The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-GBM glomerulonephritis

International Journal of Clinical and Experimental Pathology

Volumn 4, Issue 6, 2011, Pages 606-615

  Zitt, Emanuel ^a,c   Eller, Kathrin ^b,c   Huber, Julia M ^c   Kirsch, Alexander H ^b,c   Tagwerker, Andrea ^c   Mayer, Gert ^c   Rosenkranz, Alexander R ^a,b,c  

^a Academic Teaching Hospital Feldkirch   (Austria)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

^c INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Aldosterone antagonism; Eplerenone; Glomerulonephritis; Renal inflammation

Indexed keywords

ALDOSTERONE ANTAGONIST; ALDOSTERONE RECEPTOR; CYTOKINE; DRUG DERIVATIVE; EPLERENONE; IMMUNOGLOBULIN G; SPIRONOLACTONE;

ALBUMINURIA; ANIMAL; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DRUG ANTAGONISM; DRUG EFFECT; GLOMERULONEPHRITIS; GLOMERULUS; IMMUNOLOGY; LYMPH NODE; MALE; METABOLISM; MOUSE; PATHOLOGY; RABBIT; SPLEEN;

ALBUMINURIA; ALDOSTERONE ANTAGONISTS; ANIMALS; ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CYTOKINES; IMMUNOGLOBULIN G; KIDNEY GLOMERULUS; LYMPH NODES; MALE; MICE; RABBITS; RECEPTORS, ALDOSTERONE; SPIRONOLACTONE; SPLEEN;

EID: 80055060496     PISSN: None     EISSN: 19362625     Source Type: Journal    
DOI: None     Document Type: Article

References (44)

