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Das Renin-Angiotensin-Aldosteron-System als Zentraler Mediator der Progression der Niereninsuffizienz

The renin-angiotensin-aldosterone system as a pivotal mediator for the progression of renal insufficiency

  • Leitthema
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Der Nephrologe Aims and scope

Zusammenfassung

Das komplexe RAAS spielt eine entscheidende Rolle bei der Progression der chronischen Niereninsuffizienz. Renin und Aldosteron können unabhängig von ANG II über die TGFβ−Synthese zur Nierenfibrose beitragen. Genpolymorphismen der Komponenten des RAAS, agonistische AK gegen den AT1-Rezeptor und AT1-Rezeptor-Dimere können zusätzlich zur Funktionsverschlechterung der Niere beitragen. ACE-Hemmer und AT1-Rezeptor-Antagonisten in Standarddosierungen hemmen die eigenständigen RAAS der Organe nur unvollständig. Zur Kontrolle des Blutdrucks und der Proteinurie sollten ACE-Hemmer oder AT1-Rezeptor-Antagonisten ausdosiert und indikationsgerecht eingesetzt werden. Eine Doppelblockade sollte bei Patienten mit chronischer Niereninsuffizienz und einer Proteinurie über 1 g/Tag erwogen werden. Empfehlungen zur zusätzlichen Gabe eines Aldosteron-Antagonisten sind derzeit aufgrund der mangelnden Datenlage bei Patienten mit Niereninsuffizienz nicht auszusprechen. Eine Zulassung für Renin-Inhibitoren existiert z. Z. nicht.

Abstract

The complex renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of renal insufficiency. Renin and aldosterone can contribute independently of ANG II to renal fibrosis via the induction of TGFβ synthesis. Genetic polymorphisms involving the components of RAAS, agonistic antibodies against the AT1 receptor as well as AT1 receptor dimers can all contribute further to deterioration in renal function. ACE inhibitors and AT1 receptor antagonists in standard dosages incompletely inhibit intrarenal RAAS. To control blood pressure and proteinuria, ACE inhibitors or AT1 receptor antagonists should be prescribed up to the recommended dose. Double blockade should be considered for patients with chronic renal failure and a proteinuria of more than 1 g/day. Recommendations for the additional use of aldosterone antagonists can currently not be made due to lack of data from clinical studies. Renin inhibitors are not yet licensed for the German market.

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Literatur

  1. Abdalla S, Lother H, Langer A et al. (2004) Factor XIIIA transglutaminase crosslinks AT1 receptor dimers of monocytes at the onset of atherosclerosis. Cell 119: 343–354

    Article  PubMed  Google Scholar 

  2. Abrahamsen CT, Pullen MA, Schnackenberg CG et al. (2002) Effects of angiotensin II and IV on blood pressure, renal function, and PAI-1 expression in the heart and kidney of the rat. Pharmacology 66: 26–30

    Article  Google Scholar 

  3. Azizi M, Webb R, Nussberger J, Hollenberg NK (2006) Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens 24: 243–256

    Article  PubMed  Google Scholar 

  4. Barnett AH, Bain SC, Bouter P et al.; Diabetics Exposed to Telmisartan and Enalapril Study Group (2004) Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 351: 1952–1961

    Article  PubMed  Google Scholar 

  5. Beutler KT, Masilamani S, Turban S et al. (2003) Long-term regulation of ENaC expression in kidney by angiotensin II. Hypertension 41: 1143–1150

    Article  Google Scholar 

  6. Brenner BM (1985) Nephron adaptation to renal injury or ablation. Am J Physiol 249: F324–337

    PubMed  Google Scholar 

  7. Campbell R, Sangalli F, Perticucci E et al. (2003) Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int 63: 1094–1103

    Article  PubMed  Google Scholar 

  8. Carey RM (2005) Update of the role of the AT2 receptor. Curr Opin Nephrol Hypertens 14: 67–71

    PubMed  Google Scholar 

  9. Chun TY, Pratt JH (2004) Non-genomic effects of aldosterone: new actions and questions. Trends Endocrinol Metab 15: 353–354

