Renal effects of anti-angiogenesis therapy: update for the internist.

Angiogenesis has become an innovative target in cancer therapy. Agents that inhibit vascular endothelial growth factor (VEGF), one of the most potent promoters of angiogenesis, and its receptor have significant implications for clinical practice. Bevacizumab, sorafenib, sunitinib and other anti-VEGF drugs are frequently complicated by mild proteinuria and hypertension. Other unique renal effects, such as high-grade proteinuria and acute kidney injury, have been described. The most common histopathologic kidney lesion is thrombotic microangiopathy, with other glomerular lesions and interstitial nephritis occurring less frequently. The mechanism for anti-VEGF therapy-induced hypertension is not well understood; however, nitric oxide pathway inhibition, rarefaction, and oxidative stress may be important in its pathogenesis. Glomerular injury may develop from loss of VEGF effect on maintaining the filtration barrier. Adverse effects of anti-VEGF class of drugs are manageable but require close attention and follow-up. Understanding the fundamentals of anti-VEGF drugs' mechanism of action and their clinical implications is crucial when caring for patients receiving anti-VEGF therapy.

The effect of intranasal steroid budesonide on the congestion-related sleep disturbance and daytime somnolence in patients with perennial allergic rhinitis.

Patients with perennial allergic rhinitis (PAR) often present with nasal congestion, poor sleep, daytime fatigue, and daytime somnolence. Pharmacologic therapy that reduces nasal congestion should improve the PAR patients' sleep quality and reduce daytime somnolence and fatigue. Our hypothesis is that intranasal steroid budesonide (BUD), an effective topical anti-inflammatory agent, will reduce nasal congestion and improve the patients' quality of life. The objective of this study was to determine whether topical steroid BUD improves sleep, daytime somnolence, and fatigue in patients with PAR. Twenty-six subjects were enrolled in a double-blind, placebo-controlled, crossover study using Balaam's design. Patients were treated with intranasal steroid spray BUD or placebo. The Epworth Sleepiness Scale, daily diary, and questionnaires were used as tools for subjective data analysis, which focused on nasal symptoms, sleep quality, daytime somnolence, and fatigue. The results were summarized and compared by PROC MIXED in SAS. The daily diary data showed significant improvement in self-reported nasal congestion (p = 0.04) and daytime sleepiness (p = 0.01) and a trend in reduction of daytime fatigue (p = 0.08) in the BUD group compared with the placebo group. The sleep measures showed statistically significant improvement in total sleep measures score (p = 0.04), "sleep compared with absolute" (p = 0.01), and "refreshing and restorative" sleep (p = 0.04) in the active group. Nasal corticosteroid BUD is effective in reducing nasal congestion, daytime somnolence, and daytime fatigue, and improving sleep quality in PAR.

The correlation between allergic rhinitis and sleep disturbance.

Nasal congestion, a common symptom related to allergic rhinitis (AR), often is associated with poor sleep quality, leading to decreased learning ability, decreased productivity at work or school, and a reduced quality of life. The release of inflammatory mediators and activation of inflammatory cells results in nasal congestion, causing disrupted sleep and subsequent daytime somnolence. Therefore it is important to treat AR with medications that improve congestive symptoms without exacerbating sedation. Second-generation antihistamines and anticholinergic drugs are well tolerated but have little effect on congestion and therefore are limited in their ability to reduce AR-associated daytime somnolence. However, intranasal corticosteroids reduce congestion, improve sleep and sleep problems, and reduce daytime sleepiness, fatigue, and inflammation. Recently, montelukast, a leukotriene receptor antagonist, has joined the approved therapies for AR. Montelukast significantly improves both daytime and nighttime symptoms. AR treatment should endeavor to improve daytime and nighttime symptoms, sleep, and productivity, thereby improving quality of life.