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Erschienen in: Die Nephrologie 4/2022

03.05.2022 | Chronische Niereninsuffizienz | Leitthema

Aldosteronantagonisten „revisited“

verfasst von: Dr. med. Jutta Swolinsky, Prof. Dr. med. Kai Schmidt-Ott

Erschienen in: Die Nephrologie | Ausgabe 4/2022

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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.
Literatur
2.
Zurück zum Zitat 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 CrossRef 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 CrossRef
3.
Zurück zum Zitat 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 CrossRef 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 CrossRef
4.
Zurück zum Zitat 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 CrossRef 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 CrossRef
5.
Zurück zum Zitat 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 CrossRef 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 CrossRef
6.
Zurück zum Zitat 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 CrossRef 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 CrossRef
7.
Zurück zum Zitat Barrera-Chimal J, Girerd S, Jaisser F (2019) Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int 96:302–319 CrossRef Barrera-Chimal J, Girerd S, Jaisser F (2019) Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int 96:302–319 CrossRef
8.
Zurück zum Zitat Bomback AS, Klemmer PJ (2007) The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol 3:486–492 CrossRef Bomback AS, Klemmer PJ (2007) The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol 3:486–492 CrossRef
9.
10.
Zurück zum Zitat 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 CrossRef 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 CrossRef
11.
Zurück zum Zitat 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 CrossRef 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 CrossRef
13.
Zurück zum Zitat 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 CrossRef 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 CrossRef
14.
Zurück zum Zitat Erraez S, Lopez-Mesa M, Gomez-Fernandez P (2021) Mineralcorticoid receptor blockers in chronic kidney disease. Nefrologia 41:258–275 CrossRef Erraez S, Lopez-Mesa M, Gomez-Fernandez P (2021) Mineralcorticoid receptor blockers in chronic kidney disease. Nefrologia 41:258–275 CrossRef
15.
Zurück zum Zitat 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 CrossRef 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 CrossRef
16.
Zurück zum Zitat 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 CrossRef 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 CrossRef
17.
Zurück zum Zitat 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 CrossRef 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 CrossRef
18.
Zurück zum Zitat 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 CrossRef 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 CrossRef
20.
Zurück zum Zitat 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 CrossRef 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 CrossRef
21.
Zurück zum Zitat 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 CrossRef 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 CrossRef
22.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat 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 CrossRef 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 CrossRef
24.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 CrossRef 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 CrossRef
26.
Zurück zum Zitat 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 CrossRef 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 CrossRef
27.
Zurück zum Zitat 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 CrossRef 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 CrossRef
28.
Zurück zum Zitat 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 CrossRef 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 CrossRef
29.
Zurück zum Zitat 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 CrossRef 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 CrossRef
30.
Zurück zum Zitat 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 CrossRef 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 CrossRef
31.
Zurück zum Zitat 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 CrossRef 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 CrossRef
Metadaten
Titel
Aldosteronantagonisten „revisited“
verfasst von
Dr. med. Jutta Swolinsky
Prof. Dr. med. Kai Schmidt-Ott
Publikationsdatum
03.05.2022
Verlag
Springer Medizin
Erschienen in
Die Nephrologie / Ausgabe 4/2022
Print ISSN: 2731-7463
Elektronische ISSN: 2731-7471
DOI
https://doi.org/10.1007/s11560-022-00576-9

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