DÄ internationalArchive1/2026The synergistic treatment of heart and kidney disease

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The synergistic treatment of heart and kidney disease

Dtsch Arztebl Int 2026; 123: 19-26. DOI: 10.3238/arztebl.m2025.0131

Mahfoud, F; Götzinger, F; Kramann, R; Marx, N; Schwenger, V

For technical reasons, the English full text will be published approximately two weeks after the German print edition has been published.

Universitäres Herzzentrum Basel, Universitätsspital Basel, Universität Basel, Schweiz: Prof. Dr. med. Felix Mahfoud, M.A.; Dr. med. Felix Götzinger
Cardiovascular Research Institute Basel (CRIB), University Heart Center Basel, Universität Basel, Schweiz: Prof. Dr. med. Felix Mahfoud, M.A.; Dr. med. Felix Götzinger
Klinik für Nieren und Hochdruckkrankheiten, Rheumatologische und Immunologische Erkrankungen, Uniklinik RWTH Aachen: Prof. Dr. med. Rafael Kramann
Medizinischen Klinik I – Kardiologie, Angiologie und Internistische Intensivmedizin, Uniklinik Aachen, RWTH Aachen: Prof. Dr. med. Nikolaus Marx
Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen, Klinikum der Landeshauptstadt Stuttgart gKAöR, Katharinenhospital, Stuttgart: Prof. Dr. med. Vedat Schwenger
1.Magnussen C, Ojeda FM, Leong DP, et al.: Global effect of modifiable risk factors on cardiovascular disease and mortality. N Engl J Med 2023; 389: 1273–85 CrossRef MEDLINE PubMed Central
2.Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–305 CrossRef MEDLINE
3.Rossing P, Caramori ML, Chan JCN, et al.: KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2022; 102: S1–S127 CrossRef MEDLINE
4.Girndt M, Trocchi P, Scheidt-Nave C, Markau S, Stang A: The prevalence of renal failure—results from the German health interview and examination survey for adults, 2008–2011 (DEGS1). Dtsch Arztebl Int 2016; 113: 85–91 CrossRef VOLLTEXT
5.Ndumele CE, Neeland IJ, Tuttle KR, et al.: A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: A scientific statement from the American Heart Association. Circulation 2023; 148: 1636–64 CrossRef CrossRef
6.Koskinas KC, Van Craenenbroeck EM, Antoniades C, et al.: Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J 2024; 45: 4063–98 CrossRef MEDLINE
7.Massie BM, Carson PE, McMurray JJ, et al.: Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359: 2456–67 CrossRef MEDLINE
8.Ostrominski JW, Claggett BL, Miao ZM, et al.: Cardiovascular-kidney-metabolic overlap in heart failure with mildly reduced or preserved ejection fraction. J Am Coll Cardiol 2024; 84: 223–8 CrossRef MEDLINE
9.Solomon SD, McMurray JJV, Vaduganathan M, et al.: Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2024; 391: 1475–85 CrossRef MEDLINE
10.Pitt B, Pfeffer MA, Assmann SF, et al.: Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383–92 CrossRef MEDLINE
11.Solomon SD, McMurray JJV, Claggett B, et al.: Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Eng J Med 2022; 387: 1089–98 CrossRef MEDLINE
12.Solomon SD, McMurray JJV, Anand IS, et al.: Angiotensin—neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019; 381: 1609–20 CrossRef MEDLINE
13.Bundesärztekammer (BÄK) KB (KBV), A der WMF (AWMF): Nationale Versorgungsleitlinie Typ-2-Diabetes – Langfassung. AWMF 2023. https://register.awmf.org/de/leitlinien/detail/nvl-001 (last accessed on 12 September 2025).
14.Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM) Deutsche Gesellschaft für Nephrologie (DGfN): Versorgung von Patient*innen mit chronischer, nicht-nierenersatztherapiepflichtiger Nierenkrankheit in der Hausarztpraxis. AWMF 2024.
