SILVIA MARIA DE OLIVEIRA TITAN
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- Bisphosphonate utilization across the spectrum of eGFR(2020) TITAN, Silvia M.; LAUREATI, Paola; SANG, Yingying; CHANG, Alex R.; EVANS, Marie; TREVISAN, Marco; LEVEY, Andrew S.; GRAMS, Morgan E.; INKER, Lesley A.; CARRERO, Juan-JesusBisphosphonates are the most common treatment for osteoporosis but there are concerns regarding its use in CKD. We evaluated the frequency of BSP by eGFR categories among patients with osteoporosis from two healthcare systems. Our results show that 56% of patients were treated, with reduced odds in those with lower eGFR. Introduction Osteoporosis is common in patients with chronic kidney disease (CKD). Bisphosphonates (BSP) are the most common treatment but there are concerns regarding its efficacy and toxicity in CKD. We evaluated the frequency of BSP use by level of estimated glomerular filtration rate (eGFR) in patients with osteoporosis. Methods We assessed BSP use in patients with incident osteoporosis from the SCREAM-Cohort, Stockholm-Sweden, and Geisinger Healthcare, PA, USA. Osteoporosis was defined as the first encountered ICD diagnosis, and BSP use was defined as the dispensation or prescription of any BSP from 6 months prior to 3 years after the diagnosis. Multinomial logistic regression was used to account for the competing risk of death. Results A total of 15,719 women and 3011 men in SCREAM and 17,325 women and 3568 men in Geisinger with incident osteoporosis were included. Overall, 56% of individuals used BSP in both studies, with a higher proportion in women. After adjustments, the odds of BSP was lower across lower eGFR in SCREAM, ranging from 0.90 (0.81-0.99) for eGFR 75-89 mL/min/1.73m(2) to 0.56 (0.46-0.68) for eGFR 30-44 mL/min/1.73m(2) in women and from 0.72 (0.54-0.97) for eGFR of 60-74 to 0.42 (0.25-0.70) for eGFR 30-44 mL/min/1.73m(2) in men. In Geisinger, odds were lower for eGFR < 30 mL/min/1.73m(2) in both sexes and the frequency of BSP use dropped over time. Conclusion In the two healthcare systems, approximately half of the people diagnosed with osteoporosis received BSP. Practices of prescription in relation to eGFR varied, but those with lower eGFR were less likely to receive BSP.
- 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.
- Calcitriol and FGF-23, but neither PTH nor sclerostin, are associated with calciuria in CKD(2019) RAMALHO, J.; PETRILLO, E. M.; TAKEICHI, A. P. M.; MOYSES, R. M. A.; TITAN, S. M.Purpose The recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort. Methods Baseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a-G4, were analyzed according to UCE (24 h urine collection). Results Median 24 h UCE was 38 mg/day (IQR 21-68 mg/day) and 0.48 mg/kg/day (IQR 0.28-0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)(2-)vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)(2)-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)(2)-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations. Conclusion Our results showed that CKD is associated with very low levels of UCE and that 1,25(OH)(2)-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD.
- Metabolites related to eGFR: Evaluation of candidate molecules for GFR estimation using untargeted metabolomics(2019) TITAN, S. M.; VENTURINI, G.; PADILHA, K.; TAVARES, G.; ZATZ, R.; BENSENOR, I; LOTUFO, P. A.; RHEE, E. P.; I, R. Thadhani; PEREIRA, A. C.Background: Metabolomics can be used to identify novel metabolites related to renal function and that could therefore be used for estimating GFR. We evaluated metabolites replicated and related to eGFR in 3 studies (CKD) and general population). Methods: Metabolomics was performed by GC-MS. The Progredir Cohort (n = 454, class 3 and 4 CKD) was used as the derivation study and adjusted linear regression models on eGFR-CKDEPI were built. Bonferroni correction was applied for selecting metabolites to be independently validated in the Diabetic Nephropathy Study (n = 56 macroalbuminuric DN) and in the Baependi Heart Study (BHS, n = 1145, general population). Results: In the Progredir Cohort, 72 metabolites where associated with eGFR. Of those, 11 were also significantly associated to eGFR in the DN Study and 8 in the BHS. Four metabolites were replicated and significantly associated to eGFR in all 3 studies: D-threitol, myo-inositol, 4-deoxierythronic acid and galacturonic acid. In addition, pseudouridine was strongly correlated to eGFR only in the 2 CKD populations. Conclusions: Our results demonstrate metabolites that are potential biomarkers of renal function: D-threitol, myo-inositol, 4-deoxierythronic acid, galacturonic acid and pseudouridine. Further investigation is needed to determine their performance against otherwise gold-standard methods, most notably among those with normal eGFR.