Table 3.

Therapeutic options to prevent or treat calcineurin inhibitor nephrotoxicity

OptionRationaleEffect in Animal StudiesEffect in Human StudiesComment
Decrease exposure to calcineurin inhibitors
CNI avoidanceCompletely avoid exposure to CNIsNA+/−Increased rejection risk, maybe not with costimulatory blockers (e.g., belatacept)
CNI withdrawalExposure to CNIs for only a limited time, to bridge the high rejection risk period early after transplantationNA+/−Increased rejection risk
CNI minimizationLower but continuous exposure to CNIsNA+Safe on short-term; long-term results not known
Decrease exposure to calcineurin inhibitor metabolites
Inhibitors of CYP3A (e.g., ketoconazole)Lower exposure to potentially toxic cyclosporine or tacrolimus metabolites?+More frequent monitoring because of risk for overdosing/cost saving, but only very few studies
Decrease local renal susceptibility to CNI nephrotoxicity
Dihydropyridine calcium antagonists (nifedipine, lacidipine, amlodipine)Counteract the vasoconstrictory mechanisms of CNI use++Positive effects both on GFR and on long-term outcome
ACE inhibitors and angiotensin II receptor blockersCounteract the pivotal role of the RAS in the development of CNI nephrotoxicity++/−RAS inhibition in itself causes renovascular changes, GFR is unaltered but chronic damage may be avoided
SpironolactoneCounteract the pivotal role of aldosterone in the development of CNI nephrotoxicity+?No human studies available
Vasodilatory prostanoidsCounteract the vasoconstrictory mechanisms of CNI use+No effectOnly very few human studies available
NO donorsCounteract the vasoconstrictory mechanisms of CNI use+No effectOnly very few human studies available
Anti-oxidantsCounteract the pivotal role of oxidative stress in the development of CNI nephrotoxicity+?No human studies available
Anti-TGF-β antibodiesCounteract the pivotal role of TGF-β in the development of CNI nephrotoxicity+?No human studies available
StatinsEffects on vascular smooth-muscle cells and on the progression of kidney diseases+?No human studies available
Magnesium supplementationCounteract the potential influence of hypomagnesemia on acute and chronic CNI nephrotoxicity+?No human studies available
  • References are provided in the text. NA, not appropriate; CNI, calcineurin inhibitor.