15.Mancia G, Kreutz R, Brunström M, et al.: 2023 ESH guidelines for the management of arterial hypertension the task force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023; 41: 1874–2071 CrossRef MEDLINE
16.McEvoy JW, McCarthy CP, Bruno RM, et al.: 2024 ESC guidelines for the management of elevated blood pressure and hypertension. Eur Heart J 2024; 45: 3912–4018 CrossRef MEDLINE
17.Vaduganathan M, Docherty KF, Claggett BL, et al.: SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet 2022; 400 (10354): 757–67 CrossRef MEDLINE
18.Zelniker TA, Wiviott SD, Raz I, et al.: SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393: 31–9 CrossRef MEDLINE
19.Marx N, Federici M, Schütt K, et al.: 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023; 44: 4043–140 CrossRef MEDLINE
20.McDonagh TA, Metra M, Adamo M, et al.: 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42: 3599–726 CrossRef MEDLINE
21.McMurray JJV, Solomon SD, Inzucchi SE, et al.: Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381: 1995–2008 CrossRef MEDLINE
22.Zinman B, Wanner C, Lachin JM, et al.: Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117–28 CrossRef MEDLINE
23.Packer M, Anker SD, Butler J, et al.: Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383: 1413–24 CrossRef MEDLINE
24.Zannad F, Ferreira JP, Pocock SJ, et al.: SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 2020; 396: 819–29 CrossRef MEDLINE
25.Anker SD, Butler J, Filippatos G, et al.: Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021; 385: 1451–61 CrossRef MEDLINE
26.EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al.: Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023; 388: 117–27 CrossRef MEDLINE PubMed Central
27.Wanner C, Inzucchi SE, Lachin JM, et al.: Empagliflozin and progression of kidney disease in type 2 diabetes. N Eng J Med 2016; 375: 323–34 CrossRef MEDLINE
28.The EMPA-KIDNEY Collaborative Group: Long-term effects of empagliflozin in patients with chronic kidney disease. N Engl J Med 2025; 392: 777–87 CrossRef MEDLINE PubMed Central
29.Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al.: Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020; 383: 1436–46 CrossRef MEDLINE
30.McDonagh TA, Metra M, Adamo M, et al.: 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023; 44: 3627–39 CrossRef MEDLINE
31.Ussher JR, Drucker DJ: Glucagon-like peptide 1 receptor agonists: Cardiovascular benefits and mechanisms of action. Nat Rev Cardiol 2023; 20: 463–74 CrossRef MEDLINE
32.Wilding JPH, Batterham RL, Calanna S, et al.: Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021; 384: 989–1002 CrossRef MEDLINE
33.Marso SP, Bain SC, Consoli A, et al.: Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Eng J Med 2016; 375: 1834–44 CrossRef CrossRef MEDLINE PubMed Central
34.Husain M, Birkenfeld AL, Donsmark M, et al.: Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019; 381: 841–51 CrossRef MEDLINE
35.Perkovic V, Tuttle KR, Rossing P, et al.: Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med 2024; 391: 109–21 CrossRef MEDLINE
36.Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al.: Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Eng J Med 2023; 389: 1069–84 CrossRef MEDLINE
37.Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.: Semaglutide and cardiovascular outcomes in obesity without diabetes. N Eng J Med 2023; 389: 2221–32 CrossRef MEDLINE
38.Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale VersorgungsLeitlinie Chronische Herzinsuffizienz – Langfassung. https://register.awmf.org/de/leitlinien/detail/nvl-006 (last accessed on 12 Septmber 2025).
39.Pitt B, Filippatos G, Agarwal R, et al.: Cardiovascular events with finerenone in kidney disease and type 2 Diabetes. N Engl J Med 2021; 385: 2252–63 CrossRef MEDLINE
40.Neuen BL, Heerspink HJL, Vart P, et al.: Estimated lifetime cardiovascular, kidney, and mortality benefits of combination treatment with SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal MRA compared with conventional care in patients with type 2 diabetes and albuminuria. Circulation 2024; 149: 450–62 CrossRef MEDLINE
e1.Ronco C, McCullough P, Anker SD, et al.: Cardio-renal syndromes: Report from the consensus conference of the acute dialysis quality Initiative. Eur Heart J 2010; 31: 703–11 CrossRef MEDLINE PubMed Central
