Summary Goals Randomized controlled trials have demonstrated the efficacy of mineralocorticoid receptor (MR) antagonism in slowing the progression of chronic kidney disease (CKD) in diabetes; However, they have not investigated the role of aldosterone or whether these beneficial effects could be achieved in people without diabetes. Methods and results The association between serum aldosterone concentrations and kidney disease progression was investigated among 3680 participants in the chronic kidney disease cohort. The primary outcome was CKD progression [defined as the combination of a 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease, whichever occurred first]. Associations between serum aldosterone and kidney disease outcomes were assessed using Cox proportional hazards models. At baseline, higher aldosterone concentrations were associated with lower eGFR, lower serum potassium, higher urinary potassium, and protein excretion. During a median follow-up of 9.6 years, 1412 participants developed CKD progression. In adjusted models, each doubling of serum aldosterone was associated with an 11% increase in the risk of CKD progression [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.04–1 ,18]. Individuals with the highest quartile of serum aldosterone had a 45% increased risk of CKD progression (HR 1.45, 95% CI 1.22–1.73) compared with the lowest quartile. The risk of CKD progression was similar regardless of whether patients had concomitant diabetes (interaction P = 0.10). Conclusion Higher serum aldosterone levels among people with CKD are independently associated with an increased risk of kidney disease progression, regardless of concomitant diabetes. These findings provide mechanistic support for MR antagonists in slowing CKD progression and suggest that they may also have a role in people without diabetes. |
Aldosterone in chronic kidney disease and renal outcomes: study design and summary results. CI: confidence interval; CKD, chronic kidney disease; eGFR: estimated glomerular filtration rate; ESKD, end-stage kidney disease; HR: hazard ratio; MR, mineralocorticoid receptor.
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The steroid hormone aldosterone is linked to an increased risk of kidney failure in patients with chronic kidney disease (CKD), according to a study published in the European Heart Journal . The risk of CKD worsening and developing into end-stage kidney disease was independent of whether or not patients had diabetes.
The findings are important because they suggest that aldosterone plays a role in the progression of not only CKD but also heart and blood vessel problems, and that an existing drug that targets the action of aldosterone may help prevent CKD worsens.
Aldosterone is a steroid hormone secreted by the adrenal glands, which are located above the kidneys. Its main role is to regulate salt and water in the body, which is why it plays a central role in controlling blood pressure. Too much can cause high blood pressure, cardiovascular and kidney diseases.
Study lead author Dr Ashish Verma, assistant professor at Boston University School of Medicine, US, said: "Recent randomized controlled trials have shown that a drug called finerenone is effective in delaying CKD progression and adverse cardiovascular outcomes in patients with chronic kidney disease and diabetes. However, the role of aldosterone in this process was not directly investigated and levels of the hormone were not measured.”
Finerenone targets the non-steroidal mineralocorticoid (MR) receptor. When this receptor is activated by aldosterone, elevated levels of the hormone cause high blood pressure, cardiovascular and kidney diseases.
“Since excessive aldosterone levels are very common, but mostly unrecognized , we hypothesized that one of the reasons finerenone was effective in reducing the risk of CKD progression was that it was treating high concentrations. unrecognized hormones,” said Dr. Verma.
Dr. Verma and colleagues investigated associations between blood aldosterone concentrations and kidney disease progression among 3,680 participants in the Chronic Renal Insufficiency Cohort study, which was conducted at seven clinics in the US between 2003. and 2008. Participants were between 21 and 74 years old.
They focused on the progression of CKD , which was defined as a 50% decrease in the kidneys’ ability to filter blood through the glomerular blood vessels, known as estimated glomerular filtration rate (eGFR), or kidney disease. in the terminal stage, whichever comes first. They followed the patients for an average (median) of almost ten years. During this time, CKD progression occurred in 1412 (38%) of participants.
They found that higher concentrations of aldosterone were associated with lower eGFR, lower levels of potassium in the blood, and higher concentrations of potassium and protein in the urine.
After adjusting for factors that could affect the results, such as medications, other medical conditions, age, race, height and weight, they found that each doubling of blood aldosterone concentrations was associated with an 11-fold increase. % in the risk of CKD progression. Patients with concentrations in the top 25% of the group had a 45% increased risk compared to the 25% of patients with the lowest aldosterone concentrations. The risk was similar regardless of whether the patients also had diabetes or not.
Dr Verma said: “These findings are important as they suggest that higher concentrations of aldosterone may play a role in the progression of CKD and cardiovascular disease in patients with CKD. “This study provides evidence of the mechanism by which mineralocorticoid receptor antagonists may delay the progression of CKD and supports investigation of their value in patients without diabetes.”
The US Food and Drug Administration (FDA) has approved the use of finerenone for patients with CKD and diabetes. Now, a randomized controlled clinical trial is investigating the efficacy and safety of finerenone in non-diabetic CKD patients. “This trial will play an important role in answering the question of whether MR antagonist therapy will be useful in slowing the progression of CKD in patients with CKD and without diabetes,” Dr. Verma said.
Professor George Bakris, from the University of Chicago Medicine, USA, who was not involved in the research but was involved in the randomized controlled trials of finerenone in diabetic patients, has written an editorial to accompany the study. “Taken together, these studies suggest that aldosterone levels should be assessed in all patients at risk for and/or in the presence of cardiorenal disease , especially if they have central obesity and/or resistant hypertension .”
“We now have relatively safe and better tolerated agents than traditional steroid agents that can and should be used to reduce cardiorenal risk in these patient groups,” he writes.
Limitations of the study include: 1) there were no measurements of a protein called albumin in urine, or of another protein, renin, in blood samples; This could indicate whether or not high aldosterone levels were dependent on renin, which is released by the kidneys and also plays a role in blood pressure; 2) aldosterone levels were only measured once at the beginning of the study; 3) no data were available on the duration of use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which could affect aldosterone levels; and 4) the study is observational and cannot demonstrate that aldosterone causes CKD progression, only that it is associated with it.
In 2017, CKD affected 9.1% of the world’s population, 697.5 million cases.
Co-authors of the study were Anand Vaidya of Brigham and Women’s Hospital, Boston, Sonu Subudhi of Massachusetts General Hospital, Boston, and Sushrut S. Waikar of Boston University School of Medicine.
