Can cyclosporine cause nephrotoxicity?

Although indispensable in the management of solid organ transplantation, cyclosporine and tacrolimus can cause acute and chronic nephrotoxicity. The mechanism appears to be dependent largely on the potent vasoconstrictive effects of these drugs.

What is cyclosporine induced nephrotoxicity?

Cyclosporine-induced renal injury has been described in solid organs recipients and in patients treated for autoimmune diseases. It is manifested in 2 distinct and well characterized forms, acute nephrotoxicity and chronic nephrotoxicity.

How does cyclosporine cause acute kidney injury?

Drugs may produce acute renal failure by prerenal, intrarenal and obstructive (postrenal) mechanisms. Prerenal processes usually develop from an imbalance of the normal counterbalancing vasoconstrictor and vasodilatory substances regulating RBF, resulting in a predominant vasoconstrictive state.

How does cyclosporine affect the kidneys?

The depression of renal function caused by cyclosporin does not generally reflect permanent kidney damage but is caused by a reversible vasoconstriction, with no relevant changes in tubular function.

How is cyclosporine related to renal vasoconstriction?

In addition, cyclosporine induces imbalances in the vasodilator/vasoconstrictor ratio of arachidonic acid metabolites (eicosanoids), which ultimately promotes renal vasoconstriction. An explanation could be found in the association of NFAT and cyclooxygenase-2 (COX-2).

Is the nephrotoxicity of cyclosporine similar to tacrolimus?

The effects of tacrolimus are considered to be similar (see below). The nephrotoxicity of cyclosporine was reported in the first publications on the clinical use of cyclosporine in humans after renal transplantation ( 1, 2 ), whereas prior animal studies had not observed this important side effect ( 26, 27 ).

When was cyclosporine introduced for kidney transplantation?

The introduction of the calcineurin inhibitor (CNI) cyclosporine in human kidney transplantation in the late 1970s revolutionized transplantation medicine, and made transplantation a preferable therapeutic intervention for end-stage renal diseases ( 1, 2 ).

How does cyclosporine affect the smooth muscle cells?

The molecular mechanisms by which cyclosporine stimulates renin synthesis in the juxtaglomerular cells, induces recruitment of renin-containing cells in the afferent arterioles, and leads to alterations in the vascular smooth muscle cells are currently not known.