(acute tubular (tubuloglomerular feedback mechanism) necrosis, ATN)

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1 (acute tubular (tubuloglomerular feedback mechanism) necrosis, ATN) 1. (ET) 21 [1] [2] (cyclosporine) 48 [3] 2. (dopamine) (endothelin, ET) D 1 D 2 (angiotensin II) (serotonin) D 1 (D 1 -like) D 2 (D 2 -like) (0.5 3 µg/kg/min)

2 µg/kg/min ß α [6] Urodilatin (ularitide) ANP ANP Na-K ATPase urodilatin [4] [4] 4. (adenosine) [5] A 1 A 3 [7] theophylline ( ) 165 mg [4] 3. (atrial natriuretic peptide, ANP) ANP ANP aminophylline 0.45% ANP 5. (nitric oxide, NO) theophylline (endothelium-derived relaxing factor, EDRF) bradykinin (mannitol) (histamine) (acetylcholine) ANP (mediator) ANP (angiotensin II) [1] [4] ANP anaritide 6. (prostaglandin E 1, PGE 1 ) (ADH) (catecholamines)

3 4. (α-melanocyte-stimulating PGE 2 PGI 2 hormone, α-msh) PGEs [1] (cytokine) PGE 1 6 ICAM-1 [9] 1. (intercellular adhesion molecule- 1, ICAM-1) ATP (reactive oxygen species) ICAM-1 1. ICAM-1 ICAM-1 (thick ascending limb of the loop of ICAM-1 (antisense oligodeoxyribonucleotide) ICAM-1 [10] 2. (platelet-activating factor, PAF) PAF ICAM-1 [11] PAF (compartment syndrome) [4] PAF ( ) 3. [13] Henle) NADPH [12]

4 Integrins RGD (arginine-glycine-aspar- tic acid) RGD [14] 3. (cysteine proteases) (isolated) ( 1,050 mg/dl) furosemide bumetanide Na-K ATPase (bolus) calpain ( [15] ) 24 caspases (apoptosis) furosemide caspases furosemide ethacrynic acid aminoglycosides [4] 2.Na-K ATPase integrins (polarity) (basolateral membrane) Na-K ATPase P450 (cytochrome P450) (gradient) (apical membrane) [16] 4. Na-K ATPase (cytoskeletal proteins) (outer medulla) (inos) inos mrna inos inos integrins NOS NOS integrins [14] calpain

5 peroxynitrite (OONO ) [17] NOS calpain 5.Osteopontin Osteopontin osteopontin osteopontin 56. [18] osteopontin failure. Drugs 2000; 59: [19] 6. (insulin-like growth factor-1, IGF-1) osteopontin osteopontin IGF- 1 [20] 1. Peter JR: The pathophysiology of acute renal failure in; Alex MD, Stewart C, Jean-Pierre G, David NSK, Eberhard R, Christopher GW, eds Oxford textbook of clinical nephrology. 2nd ed. New York: Oxford University Press, Inc 1998; Gellai M, Jugus M, Fletcher T et al: Nonpeptide endothelin receptor antagonists. V. Prevention and reversal of acute renal failure in the rat by SB J Pharmacol Exp Ther 1995; 275: Wang A, Holcsclaw T, Bashore TA et al: Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism. Kidney Int 2000; 57: Michael KD, John AK: An evaluation of pharmacological strategies for the prevention and treatment of acute renal 5. Burton CJ, Tomson CR: Can the use of low-dose dopamine for treatment of acute renal failure be justified? Postgrad Med J 1999; 75: Allgren RL, Marbury TC, Rahman SN, et al: Anaritide in acute tubular necrosis: Auriculin Anaritide Acute Renal Failure Study Group. N Engl J Med 1997; 336: Lee HT, Emala CW: Protective effects of renal ischemic preconditioning and adenosine pretreatment: Role of A(1) and A(3) receptors. Am J Physiol 2000; 278: F Norbert L, Raymond V: Pathophysiologic features and prevention of human and experimental acute tubular necrosis. J Am Soc Nephrol 2001; 12: S Koch JA, Plum J, Grabensee B, Modder U: Prostaglandin E1: A new agent for the prevention of renal dysfunction in high risk patients causes by radiocontrast media? PGE 1 Study Group. Nephrol Dial Transplant 2000; 15: Haller H, Dragun D, Miethke A, et al: Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat. Kidney Int 1996; 50: Kelly KJ, Tolkoff-Rubin NE, Rubin RH, et al: An oral plateletactivating factor antagonist, Ro , protects the rat kidney from ischemic injury. Am J Physiol 1996; 271: F Lauriat S, Linas SL: The role of neutrophils in acute renal failure. Semin Nephrol 1998; 18: Chiao H, Kohda Y, McLeroy P, Craig L, Linas S, Star RA: α- Melanocyte-stimulating hormone inhibits renal injury in the absence of neutrophils. Kidney Int 1998; 54: Noiri E, Romanov V, Forest T, et al: Pathophysiology of renal tubular obstruction: Therapeutic role of synthetic RGD peptides in acute renal failure. Kidney Int 1995; 48: Edelstein CL, Yaqoob MM, Alkhunaizi AA, et al: Modulation of

6 hypoxia-induced calpain activity in rat renal proximal tubules. Kidney Int 1996; 50: Ladefoged SD, Andersen CB: Calcium channel blockers in kidney transplantation. Clin Transplant 2000; 8: Wangsiripaisan A, Gengaro PE, Nemenoff RA, Ling H, Edelstein CL, Schrier RW: Effect of nitric oxide donors on renal tubular epithelial cell-matrix adhesion. Kidney Int 1999; 55: Persy VP, Verstrepen WA, Ysebaert DK, De Greef KE, De Broe ME: Differences in osteopontin up-regulation between proximal and distal tubules after renal ischemia/reperfusion. Kidney Int 1999; 56: Vukicevic S, Basic V, Rogic D, et al: Osteogenic protein-1 (bone morphogenic protein-7) reduces severity of injury after ischemic acute renal failure in rat. J Clin Invest 1998; 102: Franklin SC, Moulton M, Sicard GA, Hammerman MR, Miller SB: Insulin-like growth factor 1 preserves renal function postoperatively in patients at risk to develop acute renal failure. Am J Physiol 1997; 272: F

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