Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy.

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Objectives: Endotracheal intubation is associated with hemodynamic adverse events, including cardiac arrest, especially in patients with cardiac disease. There are only a few studies that have evaluated the rate of and risk factors for endotracheal intubation hemodynamic complications in critically ill pediatric patients. Although some of these studies have assessed hemodynamic complications during intubation in pediatric cardiac patients, the frequency of and risk factors for peri-intubation cardiac arrest have not been adequately described in high acuity cardiac patients. This study aims to describe the frequency of and risk factors for peri-intubation cardiac arrest in critically ill pediatric cardiac patients admitted to specialized cardiac ICUs. Design: Multicenter retrospective cohort study. Setting: Three pediatric cardiac ICUs in the United States. Patients: Critically ill pediatric patients with congenital or acquired heart disease requiring endotracheal intubation. Interventions: None. Measurements and Main Results: Endotracheal intubations performed in three cardiac ICUs between January 2015 and December 2017 were reviewed. Clinical variables—including data on patients, clinical providers, and procedure—were evaluated for their association with peri-intubation cardiac arrest. There was a total of 186 intubation events studied, occurring in 151 individual (index) patients. The rates of peri-intubation cardiac arrest and peri-intubation mortality in this cohort were 7% and 1.6%, respectively. Among those patients with moderate or severe systolic dysfunction of the systemic ventricle, peri-intubation cardiac arrest rate was 20.7%. Statistically significant risk factors for peri-intubation cardiac arrest included: significant systolic dysfunction of the systemic ventricle, pre-intubation hypotension, pre-intubation lactate elevation, lower pre-intubation pH, and documented oxygen desaturations (> 10%) during intubation procedure. Conclusions: Our most significant finding was a peri-intubation cardiac arrest rate which was much higher than previously published rates for both cardiac and noncardiac children who underwent endotracheal intubation in ICUs. Peri-intubation mortality was also high in our cohort. Regarding risk factors for peri-intubation arrest, significant systolic dysfunction of the systemic ventricle was strongly associated with cardiac arrest in this cohort.

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