SILVIA MARIA DE OLIVEIRA TITAN
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- Chronic kidney disease - determinants of progression and cardiovascular risk. PROGREDIR cohort study: design and methods(2017) DOMINGOS, Maria Alice Muniz; GOULART, Alessandra Carvalho; LOTUFO, Paulo Andrade; BENSENOR, Isabela Judith Martins; TITAN, Silvia Maria de OliveiraCONTEXT AND OBJECTIVE: Chronic kidney disease (CKD) has become an important public health issue. The socioeconomic burden of renal replacement therapy (RRT) is very high, as is CKD-related cardiovascular mortality and morbidity. Preventive and therapeutic measures only have modest impact and more research is needed. Few cohort studies have been conducted on populations with CKD. Our aim was to establish a cohort that would include more advanced forms of CKD (stages 3 and 4). Data collection was focused on renal and cardiovascular parameters. DESIGN AND SETTING: Prospective cohort study; Sao Paulo, Brazil. METHODS: Recruitment took place in Hospital das Clinicas, Sao Paulo, from March 2012 to December 2013. Data relating to medical history, food-frequency questionnaire, anthropometry, laboratory work-up, calcium score, echocardiography, carotid intimal-medial thickness, pulse-wave velocity, retinography and heart rate variability were collected. A biobank including serum, plasma, post-oral glucose tolerance test serum and plasma, urine (morning and 24-hour urine) and DNA was established. RESULTS: 454 participants (60% men and 50% diabetics) of mean age 68 years were enrolled. Their mean estimated glomerular filtration rate-CKD Epidemiology Collaboration was 38 ml/min/1.73m(2). Follow-up is ongoing and the main outcomes are the start of RRT, cardiovascular events and death. CONCLUSIONS: The PROGREDIR cohort is a promising prospective study that will allow better understanding of CKD determinants and validation of candidate biomarkers for the risks of CKD progression and mortality.
- 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.
- Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients(2020) BAPTISTA, A.L.; PADILHA, K.; MALAGRINO, P.A.; VENTURINI, G.; ZERI, A.C.M.; REIS, L.M. dos; MARTINS, J.S.; JORGETTI, V.; PEREIRA, A.C.; TITAN, S.M.; MOYSES, R.M.A.Bone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end-stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N-acetylornithine. The receiver-operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver-operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Parathyroidectomy Improves Survival In Patients with Severe Hyperparathyroidism: A Comparative Study(2013) GOLDENSTEIN, Patricia Taschner; ELIAS, Rosilene Motta; CARMO, Lilian Pires de Freitas do; COELHO, Fernanda Oliveira; MAGALHAES, Luciene Pereira; ANTUNES, Gisele Lins; CUSTODIO, Melani Ribeiro; MONTENEGRO, Fabio Luiz de Menezes; TITAN, Silvia Maria; JORGETTI, Vanda; MOYSES, Rosa Maria AffonsoBackground and objectives: Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. Methods: This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. Results: Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. Conclusions: Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.
- Association between Dietary Intake and Coronary Artery Calcification in Non-Dialysis Chronic Kidney Disease: The PROGREDIR Study(2018) MACHADO, Alisson Diego; GOMEZ, Luz Marina; MARCHIONI, Dirce Maria Lobo; ANJOS, Fernanda Silva Nogueira dos; MOLINA, Maria del Carmen Bisi; LOTUFO, Paulo Andrade; BENSENOR, Isabela Judith Martins; TITAN, Silvia Maria de OliveiraCoronary artery calcification (CAC) is a widespread condition in chronic kidney disease (CKD). Diet may play an important role in CAC, but this role is not clear. This study evaluated the association between macro-and micronutrient intakes and CAC in non-dialysis CKD patients. We analyzed the baseline data from 454 participants of the PROGREDIR study. Dietary intake was evaluated by a food frequency questionnaire. CAC was measured by computed tomography. After exclusion of participants with a coronary stent, 373 people remained for the analyses. The highest tertile of CAC was directly associated with the intake of phosphorus, calcium and magnesium. There was a higher intake of pantothenic acid and potassium in the second tertile. After adjustments for confounding variables, the intake of pantothenic acid, phosphorus, calcium and potassium remained associated with CAC in the generalized linear mixed models. In order to handle the collinearity between these nutrients, we used the LASSO (least absolute shrinkage and selection operator) regression to evaluate the nutrients associated with CAC variability. In this approach, the nutrients that most explained the variance of CAC were phosphorus, calcium and potassium. Prospective studies are needed to confirmthese findings and assess the role of interventions regarding these micronutrients on CAC prevention and progression.
