Administration of iodinated contrast media (CM) for radiographic purposes is a preoccupying cause of acute renal failure. This review of the literature deals with what is known about physiopathology, clinical course, risk factors and prevention. Factors involved in the pathophysiology of CM-induced acute renal failure are vasoconstriction, direct tubular cell injury and tubular obstruction by casts. In the case of pre-existing renal hypoperfusion, CM may disturb the complex interaction between factors which modulate renal haemodynamics by increasing vasoconstrictor factors, notably endothelin peptides. The renal medulla, a zone characterized by a high metabolic activity and a low oxygen tension, may be a specific target for CM-induced effects. CM-induced nephropathy (CMN) is essentially observed in patients with one or more associated risk factors (chronic renal failure, dehydration, diabetes mellitus with impaired renal function, multiple myeloma, large CM volume, intra-arterial rather than intravenous route, etc). There is much debate as to whether newer low osmolar CM (LOCM) are better tolerated than conventional high osmolar CM (HOCM). Most of the animal studies clearly demonstrate the advantages of LOCM over HOCM. Clinical literature is far more confusing, although some recent studies and one meta-analysis demonstrate that LOCM are better tolerated in patients with impaired renal function. The low number of comparative clinical trials carried out in high risk patients, wide variability in CMN definitions, limited number of patients enrolled and inadequacy of various selected endpoints may explain difficulties experienced in demonstrating this advantage. Furthermore, while hydration is correctly maintained during clinical trials, this is not always true in clinical practice. Such a discrepancy could lead to underestimation of the potential advantage of LOCM over HOCM. Effective prevention should associate the correct hydration of patients, identification and, when possible, optimal correction of risk factors, avoidance of repeated CM injections within a short period of time and temporary disruption of treatment with other nephrotoxic drugs (non steroidal antiinflammatory drugs, aminoglycosides, etc).

Lipid-containing nanostructures, in the form of solid lipid nanoparticles or iron oxide nanoparticles (NPs) coated with a lipid shell, were used as case studies for assessing and optimizing staining for transmission electron microscopy structural and compositional characterization. These systems are of paramount importance as drug delivery systems or as bio-compatible contrast agents. In particular, we have treated the systems with a negative (phospshotungstic acid) or with a positive (osmium tetroxide) staining agent. For iron-oxide NPs coated with the lipid shell, negative staining was more efficient with respect to the positive one. Nevertheless, in particular cases the combination of the two staining procedures provided more complete morphological and compositional characterization of the particles.

The purpose of this study was to determine the diagnostic value of ultrasmall particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations to evaluate experimental nephropathy. This study was conducted in 23 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Eleven rats received selective intra-arterial renal administration of diatrizoate (370 mg I/ml) and were compared to two control groups, including five animals injected with isotonic saline and seven noninjected animals. MR imaging was performed 28 hours after the procedure, including T1- and T2-weighted images before and after intravenous administration of successively 5 mumol Fe/kg and 60 mumol/kg of USPIO. Results were interpreted qualitatively and quantitatively with respect to pathologic data, and differences were studied statistically. The maximal signal intensity decrease was noted in normal kidneys in cortex (-65 +/- 4%) and medulla (-84 +/- 5%) on T2-weighted images after injection of 60 mumol/kg of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative analysis showed that the highest sensitivity and specificity to diagnose kidney involvement were obtained with T2-weighted MR images (75% and 91%, respectively) when 60 mumol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo evaluation of the severity of experimentally induced iodinated contrast media renal impairment in animals.

BACKGROUND AND PURPOSEHyperphosphataemia is common in patients with nephrogenic systemic fibrosis (NSF). NSF has been linked to administration of gadolinium (Gd) chelates (GCs) and elevated serum phosphate levels accelerate the release of Gd from linear, non-ionic GCs but not macrocyclic GCs. Hence, we determined whether hyperphosphataemia is a cofactor or risk factor for NSF by investigating the role of hyperphosphataemia in renally impaired rats. EXPERIMENTAL APPROACHFirstly, the clinical, pathological and bioanalytical consequences of hyperphosphataemia were investigated in subtotal nephrectomized (SNx) Wistar rats following i.v. administration of the non-ionic, linear GC gadodiamide (5 ¥ 2.5 mmol·kg). Secondly, the effects of several GCs were compared in these high-phosphate diet fed rats. Total Gd concentration in skin, femur and plasma was measured by inductively coupled plasma mass spectrometry (ICP-MS) and free Gd 3+ in plasma by liquid chromatography coupled to ICP-MS. Relaxometry was used to measure dissociated Gd in skin and bone. KEY RESULTSFour out of seven SNx rats fed a high-phosphate diet administered gadodiamide developed macroscopic and microscopic (fibrotic and inflammatory) skin lesions, whereas no skin lesions were observed in SNx rats treated with saline, the other GCs and free ligands or in the normal diet, gadodiamide-treated group. Unlike the other molecules, gadodiamide gradually increased the r1 relaxivity value, consistent with its in vivo dissociation and release of soluble Gd. CONCLUSIONS AND IMPLICATIONSHyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide. Unlike the other GCs investigated, gadodiamide gradually dissociates in vivo. Our data confirm that hyperphosphataemia is a risk factor for NSF. Abbreviationsa-SMA, a-smooth muscle actin; DTPA, diethylene triamine pentaacetic

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