    Article  PubMed  Google Scholar 

  10. Dragun D, Muller DN, Brasen JH et al. (2005) Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 352: 558–569

    Article  PubMed  Google Scholar 

  11. Fu ML, Herlitz H, Schulze W et al. (2000) Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 18: 945–953

    Article  PubMed  Google Scholar 

  12. Gonzalez-Villalobos R, Klassen RB, Allen PL et al. (2005) Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol 288: F420–427

    Article  PubMed  Google Scholar 

  13. Hou FF, Zhang X, Zhang GH et al. (2006) Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 354: 131–140

    Article  PubMed  Google Scholar 

  14. Huang XR, Chen WY, Truong LD, Lan HY (2003) Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol 14: 1738–1747

    Article  PubMed  Google Scholar 

  15. Huang Y, Wongamorntham S, Kasting J et al. (2006) Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney Int 69: 105–113

    Article  PubMed  Google Scholar 

  16. Imig JD, Navar GL, Zou LX et al. (1999) Renal endosomes contain angiotensin peptides, converting enzyme, and AT(1A) receptors. Am J Physiol Renal Physiol 277: F303–311

    Google Scholar 

  17. Kanno Y, Takenaka T, Nakamura T, Suzuki H (2006) Add-on angiotensin receptor blocker in patients who have proteinuric chronic kidney diseases and are treated with angiotensin-converting enzyme inhibitors. Clin J Am Soc Nephrol 1: 730–737

    Article  Google Scholar 

  18. Kobori H, Nishiyama A, Harrison-Bernard LM, Navar LG (2003) Urinary angiotensinogen as an indicator of intrarenal angiotensin status in hypertension. Hypertension 41: 42–49

    Article  PubMed  Google Scholar 

  19. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329: 1456–1462

    Article  PubMed  Google Scholar 

  20. Lewis EJ, Hunsicker LG, Clarke WR et al.; Collaborative Study Group (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345: 851–860

    Article  PubMed  Google Scholar 

  21. Li N, Zimpelmann J, Cheng K et al. (2005) The role of angiotensin converting enzyme 2 in the generation of angiotensin 1–7 by rat proximal tubules. Am J Physiol Renal Physiol 288: F353–362

    Article  PubMed  Google Scholar 

  22. Lods N, Ferrari P, Frey FJ et al. (2003) Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis. J Am Soc Nephrol 14: 2861–2872

    Article  PubMed  Google Scholar 

  23. Macconi D, Abbate M, Morigi M et al. (2006) Permselective dysfunction of podocyte-podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention. Am J Pathol 168: 1073–1085

    PubMed  Google Scholar 

  24. Mazak I, Fiebeler A, Muller DN et al. (2004) Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells. Circulation 109: 2792–2800

    Article  PubMed  Google Scholar 

  25. Nakao N, Yoshimura A, Morita H et al. (2003) Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 361: 117–124

    Article  PubMed  Google Scholar 

  26. Navar LG, Nishiyama A (2004) Why are angiotensin concentration so high in the kidney ? Curr Opin Nephrol Hypertens 13: 107–115

    PubMed  Google Scholar 

  27. Nguyen G, Delarue F, Burckle C et al. (2002) Pivotal role of the renin/prorenin in angiotensin II production and cellular responses to renin. J Clin Invest 109: 1417–1427

    Article  PubMed  Google Scholar 

  28. Nishiyama A, Seth DM, Navar LG (2002) Renal interstitial fluid angiotensin I and angiotensin II concentrations during local angiotensin converting enzyme inhibition. J Am Soc Nephrol 13: 2207–2212

    Article  PubMed  Google Scholar 

  29. Oudit GY, Herzenberg AM, Kassiri Z et al. (2006) Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am J Pathol 168: 1808–1820

    Article  PubMed  Google Scholar 

  30. Perico N, Codreanu I, Schieppati A, Remuzzi G (2005) Pathophysiology of disease progression in proteinuric nephropathies. Kidney Int 94: S79–82