- GlycA, a marker of protein glycosylation, is related to albuminuria and estimated glomerular filtration rate: the ELSA-Brasil study(2017) TITAN, Silvia M.; PECOITS-FILHO, Roberto; BARRETO, Sandhi M.; LOPES, Antonio Alberto; BENSENOR, Isabela J.; LOTUFO, Paulo A.Background: Systemic inflammation has been implicated in several chronic diseases. GlycA is a new nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation that reflects protein glycosylation. We evaluated the association of GlycA with albuminuria and eGFR in the ELSA-Brasil Study. Methods: The cross-sectional association between GlycA (automated NMR LipoProfile (R) test spectra, LabCorp, Raleigh, NC), and overnight 12 h-albuminuria and CKD-EPI eGFR was evaluated among 5050 participants. Results: GlycA was higher among older, women, smokers, alcohol abstemious, obese and in those with diabetes, hypertension or dyslipidemia. In addition, both eGFR and albuminuria were associated to GlycA. In linear regression, GlycA was independently associated with log albuminuria (B 0.03; 95% CI 0.02-0.04, P < 0.0001, per 1sd increase) and inversely related to eGFR (B -0.53; 95% CI -0.99 -0.07, P < 0.02), even after adjustments including hsCRP. In logistic regression, GlycA was independently related to the risk of A2 or A3 albuminuria (OR 1.42, 95% CI 1.27-1.57, p < 0. 0001, per 1sd increase), of having an eGFR < 60 ml/min/1.73m(2) (OR 1.26, 95% CI 1.12-1.41, p = 0.0003, per 1 sd) or of a combined diagnosis of both conditions (OR 1.35, 95% CI 1.23-1.46, p < 0.0001, per 1 sd). In the ROC curve, GlycA had a higher AUC in comparison to hsCRP (AUC 0.67 vs. 0.62, p = 0.06) for the association with albuminuria A2 or A3. Conclusions: The present study demonstrates that GlycA is associated with albuminuria and eGFR, independently of major risk factors for CKD progression, including (and with a stronger association than) hsCRP. GlycA should be further evaluated in CKD progression.
- Dietary intake of non-dialysis chronic kidney disease patients: the PROGREDIR study. A cross-sectional study(2018) MACHADO, Alisson Diego; ANJOS, Fernanda Silva Nogueira dos; DONNINGOS, Maria Alice Muniz; MOLINA, Maria del Carmen Bisi; MARCHIONI, Dirce Maria Lobo; BENSENOR, Isabela Judith Martins; TITAN, Silvia Maria de OliveiraBACKGROUND: Despite evidence that diet is very important in relation to chronic kidney disease (CKD) progression, studies in this field are scarce and have focused only on some specific nutrients. We evaluated the energy, macronutrient and micronutrient intakes and dietary patterns of non-dialysis CKD participants in the PROGREDIR study. DESIGN AND SETTING: Cross-sectional study; CKD cohort, Sao Paulo, Brazil. METHODS: Baseline data on 454 participants in the PROGREDIR study were analyzed. Dietary intake was evaluated through a food freguency questionnaire. Dietary patterns were derived through principal component analysis. Energy and protein intakes were compared with National Kidney Foundation recommendations. Linear regression analysis was performed between energy and nutrient intakes and estimated glomerular filtration rate(eGFR), and between sociodemographic and clinical variables and dietary patterns. RESULTS: Median energy and protein intakes were 25.0 kcal/kg and 1.1 g/kg, respectively. In linear regression, protein intake (beta = -3.67; P = 0.07) was related to eGFR. Three dietary patterns (snack, mixed and traditional) were retained. The snack pattern was directly associated with male gender (beta = 0.27; P = 0.006) and inversely with diabetes (p = -0.23; P = 0.02). The traditional pattern was directly associated with male gender (beta = 0.27; P = 0.007) and schooling (beta = 0.40; P < 0.001) and inversely with age (p = -0.01; P = 0.001) and hypertension (beta = -0.34; P = 0.05). CONCLUSIONS: We identified low energy and high protein intake in this population. Protein intake was inversely related to eGFR. Dietary patterns were associated with age, gender, schooling level, hypertension and diabetes.
