Renal news and stories
Adding dimensions to kidney disease research
TechnologiesProteinuria as a target for chronic kidney disease
Disease understanding
Renal
The kidneys’ vital role and function
The kidneys play a critical role in the body, removing toxins and waste, controlling blood pressure, and balancing fluids, salts, and minerals, to ensure optimal conditions for many of the body’s organ systems.1,2
Advanced understanding of the mechanisms behind co-existing conditions in chronic kidney disease enables us to transform care by driving earlier diagnosis and intervention, helping to prevent or slow the progression of the disease.3,4
What is chronic kidney disease?
Chronic kidney disease (CKD) is an umbrella term for many renal diseases encompassing various primary disorders and stages of progression.5 CKD is one of the biggest health challenges we face, affecting one in 10 people worldwide.6 People living with CKD progressively lose kidney function, which can eventually lead to kidney failure.7
The most common causes of kidney disease are diabetes, hypertension, and glomerulonephritis.7 Most people (90%) with CKD are unaware that they have the disease.8,9 Approximately half of those with severely reduced kidney function (stages 3-5) remain undiagnosed even as symptoms become apparent.10
Today it is possible to slow down CKD progression and delay the need for dialysis. Ultimately, our goal is to stop the progression to kidney failure.
The 5 stages of chronic kidney disease
Addressing hyperkalaemia to improve kidney health
Hyperkalaemia can be a serious, chronic condition where potassium (K+) levels in the blood are higher than normal, requiring long-term and proactive treatment.11,12 Up to 48% of people with chronic kidney disease and heart failure also have hyperkalaemia.13
Hyperkalaemia is often asymptomatic, however, left untreated, it can result in significant and potentially life-threatening cardiovascular (CV) complications, including arrhythmias and cardiac arrest.12
When I first learned about my condition, I didn’t know it was serious. There are often no symptoms in kidney disease. It is only later on I began to realise it is really, really very serious. I’m frustrated because I have watched my diet carefully but still, my potassium levels are high.
Renin–angiotensin–aldosterone system inhibitor (RAASi) therapy is a guideline-recommended treatment for chronic kidney disease and heart failure.14-16 But this treatment comes with a risk, as one in three patients on RAASi therapy may develop hyperkalaemia.17,18 When hyperkalemia is diagnosed, lifesaving RAASi medication is often reduced or discontinued, which can have serious consequences.18-20
The impact of hyperkalaemia
Global State of Hyperkalaemia study
In the first-ever Global State of Hyperkalaemia Survey, conducted by AstraZeneca, a total of 1000 patients and 500 nephrologists and cardiologists participated from across five countries.21 Survey findings along with recent real-world evidence (RWE) paint a stark picture of the serious, unmet need that patients with hyperkalaemia face, leading to higher cardiac risk and incidence of hospitalisations, especially for those treated with RAASi therapy.22,23
We are working to change the perception, awareness, and management of hyperkalaemia to optimise treatment across the full spectrum of cardiorenal diseases and ensure that patients receive internationally recognised guideline-directed treatment and better patient-centric disease management, to improve their outcomes and quality of life.
CKD-related diseases
High proteinuria: Exploring AI as an alternative to urine testing in CKD treatment
Elevated levels of protein in the urine – known as ‘albuminuria’ or ‘proteinuria’ – are associated with an increased risk of kidney function loss over time, leading to CKD.24 Clinical research has demonstrated that the level of proteinuria reduction positively correlates with long-term renal protection; so, the larger the initial reduction in proteinuria in the first few months of treatment, the lower the risk of end-stage renal disease during treatment.25 However a number of patients carry residual proteinuria although on the current standard of care, remaining at risk for renal disease progression.26
Measurement of urine albumin is an important tool for diagnosing and monitoring the progression of chronic kidney disease (CKD) and is currently measured via a urine ACR (albumin-to-creatinine ratio) test.27 Currently, only a minority of patients with diabetes, and rarely individuals without diabetes, are screened for proteinuria in a systematic way.28
We are developing a new diagnostic approach to identify patients with proteinuria using machine learning to predict ACR levels from Electronic Health Records without needing to take a urine test at all. The model shows overall good diagnostic accuracy for proteinuria without requiring urine tests.
Heart failure in chronic kidney disease
CKD is bi-directionally linked with heart failure (HF), meaning worsening of one condition induces the worsening of the other. 40%–50% of patients with HF have CKD.29 HF is a complex syndrome that occurs when the heart cannot pump enough blood around the body.30 Coronary artery disease (CAD) can weaken the heart muscle over time, and this may lead to HF, but it isn’t the only reason why hearts can fail.31,32
Hypertension - How high blood pressure and kidney disease are related
Chronic kidney disease (CKD) and hypertension often coexist and can have a bidirectional relationship, presenting a significant health challenge for individuals affected by both conditions. Managing both conditions is crucial to prevent further kidney damage and reduce the risk of complications such as heart disease and stroke.35,36
Persistent high blood pressure can damage the blood vessels in the kidneys, affecting their ability to function properly. The kidneys have a network of tiny blood vessel knots called glomerulus that filter waste products and excess fluid from the blood. High blood pressure thickens and scars these blood vessels, leading to narrowing and eventual obstruction, reducing blood flow to the kidneys, and impairing their ability to filter waste effectively. Over time, this can lead to kidney damage or kidney failure.37
At the same time, the kidneys play a crucial role in regulating blood pressure. They help maintain a balance of electrolytes, fluids, and hormones that influence blood pressure.38 When the kidneys are damaged due to kidney disease, they may not be able to regulate blood pressure effectively.
