Investigation of Renal Decline and New Onset Dialysis Following Endovascular Aneurysm Repair in the Vascular Quality Initiative.

INTRODUCTION: The purpose of this study is to identify variables significantly associated with renal function decline after elective endovascular infra-renal abdominal aortic aneurysm repair and to identify the rate and risks of subsequent progression to dialysis. Specifically, we investigate the long-term impact of supra-renal fixation, female gender, and physiologically stressful perioperative events on renal function following endovascular aneurysm repair (EVAR). METHODS: Review of all EVAR cases in the Vascular Quality Initiative between 2003 and 2021 was conducted to investigate variable associations with three primary outcomes: postoperative acute renal insufficiency (ARI); greater than 30% decline in glomerular filtration rate (GFR) in patients beyond 1 year of follow up; and new onset dialysis requirement at any point in follow up. Binary logistic regression analysis was performed for the events of acute renal insufficiency and new onset dialysis requirement. Cox proportional hazard regression was performed regarding long term GFR decline. RESULTS: Postoperative ARI occurred in 3.4% (1692/49 772) of patients. Significant (P < .05) association with postoperative ARI was noted for: age (OR 1.014/year, 95% CI 1.008-1.021); female gender (OR 1.44, 95% CI 1.27-1.67); hypertension (OR 1.22, 95% CI 1.04-1.44); chronic obstructive pulmonary disease (OR 1.34, 95% CI 1.20-1.50); anemia (OR 4.24, 95% CI 3.71-4.84); reoperation at index admission (OR 7.86, 95% CI 6.47-9.54); baseline renal insufficiency (OR 2.29, 95% CI 2.03-2.56); larger aneurysm diameter; increased blood loss; and higher volumes of intra-operative crystalloid. Risk factors (P < .05) correlating with a decline of 30% in GFR at any time beyond 1 year were: female gender (HR 1.43, 95% CI 1.24-1.65); body mass index (BMI) less than 20 (HR 1.34, 95% CI 1.03-1.74); hypertension (HR 1.38, 95% CI 1.15-1.64); diabetes (HR 1.34, 95% CI 1.17-1.53); COPD (HR 1.21, 95% CI 1.07-1.37); anemia (HR 1.92, 95% CI 1.52-2.42); baseline renal insufficiency (HR 1.31, 95% CI 1.15-1.49); absence of discharge ace-inhibitor (HR 1.27, 95% CI 1.13-1.42); long term re-intervention (HR 2.43, 95% CI 1.84-3.21) and larger AAA diameter. Patients who experienced long term GRF decline had a significantly higher long-term morality. New onset dialysis following EVAR occurred in .47% (234/49 772) of those meeting inclusion criteria. Higher rate (P < .05) of new onset dialysis was associated with age (OR 1.03/year, 95% CI 1.02-1.05); diabetes (OR 1.376, 95% CI 1.005-1.885); baseline renal insufficiency (OR 6.32, 95% CI4.59-8.72); Reoperation at index admission (OR 2.41, 95% CI 1.03-5.67); postoperative ARI (OR 23.29, 95% CI 16.99-31.91); absence of beta blocker (OR 1.67, 95% CI 1.12-2.49); long term graft encroachment on renal arteries (OR 4.91, 95% CI 1.49-16.14). CONCLUSIONS: New onset dialysis following EVAR is a rare event. Perioperative variables influencing renal function following EVAR include blood loss, arterial injury, and reoperation. Supra-renal fixation is not associated with postoperative acute renal insufficiency or new onset dialysis in long term follow up. Renal protective measures are recommended for patients with baseline renal insufficiency undergoing EVAR as acute renal insufficiency following EVAR portends a 20-fold increased risk of new onset dialysis in long term follow up.

The Effect of Smoking Status on Perioperative Morbidity and Mortality after Open and Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: This study quantifies the extent to which active tobacco smoking is deleterious toward outcomes following open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Open and endovascular AAA repairs between January 2003 and June 2020 in the Vascular Quality Initiative were queried. Rupture, symptomatic status, and lack of 90 day follow-up were exclusions. Patients were then placed into 1 of 6 groups: open AAA with active smoking (n = 3,788), open AAA with prior smoking (n = 4,614), open AAA never smokers (817), endovascular AAA active smokers (n = 14,173), endovascular AAA former smokers (n = 25,831), and endovascular AAA never smokers (n = 6,064). Comparison of baseline characteristics, comorbidities, and adverse outcomes across each of the 6 cohorts was performed with open AAA in active smokers serving as the reference. Subanalysis investigating open AAA repair in active smokers relative to open AAA in patients confirmed in Vascular Quality Initiative to have quit smoking between 30 and 90 days before surgery was performed. Smoking cessation for a minimum of 30 days before surgery was required to fall into the former smoker category. RESULTS: In comparing open AAA in active smokers to open AAA in former and never smokers, the active smokers experienced significantly higher rates of pneumonia (P < 0.001). Combined additive morbidity and mortality was highest (54%) in active smokers (P < 0.001) relative to all cohorts other than open AAA former smokers (P = 0.21). Smoking status did not impact morbidity or mortality incidence across individuals undergoing endovascular aneurysm repair. Binary logistic regression for all AAA patients (open and endovascular combined) revealed those with any history of smoking to be more likely to experience 90 day mortality (adjusted odds ratio [OR] 2.5 [2.2-2.9], P < 0.001) relative to never smokers. Active smokers were similarly more likely to experience 90 day mortality than prior/never smokers combined (OR 1.23 [1.07-1.38], P < 0.001). Mortality within 90 days was significantly more likely (P < 0.001) with aging, female gender, larger aneurysms, preoperative history of congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency, peripheral artery disease, and body mass index less than 20 and more than 35 mg/kg2. Diabetes and coronary artery disease were also associated with 90 day mortality (P = 0.045 and 0.049, respectively). Quitting smoking between 30 and 90 days before open repair reduced combined additive morbidity and mortality relative to active smokers (OR 1.34, P = 0.038). CONCLUSIONS: Smoking cessation 30 days before open AAA repair reduces perioperative morbidity and mortality. Smoking status does not impact morbidity and mortality in patients undergoing endovascular AAA repair. When combining all patients (open and endovascular), higher rates of 90 day mortality are associated with any history of smoking, aging, female gender, and advanced pre-existing comorbidities on a multivariable analysis.

A novel mode of capping protein-regulation by twinfilin.

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first 'pro-capping' ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle.