEVR and independent variables, lower SEVR was independently associated to lower serum 25-Vitamin-D levels (p = 0.005), female sex (p = 0.012) and more time spent under severe SHPT (p = 0.001) in a model adjusted for age, serum cholesterol, and blood pressure (adjusted r² = 0.545, p = 0.001). Conclusion: Subendocardial perfusion was lower in patients with BMD, reflecting higher cardiovascular risk in this population. Whether early parathyroidectomy in the course of kidney disease could modify such results still deserves further investigation.

10.6084/m9.figshare.19963968

Cite

Citations (0)

Persistence of Bone and Mineral Disorders 2 Years After Successful Kidney Transplantation

Transplantation (2013)

Carolina Lara Neves Luciene M. dos Reis Daniella Guimarães Batista Melani Ribeiro Custódio Fabiana G. Graciolli

Studies that have conducted bone biopsies after kidney transplantation are scarce, and the results are conflicting.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.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.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.

Osteoid

Hypophosphatemia

Bone remodeling

Apposition

10.1097/tp.0b013e3182985468

Cite

Citations (42)

Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system

Nephrology Dialysis Transplantation (2011)

Melani Ribeiro Custódio Márcia Kiyomi Koike Kátia R. Neves Luciene M. dos Reis Fabiana G. Graciolli

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.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, α-actin, transforming growth factor-beta (TGF-β) 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.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-β, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-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.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.

Uremia

Myocardial fibrosis

Cardiac Fibrosis

10.1093/ndt/gfr447

Cite

Citations (73)

Mineral bone disorder in chronic kidney disease: head-to-head comparison of the 5/6 nephrectomy and adenine models

BMC Nephrology (2014)

G Ferrari Juliana Caires de Oliveira Achili Ferreira Raquel T. Cavallari Kátia R. Neves Luciene M. dos Reis

Experimental models are important to the understanding of the pathophysiology of, as well as the effects of therapy on, certain diseases. In the case of chronic kidney disease-mineral bone disorder, there are currently two models that are used in evaluating the disease: 5/6 nephrectomy (Nx) and adenine-induced renal failure (AIRF). However, the two models have never been compared in studies using animals maintained under similar conditions. Therefore, we compared these two models, focusing on the biochemical, bone histomorphometry, and vascular calcification aspects. Wistar rats, initially fed identical diets, were divided into two groups: those undergoing 5/6 Nx (5/6Nx group) and those that were switched to an adenine-enriched diet (AIRF group). After 9 weeks, animals were sacrificed, and we conducted biochemical and bone histomorphometry analyses, as well as assessing vascular calcification. At sacrifice, the mean body weight was higher in the 5/6Nx group than in the AIRF group, as was the mean blood pressure. No differences were seen regarding serum phosphate, ionized calcium, intact parathyroid hormone (PTH), or fibroblast growth factor 23 (FGF23). However, creatinine clearance was lower and fractional excretion of phosphate (FeP) was higher in the AIRF group rats, which also had a more severe form of high-turnover bone disease. Vascular calcification, as evaluated through von Kossa staining, was not observed in any of the animals. Overt vascular calcification was not seen in either model as applied in this study. Under similar conditions of diet and housing, the AIRF model produces a more severe form of bone disease than does 5/6 Nx. This should be taken into account when the choice is made between these models for use in preclinical studies.

Nephrology

Nephrocalcinosis

10.1186/1471-2369-15-69

Cite

Citations (51)

Fibroblast Growth Factor 23 in Hemodialysis Patients: Effects of Phosphate Binder, Calcitriol and Calcium Concentration in the Dialysate

Nephron Clinical Practice (2010)

Ana L.E. Cancela Rodrigo Cardoso de Oliveira Fabiana G. Graciolli Luciene M. dos Reis Fellype Carvalho Barreto

Background: Fibroblast growth factor 23 (FGF23) concentrations increase early in chronic kidney disease (CKD), and the influence of current CKD-mineral and bone disorder (MBD) therapies on serum FGF23 levels is still under investigation. Methods: In this post-hoc analysis of a randomized clinical trial, phosphate binders and calcitriol were washed out of 72 hemodialysis patients who were then submitted to bone biopsy, coronary tomography and biochemical measures, including FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year and the prescription of calcitriol and the calcium concentration in the dialysate were adjusted according to serum calcium, phosphate and PTH and bone biopsy diagnosis. Results: At baseline, bone biopsy showed that 58.3% had low-turnover bone disease, whereas 38.9% had high-turnover bone disease, with no significant differences between them with regard to FGF23. Median baseline FGF23 serum levels were elevated and correlated positively with serum phosphate. After 1 year, serum FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the administration of calcitriol and a calcium-based phosphate binder were associated with higher final serum FGF23 levels.Conclusions: Taken together, our results confirm that the current CKD-MBD therapies have an effect on serum levels of FGF23. Since FGF23 is emerging as a potential treatment target, our findings should be taken into account in the decision on how to manage CKD-MBD therapy.

Phosphate binder

Nephrology

10.1159/000319650

Cite

Citations (67)