title: Regulation of sodium transporters in the kidney during cyclosporine treatment.
abstract: Cyclosporine (CsA) is among the most widely used immunosuppressants for preventing graft rejection and autoimmune diseases. However, its clinical use is hampered by its significant nephrotoxicity and effects as a cause of hypertension. The proximal tubular Na+-H+ exchanger (NHE3) is responsible for transcellular reabsorption of 30%-60% of the sodium filtered by the glomerulus. CsA induces a reduction of absolute sodium reabsorption, and this effect is, most probably, correlated with the decrease of NHE3 activity. In Henle's loop, in physiological conditions, the Na+-K+-2Cl- cotransporter (NKCC2) reabsorbs approximately 20% of the filtered Na+ and Cl-. CsA increases the NKCC2 activity in cultured bovine renal NBL-1 cells. In the collecting duct, CsA may cause hypertension by stimulating the epithelial Na+ channel (ENaC) through a pathway associated with inhibition of ABCA1 and consequent elevation of cholesterol in the cells. It is still unclear whether CsA regulates the Na+-Cl- cotransporter in the distal tubule and ENaC in the collecting duct. Aside from this, there is evidence suggesting the possible involvement of free radicals during the development of CsA-induced hypertension. The hypertensive effect is, most probably, correlated with higher levels of superoxide (O2-) that decreases glomerular filtration rate and may affect fluid reabsorption along the nephron.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Second University of Naples, Naples, Italy. saradamiano81@libero.it
authors.forename: Sara
authors.initials: S
authors.lastname: Damiano
authors.forename: Roberto
authors.initials: R
authors.lastname: Scanni
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciarcia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Florio
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
mesh_terms: D000042:Absorption; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D053503:Epithelial Sodium Channels / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000502:physiology; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D064466:Solute Carrier Family 12, Member 1
chemical_list: D053503:Epithelial Sodium Channels; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; C578714:SLC12A1 protein, human; C000613385:SLC9A3 protein, human; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D016572:Cyclosporine; D012964:Sodium