Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy.

The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC.

Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model.

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.

The incidence of skin lesions in contrast media-induced chemical hypersensitivity.

Contrast agents are used in radiology to increase the sensibility and specificity of radiological techniques. Some of these compounds have side effects that include organ toxicity (with kidney being the most affected organ) and hypersensitivity reactions. We performed multiple PubMed searches from January, 2008 to January, 2018 for studies regarding adverse reactions to compounds used as contrast agents in imagistic techniques. The initial research identified 929 records written in English. After further excluding 223 non-human studies, 292 articles that had irrelevant designs as reviews, meta-analysis, commentaries, editorials and case reports, 414 studies were selected for retrieval. After reading the abstracts, we excluded 363 studies as they had little relevance to the study. In total, 51 full-articles were assessed for eligible studies to be included. Finally, 20 articles were included in the analysis. In our systematic literature search the incidence of overall skin immediate reactions to iodinated contrast media (ICM) had an incidence between 1.15 and 0.12%, depending on the cohort analyzed in the studies. The percentage of cutaneous manifestations in the cohort that experienced immediate hypersensitivity reactions was between 33.33 and 87.7%. The most frequent skin manifestations were urticaria, rashes, pruritus and limited facial edema. Non-iodinated contrast agents have a safer profile compared with ICM, the incidence of immediate adverse reactions being very low in gadolinium-based contrast agents and other agents used for contrast-enhanced ultrasound. The incidence of delayed reactions was between 10.1 and 0.03%. In the studies analyzed by us the main adverse reactions due to delayed hypersensitivity phenomena were cutaneous manifestations that were present between 70.27 and 100% of the cases. Regarding the risk factors for developing immediate adverse reactions, being female was a predisposing factor accompanied by history of allergy and history of reactions to contrast media. An accurate anamnesis of the patients and a correctly conducted pretreatment can limit the incidence and the severity of the adverse reactions and also can avoid the life occurrence of life-threatening reactions.