Boston University: Aldosterone Involved in Chronic Kidney Disease

Chronic kidney disease affects more than 9% of the world’s population, representing a prevalence of nearly 700 million cases. A team of researchers showed that aldosterone, a steroid hormone secreted by the adrenal glands, is associated with an increased risk of developing chronic kidney disease and end-stage renal disease. The study which was published in the European Heart Journal, suggests that an existing drug that targets the action of aldosterone could help prevent the onset of chronic kidney disease.

Kidney

Kidney

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Aldosterone, secreted by the adrenal glands via the kidneys, regulates salt and water in the body and plays a key role in controlling blood pressure. It is also known that too much aldosterone can lead to high blood pressure, cardiovascular disease, and kidney disease.

The Boston University team confirmed that aldosterone plays a role in certain cardiovascular diseases. Additionally, the risk of worsening kidney failure and progression to end-stage renal disease appears to be independent of whether patients have diabetes. The study’s lead author, Dr. Ashish Verma, a professor at Boston University, points to recent randomized controlled trials that have shown that finerenone, used to treat heart failure, is also effective in treating diabetic nephropathy and may delay the development of chronic kidney failure. Still, the role of aldosterone in kidney failure has never been directly studied.

Possible beneficial effects of finerenone

The drug targets mineralocorticoid receptors, which, when activated by aldosterone, promote hypertension, cardiovascular, and kidney disease. Although excessive aldosterone levels are very common but usually undiagnosed, finerenone appears to be effective in reducing high levels and thus the development of kidney failure.

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The study

The team validated this hypothesis by assessing the association between blood aldosterone concentrations and the development of kidney disease in 3,680 patients aged 21 to 74 years who participated in the Chronic Kidney Disease Cohort Study, which was conducted between 2003 and 2008 and followed for an average of 10 years. Progression of chronic kidney disease is defined as a 50% decrease in the ability of the kidneys to filter blood through the blood vessels (estimated glomerular filtration rate – eGFR). During this period, 1,412 or 38% of participants experienced kidney failure.

The analysis showed that:

  • Higher aldosterone concentrations are well associated with lower eGFR, lower blood potassium levels, and higher urine potassium and protein concentrations.
  • After adjusting for possible confounders such as medications, other medical conditions, age, ethnicity, height, and weight, each doubling of blood aldosterone levels are associated with an 11% increased risk of progression to kidney failure.
  • Patients with the highest blood aldosterone levels (25%) have a 45% increased risk of chronic kidney disease compared to the 25% of patients with the lowest blood aldosterone levels.
  • These risk levels are similar whether or not patients also have diabetes, suggesting that aldosterone levels are an independent risk factor for chronic kidney disease.

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Final Thoughts

The authors of the study have for the first time explained the mechanism by which mineralocorticoid receptor antagonists can delay the onset of kidney failure – even in nondiabetic patients. The US Food and Drug Administration (FDA) has approved finerenone for use in patients with chronic kidney disease and diabetes. A randomized controlled trial is ongoing to validate the efficacy and safety of finerenone in patients with non-diabetic kidney disease.

Finally, the study suggests that aldosterone levels should be assessed in all patients at risk and/or with a cardiorenal disease, especially if they are obese and/or suffer from resistant hypertension.

References

Aldosterone in chronic kidney disease and renal outcomes

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