Illustration of different drug targets in the podocyte. Positive effects of drugs on podocyte function are shown in green and negative effects of drugs on podocyte function are shown in red . Please note that mammalian target of rapamycin ( mTOR ) inhibitors are mentioned in both colours as they have pro-survival effects in diabetic nephropathy but can cause negative side effects on podocytes in other clinical settings. Here mTOR inhibitors can lead to proteinuria and podocyte apoptosis by de- creasing the expression of synaptopodin, podocin and nephrin.
In the name of God
Mofid children’s hospital
Shahid beheshti medical university
Describes the effect a drug has on the body. This includes the
agent‘s therapeutic activity (its mechanism of action) and any
untoward effects it may cause (its adverse effect profile)
Calcineurin Inhibitors: Mechanism of Action
FKBP: FK Binding Protein
NF-AT: Nuclear Factor of
Activated T-cells (c- cytosolic
component; n- nuclear
Stepkowski, Expert Rev
Mol Med, 2000;2(4):1
Mechanism of antiproteinuric effect of
Role of podocytes in preteinuria
• Two agents in clinical practice:
• Cyclosporine (Sandimmune®, Gengraf®, Neoral®, generic; CysA)
• Tacrolimus (Prograf®, supratac,generic; FK506).
• Generics NOT clinically therapeutically equivalent.
• At present are key to maintenance immunosuppression and a
component of the majority of transplant protocols.
Calcineurin Inhibitors: Adverse Effects
• Functional decrease in blood flow from afferent arteriolar
• Thrombotic microangiopathy (rare).
• Chronic interstitial fibrosis.
• Hyperkalemia, hypomagnesemia and type IV renal tubular
• Cyclosporine thought to be more nephrotoxic.