Title: Role of Apoptosis in the Pathogenesis of Contrast Media-induced Nephropathy and Hints for its Possible Prevention by Drug Treatment
Volume: 5
Issue: 2
Author(s): J.- M. Idee, J. Boehm, P. Prigent, S. Ballet and C. Corot
Affiliation:
Keywords:
Iodinated contrast media, gadolinium chelates, apoptosis, contrast-induced nephropathy
Abstract: Contrast-induced nephropathy (CIN) is a worrying concern in at-risk patients. Its pathophysiological mechanism remains speculative and is possibly modulated according to the risk factor(s) and clinical presentation of the patients. Overall, iodinated contrast media (CM) have been shown, in animal models, to induce medullary hypoxia. Furthermore, numerous studies have demonstrated that they have a direct cytotoxic potential on proximal (LLC-PK1) as well as distal (MDCK) tubular cell lines and mesangial cells. A pro-apoptotic potential of such molecules has been found on various cell types including renal tubular and mesangial cells, both in vitro and in vivo. This pro-apoptotic effect on tubular cells has been found to be concentration- and time-dependent. In addition to periprocedural hydration, which is the cornerstone of CIN, several drugs have been investigated for the pharmacological prophylaxis of CIN, either on pre-clinical models or in clinical studies. Some of them (theophylline, Nacetylcysteine, the prostacyclin analogue beraprost or taurine) are known to interfere with the apoptosis pathways. This article reviews and critically discusses the available data concerning the role of apoptosis in the mechanism of CIN and its pharmacological prophylaxis. It also reviews the putative interaction of gadolinium chelates, used as CM for magnetic resonance imaging, with apoptosis pathways.
