In liver transplantation, what is the Calcineurin Inhibitor (CNI)-related nephrotoxicity mechanism, and which immunosuppressive agent is preferred to minimize renal damage in CNI-intolerant recipients?

• A CNIs (cyclosporin/tacrolimus) cause afferent arteriolar vasoconstriction; mTOR inhibitors (sirolimus/everolimus) are used in CNI-intolerant patients ✓
• B CNIs damage tubular cells by direct mitochondrial toxicity; mycophenolate mofetil replaces CNIs
• C CNIs cause immune-mediated glomerulonephritis; azathioprine is the CNI-sparing agent
• D CNI nephrotoxicity is irreversible; renal transplantation is always required after liver transplantation

Explanation

Calcineurin inhibitors (cyclosporin and tacrolimus) cause nephrotoxicity primarily through afferent arteriolar vasoconstriction, reducing renal blood flow and GFR. This can progress to chronic renal fibrosis. In CNI-intolerant liver transplant recipients (eGFR <30 mL/min), mTOR inhibitors (sirolimus, everolimus) allow CNI minimization or withdrawal while maintaining immunosuppression. Mycophenolate mofetil (MMF) is used as an adjunct but is not adequate as sole immunosuppression post-transplant. mTOR inhibitors also have anti-proliferative properties beneficial in HCC transplant recipients.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.