There is a need for comprehensive approaches that address both CKD and hypertension, including lifestyle modifications, optimised medication regimens, and integrated care models involving collaboration between nephrologists, cardiologists, and other specialists, as well as primary care providers.
Type 2 Diabetes and chronic kidney disease
Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), which is associated with increased mortality, poor cardiovascular outcomes, and high economic burden.33 More than one-third of people with T2D also have CKD, and this population is associated with a 10-fold or greater increase in all-cause mortality compared with T2D alone.33 Obesity and insulin resistance are two key drivers in the development of T2D and are also connected to the development of diseases of the heart and circulation, liver, and kidneys.34
Collaborations to improve kidney treatment
We are proud to work with HCPs, patients, governments, and policymakers to improve access to healthcare, remove barriers to diagnosis and optimal treatment, changing how cardiovascular, renal and metabolic (CVRM) diseases are detected, diagnosed and treated to accelerate medical practice change together to make a difference for patients.
ACT on CKD
ACT (Accelerate Change Together) on CKD aims to drive comprehensive partnerships across the healthcare ecosystem, including with professional societies, patient organisations, policy makers, diagnostic providers, and healthcare decision-makers, to increase awareness of CKD, drive routine screening and early diagnosis, and ultimately reduce the risk of disease progression and complications.
These collaborations have significantly advanced the CKD landscape via extensive education and awareness (e.g., ‘The Pressure is On’ campaign), diagnostic enhancements (e.g., electronic medical record-based patient identification, point-of-care urine, and blood testing, etc.) and patient-centric reforms of worldwide policies and protocols. Since the start of ACT on CKD in 2021, we estimate that our efforts have resulted in over 32 million patients screened globally and over 10 million diagnosed (Q1 2023).39
Our people
Built on an impressive legacy in Cardiovascular, Renal and Metabolic (CVRM) research, we are uniquely positioned to build a healthier and longer future for people with these diseases. Our team of over 1,000 people spans more than 23 functions including early and late R&D, medical and commercial.
Our employees are accomplished and experienced scientists, researchers, clinicians, and healthcare and commercial professionals dedicated to advancing novel science and driving practice change to benefit patients with CVRM diseases.
References
1. NIH National Institute of Diabetes and Digestive and Kidney Diseases [Internet]. Your Kidneys & How They Work [cited 2023 July 21]. Available from: http://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work
2. National Kidney Foundation [Internet]. How Your Kidneys Work [cited 2023 July 21]. Available from: http://www.kidney.org/kidneydisease/howkidneyswrk
3. Tangri N, et al. Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study. BMJ Open. May 22 2023;13(5):e067386.
4. World Economic Forum [Internet]. Dobber R. Early detection of chronic kidney disease can save lives and cut costs [cited 2023 July 21]. Available from: http://www.weforum.org/agenda/2021/03/early-detection-chronic-kidney-disease-save-lives-cut-costs/
5. Smart BTH, et al. Is "chronic kidney disease" a disease? J Eval Clin Pract. Oct 2018;24(5):1033-1040.
6. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). Apr 2022;12(1):7-11.
7. National Kidney Foundation [Internet]. Kidney Disease: The Basics [cited 2023 July 21]. Available from: http://www.kidney.org/news/newsroom/fsindex
8. Tuot DS, et al. Chronic kidney disease awareness among individuals with clinical markers of kidney dysfunction. Clin J Am Soc Nephrol. Aug 2011;6(8):1838-44.
9. World Kidney Day [Internet]. Chronic Kidney Disease [cited 2023 July 21]. Available from: http://www.worldkidneyday.org/facts/chronic-kidney-disease/#:~:text=A%20person%20can%20lose%20up,the%20urine%20and%20foamy%20urine
10. Carpio EM, et al. Hypertension and cardiovascular risk factor management in a multi-ethnic cohort of adults with CKD: a cross sectional study in general practice. J Nephrol. Apr 2022;35(3):901-910
11. National Kidney Foundation [Internet].Hyperkalemia (high potassium). [cited 2023 July 21]. Available from: http://www.kidney.org/atoz/content/what-hyperkalemia
12. Simon L, et al. Hyperkalemia. [Updated 2023 Feb 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470284/
13. Latts LM et al. Hyperkalemia Is Prevalent in Patients with Cardiorenal Comorbidities. presented at: ISPOR 20th Annual International Meeting, 2015 May 16 - 20, Philadelphia PA.
