Kidney Alert: How Common Medications Can Turn Toxic During Immunotherapy

Immunotherapy is a cancer treatment approach that leverages the body's immune system to fight cancer cells. Specifically, immune checkpoint inhibitors (ICPIs), like anti-PD-1 and anti-CTLA-4 antibodies, are a type of immunotherapy. While effective, ICPIs can sometimes lead to acute tubulointerstitial nephritis (ATIN), a kidney injury. This is because ICPIs can disrupt the body's immune tolerance, causing it to react to medications that were previously harmless, which in turn can trigger inflammation in the kidneys and lead to kidney damage.

The danger arises because ICPIs, such as anti-PD-1 antibodies, can disrupt the body's immune tolerance. Immune tolerance is the process where the immune system recognizes and ignores certain substances, including medications. When ICPIs interfere with this, the immune system may start attacking drugs that were previously well-tolerated. A specific case involves lansoprazole, a proton pump inhibitor (PPI), which, when combined with the anti-PD-1 antibody nivolumab, caused ATIN in a patient who had safely used lansoprazole for years.

ATIN is a type of kidney injury where the spaces between the kidney tubules become inflamed, disrupting normal kidney function. In the context of immunotherapy, specifically with ICPIs, ATIN is a concerning complication. ICPIs can trigger this inflammation, potentially leading to kidney damage. The risk is increased when ICPIs interact with other medications, which can result in the development of ATIN even with drugs that have been safely used for a long time.

In the case study, a 67-year-old man with stage IV non-small-cell lung cancer developed kidney injury while undergoing nivolumab (an anti-PD-1 antibody) therapy. The patient was also taking lansoprazole, a PPI, for acid reflux. The kidney injury was diagnosed as ATIN. The key point is that the patient had been safely taking lansoprazole for four years before nivolumab treatment. After starting nivolumab, his immune system seemingly lost its tolerance to lansoprazole, leading to an inflammatory response in the kidneys. This highlights that ICPIs like nivolumab can make safe drugs, like lansoprazole, dangerous, emphasizing the need to carefully review and monitor medications during immunotherapy.

Protecting kidney health during immunotherapy requires vigilance and careful drug management. Healthcare providers and patients need to work together to ensure all medications are thoroughly reviewed and monitored throughout the treatment process. If kidney injury arises, recognizing and discontinuing concomitant drugs, especially those known to cause ATIN, is essential. While corticosteroids are often used to manage ICPI-associated kidney injury, identifying and addressing the offending medications, such as lansoprazole in the case study, is crucial for a positive outcome. The key is proactive monitoring and awareness of potential drug interactions.