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Aldosteronantagonisten „revisited“

Aldosterone antagonists revisited

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Zusammenfassung

Aldosteron und die Aktivierung des Mineralokortikoidrezeptors (MR) sind durch Induktion von Fibrose, Inflammation und Proteinurie pathophysiologisch an Entstehung und Fortschreiten der chronischen Nierenerkrankung („chronic kidney disease“, CKD) beteiligt. Klinische Studien liefern Hinweise, dass eine Ergänzung der Blockade des Renin-Angiotensin-Aldosteron-Systems (RAAS) durch ACE(„angiotensin-converting enzyme“)-Inhibitoren oder AT1(Angiotensin-II-Rezeptor Subtyp 1)-Blocker um die Aldosteronantagonisten (MR-Antagonisten, MRA) bei CKD das Auftreten ungünstiger Verläufe verringert. Insbesondere hat sich die Datenlage in Bezug auf den Einsatz des selektiven, nichtsteroidalen MRA Finerenon bei Patienten/Patientinnen mit Typ-2-Diabetes und CKD durch zwei große multizentrische Studien verbessert. Dabei zeigt Finerenon günstige Effekte auf renale und kardiovaskuläre Endpunkte bei einem akzeptablen Hyperkaliämierisiko. Dagegen ist die Datenlage in Bezug auf den Einsatz der älteren MRA Eplerenon und Spironolacton und die Rolle von MRA bei Patienten/Patientinnen mit nichtdiabetischer CKD derzeit weniger klar. Dieser Artikel gibt einen Überblick über die aktuellen Studiendaten zur Kardio- und Nephroprotektion durch MRA bei CKD und geht auf die Evidenzlage zu den einzelnen Wirkstoffgenerationen ein.

Abstract

Aldosterone and mineralocorticoid receptor (MR) activation are pathophysiologically involved in the development and progression of chronic kidney disease (CKD) by induction of fibrosis, inflammation and proteinuria. Clinical studies provide evidence that adding aldosterone antagonists (mineralocorticoid receptor antagonists, MRA) to the renin-angiotensin-aldosterone system (RAAS) block by angiotensin-converting enzyme inhibitors or angiotensin II receptor subtype 1 blockers reduces the incidence of adverse outcomes in CKD. In particular, two large multicenter trials have provided new evidence that the selective nonsteroidal MRA finerenone reduces adverse renal and cardiovascular outcomes with an acceptable risk profile for hyperkalemia in patients with type 2 diabetes and CKD. In contrast, the data situation is currently less clear regarding the use of the older MRA eplerenone and spironolactone and the role of MRA in patients with nondiabetic CKD. This article provides a review of the current trial data on cardioprotection and nephroprotection by MRA in CKD and reviews the evidence for each generation of MRA.

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Literatur

  1. Agarwal R, Anker SD, Bakris G et al (2020) Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfaa294

    Article  PubMed  PubMed Central  Google Scholar 

  2. Agarwal R, Kolkhof P, Bakris G et al (2021) Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J 42:152–161

    Article  CAS  Google Scholar 

  3. Alexandrou ME, Papagianni A, Tsapas A et al (2019) Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials. J Hypertens 37:2307–2324

    Article  CAS  Google Scholar 

  4. Bakris GL, Agarwal R, Anker SD et al (2020) Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 383:2219–2229

    Article  CAS  Google Scholar 

  5. Bakris GL, Agarwal R, Chan JC et al (2015) Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 314:884–894

    Article  CAS  Google Scholar 

  6. Bakris GL, Woods SD, Alvarez PJ et al (2021) Hyperkalemia management in older adults with diabetic kidney disease receiving renin-angiotensin-aldosterone system inhibitors: a post hoc analysis of the AMETHYST-DN clinical trial. Kidney Med 3:360–367e361

    Article  Google Scholar 

  7. Barrera-Chimal J, Girerd S, Jaisser F (2019) Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int 96:302–319

    Article  CAS  Google Scholar 

  8. Bomback AS, Klemmer PJ (2007) The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol 3:486–492

    Article  CAS  Google Scholar 

  9. Bundesärztekammer (Bäk) KBK, Arbeitsgemeinschaft Der Wissenschaftlichen Medizinischen Fachgesellschaften (Awmf). Nationale Versorgungsleitlinie Chronische Herzinsuffizienz – Langfassung, 3. Auflage. Version 3. 2019 [Cited: 2022-02-19]. https://doi.org/10.6101/Azq/000482.

