Acetylcysteine and contrast agent-associated nephrotoxicity

Contrast-Induced Nephropathy

https://www.ajkd.org/article/S0272-6386(97)90004-4/pdf

Endothelins in the normal and diseased kidney

WITH THE INCREASING USE OF CONTRAST MEDIA in diagnostic and interventional procedures, nephropathy induced by contrast media has become the third leading cause of hospital-acquired acute renal failure. It is also associated with a significant risk of morbidity and death. The current understanding of the pathogenesis indicates that contrast-medium nephropathy is caused by a combination of renal ischemia and direct toxic effects on renal tubular cells. Patients with pre-existing renal insufficiency, diabetes mellitus and congestive heart failure are at highest risk. Risk factors also include the type and amount of contrast medium administered. Therapeutic prevention strategies are being extensively investigated, but there is still no definitive answer. In this article, we review the current evidence on the causes, pathogenesis and clinical course of contrast-medium nephropathy as well as therapeutic approaches to its prevention evaluated in clinical trials.

/pdf/nephropathy-induced-by-contrast-media-pathogenesis-risk-19rfqe49uq.pdf

Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies

Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.

/pdf/nitric-oxide-and-prostanoids-protect-the-renal-outer-medulla-duph3kvxuv.pdf

Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

Prodrugs of COX-2 inhibitors are described as being useful in treating inflammation and inflammation-related disorders.

Prodrugs of benzenesulfonamide-containing COX-2 inhibitors

https://www.kidney-international.org/article/S0085-2538(15)58252-5/pdf

Role of endothelin and prostaglandins in radiocontrast-induced renal artery constriction.

A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically-acceptable salt thereof.

Substituted pyrazolyl benzenesulfonamides for the treatment of gastrointestinal conditions

A class of dihydrobenzopyrans, dihydrobenzothiopyrans, tetrahydroquinolines, tetrahydronaphthalenes, and analogs thereof, is described for use in treating cyclooxygenase-2 mediated disorders. Compounds of particular interest are defined by Formula (I) wherein X, A?1, A2, A3, A4?, R, R'', R?1 and R2? are as described in the specification.

Carter Jeffery S

Papers

Prodrugs of benzenesulfonamide-containing COX-2 inhibitors

Role of endothelin and prostaglandins in radiocontrast-induced renal artery constriction.

Substituted pyrazolyl benzenesulfonamides for the treatment of gastrointestinal conditions

Dihydrobenzopyrans, dihydrobenzothiopyrans, and tetrahydroquinolines for the treatment of cox-2-mediated disorders

Thiol and hydroxamic acid containing inhibitors of endothelin converting enzyme