e2.Bauersachs J, Jaisser F, Toto R: Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension 2015; 65: 257–63 CrossRef MEDLINE
e3.Dicker D, Nguyen G, Abate D, et al.: Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: A systematic analysis for the global burden of disease study 2017. Lancet 2018; 392: 1684–735 CrossRef MEDLINE
e4.Murray CJL, Aravkin AY, Zheng P, et al.: Global burden of 87 risk factors in 204 countries and territories, 1990–2019: A systematic analysis for the global burden of disease study 2019. Lancet 2020; 396: 1223–49 CrossRef MEDLINE
e5.Naghavi M, Ong KL, Aali A, et al.: Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: A systematic analysis for the global burden of disease study 2021. Lancet 2024; 403: 2100–32 CrossRef MEDLINE
e6.Ensminger S, Thiele H, Falk V, Rudolph V: Der Deutsche Herzbericht – Update 2024 – Eine Zusammenfassung der wichtigsten Erkenntnisse. Kardiologie 2024; 18: 476–84 CrossRef
e7.Zhou B, Carrillo-Larco RM, Danaei G, et al.: Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398: 957–80 CrossRef MEDLINE
e8.Jadoul M, Aoun M, Masimango Imani M: The major global burden of chronic kidney disease. Lancet Glob Health 2024; 12: e342–e3 CrossRef MEDLINE
e9.Chong B, Jayabaskaran J, Jauhari SM, et al.: Global burden of cardiovascular diseases: Projections from 2025 to 2050. Eur J Prev Cardiol 2024; zwae281. doi: 10.1093/eurjpc/zwae281. Online ahead of print CrossRef MEDLINE
e10.Ong KL, Stafford LK, McLaughlin SA, et al.: Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the global burden of disease study 2021. Lancet 2023; 402: 203–34 CrossRef MEDLINE
e11.Alla F, Zannad F, Filippatos G: Epidemiology of acute heart failure syndromes. Heart Fail Rev 2007; 12: 91–5 CrossRef MEDLINE
e12.Rudiger A, Harjola VP, Müller A, et al.: Acute heart failure: Clinical presentation, one-year mortality and prognostic factors. Eur J Heart Fail 2005; 7: 662–70 CrossRef MEDLINE
e13.Jackson CE, Solomon SD, Gerstein HC, et al.: Albuminuria in chronic heart failure: Prevalence and prognostic importance. Lancet 2009; 374: 543–50 CrossRef MEDLINE
e14.Bailey LN, Levitan EB, Judd SE, et al.: Association of urine albumin excretion with incident heart failure hospitalization in community-dwelling adults. JACC Heart Fail 2019; 7: 394–401 CrossRef MEDLINE PubMed Central
e15.Sharma A, Zhao X, Hammill BG, et al.: Trends in noncardiovascular comorbidities among patients hospitalized for heart failure. Circ Heart Fail 2018; 11: e004646 CrossRef MEDLINE
e16.Streng KW, Nauta JF, Hillege HL, et al.: Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. Int J Cardiol 2018; 271: 132–9 CrossRef MEDLINE
e17.Stevens PE, Ahmed SB, Carrero JJ, et al.: KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2024; 105: S117–S314 CrossRef MEDLINE
e18.Wu HY, Peng YS, Chiang CK, et al.: Diagnostic performance of random urine samples using albumin concentration vs ratio of albumin to creatinine for microalbuminuria screening in patients with diabetes mellitus. JAMA Intern Med 2014; 174: 1108 CrossRef MEDLINE
e19.Schmieder RE, Schutte R, Schumacher H, et al.: Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: An analysis of the ONTARGET and TRANSCEND studies. Diabetologia 2014; 57: 2019–29 CrossRef MEDLINE
e20.Gerstein HC, Mann JF, Yi Q, et al.: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6 CrossRef MEDLINE
e21.Ortiz A, Wanner C, Gansevoort R, et al.: Chronic kidney disease as cardiovascular risk factor in routine clinical practice: A position statement by the Council of the European Renal Association. Eur J Prev Cardiol 2022; 29: 2211–5 CrossRef MEDLINE
e22.Inker LA, Eneanya ND, Coresh J, et al.: New creatinine—and cystatin C–based equations to estimate GFR without race. N Eng J Med 2021; 385: 1737–49 CrossRef MEDLINE PubMed Central
e23.van der Giet M, Nitschmann S: Cystatin C-basierte Schätzung der glomerulären Filtrationsrate. Inn Med 2023; 64: 711–4 CrossRef MEDLINE
e24.Manetti L, Pardini E, Genovesi M, et al.: Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 2005; 28: 346–9 CrossRef MEDLINE
e25.Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C: Impact of thyroid dysfunction on serum cystatin C. Kidney Int 2003; 63: 1944–7 CrossRef MEDLINE
e26.Risch L, Herklotz R, Blumberg A, Huber AR: Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001; 47: 2055–9 CrossRef
