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Item The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial(Nature, 2016-03) Chang, T. I.; Abdalla, S.; London, G. M.; Block, G. A.; Correa-Rotter, R.; Drüeke, T. B.; Floege, J.; Herzog, C. A.; Mahaffey, K. W.; Moe, Sharon M.; Parfrey, P. S.; Wheeler, D. C.; Dehmel, B.; Goodman, W. G.; Chertow, G. M.; Department of Medicine, IU School of MedicinePatients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4–20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.Item Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells(Nature Publishing group, 2018-02-23) Liu, Jing; Livingston, Man J.; Dong, Guie; Tang, Chengyuan; Su, Yunchao; Wu, Guangyu; Yin, Xiao-Ming; Dong, Zheng; Pathology and Laboratory Medicine, School of MedicineHistone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells. Notably, inhibition of autophagy by chloroquine or by autophagy gene 7 (Atg7) ablation diminished the protective effect of TSA. In mice, TSA increased autophagy in renal proximal tubules and protected against cisplatin-induced AKI. The in vivo effect of TSA was also abolished by chloroquine and by Atg7 knockout specifically from renal proximal tubules. Mechanistically, TSA stimulated AMPK and inactivated mTOR during cisplatin treatment of proximal tubule cells and kidneys in mice. Together, these results suggest that HDACi may protect kidneys by activating autophagy in proximal tubular cells.Item Metastatic pulmonary calcification(2016) Peungjesada, Silanath; Baskin, Mark Harold; Winer-Muram, Helen T.; Department of Radiology and Imaging Sciences, IU School of MedicineMetastatic pulmonary calcification (MPC) may develop in patients with secondary hyperparathyroidism, related to end-stage renal disease (ESRD).1 The histologic pulmonary findings show calcium deposition in the lung interstitium, alveolar septa and bronchial walls.2 We present a patient with CT findings of MPC that resolved with medical treatment for secondary hyperparathyroidism. To our knowledge, complete resolution of metastatic pulmonary calcification following treatment has not been previously described in the literature.