The effect of angiotensin-(1-7) in mouse unilateral ureteral obstruction.

Angiotensin-(1-7) is a ligand for the Mas receptor and may protect against tissue injury associated with renin-angiotensin system activation. We determined the effects of endogenous or exogenous angiotensin-(1-7) in mice with unilateral ureteral obstruction (UUO). Mice with UUO were treated with or without the angiotensin-(1-7) antagonist A779 or with 6, 24, or 62 µg/kg per hour exogenous angiotensin-(1-7). After 10 days, kidneys were harvested for histology, immunoblots, and measurement of NADPH oxidase. Compared with controls, A779 treatment significantly increased fibronectin, transforming growth factor-ß, and α-smooth muscle actin expression in obstructed kidneys and enhanced tubulointerstitial injury, apoptosis, and NADPH oxidase. Unexpectedly, administration of angiotensin-(1-7) to mice with UUO caused injury in obstructed kidneys compared with controls and increased macrophage infiltration. In obstructed kidneys from mice with gene deletion of Mas (Mas(-/-)), apoptosis and macrophage infiltration were increased compared with wild-type mice. Angiotensin-(1-7) (but not A779) further increased apoptosis and macrophage influx in obstructed kidneys from Mas(-/-) mice, compared with untreated Mas(-/-) mice. These data indicate that endogenous angiotensin-(1-7) protects against kidney injury in UUO. In mice with or without the Mas receptor, however, delivery of exogenous angiotensin-(1-7) worsens kidney damage. The results suggest dose-dependent effects of angiotensin-(1-7) in the kidney in UUO, with endogenous angiotensin-(1-7) promoting repair pathways via interaction with Mas and higher amounts exacerbating injury.

Anticoagulant and antiplatelet therapy in patients with chronic kidney disease: risks versus benefits review.

PURPOSE OF REVIEW: Atrial fibrillation and cardiovascular death are increased in end-stage renal disease (ESRD) patients compared to the general population. The effect of anticoagulant and antiplatelet medications for these indications in ESRD is unclear. However, both classes of medications have been used for the preservation of vascular access. This review explores the risks and benefits of anticoagulant and antiplatelet medications in ESRD. RECENT FINDINGS: ESRD patients with atrial fibrillation have a two and three-fold greater risk of death and stroke, respectively, than ESRD patients without atrial fibrillation. Warfarin does not appear to decrease this risk, and increases the risk of bleeding and vascular calcification. Warfarin also does not appear to be effective for vascular access preservation. In a few large observational studies, antiplatelet agents did not decrease the risk of cardiovascular death, but confounding by indication is likely. Antiplatelet agents do appear to prolong unassisted arteriovenous graft patency, but the effect is modest. SUMMARY: The role of anticoagulant and antiplatelet agents for atrial fibrillation and cardiovascular disease in ESRD remains unclear. Well designed randomized controlled trials to determine the role of anticoagulation in ESRD patients with atrial fibrillation, and anticoagulant and antiplatelet medications in the preservation of central venous catheter function are required.