1. Lewis EJ, Hunsicker LG, Bain RP and Rohde RD. The effect of angiotensin-convertingenzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456-1462.
2. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R and Raz I. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851-860.
3. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z and Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861-869.
4. Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R and Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN followup trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet 1998; 352: 1252-1256.
5. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet 1997; 349: 1857-1863.
6. Greene EL, Kren S and Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest 1996; 98: 1063-1068.
7. Kiyomoto H, Rafiq K, Mostofa M and Nishiyama A. Possible underlying mechanisms responsible for aldosterone and mineralocorticoid receptor-dependent renal injury. J Pharmacol Sci 2008; 108: 399-405.
8. Rocha R, Chander PN, Khanna K, Zuckerman A and Stier CT, Jr. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31: 451-458.
9. Guo C, Martinez-Vasquez D, Mendez GP, Toniolo MF, Yao TM, Oestreicher EM, Kikuchi T, Lapointe N, Pojoga L, Williams GH, Ricchiuti V and Adler GK. Mineralocorticoid receptor antagonist reduces renal injury in rodent models of types 1 and 2 diabetes mellitus. Endocrinology 2006; 147: 5363-5373.
10. Navaneethan SD, Nigwekar SU, Sehgal AR and Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009; 4: 542-551.
11. Hansen PR, Rieneck K and Bendtzen K. Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells. Immunol Lett 2004; 91: 87-91.
12. Bendtzen K, Hansen PR and Rieneck K. Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis factor-alpha and interferon-gamma, and has potential in the treatment of arthritis. Clin Exp Immunol 2003; 134: 151-158.
13. Fujisawa G, Okada K, Muto S, Fujita N, Itabashi N, Kusano E and Ishibashi S. Spironolactone prevents early renal injury in streptozotocin-induced diabetic rats. Kidney Int 2004; 66: 1493-1502.
14. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML and McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63: 1791-1800.
15. Aldigier JC, Kanjanbuch T, Ma LJ, Brown NJ and Fogo AB. Regression of existing glomerulosclerosis by inhibition of aldosterone. J Am Soc Nephrol 2005; 16: 3306-3314.
16. Asai M, Monkawa T, Marumo T, Fukuda S, Tsuji M, Yoshino J, Kawachi H, Shimizu F, Hayashi M and Saruta T. Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis. Hypertens Res 2004; 27: 971-978.
17. Delyani JA. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int 2000; 57: 1408-1411.
18. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J and Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-1321.
19. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ and Pitt B. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11-21.
20. Rocha R, Martin-Berger CL, Yang P, Scherrer R, Delyani J and McMahon E. Selective aldosterone blockade prevents angiotensin II/saltinduced vascular inflammation in the rat heart. Endocrinology 2002; 143: 4828-4836.
21. Rosenkranz AR, Mendrick DL, Cotran RS and Mayadas TN. P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation. J Clin Invest 1999; 103: 649-659.
22. Wolf D, Hochegger K, Wolf AM, Rumpold HF, Gastl G, Tilg H, Mayer G, Gunsilius E and Rosenkranz AR. CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J Am Soc Nephrol 2005; 16: 1360-1370.
23. Qin W, Rudolph AE, Bond BR, Rocha R, Blomme EA, Goellner JJ, Funder JW and McMahon EG. Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res 2003; 93: 69-76.
24. Kobayashi N, Hara K, Tojo A, Onozato ML, Honda T, Yoshida K, Mita S, Nakano S, Tsubokou Y and Matsuoka H. Eplerenone shows renoprotective effect by reducing LOX-1 -mediated adhesion molecule, PKCepsilon-MAPK-p90RSK, and Rho-kinase pathway. Hypertension 2005; 45: 538-544.
25. Rosenkranz AR, Knight S, Sethi S, Alexander SI, Cotran RS and Mayadas TN. Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis. Kidney Int 2000; 58: 1055-1066.
26. Hochegger K, Siebenhaar F, Vielhauer V, Heininger D, Mayadas TN, Mayer G, Maurer M and Rosenkranz AR. Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis. Eur J Immunol 2005; 35: 3074-3082.
27. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T and Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salthypertensive rats and is reversed by aldosterone blocker. Hypertension 2006; 47: 1084-1093.
28. Ikeda H, Tsuruya K, Toyonaga J, Masutani K, Hayashida H, Hirakata H and Iida M. Spironolactone suppresses inflammation and prevents L-NAME-induced renal injury in rats. Kidney Int 2009; 75: 147-155.
29. Kang YM, Zhang ZH, Johnson RF, Yu Y, Beltz T, Johnson AK, Weiss RM and Felder RB. Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemiainduced heart failure. Circ Res 2006; 99: 758-766.
30. Kuster GM, Kotlyar E, Rude MK, Siwik DA, Liao R, Colucci WS and Sam F. Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 2005; 111: 420-427.
31. Suzuki J, Iwai M, Mogi M, Oshita A, Yoshii T, Higaki J and Horiuchi M. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol 2006; 26: 917-921.
32. Brandish PE, Forest TW, Chen H, Gatto NT, Molon-Noblot S, Zwierzynski I, Szczerba P, Adamson GE, Ma BK, Flores OA and Hershey JC. Eplerenone Decreases Inflammatory Foci in Spontaneously Hypertensive Rat Hearts With Minimal Effects on Blood Pressure. J Cardiovasc Pharmacol 2009;
33. Keidar S, Hayek T, Kaplan M, Pavlotzky E, Hamoud S, Coleman R and Aviram M. Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol 2003; 41: 955-963.
34. Keidar S, Kaplan M, Pavlotzky E, Coleman R, Hayek T, Hamoud S and Aviram M. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation 2004; 109: 2213-2220.
35. Han SY, Kim CH, Kim HS, Jee YH, Song HK, Lee MH, Han KH, Kim HK, Kang YS, Han JY, Kim YS and Cha DR. Spironolactone prevents diabetic nephropathy through an antiinflammatory mechanism in type 2 diabetic rats. J Am Soc Nephrol 2006; 17: 1362-1372.
36. Tipping PG and Holdsworth SR. T cells in crescentic glomerulonephritis. J Am Soc Nephrol 2006; 17: 1253-1263.
37. Miossec P, Korn T and Kuchroo VK. Interleukin -17 and type 17 helper T cells. N Engl J Med 2009; 361: 888-898.
38. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT and Weber KT. Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am J Pathol 2002; 161: 1773-1781.
39. Zhou W, Hashimoto K, Goleniewska K, O'Neal JF, Ji S, Blackwell TS, Fitzgerald GA, Egan KM, Geraci MW and Peebles RS, Jr. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. J Immunol 2007; 178: 702-710.
40. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006; 8 Suppl 2: S2.
41. Lim HY, Muller N, Herold MJ, van den Brandt J and Reichardt HM. Glucocorticoids exert opposing effects on macrophage function dependent on their concentration. Immunology 2007;
42. Armanini D, Endres S, Kuhnle U and Weber PC. Parallel determination of mineralocorticoid and glucocorticoid receptors in T- and Blymphocytes of human spleen. Acta Endocrinol (Copenh) 1988; 118: 479-482.
43. Klanke B, Cordasic N, Hartner A, Schmieder RE, Veelken R and Hilgers KF. Blood pressure versus direct mineralocorticoid effects on kidney inflammation and fibrosis in DOCA-salt hypertension. Nephrol Dial Transplant 2008; 23: 3456-3463.
44. Koh PJ, Koitka A, Cooper ME and Allen TJ. Eplerenone does not attenuate diabetesassociated atherosclerosis. J Hypertens 2009; 27: 1431-1438.