Pharmacokinetics of amphotericin B after accidental overdose in an adult critically ill patient treated with plasmapheresis: a case report and review of literature

Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated

Supplementary Material, Supplementary_Material_-_Survey – No consensus on physicians’ preferences on vascular access management after kidney transplantation: Results of a multi-national survey

<p>Supplementary Material, Supplementary_Material_-_Survey for No consensus on physicians’ preferences on vascular access management after kidney transplantation: Results of a multi-national survey by Bram M Voorzaat, Cynthia J Janmaat, Esther D Wilschut, Koen EA Van Der Bogt, Friedo W Dekker and Joris I Rotmans in The Journal of Vascular Access</p

Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas

The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout (Rxfp1-/-) onAVFmaturation inamurinemodel ofAVFfailure. Rxfp1-/-mice showed a22% decrease in vessel size at the venous outflow tract 14 d afterAVF surgery. Furthermore, a 43% increase in elastin contentwas observed in the lesions of Rxfp1-/-mice and coincided with a 41%reduction in elastase activity. In addition, Rxfp1-/- mice displayed a 6-fold increase in CD45+ leukocytes, along with a 2-fold increase in monocyte chemoattractant protein 1 (MCP1) levels, when compared with wild-type mice. In vitro, VSMCs from Rxfp1-/- mice exhibited a synthetic phenotype, as illustrated by augmentation of collagen, fibronectin, TGF-b, and platelet-derived growth factor mRNA. In addition, VSMCs derived from Rxfp1-/- mice showed a 5-fold increase in cell migration. Finally, RXFP1 and RLN expression levels were increased in human AVFs when compared with unoperated cephalic veins. In conclusion, RXFP1 deficiency hampers elastin degradation and results in induced vascular inflammation after AVF surgery. These processes impair OR in murine AVF, suggestingthat theRLNaxis couldbe apotential therapeutic target for promoting AVF maturation

Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas

The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout (Rxfp1-/-) onAVFmaturation inamurinemodel ofAVFfailure. Rxfp1-/-mice showed a22% decrease in vessel size at the venous outflow tract 14 d afterAVF surgery. Furthermore, a 43% increase in elastin contentwas observed in the lesions of Rxfp1-/-mice and coincided with a 41%reduction in elastase activity. In addition, Rxfp1-/- mice displayed a 6-fold increase in CD45+ leukocytes, along with a 2-fold increase in monocyte chemoattractant protein 1 (MCP1) levels, when compared with wild-type mice. In vitro, VSMCs from Rxfp1-/- mice exhibited a synthetic phenotype, as illustrated by augmentation of collagen, fibronectin, TGF-b, and platelet-derived growth factor mRNA. In addition, VSMCs derived from Rxfp1-/- mice showed a 5-fold increase in cell migration. Finally, RXFP1 and RLN expression levels were increased in human AVFs when compared with unoperated cephalic veins. In conclusion, RXFP1 deficiency hampers elastin degradation and results in induced vascular inflammation after AVF surgery. These processes impair OR in murine AVF, suggestingthat theRLNaxis couldbe apotential therapeutic target for promoting AVF maturation

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study - a randomized controlled trial

Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturatio

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study – a randomized controlled trial

Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturatio