Scientists studied how a hormone in your body called aldosterone might harm your kidneys by causing scarring. Using mice and human cells in the lab, researchers found that aldosterone triggers inflammation and causes special blood vessel cells to change into scar-forming cells. They also tested a drug called esaxerenone that blocked aldosterone’s harmful effects. This research helps explain why some people with high blood pressure develop kidney problems, and suggests that blocking aldosterone might prevent kidney scarring. The findings could lead to new treatments for kidney disease.

The Quick Take

  • What they studied: Whether a hormone called aldosterone causes kidney damage by triggering inflammation and changing blood vessel cells into scar-forming cells
  • Who participated: 30 male laboratory mice divided into three groups: a control group, a group given aldosterone, and a group given a drug that blocks aldosterone
  • Key finding: Mice given aldosterone developed more inflammation, more new blood vessels in their kidneys, and more scar tissue. A drug called esaxerenone reduced these harmful effects by blocking aldosterone
  • What it means for you: This research suggests that controlling aldosterone levels might help prevent kidney scarring in people with high blood pressure or kidney disease, though human studies are still needed to confirm this

The Research Details

Researchers conducted an experiment using 30 laboratory mice to understand how aldosterone affects the kidneys. They divided the mice into three groups: one that received no treatment (control), one that received aldosterone through a small pump for 12 weeks, and one that received a drug called esaxerenone through their food. The scientists then examined kidney tissue and cells to measure inflammation, new blood vessel growth, and scar tissue formation.

They also performed laboratory experiments using human kidney cells grown in dishes. These cells were exposed to aldosterone and other substances to see how they changed and whether the drug esaxerenone could stop the harmful changes. The researchers used several techniques to measure what was happening, including staining tissue samples with special dyes to see specific cells and proteins, and using flow cytometry (a machine that counts and analyzes individual cells).

This combination of animal studies and laboratory cell experiments allowed the researchers to understand both what happens in a living body and the specific mechanisms at the cellular level.

This research approach is important because it combines real-world effects (what happens in living mice) with detailed cellular explanations (what happens to individual cells). By studying both levels, scientists can understand not just that aldosterone causes kidney damage, but exactly how it does so. This helps identify potential targets for new medicines.

This study was conducted in a controlled laboratory setting with specific mouse strains, which allows for precise measurements but may not perfectly match what happens in humans. The sample size of 30 mice is reasonable for this type of research. The study used multiple measurement methods to confirm findings, which increases reliability. However, because this is primarily an animal study with some laboratory cell work, results need to be tested in humans before being used as medical treatment.

What the Results Show

When mice received aldosterone, their kidneys showed significant increases in new blood vessel growth and inflammation compared to the control group. The researchers found higher levels of inflammatory chemicals (including IL-1β, TNF-α, and TGF-β1) in the kidneys of aldosterone-treated mice. Importantly, they discovered that special immune cells called macrophages were producing a growth factor called VEGFC, which stimulated the growth of new lymphatic vessels (tiny drainage vessels in the kidney).

The most striking finding was that blood vessel cells in the kidneys underwent a transformation: they started expressing proteins normally found in scar-forming cells (vimentin and α-SMA). This transformation, called endothelial-to-mesenchymal transition (EndMT), appears to be a key step in how aldosterone causes kidney scarring.

When the researchers gave mice the drug esaxerenone (which blocks aldosterone’s effects), these harmful changes were significantly reduced. The drug decreased inflammation, reduced new blood vessel growth, and prevented the transformation of blood vessel cells into scar-forming cells.

Laboratory experiments with human kidney cells confirmed these findings: aldosterone caused the cells to migrate more, form tube-like structures (mimicking blood vessel formation), and transform into scar-forming cells. The drug esaxerenone blocked these changes.

The research revealed that macrophages (immune cells) play a central role in this process by producing VEGFC in response to aldosterone-induced inflammation. The study also showed that the harmful effects of aldosterone depend on a specific receptor called the mineralocorticoid receptor (MR), since blocking this receptor with esaxerenone prevented the damage. Additionally, a signaling pathway involving TGF-β1 (a protein that promotes scarring) appears to be important in how aldosterone causes kidney damage.

This research builds on previous studies showing that aldosterone can cause kidney damage and that blood vessel cell transformation contributes to kidney scarring. However, this study provides new details about the specific mechanisms involved, particularly the role of lymphatic vessel growth and the involvement of macrophages in producing growth factors. The findings support the idea that blocking aldosterone might be beneficial for kidney health, which aligns with clinical observations that aldosterone-blocking drugs help some patients with kidney disease.

This study was conducted entirely in mice and laboratory cell cultures, so results may not directly apply to humans. The study used only male mice, so it’s unclear whether the findings apply equally to females. The research focused on one specific pathway and drug, so other mechanisms of kidney damage may not be captured. Additionally, the study examined relatively short-term effects (12 weeks in mice), so long-term consequences remain unknown. Finally, while the drug esaxerenone showed promise in this study, its safety and effectiveness in humans require separate clinical trials.

The Bottom Line

Based on this research, blocking aldosterone appears to be a promising strategy for preventing kidney scarring (moderate confidence level, pending human studies). People with high blood pressure or kidney disease should discuss with their doctor whether aldosterone-blocking medications might be appropriate for them. This research does not yet support self-treatment or changes to existing medications without medical guidance.

This research is most relevant to people with high blood pressure, chronic kidney disease, or heart disease, as aldosterone plays a role in these conditions. Healthcare providers treating kidney disease should be aware of these findings. Researchers developing new kidney disease treatments should consider these mechanisms. The general public should understand that this is early-stage research that may eventually lead to new treatments, but is not yet ready for clinical use.

In animal studies, kidney changes developed over 12 weeks of aldosterone exposure. If similar mechanisms apply to humans, benefits from aldosterone-blocking treatment might take weeks to months to become apparent. However, preventing future kidney damage may be more realistic than reversing existing scarring. Individual responses vary significantly, and some people may see benefits faster than others.

Want to Apply This Research?

  • Users should track kidney function markers (if available through their healthcare provider) such as creatinine levels and estimated glomerular filtration rate (eGFR) every 3-6 months, along with blood pressure readings daily. This creates a record showing whether kidney function is stable, improving, or declining.
  • Users taking aldosterone-blocking medications should set daily reminders to take their medication consistently, as the benefits depend on regular use. They should also track blood pressure and note any changes in urination patterns or swelling, reporting these to their healthcare provider.
  • Establish a long-term tracking system that records blood pressure readings, medication adherence, kidney function test results (when available), and any symptoms like fatigue or swelling. Review trends monthly with a healthcare provider to assess whether the treatment approach is working effectively.

This research is preliminary and was conducted in laboratory animals and cell cultures. It does not yet constitute medical advice for humans. Do not start, stop, or change any kidney or blood pressure medications based on this research without consulting your healthcare provider. If you have kidney disease or high blood pressure, work with your doctor to determine the most appropriate treatment for your individual situation. This summary is for educational purposes only and should not replace professional medical guidance.