From the Guidelines
Spironolactone does not cause renal cell carcinoma in humans at therapeutic doses, despite evidence of tumorigenicity in animal studies at much higher doses. The evidence from animal studies, such as those cited in 1, suggests that spironolactone can cause renal tumors in rats, particularly at high doses. However, the doses used in these studies are significantly higher than those used in clinical practice, and the mechanism of tumorigenicity appears to be species-specific.
- Key points to consider:
- The doses used in animal studies are much higher than therapeutic doses used in humans (typically 25-200 mg daily)
- The mechanism of tumorigenicity involves the formation of reactive metabolites that can damage DNA and promote carcinogenesis in rat kidney tissue
- There is no convincing evidence that spironolactone causes renal cell carcinoma in humans at therapeutic doses
- Several large cohort studies with over 30 million person-years of combined follow-up have not confirmed such a risk when used in typical clinical practice, as noted in 1
- In clinical practice, the benefits of spironolactone in treating conditions such as acne and heart failure often outweigh the potential risks, and patients can be reassured that the risk of renal cell carcinoma is extremely low when used at therapeutic doses. The study by 1 highlights the importance of considering the species-specific mechanism of action and the extremely high doses used in animal studies when evaluating the risk of spironolactone in humans.
From the FDA Drug Label
In an 18-month study using doses of about 50,150, and 500 mg/kg/day, there were statistically significant increases in benign adenomas of the thyroid and testes and, in male rats, a dose-related increase in proliferative changes in the liver (including hepatocytomegaly and hyperplastic nodules) In a 24-month study in which the same strain of rat was administered doses of about 10,30, and 100 mg spironolactone/kg/day, the range of proliferative effects included significant increases in hepatocellular adenomas and testicular interstitial cell tumors in males, and significant increases in thyroid follicular cell adenomas and carcinomas in both sexes
The FDA drug label does not mention renal cell carcinoma in rats as a result of spironolactone administration. Key points include:
- Tumorigenic effects were observed in endocrine organs and the liver
- Proliferative changes were seen in the liver, thyroid, and testes
- No mention of renal cell carcinoma is made in the provided text 2
From the Research
Spironolactone and Renal Cell Carcinoma in Rats
- There is no direct evidence from the provided studies that spironolactone causes renal cell carcinoma in rats 3, 4, 5, 6, 7.
- The studies primarily focus on the effects of spironolactone on kidney function, ischemia-reperfusion injury, and its potential to prevent chronic kidney disease in rats 3, 4.
- One study examines the association between spironolactone use and the risk of urinary tract cancer, including renal cancer, in humans, but does not provide conclusive evidence of a causal relationship 6.
- Another study investigates the association between spironolactone use and the risk of various types of cancer, including kidney cancer, but finds no statistically significant association 7.
Key Findings
- Spironolactone has been shown to prevent the development of chronic kidney disease after ischemic injury in rats 3.
- Spironolactone treatment after mild ischemia prevents long-term structural and molecular changes that may compromise renal function in later stages 3.
- There is no clear evidence to suggest that spironolactone causes renal cell carcinoma in rats, but high cumulative doses of spironolactone may be associated with an elevated risk of renal cancer in humans 6.