  10. Charytan DM, Himmelfarb J, Ikizler TA et al (2019) Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int 95:973–982

    Article  CAS  Google Scholar 

  11. Chrysostomou A, Becker G (2001) Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med 345:925–926

    Article  CAS  Google Scholar 

  12. Chung EY, Ruospo M, Natale P et al (2020) Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD007004.pub4

    Article  PubMed  PubMed Central  Google Scholar 

  13. Currie G, Taylor AH, Fujita T et al (2016) Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol 17:127

    Article  Google Scholar 

  14. Erraez S, Lopez-Mesa M, Gomez-Fernandez P (2021) Mineralcorticoid receptor blockers in chronic kidney disease. Nefrologia 41:258–275

    Article  Google Scholar 

  15. Filippatos G, Anker SD, Bohm M et al (2016) A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J 37:2105–2114

    Article  CAS  Google Scholar 

  16. Gardiner P, Schrode K, Quinlan D et al (1989) Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol 29:342–347

    Article  CAS  Google Scholar 

  17. Grune J, Beyhoff N, Smeir E et al (2018) Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension 71:599–608

    Article  CAS  Google Scholar 

  18. Hammer F, Malzahn U, Donhauser J et al (2019) A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients. Kidney Int 95:983–991

    Article  CAS  Google Scholar 

  19. Hasegawa T, Nishiwaki H, Ota E et al (2021) Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD013109.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hill NR, Lasserson D, Thompson B et al (2014) Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial‑a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone: study protocol for a randomized controlled trial. Trials 15:160

    Article  Google Scholar 

  21. Juurlink DN, Mamdani MM, Lee DS et al (2004) Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351:543–551

    Article  CAS  Google Scholar 

  22. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 3(Suppl):1–150

    Google Scholar 

  23. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group (2021) KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int 99:S1–S87

    Article  Google Scholar 

  24. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group (2020) KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 98:S1–S115

  25. Kolkhof P, Delbeck M, Kretschmer A et al (2014) Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 64:69–78

    Article  CAS  Google Scholar 

  26. Matsumoto Y, Mori Y, Kageyama S et al (2014) Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol 63:528–536

    Article  CAS  Google Scholar 

  27. Pei H, Wang W, Zhao D et al (2018) The use of a novel non-steroidal mineralocorticoid receptor antagonist finerenone for the treatment of chronic heart failure: A systematic review and meta-analysis. Medicine 97:e254

    Article  CAS  Google Scholar 

  28. Pitt B, Filippatos G, Agarwal R et al (2021) Cardiovascular events with Finerenone in kidney disease and type 2 diabetes. N Engl J Med 385:2252–2263

    Article  CAS  Google Scholar 

  29. Pitt B, Kober L, Ponikowski P et al (2013) Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J 34:2453–2463

    Article  CAS  Google Scholar 

  30. Pitt B, Remme W, Zannad F et al (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309–1321

    Article  CAS  Google Scholar 

  31. 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  CAS  Google Scholar 

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Correspondence to Jutta Swolinsky.

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Interessenkonflikt

K. Schmidt-Ott hat Beratungshonorare der Firma Bayer AG erhalten. J. Swolinsky gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Hermann Haller, Hannover

Joachim Hoyer, Marburg

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Swolinsky, J., Schmidt-Ott, K. Aldosteronantagonisten „revisited“. Nephrologie 17, 239–245 (2022). https://doi.org/10.1007/s11560-022-00576-9

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