Summary

• What’s Spironolactone? It’s a medicine used in hormone therapy to block male hormones and in treating heart problems. It works by affecting hormones that control water and salt in the body.
• Side Effects? Common issues are low blood pressure (can make you faint or feel drowsy) and high potassium levels in the blood (can cause heart problems).
• Spironolactone with Kidney Disease: It’s tricky to use spironolactone if you have chronic kidney disease. Kidney disease can already raise potassium levels, and spironolactone can make this worse.
• What’s Chronic Kidney Disease? It’s when your kidneys don’t work well over a long time. They’re supposed to clean your blood and balance water and salt. The disease can be mild to severe (stages 1 to 5).
• Spironolactone in Different Kidney Disease Stages:
  • Stage 5 (severe): Not safe to use spironolactone because it can lead to hospital stays and other health problems.
  • Stage 3-4 (moderate to severe): Spironolactone can slow down kidney damage but really increases the risk of high potassium.
  • Stage 1-2 (mild): Might be okay to use, but you need to check your blood regularly.
• For Hormone Therapy: If you have severe kidney disease (stage 3-5), spironolactone isn’t a good choice because of the potassium problem. In a hospital, doctors can check your blood often, but it’s hard to do this at home.
• Recommendations: Don’t use spironolactone if your potassium is already high or if your kidney disease is moderate to severe. If your kidneys are working okay (mild disease), you can use it but you will need regular blood tests.

What is spironolactone?

Spironolactone is a medication that is used in feminising hormone treatment as an antiandrogen. It works via several different mechanisms, including the stimulation of progesterone receptors, the stimulation of oestrogen receptors, and suppressing the production of testosterone. It is also used to treat hypertension and heart failure, as it acts on hormones that influence the levels of water and electrolytes in the body.

Does spironolactone have adverse effects?

Common adverse effects of spironolactone are hypotension and hyperkalaemia. Hypotension is a decrease in blood pressure, which can cause symptoms such as fainting, drowsiness, confusion, and decreased blood flow to the organs. Hyperkalaemia is an increase in the level of potassium in the blood, which can cause an irregular heartbeat that can be fatal.

Because spironolactone can influence the levels or water and electrolytes in the body, some caution may be required regarding its use in people with chronic kidney disease. Specifically, chronic kidney disease can increase the risk of hyperkalaemia, which could be further increased by spironolactone.

What is chronic kidney disease?

The kidneys are organs that excrete waste products from the body and regulate the levels of water and electrolytes in the body. Chronic kidney disease is a longstanding condition where the kidneys do not excrete waste products or regulate the levels of water and electrolytes as well as they typically do. Chronic kidney disease can have many causes, including hypertension, diabetes, high cholesterol, autoimmune conditions, infections, blockages due to kidney stones or an enlarged prostate, and certain drugs or toxins.

How is chronic kidney disease staged?

The staging of chronic kidney disease is based on the estimated glomerular filtration rate (eGFR), which is an estimation of how well the kidneys are excreting waste products based on the levels of waste products in your blood that are measured through a blood test. It is classified from stage 1 to stage 5, with stage 1 being the mildest and stage 5 being the most severe (National Health Service, 2023).

• Stage 1: eGFR >90 ml/min but other tests have shown kidney damage
• Stage 2: eGFR 60–90 ml/min
• Stage 3: eGFR 30–60 ml/min
• Stage 4: eGFR 15–30 ml/min
• Stage 5: eGFR <15 ml/min

How does spironolactone interact with chronic kidney disease?

The effects of spironolactone on chronic kidney disease are mixed and depend on the stage of chronic kidney disease.

Research has shown that spironolactone use in people with stage 5 chronic kidney disease was associated with increased rates of hospitalisation, infection, and mortality (Tseng et al., 2017). This indicates that spironolactone is not recommended in people with stage 5 chronic kidney disease.

However, results are different for people with other stages of chronic kidney disease. A recent study showed that spironolactone has benefits and risks for people with stage 3–4 chronic kidney disease (Yang et al., 2018). A benefit was that spironolactone slowed down the progression of chronic kidney disease. A risk was that spironolactone was associated with a threefold increase in the incidence of hyperkalaemia. Hence, the use of spironolactone in people with stage 3–4 chronic kidney disease involves a fine balance. While spironolactone appears to be effective for slowing down the progression of chronic kidney disease, it carries a significant risk of hyperkalaemia in this population.

Other studies have highlighted the increased risk of hyperkalaemia with spironolactone in people with stage 3–4 chronic kidney disease. While spironolactone had potential benefits with regards to the progression of chronic kidney disease and the treatment of comorbid heart failure, hyperkalaemia was a significant risk (Beldhuis et al., 2019; Buckallew et al., 2017). Furthermore, the risk of hyperkalaemia increased as eGFR decreased.

What are the implications for feminising hormone treatment?

Spironolactone is not recommended as an antiandrogen for people with stage 5 chronic kidney disease.

Although spironolactone can have benefits for people with stage 3–4 chronic kidney disease, the significant risk of hyperkalaemia in this population indicates that close monitoring of potassium levels is recommended. Such close monitoring may be feasible in an inpatient hospital setting, but it is unfeasible in a community setting, where such blood testing is usually only performed every three months. Therefore, given the infeasibility of frequent blood testing for hyperkalaemia, spironolactone is unsuitable as an antiandrogen for people with stage 3–4 chronic kidney disease.

While hyperkalaemia is a potential risk for anyone who is taking spironolactone, research suggests that the risk of hyperkalaemia increases with decreasing eGFR (Beldhuis et al., 2019). Therefore, spironolactone may be a suitable antiandrogen for people with stage 1–2 chronic kidney disease. However, blood testing is required every three months to check the potassium levels.

What are the recommendations?

1. Spironolactone should not be prescribed if the potassium level is >5.1 mmol/l, regardless of the stage of chronic kidney disease.
2. If the eGFR is >60 ml/min (stage 1–2 chronic kidney disease), then spironolactone may be prescribed, but blood tests must be performed every three months to check the potassium levels.
3. If the eGFR is <60 ml/min (stage 3–5 chronic kidney disease), then spironolactone should not be prescribed, but a different antiandrogen should be recommended.