    Article  Google Scholar 

  31. Pitt B, Remme W, Zannad F et al.; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321

    Article  PubMed  Google Scholar 

  32. Pitt B, Zannad F, Remme WJ et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341: 709–717

    Article  PubMed  Google Scholar 

  33. Remuzzi G, Ruggenenti P, Perna A et al.; RENAAL Study Group (2004) Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. J Am Soc Nephrol 15: 3117–3125

    Article  PubMed  Google Scholar 

  34. Rossing K, Schjoedt KJ, Smidt UM et al. (2005) Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care 28: 2106–2112

    PubMed  Google Scholar 

  35. Ruggenenti P, Perna A, Loriga G et al.; REIN-2 Study Group (2005) Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet 365: 939–946

    Article  PubMed  Google Scholar 

  36. Sato A, Hayashi K, Naruse M, Saruta T (2003) Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension 4: 64–68

    Article  Google Scholar 

  37. Schjoedt KJ, Rossing K, Juhl TR et al. (2005) Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int 68: 2829–2836

    Article  PubMed  Google Scholar 

  38. Schjoedt KJ, Rossing K, Juhl TR et al. (2006) Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int 70: 536–542

    PubMed  Google Scholar 

  39. Schling P, Loffler G (2001) Effects of angiotensin II on adipose conversion and expression of genes of the renin-angiotensin system in human preadipocytes. Horm Metab Res 33: 189–195

    Article  PubMed  Google Scholar 

  40. Seikaly MG, Arant BS Jr, Seney FD Jr (1990) Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. Clin Invest 86: 1352–1357

    Google Scholar 

  41. Thway TM, Shlykov SG, Day MC et al. (2004) Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation. Circulation 110: 1612–1619

    Article  PubMed  Google Scholar 

  42. Walters PE, Gaspari TA, Widdop RE (2005) Angiotensin-(1–7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension 45: 1–7

    Article  Google Scholar 

  43. Wenzel UO (2001) Angiotensin-converting enzyme inhibitors and progression of renal disease: evidence from clinical studies. Contrib Nephrol 135: 200–211

    PubMed  Google Scholar 

  44. Wenzel UO, Dominiak P, Neumayer HH, Wolf G (2003) Hemmung der Progression von chronischen Nierenerkrankungen. Dtsch Arztebl 100: A2072–2079

    Google Scholar 

  45. Wolf G (2004) New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur J Clin Invest 34: 785–796

    Article  PubMed  Google Scholar 

  46. Wolf G (2005) Das Renin-Angiotensin-Aldosteron-System – komplexer als bisher gedacht. Med Klinik 100: 471–477

    Article  Google Scholar 

  47. Wolf G, Butzmann U, Wenzel UO (2003) The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology. Nephron Physiol 93: 3–13

    Article  Google Scholar 

  48. Wolf G, Mentzel S, Assmann KJ (1997) Aminopeptidase A: a key enzyme in the intrarenal degradation of angiotensin II. Exp Nephrol 5: 364–369

    PubMed  Google Scholar 

  49. Wolf G, Ritz E (2005) Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int 67: 799–812

    Article  PubMed  Google Scholar 

  50. Wolf G, Ziyadeh FN, Thaiss F et al. (1997) Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of angiotensin type 2 receptor. J Clin Invest 100: 1047–1058

    PubMed  Google Scholar 

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  1. Klinik für Innere Medizin III, Friedrich-Schiller-Universität Jena, Erlanger Allee 101, 07740, Jena

    K. A. Pöschel & G. Wolf

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  1. K. A. Pöschel
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  2. G. Wolf
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Correspondence to K. A. Pöschel.

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Pöschel, K.A., Wolf, G. Das Renin-Angiotensin-Aldosteron-System als Zentraler Mediator der Progression der Niereninsuffizienz. Nephrologe 1, 233–240 (2006). https://doi.org/10.1007/s11560-006-0041-3

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