Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
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Nephrol. Dial. Transplant. · Nov 2018
Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease.
The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD). ⋯ Dapagliflozin did not decrease HbA1c in patients with type 2 diabetes and Stages 3b-4 CKD, but decreased UACR, BP and body weight to a clinically meaningful extent. These results support a large outcome trial in this population to confirm long-term safety and efficacy in reducing adverse clinical endpoints.
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Nephrol. Dial. Transplant. · Nov 2018
Meta Analysis Comparative StudyComparative efficacy of individual renin-angiotensin system inhibitors on major renal outcomes in diabetic kidney disease: a network meta-analysis.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are two drug classes with well-documented renal protective effects. However, whether there is any difference among individual drugs remains unknown. In this study, we aimed to compare the efficacy of individual ACEIs/ARBs on major renal outcomes in adults with diabetic kidney disease (DKD). ⋯ Based on the available evidence, individual ACEIs and ARBs at goal doses appeared to have no or little differences in their effect on major renal outcomes.
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Nephrol. Dial. Transplant. · Nov 2018
ReviewTargeting epigenetic DNA and histone modifications to treat kidney disease.
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease. ⋯ Several drugs targeting epigenetic regulators are in clinical development or use, most of them for malignancy. The BET inhibitor apabetalone is in Phase 3 trials for atherosclerosis, kidney function being a secondary endpoint, but nephrotoxicity was reported for DNA and HDAC inhibitors. While research into epigenetic modulators may provide novel therapies for kidney disease, caution should be exercised based on the clinical nephrotoxicity of some drugs.