The cardiorenal connection:
Managing the kidneys and heart holistically

Diseases affecting the heart and kidneys, such as chronic kidney disease (CKD) and heart failure (HF), fall on an interconnected spectrum of cardiovascular, renal and metabolic (CVRM) conditions.

CKD is a serious, progressive condition that gradually decreases a person’s kidney function.1 Nearly 850 million people worldwide are affected by CKD and the majority are still undiagnosed — in fact, nine out of 10 people with CKD don’t even know they have it.2,3 A silent disease in its early stages means CKD is often diagnosed late and left untreated for too long even though it affects more than 10% of the general population worldwide.4,5 There is currently no cure for CKD, and if the disease progresses to kidney failure, patients need dialysis or kidney transplants.6

CKD is expected to become the world’s fifth leading cause of mortality by 2040, making this condition a growing public health problem that presents a significant burden for patients and health systems.7,8 For patients with CKD, it’s possible to slow the progression through early diagnosis and intervention.9

While CKD can be difficult to diagnose and treat on its own, it can also increase the risk of cardiovascular (CV) diseases. Research continues to show the connection between cardiovascular and renal conditions, and since the heart and kidneys are so closely related, CKD can cause or worsen CV conditions such as HF.10,11

Up to one in five patients diagnosed with CKD develops HF, making it the leading CV complication in CKD patients. CKD has also been associated with increased mortality in patients with HF. Within each type of ejection fraction (reduced, midrange, or preserved), patients with CKD had worse outcomes in both the short and long term (one and five years respectively).10-12

Patients more likely to develop CKD and HF typically have similar risk factors including diabetes, obesity, and hypertension.6,13,14 Once patients develop CKD and HF, they’re also likely to share similar related complications such as hyperkalaemia, or elevated potassium levels in the blood. 15 If these complications are severe and left untreated, they can be fatal and impact patients’ ability to continue guideline-recommended treatment options, such as RAAS inhibitors, an essential treatment for patients with CKD and/or HF in slowing the progression of CKD and reducing mortality in HF with reduced ejection fraction.16-18

The kidneys and heart are so closely connected that identifying CKD and intervening early can help slow disease progression, preserve renal function and reduce cardiovascular complications, which include heart failure.6

Diagnosing kidney disease early can help prevent other complications or comorbidities such as heart disease.5,9,19

Early interventions for CKD patients can help improve outcomes and quality of life.9 Identifying CKD early helps slow the progression of the disease and reduce its complications.5 Since HF and CKD are so closely connected, slowing the progression of one may help slow the progression of the other disease. 9,10,20

In the early stages of CKD and HF patients can implement certain lifestyle changes to help manage their condition and slow disease progression such as exercising, eating a healthy diet, stopping smoking and taking recommended medicines.9,21,22  As CKD progresses, care teams may shift to focusing on medical interventions, slowing disease progression, reducing cardiovascular risk and managing other complications.9 As HF progresses, physicians and patients may focus on reducing hospital readmissions, improving patients’ clinical condition, quality of life and implementing tools such as guideline-directed medical therapy (GDMT).16,22

In the late stages of CKD, physicians continue to work to slow kidney damage as well as begin to plan ahead with patients for possible treatments for kidney failure like dialysis.7,9  Once HF progresses to the late stage, the focus remains on medical interventions, continuing to leverage GDMT, and physicians may begin to assess patients for advanced HF therapies like transplants.22

Leveraging medical guidelines and guideline-directed medical therapies (GDMT) can help manage disease progression in CKD and HF patients.16,23    

To overcome challenges and improve outcomes for patients with CKD and HF, we must continue to accelerate earlier detection and coordinated care that can help address the complexities and interconnectedness of cardiovascular and renal diseases. Medical guidelines and guideline-directed medical therapies are an important part of the solution as they help provide patient-centric recommendations for clinicians to diagnose and manage patients.

In the renal space, medical guidelines include the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD.23 For HF care teams, the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and more recently the 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America Guidelines for the Management of Heart Failure provide insights into the distinct types of HF, how to approach the disease, and how to diagnose and intervene early.22,24

Leveraging these guidelines in tandem offers direction on the management of both CKD and HF —effective implementation of the guidelines is key to saving lives. 

Scientists and the healthcare system can improve outcomes by advancing the science, focusing on patient-centric care, delivering innovative treatments and championing the use of GDMT. By continuing to build our collective understanding of CKD and HF, we can improve pathways to better care.

Addressing diseases across the cardiorenal continuum, from earliest detection to late stage.

Our ambition is to fundamentally transform CVRM care and advance patient outcomes by unravelling the underlying causes of disease, developing diagnostic strategies and delivering innovative, life-changing solutions for the millions of people affected by this interconnected spectrum of diseases.

Through partnering with organisations such as the International Society of Nephrology to create a quick one-minute quiz that offers insight into whether people may be at risk for CKD to working with physicians and researchers to create better outcomes for people facing CKD and HF — we are working to build a deeper understanding of the cardiorenal connection.

“Scientific advances are revealing the connection between cardiovascular, renal and metabolic diseases, helping to drive earlier diagnosis and opportunities for integrated treatment approaches.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca

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References

1. National Kidney Foundation. Kidney Disease: Causes; 2022 [cited 2022 Aug 5]. Available from: URL: https://www.kidney.org/atoz/content/kidneydiscauses.

2. Jager KJ, et al. A single number for advocacy and communication—worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-1805.

