Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obesity-induced CKD. Methods: Groups of male C57Bl/6J mice (n = 99 in total) were fed a low (10% lard) or high (45% lard) fat diet for a maximum of 52 weeks. Mice were sacrificed after 24, 40 and 52 weeks. Whole blood samples, kidneys and adipose tissues were collected. The development of adipose and renal tissue inflammation was assessed on gene expression and protein level. Adipocytokine levels were measured in plasma samples. Results: A distinct inflammatory phenotype was observed in the adipose tissue of HFD mice prior to renal inflammation, which was associated with an early systemic elevation of TNF-α, leptin and SAA (1A-C). With aging, sclerotic lesions appeared in the kidney, the extent of which was severely aggravated by HFD feeding. Lesions exhibited typical amyloid characteristics (2A) and pathological severity positively correlated with bodyweight (2B). Interestingly, more SAA protein was detected in lesions of HFD mice. Conclusion: Our data suggest a causal link between obesity induced chronic inflammation and AA amyloidosis in C57Bl/6J mice. Though future studies are necessary to prove this causal link and to determine its relevance for the human situation, obesity may hence be considered a risk factor for the development and progression of renal AA amyloidosis in the course of CKD. (Figure Presented)

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger