Recently, there has been a growing interest in understanding the role of receptor tyrosine kinases (RTK), such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (KIT), and fms-like tyrosine kinase 3 (FLT3), in promoting tumor angiogenesis, tumor growth and metastasis. Sunitinib (sunitinib malate; SU11248; SUTENT; Pfizer Inc, New York, NY, USA) is a novel, orally bio-available, oxindole, multi-targeted tyrosine kinase inhibitor with high binding affinity for VEGFR and PDGFR which has shown anti-tumor and anti-angiogenic activities. This drug recently received approval from the US Food and Administration (FDA) in two indications simultaneously: advanced renal cell carcinoma (adRCC) and gastrointestinal stromal tumors (GIST), in patients who are resistant or intolerant to the treatment with imatinib. The present article reviews the recent pharmacologic and clinical data related to the use of this new promising drug in the field of oncology.
Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a maintenance immunosuppressive agent in organ transplantation. Also, a potentially benefit of this valuable drug in some immunologic and malignant diseases is currently under scrutiny.Classical side effects: hematological (anaemia, leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity oedema and impaired wound healing have been frequently associated with the use of sirolimus. Additionally with its increased use, transplant professionals are encountering a variety of previously unreported and potentially more severe side effects.Here, we review the most recent data on sirolimus unexpected side effects (with an emphasis on pulmonary and renal toxicity), its use in renal transplantation and its new potential therapeutic indications (chronic glomerulopathies, polycystic kidney disease, different types of cancer). A brief description of the current knowledge of sirolimus therapeutic drug monitoring, methods of analysis, pharmacokinetics and drug interactions with calcineurin inhibitors is also included.
Because of the well-documented risk of acute renal failure with the iodinated contrast media in patients with underlying chronic renal insufficiency, the use of intravenous gadolinium-based contrast media in magnetic resonance imaging for diagnostic and interventional radiology procedures has become a well-established clinical practice in the recent years. Although originally thought to be safe and lack the nephrotoxic effects of iodinated contrast media, gadolinium-based contrast media have recently been reported to induce a usually reversible decrease of glomerular filtration rate in a high-risk population group, especially in patients with altered baseline renal function. Here we present the current experimental and clinical evidence on this new challenge for the nephrologist, gadolinium-induced nephrotoxicity in patients with chronic kidney disease.
Half of the nondipper dialysis patients maintain a permanently abnormal circadian rhythm, despite successful RTx. In the short term, RTx is associated with a highly abnormal diurnal profile, exclusively related to ciclosporin dose and levels. However, in the longer term, renal transplantation leads to a significant improvement of the circadian blood pressure profile, influenced by the renal function level and by the pretransplantation dipping profile.
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