Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Outcomes:True Renoprotection, Loss of Muscle Mass or Both?

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) have emerged as practice-changing treatments for patients with type 2 diabetes, reducing both the risk of cardiovascular events and kidney events. However, regarding the latter, caution is warranted, as these kidney endpoints are defined using glomerular filtration rate estimations based on creatinine, the non-enzymatic product of creatine residing in muscles. Creatinine-based estimations of the glomerular filtration rate are only valid if the treatment has no effect on changes in muscle mass over time. Yet, circumstantial evidence suggests that treatment with SGLT2 inhibitors does result in a loss of muscle mass, rendering serum creatinine-based kidney endpoints invalid. Currently, it cannot be excluded that the described renoprotective effect of SGLT2 inhibitors is in part or in whole the consequence of a loss of muscle mass. Post-hoc analyses of existing trials or new trials based on kidney function markers independent of muscle mass can provide more definitive answers on the proposed renoprotective effects of SGLT2 inhibitors

Changes in Iron Status Biomarkers with Advancing Age According to Sex and Menopause: A Population-Based Study.

BACKGROUND The risk of chronic diseases increases markedly with age and after menopause. An increase in bodily iron following menopause could contribute to this phenomenon of increased risk of chronic diseases. We aimed to investigate how various iron biomarkers change with advancing age, according to sex and menopausal status. METHODS We enrolled community-dwelling individuals with available information on ferritin, transferrin, iron, hepcidin, and soluble transferrin receptor levels from the Prevention of Renal and Vascular Endstage Disease study. The association of the iron biomarkers with age, sex, and menopausal status was investigated with linear regression models. RESULTS Mean (SD) age of the 5222 individuals (2680 women [51.3%], among whom 907 [33.8%] were premenopausal, 529 [19.7%] perimenopausal, and 785 [29.3%] postmenopausal), was 53.4 (12.0) years. Iron biomarkers showed a constant increase in women throughout their life course, in some cases at older ages surpassing values in men who, in turn, showed consistently higher levels of iron status compared to women in most age categories. Ferritin, hepcidin, and transferrin saturation levels were 3.03, 2.92, and 1.08-fold (all p < 0.001) higher in postmenopausal women compared to premenopausal. CONCLUSIONS We found that iron accumulates differently depending on sex, age, and menopausal status. An increased iron status was identified in women, especially during and after menopause

Relationship between body mass index, cardiovascular biomarkers and incident heart failure

BACKGROUND: There are limited data examining whether body-mass index (BMI) influences the association between cardiovascular biomarkers and incident heart failure (HF). METHODS AND RESULTS: Thirteen biomarkers representing key HF domains were measured: N-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-A-type natriuretic peptide (MR-proANP), cardiac troponin-T (cTnT), C-reactive protein, procalcitonin, galectin-3, C-terminal pro-endothelin-1 (CT-pro-ET-1), mid-regional pro-adrenomedullin, plasminogen activator inhibitor-1, copeptin, renin, aldosterone and cystatin-C. Associations of biomarkers with BMI were examined using linear regression models, and with incident HF using Cox regression models. We selected biomarkers significantly associated with incident HF, and evaluated whether BMI modified these associations. RESULTS: Among 8202 individuals, 41% were overweight (BMI 25-30kg/m2 ), and 16% were obese (BMI≥30kg/m2 ). Mean age of the cohort was 49 years (range 28-75), and 50% were women. All biomarkers except renin were associated with BMI: inverse associations were observed with NT-proBNP, MR-proANP, CT-pro-ET-1 and aldosterone whereas positive associations were observed with the remaining biomarkers (Pall ≤0.001). During 11.3±3.1 years follow-up, 357 HF events were recorded. Only NT-proBNP, MR-proANP and cTnT remained associated with incident HF (P0.1). Combined NT-proBNP and cTnT measurements modestly improved performance metrics of the clinical HF model in overweight (ΔC-statistic=0.024; LHRχ2 =38; P<0.001) and in obese (ΔC-statistic=0.020; LHRχ2 =32; P<0.001) individuals. CONCLUSIONS: Plasma concentrations of several cardiovascular biomarkers are influenced by obesity. Only NT-proBNP, MR-proANP and cTnT were associated with incident HF, and BMI did not modify these associations. A combination of NT-proBNP and cTnT improves HF risk prediction in overweight and in obese individuals. This article is protected by copyright. All rights reserved