Nephrotoxicity is seen with: (DNB Dec 2010)
a. Tacrolimus (FK 506) inhibits IL-2 transcription like cyclosporine does. However, it binds not to cyclophillins but to FKBP-12.
b. The drug is more potent than cyclosporine and requires therapeutic drug monitoring.
c. Patients treated with the calcineurin inhibitors cyclosporine and tacrolimus are at high risk of developing renal injury. Calcineurin inhibitor nephrotoxicity (CIN) is manifested both as acute azotemia which is largely reversible after reducing the dose, or as chronic progressive renal disease which is usually irreversible.
d. Other renal effects of the calcineurin inhibitors include tubular dysfunction, and rarely a hemolytic uremic syndrome (HUS) that can lead to acute graft loss.
e. A similar pattern of renal injury from cyclosporine is seen with the use of tacrolimus, thereby suggesting a drug class effect. It has been seen that tacrolimus causes vasoconstriction of the afferent and efferent glomerular arterioles and reductions in renal blood flow and glomerular filtration rate.
f. Azathioprine is a prodrug and that too causes tubulointerstitial nephritis, which is less common than tacrolimus. The drug causes bone marrow depression as a prominent side effect.
g. Leflunomide is an immunomodulator and is used in severe rheumatoid arthritis. It produces severe liver injury, interstitial lung diseases, myelosupression and anemia.
h. Mycophenolate is a prodrug and is an inosine monophosphate dehydrogenase inhibitor. The drug is used in refractory patients who require immunosupressives . Most common side effect is gastrointestinal upset and bone marrow depression.