- Interactions between kidney disease and diabetes: dangerous liaisons(2016) PECOITS-FILHO, Roberto; ABENSUR, Hugo; BETONICO, Carolina C. R.; MACHADO, Alisson Diego; PARENTE, Erika B.; QUEIROZ, Marcia; SALLES, Joao Eduardo Nunes; TITAN, Silvia; VENCIO, SergioBackground: Type 2 diabetes mellitus (DM) globally affects 18-20 % of adults over the age of 65 years. Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of DM2, affecting about one-third of the patients with DM2. In addition to the pancreas, adipocytes, liver, and intestines, the kidneys also play an important role in glycemic control, particularly due to renal contribution to gluconeogenesis and tubular reabsorption of glucose. Methods: In this review article, based on a report of discussions from an interdisciplinary group of experts in the areas of endocrinology, diabetology and nephrology, we detail the relationship between diabetes and kidney disease, addressing the care in the diagnosis, the difficulties in achieving glycemic control and possible treatments that can be applied according to the different degrees of impairment. Discussion: Glucose homeostasis is extremely altered in patients with DKD, who are exposed to a high risk of both hyperglycemia and hypoglycemia. Both high and low glycemic levels are associated with increased morbidity and shortened survival in this group of patients. Factors that are associated with an increased risk of hypoglycemia in DKD patients include decreased renal gluconeogenesis, deranged metabolic pathways (including altered metabolism of medications) and decreased insulin clearance. On the other hand, decrease glucose filtration and excretion, and inflammation-induce insulin resistance are predisposing factors to hyperglycemic episodes. Conclusion: Appropriate glycaemic monitoring and control tailored for diabetic patients is required to avoid hypoglycaemia and other glycaemic disarrays in patients with DM2 and kidney disease. Understanding the renal physiology and pathophysiology of DKD has become essential to all specialties treating diabetic patients. Disseminating this knowledge and detailing the evidence will be important to initiate breakthrough research and to encourage proper treatment of this group of patients.
- Risk Factors for Adverse Fetal Outcome in Hemodialysis Pregnant Women(2018) LUDERS, Claudio; TITAN, Silvia Maria; KAHHALE, Soubhi; FRANCISCO, Rossana Pulcineli; ZUGAIB, MarceloIntroduction: Pregnancy in women on dialysis is associated with a higher risk of adverse events, and the best care for this population remains to be established. Methods: In this series, we aimed to identify factors associated with the risk of adverse fetal outcomes among 93 pregnancies in women on hemodialysis. Dialysis dose was initially assigned according to the presence of residual diuresis, body weight, and years on dialysis. Subsequent adjustments on dialysis dose were performed according to several parameters. Results: The overall successful delivery rate was 89.2%, with a dialysis regimen of 2.6 +/- 0.7 h/d, 15.4 +/- 4.0 h/wk, and mean weekly standard urea Kt/V of 3.3 +/- 0.6. In the logistic models, preeclampsia, lupus, primigravida, and average midweek blood urea nitrogen (BUN) level were positively related to the risk of a composite outcome of perinatal death or extreme prematurity, whereas polyhydramnios was inversely related to it. In multivariable linear regression, preeclampsia, polyhydramnios, primigravida, average midweek BUN, and residual diuresis remained significantly and independently related to fetal weight, which is a surrogate marker of fetal outcome. An average midweek BUN of 35 mg/dl was the best value for discriminating the composite outcome, and BUN >= 3 5 mg/dl was associated with a significant difference in a Kaplan-Meier curve (P = 0.01). Conclusion: Our results showed that a good fetal outcome could be reached and that preeclampsia, lupus, primigravida, residual diuresis, polyhydramnios, and hemodialysis dose were important variables associated with this outcome. In addition, we suggested that a midweek BUN <35 mg/dl might be used as a target for adjusting dialysis dose until hard data were generated.
- MYH9 and APOL1 Gene Polymorphisms and the Risk of CKD in Patients with Lupus Nephritis from an Admixture Population(2014) COLARES, Vinicius Sardao; TITAN, Silvia Maria de Oliveira; PEREIRA, Alexandre da Costa; MALAFRONTE, Patricia; CARDENA, Mari M.; SANTOS, Sidney; SANTOS, Paulo C.; FRIDMAN, Cintia; BARROS, Rui Toledo; WORONIK, ViktoriaMYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95% CI 1.47-9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95% CI 1.2-3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.