e27.George LK, Koshy SKG, Molnar MZ, et al.: Heart failure increases the risk of adverse renal outcomes in patients with normal kidney function. Circ Heart Fail 2017; 10: e003825 CrossRef MEDLINE PubMed Central
e28.El Chamieh C, Liabeuf S, Massy Z: Uremic toxins and cardiovascular risk in chronic kidney disease: What have we learned recently beyond the past findings? Toxins (Basel) 2022; 14: 280 CrossRef MEDLINE PubMed Central
e29.Ghosh RK, Bandyopadhyay D, Hajra A, Biswas M, Gupta A: Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies. Int J Cardiol 2016; 212: 29–36 CrossRef MEDLINE
e30.Wanner C, Heerspink HJL, Zinman B, et al.: Empagliflozin and kidney function decline in patients with type 2 diabetes: A slope analysis from the EMPA-REG OUTCOME Trial. J Am Soc Nephrol 2018; 29: 2755–69 CrossRef MEDLINE PubMed Central
e31.Neeland IJ, Ross R, Després JP, et al.: Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: A position statement. Lancet Diabetes Endocrinol 2019; 7: 715–25 CrossRef MEDLINE
e32.Mahabadi AA, Massaro JM, Rosito GA, et al.: Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J 2008; 30: 850–6 CrossRef MEDLINE PubMed Central
e33.Parati G, Esler M: The human sympathetic nervous system: Its relevance in hypertension and heart failure. Eur Heart J 2012; 33: 1058–66 CrossRef MEDLINE
e34.SPRINT Research Group, Wright JT, Williamson JD, et al.: A randomized trial of intensive versus standard blood-pressure control. N Enl J Med 2015; 373: 2103–16 CrossRef MEDLINE PubMed Central
e35.Mach F, Baigent C, Catapano AL, et al.: 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111–88 CrossRef MEDLINE
e36.Wanner C, Tonelli M, Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group: KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int 2014; 85: 1303–9 CrossRef MEDLINE
e37.Tunnicliffe DJ, Palmer SC, Cashmore BA, et al.: HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev 2023; 11: CD007784 CrossRef MEDLINE PubMed Central
e38.Jhund PS, Solomon SD, Docherty KF, et al.: Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: Results of DAPA-HF. Circulation 2021; 143: 298–309 CrossRef CrossRef PubMed Central
e39.Mavrakanas TA, Tsoukas MA, Brophy JM, Sharma A, Gariani K: SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: A systematic review and meta-analysis. Sci Rep 2023; 13: 15922 CrossRef MEDLINE PubMed Central
e40.Zannad F: Aldosterone and heart failure. Eur Heart J 1995; 16 (Suppl N): 98–102 CrossRef MEDLINE
e41.Götzinger F, Kunz M, Lauder L, Böhm M, Mahfoud F: New ways of mitigating aldosterone in cardiorenal disease. Eur Heart J Cardiovasc Pharmacother 2024; 10: 557–65 CrossRef MEDLINE
e42.Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Eng J Med 1999; 341: 709–17 CrossRef MEDLINE
e43.Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21 CrossRef MEDLINE
e44.Zannad F, McMurray JJV, Krum H, et al.: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11–21 CrossRef MEDLINE
e45.Currie G, Taylor AHM, Fujita T, et al.: Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis. BMC Nephrol 2016; 17: 127 CrossRef MEDLINE PubMed Central
e46.Charytan DM, Himmelfarb J, Ikizler TA, et al.: Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): A randomized, placebo-controlled, multiple dosage trial. Kidney Int 2019; 95: 973–82 CrossRef MEDLINE PubMed Central
e47.Matsumoto Y, Mori Y, Kageyama S, et al.: Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol 2014; 63: 528–36 CrossRef MEDLINE
e48.Hammer F, Malzahn U, Donhauser J, et al.: A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients. Kidney Int 2019; 95: 983–91 CrossRef MEDLINE
e49.Ingelfinger JR, Rosen CJ: Finerenone—halting relative hyperaldosteronism in chronic kidney disease. N Eng J Med 2020; 383: 2285–6 CrossRef MEDLINE
e50.Bakris GL, Agarwal R, Anker SD, et al.: Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383: 2219–29 CrossRef MEDLINE
e51.Filippatos G, Anker SD, Agarwal R, et al.: Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation 2021; 143: 540–52 CrossRef MEDLINE PubMed Central
e52.Tamargo J, Kjeldsen KP, Delpón E, et al.: Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy. Eur Heart J Cardiovasc Pharmacother 2022; 8: 406–19 CrossRef MEDLINE
e53.Bramlage P, Sims H, Minguet J, Ferrero C: The polypill: An effective approach to increasing adherence and reducing cardiovascular event risk. Eur J Prev Cardiol 2017; 24: 297–310 CrossRef MEDLINE

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