How are calcineurin inhibitors associated with chronic tubulointerstitial nephritis?
Calcineurin inhbitors (CNIs), namely cyclosporine and tacrolimus, are used as antirejection therapy after organ transplantation and as immunosuppressive therapy for various autoimmune diseases. CNIs can cause acute and chronic nephrotoxicity.
Acutely, CNIs may cause vasoconstriction of the afferent and efferent arterioles and decreased kidney blood flow. Chronically, there is vascular damage leading to glomerular and tubular injury. On histology, there is vacuolization of the tubules and focal areas of tubular atrophy and interstitial fibrosis leading to a “striped fibrosis” pattern.
Laboratory evaluation is notable for hyperkalemia, nonanion gap metabolic acidosis, hypomagnesemia, hypophosphatemia, and hyperuricemia.
Treatment of CNI toxicity consists of lowering the dose or discontinuing the CNI when possible. Calcium channel blockers may protect against CNI-induced vasoconstriction.
