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.
- Serum RBP4 and CKD: Association with insulin resistance and lipids(2017) DOMINGOS, Maria Alice M.; QUEIROZ, Marcia; LOTUFO, Paulo Andrade; BENSENOR, Isabela Judith; TITAN, Silvia Maria de OliveiraObjective: Serum RBP4 is new adipokine and it has been related to insulin resistance and diabetes risk in animal and clinical studies. However, there is controversy on this relationship among CKD patients. In this study, we evaluated the association of serum RBP4 with insulin resistance and cardiovascular risk factors in CKD. Methods: Baseline data from the PROGREDIR Study (Sao Paulo, Brazil) comprising 454 participants (mainly stages 3 and 4) was analyzed. Results: In univariable analysis, RBP4 was inversely related to renal function, age and HDL, and positively related to other lipids, insulinemia, HOMA, glycemia, albumin, phosphorus and right hepatic lobe diameter. After adjustment for sex, age and eGFR, HOMA and lipids remained associated to RBP4. In multivariable analysis, eGFR and triglyceride remained significantly associated with RBP4, while HOMA showed no longer a significant positive association. An interaction term between RBP4 and eGFR was significantly related to HOMA. Conclusions: Renal function is inversely related to serum RBP4. As GFR decreases, the relationship between RBP4 and HOMA is attenuated. On the other hand, triglycerides remained strongly related to RBP4 and this was not affected by eGFR, suggesting that in the CKD population triglycerides may be a better marker of RBP4-associated metabolic effects.
- 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.
- Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease(2017) MALAGRINO, Pamella Araujo; VENTURINI, Gabriela; YOGI, Patricia Schneider; DARIOLLI, Rafael; PADILHA, Kallyandra; KIERS, Bianca; GOIS, Tamiris Carneiro; CARDOZO, Karina Helena Morais; CARVALHO, Valdemir Melechco; SALGUEIRO, Jessica Silva; GIRARDI, Adriana Castello Costa; TITAN, Silvia Maria de Oliveira; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaThe main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60 min) and 4, 11 and 16 h post-reperfusion, and renal cortex samples after 24 h of reperfusion. Peptides were analyzed on the Q-Exactive (TM). In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease. Biological significance: The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative biomarkers for this condition have also been identified in a number of other clinical scenarios, such as cardiovascular diseases, chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential biomarkers for kidney disease, using kidney ischemia/reperfusion as a paradigm for a kidney pathological event.
- Thyrotropin levels are associated with chronic kidney disease among healthy subjects in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2017) MIRANDA, Erique Jose F. Peixoto de; BITTENCOURT, Marcio Sommer; GOULART, Alessandra C.; SANTOS, Itamar S.; TITAN, Silvia Maria de Oliveira; LADEIRA, Roberto Marini; BARRETO, Sandhi Maria; LOTUFO, Paulo A.; BENSENOR, Isabela Judith MartinsFew studies have evaluated a possible relationship between thyrotropin levels and glomerular filtration rate (GFR) and albumin/creatinine ratio in euthyroid subjects. We aimed to analyze this association using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Cross-sectionally, we included subjects with normal thyroid function and with subclinical hypothyroidism (SCH). We excluded individuals using medications that affect thyroid function. Linear and logistic regression models evaluated GFR estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and albuminuria/creatinine ratio as dependent variables and thyrotropin quartiles in individuals with euthyroidism and SCH as independent variables, adjusted for demographical characteristics and diseases related to CKD. We included 13,193 subjects with a median age of 51 years [interquartile range, (IQR): 45-58], 6840 (51.8%) women, 12,416 (94.1%) euthyroid, and 777 (5.9%) with SCH. SCH subjects were characterized by higher age, triglycerides, frequency of white race, cardiovascular disease, CKD, and former smokers. In adjusted models, log-transformed TSH in euthyroid subjects was inversely and strongly associated with CKD (beta = -2.181, 95% CI -2.714 to -1.648), P < 0.0001 for glomerular filtration rate and 4.528 (1.190-7.865) for albuminuria/creatinine ratio. Multivariate logistic models for euthyroid subjects showed an OR of 1.45 (95% CI 1.15-1.83) for GFR and of 1.95 (95% CI 1.08-3.54) for albuminuria/creatinine ratio in the fourth quartile of TSH using the first as the reference. Thyrotropin levels are independently associated with CKD in euthyroid subjects.
- Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure(2017) VILARTA, Cristiane F.; UNGER, Marianna D.; REIS, Luciene M. dos; DOMINGUEZ, Wagner V.; DAVID-NETO, Elias; MOYSES, Rosa M.; TITAN, Silvia; CUSTODIO, Melani R.; HERNANDEZ, Mariel J.; JORGETTI, VandaOBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.