Do Mycophenolate Mofetil (MMF) and Nintedanib cause kidney injury?

Do Mycophenolate Mofetil and Nintedanib Cause Kidney Injury?

Mycophenolate mofetil (MMF) does not cause kidney injury and may actually protect against it, while nintedanib can cause kidney injury through thrombotic microangiopathy, though this is rare.

Mycophenolate Mofetil (MMF) and Kidney Function

Renal Protective Effects

• MMF has no known nephrotoxicity and may actually improve renal function in certain contexts 1, 2.
• In liver transplant patients with tacrolimus-induced nephrotoxicity, adding MMF while reducing tacrolimus dose resulted in sustained improvement in renal function in 58% of patients over 6 years, with mean serum creatinine decreasing from 2.5 to 1.9 mg/dl 2.
• MMF is specifically recommended as a nonsteroidal option for steroid-refractory immune checkpoint inhibitor-induced nephritis, indicating its safety profile in kidney disease 3.

Mechanism of Renal Protection

• Animal studies demonstrate that MMF prevents arteriolopathy and renal injury despite persistent hypertension by suppressing inflammation and preserving afferent arteriolar function 4.
• MMF prevents salt-sensitive hypertension and renal injury by inhibiting glomerulosclerosis, T-cell infiltration, and afferent arteriolar thickening 5.
• Combined MMF and angiotensin II antagonist therapy arrested established renal injury in experimental models by acting on distinct pathogenic mechanisms 6.

Clinical Use in Kidney Disease

• MMF is widely used as first-line immunosuppression for lupus nephritis at doses of 2-3 g/day, demonstrating its safety and efficacy in treating kidney disease rather than causing it 3.
• The drug is used in focal segmental glomerulosclerosis (FSGS) treatment, showing a 33% combined partial and complete remission rate 3.
• MMF is recommended for maintenance therapy following initial treatment of lupus nephritis, with no evidence of nephrotoxicity 3.

Important Caveat

• While MMF itself does not cause kidney injury, its clearance is reduced in kidney failure, requiring dose adjustments 3.
• The primary side effect is gastrointestinal (diarrhea in up to 35% of patients), not renal toxicity 1, 7.

Nintedanib and Kidney Injury

Nephrotoxic Potential

• Nintedanib can cause kidney injury through thrombotic microangiopathy (TMA), though this is rare 8.
• As a tyrosine kinase inhibitor that blocks VEGF receptor signaling, nintedanib shares nephrotoxic mechanisms with other anti-VEGF agents 3.
• A case report documented isolated proteinuria (1.3 g/g Cr) developing 3 years after nintedanib initiation, with kidney biopsy revealing TMA that resolved one month after drug cessation 8.

Mechanism of Injury

• Nintedanib blocks VEGF receptor, fibroblast growth factor, and platelet-derived growth factor receptors, which can lead to endothelial injury and TMA 8.
• Unlike other tyrosine kinase inhibitors that typically cause minimal change disease or focal segmental glomerulosclerosis, nintedanib appears to cause TMA similar to bevacizumab (a direct VEGF antibody) 8.

Clinical Monitoring

• Patients on nintedanib should be monitored for proteinuria, hypertension, and acute kidney injury 3.
• The nephrotoxicity is potentially reversible with drug discontinuation, as demonstrated by resolution of proteinuria after cessation 8.

Comparative Risk

• Nintedanib-induced nephrotoxicity appears less common than with other anti-VEGF agents, with limited pathological reports in the literature 8.
• The drug is not listed among the most common anticancer agents associated with acute kidney injury in major guidelines 3.

Clinical Implications

For MMF: This drug can be safely used in patients with kidney disease and may actually provide renal protection. Dose adjustments are needed based on gastrointestinal tolerance rather than renal function 1, 2.

For Nintedanib: Monitor renal function and urinalysis regularly during treatment. If proteinuria or renal dysfunction develops, consider kidney biopsy to evaluate for TMA and discontinue the drug if nephrotoxicity is confirmed 8.