Therapie der chronischen Niereninsuffizienz bei Diabetes mellitus

Zusammenfassung

Die Therapie der chronischen Niereninsuffizienz (CKD) bei Diabetes mellitus (DM) fokussierte sich bisher auf die Gabe von Angiotensin-Converting-Enzyme-Hemmern (ACE-Hemmern) oder Angiotensin-II-Rezeptor-Subtyp-1-Antagonisten (AT₁-Antagonisten). Weiterhin erfolgte die Kontrolle von Risikofaktoren wie Hyperglykämie, arterieller Hypertonie und Hyperlipidämie. Mit Natrium-Glukose-Kotransporter-2-Inhibitoren (SGLT-2i), Glukagonähnliches-Peptid-1-Rezeptor-Agonisten (GLP-1-RA) und einem nichtsteroidalen Mineralokortikoid-Rezeptor-Agonisten stehen neue Therapieoptionen zur Verfügung, die kardiorenale Endpunkte verbessern. Weitere Medikamentenklassen wie Endothelin-Rezeptor-Antagonisten, Aldosteron-Synthetase-Inhibitoren und Inkretin-Hormon-Therapeutika befinden sich in der klinischen Erprobung. Durch die Vielzahl der neuen Optionen wird die zukünftige Herausforderung in der Individualisierung der Therapie und Identifikation von Hochrisikopatienten liegen.

• Literatur

• 1 Robert-Koch Institut. Bericht der nationalen Diabetes-Surveillance 2019 Diabetes in Deutschland. Im Internet: Zugriff am 14. April 2025 unter: https://diabsurv.rki.de/SharedDocs/downloads/DE/DiabSurv/diabetesbericht2019.pdf?__blob=publicationFile&v=13
• 2 Wolf G, Muller N, Tschauner T. et al. Prevalence of renal insufficiency in the diabetes TUV of the Deutsche BKK. Med Klin (Munich) 2006; 101: 441-447
• 3 Kidney Disease. Improving Global Outcomes CKDWG. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2024; 105: S117-S314
• 4 Titze S, Schmid M, Kottgen A. et al. Disease burden and risk profile in referred patients with moderate chronic kidney disease: composition of the German Chronic Kidney Disease (GCKD) cohort. Nephrol Dial Transplant 2015; 30: 441-451
• 5 Kidney Disease. Improving Global Outcomes Diabetes Work G. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 2022; 102: S1-S127
• 6 Wolf G, Ziyadeh FN. The role of angiotensin II in diabetic nephropathy: emphasis on nonhemodynamic mechanisms. Am J Kidney Dis 1997; 29: 153-163
• 7 Natale P, Palmer SC, Navaneethan SD. et al. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev 2024; 4: CD006257
• 8 Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol 2006; 17: 2985-2991
• 9 Bolignano D, Palmer SC, Navaneethan SD. et al. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev 2014; CD007004
• 10 Barfacker L, Kuhl A, Hillisch A. et al. Discovery of BAY 94–8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem 2012; 7: 1385-1403
• 11 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: 2219-2229
• 12 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: 2252-2263
• 13 Agarwal R, Filippatos G, Pitt B. et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J 2022; 43: 474-484
• 14 Green JB, Mottl AK, Bakris G. et al. Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE). Nephrol Dial Transplant 2023; 38: 894-903
• 15 Gerdes C, Muller N, Wolf G. et al. Nephroprotective Properties of Antidiabetic Drugs. J Clin Med 2023; 12: 3377
• 16 Wanner C, Inzucchi SE, Lachin JM. et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med 2016; 375: 323-334
• 17 Mosenzon O, Wiviott SD, Cahn A. et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 2019; 7: 606-617
• 18 Wheeler DC, Stefansson BV, Jongs N. et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol 2021; 9: 22-31
• 19 Group E-KC. Herrington WG, Staplin N. et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2023; 388: 117-127
• 20 Group E-KC. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol 2024; 12: 51-60
• 21 Hopf M, Kloos C, Wolf G. et al. Effectiveness and Safety of SGLT2 Inhibitors in Clinical Routine Treatment of Patients with Diabetes Mellitus Type 2. J Clin Med 2021; 10
• 22 Nauck MA, Quast DR, Wefers J. et al. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update. Diabetes Obes Metab 2021; 23 (Suppl. 3) 5-29
• 23 Sattar N, Lee MMY, Kristensen SL. et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol 2021; 9: 653-662
• 24 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: 109-121
• 25 Provenzano M, Puchades MJ, Garofalo C. et al. Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial. J Am Soc Nephrol 2022; 33: 1569-1580
• 26 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: 450-462
• 27 Tang M, Morieri ML, Kalim S. et al. Combination Therapy with SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease. J Am Soc Nephrol 2025; 36: 726-729
• 28 Neuen BL, Tuttle KR, Vaduganathan M. Accelerated Risk-Based Implementation of Guideline-Directed Medical Therapy for Type 2 Diabetes and Chronic Kidney Disease. Circulation 2024; 149: 1238-1240
• 29 Kohan DE, Barton M. Endothelin and endothelin antagonists in chronic kidney disease. Kidney Int 2014; 86: 896-904
• 30 Heerspink HJL, Parving HH, Andress DL. et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet 2019; 393: 1937-1947
• 31 Heerspink HJL, Kiyosue A, Wheeler DC. et al. Zibotentan in combination with dapagliflozin compared with dapagliflozin in patients with chronic kidney disease (ZENITH-CKD): a multicentre, randomised, active-controlled, phase 2b, clinical trial. Lancet 2023; 402: 2004-2017
• 32 Tuttle KR, Hauske SJ, Canziani ME. Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial. Lancet 2024; 403: 379-390
• 33 Judge PK, Tuttle KR, Staplin N. et al. The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial. Nephrol Dial Transplant 12.11.2024; gfae263
• 34 Frias JP, Davies MJ, Rosenstock J. et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021; 385: 503-515
• 35 Karakasis P, Patoulias D, Fragakis N. et al. Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis. Diabetes Obes Metab 2024; 26: 1090-1104
• 36 Nicholls SJ, Bhatt DL, Buse JB. et al. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J 2024; 267: 1-11
• 37 Ma J, Hu X, Zhang W. et al. Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice. Endocrine 2025; 87: 159-169