14. Kidney Disease: Improving Global Outcomes Kidney Disease Writing Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. Nov 2022;102(5S):S1-S127.
15. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. Sep 21 2021;42(36):3599-3726.
16. International Society of Nephrology, Kidney Disease: Improving Global Outcomes, World Organization of Family Doctors, Primary Care Diabetes Europe [Internet]. Chronic Kidney Disease (CKD). Early Identification and Intervention in Primary Care [cited 2023 July 21]. Available from: http://www.theisn.org/wp-content/uploads/media/pcp/PCPOnePage_1Side_English.pdf
17. Zhang Y, et al. ACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3-5: A Network Meta-Analysis of Randomised Clinical Trials. Drugs. Jun 2020;80(8):797-811.
18. Epstein M, et al. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care. Sep 2015;21(11 Suppl):S212-20.
19. Riccio E, et al. RAAS Inhibitor Prescription and Hyperkalemia Event in Patients With Chronic Kidney Disease: A Single-Center Retrospective Study. Front Cardiovasc Med. 2022;9:824095.
20. Linde C, et al. Real-World Associations of Renin-Angiotensin-Aldosterone System Inhibitor Dose, Hyperkalemia, and Adverse Clinical Outcomes in a Cohort of Patients With New-Onset Chronic Kidney Disease or Heart Failure in the United Kingdom. J Am Heart Assoc. Nov 19 2019;8(22):e012655.
21. Global State of Hyperkalaemia Survey Key Findings. REF-129958. AstraZeneca Pharmaceuticals LP. Veeva ID: Z4-38799. Date of preparation: October 2021.
22. Kim K, et al. Healthcare resource utilization and cost associated with elevated potassium levels: a Danish population-based cohort study. BMJ Open. 2019;9:e026465.
23. Kanda, E., et al. Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia. BMC Nephrol 24, 18 (2023).
24. National Kidney Foundation [Internet]. Albuminuria (proteinuria)[cited 2023 July 21]. Available from: http://www.kidney.org/atoz/content/albuminuria
25. Cravedi, P., & Remuzzi, G. (2013). Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease. British journal of clinical pharmacology, 76(4), 516–523.
26. Yau K, et al. Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney Int Rep. Jul 2022;7(7):1463-1476.
27. National Kidney Foundation [Internet]. ACR [cited 2023 July 21]. Available from: http://www.kidney.org/kidneydisease/siemens_hcp_acr#:~:text=Albumin-to-creatinine%20ratio%20%28ACR%29%20is%20the%20first%20method%20of,concentration%20in%20milligrams%20by%20creatinine%20concentration%20in%20grams.
28. de Jong, et al. (2006). Screening, monitoring, and treatment of albuminuria: Public health perspectives. Journal of the American Society of Nephrology : JASN, 17(8), 2120–2126.
29. Damman K, et al. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J. Feb 2014;35(7):455-69.
30. Mayo Clinic. [Internet] Heart failure. [cited 2023 July 21] Available from: http://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142
31. American Heart Association [Internet]. What Causes Heart Failure? [cited 2023 July 21] Available from: http://www.heart.org/en/health-topics/heart-failure/causes-and-risks-for-heart-failure/causes-of-heart-failure
32. Centers for Disease Control and Prevention [Internet]. Coronary Artery Disease (CAD)[cited 2023 July 21]. Available from: http://www.cdc.gov/heartdisease/coronary_ad.htm#:~:text=Narrowed%20arteries%20can%20cause%20chest,the%20rest%20of%20your%20body.&text=Over%20time%2C%20CAD%20can%20weaken,blood%20the%20way%20it%20should
33. McGill JB, et al. Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria. BMJ Open Diabetes Research and Care 2022;10:e002806.
34. Wondmkun Y. T. (2020). Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications. Diabetes, metabolic syndrome and obesity : targets and therapy, 13, 3611–3616.
35. Cai A, Calhoun DA. Resistant Hypertension: An Update of Experimental and Clinical Findings. Hypertension. Jul 2017;70(1):5-9.
36. World Health Organization. Hypertension. Accessed June, 2023. http://www.who.int/news-room/fact-sheets/detail/hypertension
37. Cleveland Clinic [Internet]. Renal Hypertension [cited 2023 July 21]. Available from: http://my.clevelandclinic.org/health/diseases/16459-renal-hypertension
38. Coffman, T. M., & Crowley, S. D. (2008). Kidney in hypertension. Hypertension, 51(4), 811–816.
39. AstraZeneca [Internet]. Transforming kidney health and the burden of CKD. [cited 2023 July 21] Available from: http://349mi.goudounet.com/media-centre/articles/2023/transforming-kidney-health-burden-ckd.html
Veeva ID: Z4-56779
Date of preparation: August 2023