Is Linzess (linaclotide) associated with acute kidney injury?

Linzess (Linaclotide) and Acute Kidney Injury

Based on current medical evidence, there is no established association between Linzess (linaclotide) and acute kidney injury (AKI). The medical literature and clinical guidelines do not identify linaclotide as a medication associated with nephrotoxicity or risk of AKI.

Understanding Acute Kidney Injury

Acute kidney injury is defined as a 50% or greater sustained increase in serum creatinine over a short period of time, which is reflected as a rapid decrease in estimated glomerular filtration rate (eGFR) 1.

Risk Factors for AKI

Several risk factors increase the likelihood of developing AKI:

• Pre-existing chronic kidney disease
• Medications that cause kidney injury (e.g., NSAIDs)
• Medications that alter renal blood flow and intrarenal hemodynamics
• Certain antihypertensive medications (e.g., diuretics, ACE inhibitors, ARBs)
• Diabetes 1

Medications Associated with AKI

Multiple guidelines identify specific medications that can increase AKI risk:

• Nephrotoxic medications: NSAIDs, certain antibiotics, contrast media
• Medications affecting renal hemodynamics:
  • Diuretics
  • ACE inhibitors
  • Angiotensin receptor blockers (ARBs)
  • The "triple whammy" combination of renin-angiotensin system inhibitors, diuretics, and NSAIDs 1, 2

Linzess (Linaclotide) and Kidney Function

Linaclotide is a guanylate cyclase-C agonist approved for treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. It works locally in the intestinal tract with minimal systemic absorption.

There is only one case report in the literature suggesting a potential association between linagliptin (a DPP-IV inhibitor, which is a different medication than linaclotide) and AKI 3. This case involved linagliptin, not linaclotide, and occurred in a patient with pre-existing chronic kidney disease who was concurrently taking lisinopril (an ACE inhibitor).

Clinical Implications

When considering medications that might contribute to AKI risk:

• Monitor kidney function regularly in patients with risk factors for AKI
• Be vigilant about "triple whammy" combinations of medications
• Adjust medication dosages appropriately for kidney function
• Recognize that small elevations in serum creatinine (up to 30%) with RAS blockers should not be confused with AKI 1

Conclusion

While many medications can contribute to AKI risk, current medical evidence and guidelines do not identify Linzess (linaclotide) as a medication associated with acute kidney injury. The primary medications of concern for AKI include NSAIDs, certain antibiotics, contrast media, and medications that alter renal hemodynamics such as ACE inhibitors, ARBs, and diuretics.

For patients with risk factors for AKI, regular monitoring of kidney function is recommended regardless of medication regimen.