3. Bikbov B, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-733.

4. Kovesdy CP. Epidemiology of chronic kidney disease: An update 2022 [Internet]. Kidney international supplements. Elsevier; 2022 [cited 2022Oct14]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073222/

5. World Kidney Day [Internet]. Chronic kidney disease; [cited 2021 Jul 20]. Available from: https://www.worldkidneyday.org/facts/chronic-kidney-disease/#:~:text=A%20person%20can%20lose%20up,the%20urine%20and%20foamy%20urine. 

6. National Health Service. Treatment: Chronic kidney disease; 2019/08/29 [cited 2022 Oct 01]. Available from: URL: https://www.nhs.uk/conditions/kidney-disease/treatment/

7. Bello AK, et al. Global Kidney Health Atlas: A report by the International Society of Nephrology on the current state of organization and structures for kidney care across the globe. Brussels, Belgium: International Society of Nephrology; 2019. Available from: URL: https://www.theisn.org/wp-content/uploads/2021/05/GKHAtlas_2019_WebFIle-1.pdf

8. Foreman KJ et al. Forecasting Life Expectancy, Years of Life Lost, and All-Cause and Cause-Specific Mortality for 250 Causes of Death: Reference and Alternative Scenarios for 2016-40 for 195 Countries and Territories. Lancet 2018; 392:2052–90.

9. The case for early identification and intervention of chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference [Internet]. Kidney International. International Society of Nephrology; 2021 [cited 2022Oct14]. Available from: https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2820%2931210-2

10. House AA et al. Heart failure in chronic kidney disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019; 95(6):1304–17.

11. Segall L et al. Heart failure in patients with chronic kidney disease: A systematic integrative review. Biomed Res Int 2014; 2014:937398.

12. Löfman I et al. Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction. Eur J Heart Fail 2017; 19(12):1606–14.

13. Ceriello A, Catrinoiu D, Chandramouli C, Cosentino F, Dombrowsky AC, Itzhak B, Lalic NM, Prattichizzo F, Schnell O, Seferović PM, Valensi P, Standl E; D&CVD EASD Study Group. Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management. Cardiovasc Diabetol. 2021 Nov 6;20(1):218. doi: 10.1186/s12933-021-01408-1. PMID: 34740359; PMCID: PMC8571004.

14. Tourki B, Halade GV. Heart Failure Syndrome With Preserved Ejection Fraction Is a Metabolic Cluster of Non-resolving Inflammation in Obesity. Front Cardiovasc Med. 2021 Aug 2;8:695952. doi: 10.3389/fcvm.2021.695952. PMID: 34409075; PMCID: PMC8367012.

15. Montford JR et al. How Dangerous is Hyperkalaemia? J Am Soc Nephrol. 2017 Nov;28(11):3155-3165. 

16. Joseph J, P S S, James J, Abraham S, Abdullakutty J. Guideline-directed medical therapy in heart failure patients: impact of focused care provided by a heart failure clinic in comparison to general cardiology out-patient department. Egypt Heart J. 2020 Aug 24;72(1):53. doi: 10.1186/s43044-020-00088-8. PMID: 32833163; PMCID: PMC7445219.

17. Chapman, A., Arlene Chapman University of Chicago Medicine, Gunning, S., Samantha Gunning University of Chicago Medicine, Chapman, C. to: A., & Linde, C. (2019, November 12). Real‐world associations between renin‐angiotensin‐aldosterone system inhibition therapy, hyperkalemia, and outcomes: A clinical and scientific call to action. Journal of the American Heart Association. Retrieved October 27, 2022, from https://www.ahajournals.org/doi/10.1161/JAHA.119.014845

18. Epstein M, Reaven NL, Funk SE, McGaughey KJ, Oestreicher N, Knispel J. Evaluation of the Treatment Gap Between Clinical Guidelines and the Utilization of Renin-Angiotensin-Aldosterone System Inhibitors. The American Journal of Managed Care 2015; 21(11 Supplement).

19. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States 2021; [cited 2022 June 14]. Available from URL:  https://www.cdc.gov/kidneydisease/pdf/Chronic-Kidney-Disease-in-the-US-2021-h.pdf

20. Rangaswami, J., Bhalla, V., Blair, J. E. A., Chang, T. I., Costa, S., Lentine, K. L., E. V., Mezue, K., Molitch, M., Mullens, W., (2019, March 11). Cardiorenal Syndrome: Classification, pathophysiology, diagnosis, and treatment strategies: A scientific statement from the American Heart Association. Circulation. Retrieved October 24, 2022, from https://www.ahajournals.org/doi/10.1161/CIR.0000000000000664

21. Wang Y, Ng K, Byrd RJ, Hu J, Ebadollahi S, Daar Z, et al. Early detection of heart failure with varying prediction windows by structured and unstructured data in Electronic Health Records [Internet]. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference. U.S. National Library of Medicine; 2015 [cited 2022Oct23]. Available from: https://pubmed.ncbi.nlm.nih.gov/26736807/

22. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-421.

23. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease [Internet]. Official Journal of the International Society of Nephrology. International Society of Nephrology; 2012 [cited 2022Oct14]. Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf

24. McDonagh TA, Metra M, Adamo M, et al.  2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure [article and supplementary data]. Eur Heart J. 2021;42:3599-3726. doi:10.1093/eurheartj/ehab368.


Veeva ID: Z4-49281
Date of preparation: November 2022