Cyclosporine acute nephrotoxicity

Carmellini M, Frosini F, FUipponi F, Boggi U, Mosca F. Effect of cilastatin on cyclosporine-induced acute nephrotoxicity in kidney transplant recipients. Transplantation 1997 64(l) 164-6. 

Table 2. Clinical presentations of acute cyclosporine A nephrotoxicity.

Prevot A, Semama DS, Tendron A, Justrabo E, Guignard JP, Gouyon JB. Endothelin, angiotensin II and adenosine in acute cyclosporine A nephrotoxicity. Pediatr Nephrol 2000 14 927-934. 

Grieve EM, Hawksworth GM, Simpson JG, Whiting PH. Effect of thromboxane synthetase inhibition and angiotensin converting enzyme inhibition on acute cyclosporin A nephrotoxicity. Biochem Pharmacol 1990 40 2323-2329. 

Poutell-Noble C, Chapuls F, Berra N, Hadj-Aissa A, Lacavalerle B, Lefrancols N, Martin X,Touraine JL. Misoprostol In renal transplant recipients a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity. Nephrol Dial Transplant 1994 9 552-555. 

Heyne N, Wolf S, Petersen P, Merten S, Schober W, Erley CM, RislerT, Osswald FI. Adenosine receptor antagonism In the prevention of acute cyclosporine A- nephrotoxicity in normal, diabetic and hypertensive rats. Nephrol Dial Transplant 1999 14 SuppI 4 23-24. 

Kawaguchi A, Sugimoto K, Fujimura A. Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute nephrotoxicity. Life Sci 2001 68 1181-1190. 

Capasso G, Unwin R, Ciani F, Rizzo A, Russo F, Pica A, De Santo NG. Inhibition of neutral endopeptidase potentiates the effects of atrial natriuretic peptide on acute cyclosporin-induced nephrotoxicity. Nephron 2000 86 298-305. 

A second form of cyclosporine-induced nephrotoxicity is acute thrombotic microangiopathy. The mechanism for induction of this toxicity is unclear but may be due to a direct toxic effect of cyclosporine on renal arterioles and glomerular capillaries. Histologically, arterioles exhibit protein deposits while glomeruli show thrombosis and endothelial cell damage. These effects are similar in nature to transplant rejection thrombotic microangiopathy, but arcuate and interlobular arteries rather than arterioles are primarily affected with transplant rejection. 

Smeesters C, Chaland P, Giroux L, Moutquin JM, Etienne P, Douglas F, Corman J, St Louis G, Daloze P. Prevention of acute cyclosporine A nephrotoxicity by a thromboxane synthetase inhibitor. Transplant Proc 1988 20 658-664. 

Maestri M, Dafoe DC, Adams GA, Gaspari A, Luzzana F, Innocente F, Rademacher J, Dionigi P, Barbieri A, Zonta F, Zonta A, Rabkin R. Insulin-like growth factor-1 ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine. Transplantation 1997 64 185-190. 

The beneficial effect of curcumin in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine was examined in rats (Tirkey et al. 2005). Curciunin administered concurrently with for 21 days effectively attenuated cyclosporine induced nephrotoxicity through its antioxidant activity as revealed by markedly countered elevated levels of TEARS, attenuated renal dysfunction, and increased levels of antioxidant enzymes. 

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabohte of azathioprine) are sometimes used for the treatment of IBD. These agents are generally reserved for cases that are refractory to steroids and may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Cyclosporine has been of short-term benefit in acute, severe ulcerative colitis when used in a continuous infusion. 

Chamey, D., Solez, K., Rascusen, L. (2004). Nephrotoxicity of cyclosporine and other immunosuppressive and immunothera-peutic agents. In Toxicology of Kidney, 3rd edition (J.B. Hook, J.B. Tarloff, L.H. Lash, eds). CRC Press, Boca Raton FL. Choie, D.D., Longnecker, D.S., Del Capmo, A.A. (1981). Acute and chronic cisplatin nephropathy in rats. Lab. Invest. 44(5) 397 02. 

Extensive expression of KlM-1 has been found in proximal tubule cells in biopsies from patients with acute tubular necrosis [302]. KlM-1 is also expressed in other conditions where proximal tubules are dedifferentiated, including renal cell carcinoma [303, 304], chronic cyclosporine nephrotoxicity [305], a protein-overload model of tubulointerstitial disease [306], polycystic kidney disease [307], and contrast nephropathy. In several chronic conditions, KlM-1 has been found primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis and inflammation. Independent of the specific disease, renal KIM-1 correlated positively with the extent of renal damage and negatively with renal function. In these patients, urinary levels of KIM-1 were and correlated positively with tissue KIM-1 and negatively with renal function. Thus, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. Urinary KIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1. 

ATP depletion, cation shifts and oxygen-derived free radical injury Site of renal ischemia-reperfusion injury A link between proximal and distal tubular injury and recovery Tubuloglomerular feedback and autoregulation Endothelin in ischemia-reperfusion injury Treatment of ischemic acute kidney injury Nephrotoxic injury Cyclosporine... 

Paller MS, Paller MS. The prostaglandin El analog misoprostol reverses acute cyclosporine nephrotoxicity. Transplantation Proceedings 1988 20 634-637. 

The interaction of cyclosporine with the plasma and tissue renin-angiotensin-aldosterone systems (RAS) has been extensively studied [21, 22]. Sodium depletion, a condition that stimulates renin release, enhances acute CSA nephrotoxicity [23, 24]. In rats, CSA treatment enhanced plasma renin activity (PRA) [21, 25, 26], increased renal renin content [21], promoted juxtaglomerular hypertrophy and hyperplasia [27,... 

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