Owing to improvements in catheters and embolic agents, renal artery embolization (RAE) is increasingly used to treat nephrological and urological disease. RAE has become a useful adjunct to medical resuscitation in severe penetrating, iatrogenic or blunt renal traumatisms with active bleeding, and might avoid surgical intervention, particularly among patients that are haemodynamically stable. The role of RAE in pre-operative or palliative management of advanced malignant renal tumours remains debated; however, RAE is recommended as a first-line therapy for bleeding angiomyolipomas and can be used as a preventative treatment for angiomyolipomas at risk of bleeding. RAE represents an alternative to nephrectomy in various medical conditions, including severe uncontrolled hypertension among patients with end-stage renal disease, renal graft intolerance syndrome or autosomal dominant polycystic kidney disease. RAE is increasingly used to treat renal artery aneurysms or symptomatic renal arteriovenous malformations, with a low complication rate as compared with surgical alternatives. This Review highlights the potential use of RAE as an adjunct in the management of renal disease. We first compare and contrast the technical approaches of RAE associated with the various available embolization agents and then discuss the complications associated with RAE and alternative procedures.

BackgroundMammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis.MethodologyThe presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8) or lipopolysaccharide (LPS). Morphine secretion was determined by a morphine-specific ELISA. μ opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested.Principal FindingsWe confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca2+. LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca2+. LPS treatment increased μ opioid receptor expression on neutrophils. Low concentration of morphine (8 nM) significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response syndrome and healthy controls. Mass spectrometry analysis showed that endogenous morphine from serum of patient with sepsis was identical to poppy-derived morphine.ConclusionsOur results indicate that morphine concentrations are increased significantly in the serum of patients with systemic infection and that morphine is, at least in part, secreted from neutrophils during sepsis. Morphine concentrations equivalent to those found in the serum of septic patients significantly inhibited LPS-induced IL-8 secretion in neutrophils.