J Korean Med Sci.  2002 Oct;17(5):625-632. 10.3346/jkms.2002.17.5.625.

Effects of Thyroxine on Hyperkalemia and Renal Cortical Na(+), K(+) - ATPase Activity Induced by Cyclosporin A

• You CW
• Park YH
• Lee ES
• Kim YJ
• Shin SM
• Park MO

• KMID: 1127253
• DOI: http://doi.org/10.3346/jkms.2002.17.5.625

Abstract

Cyclosporin A (CsA)-induced hyperkalemia is caused by alterations in transepithelial K(+) secretion resulting from the inhibition of renal tubular Na(+), K(+) -ATPase activity. Thyroxine enhances renal cortical Na(+), K(+) -ATPase activity. This study investigated the effect of thyroxine on CsA-induced hyperkalemia. Sprague-Dawley rats were treated with either CsA, thyroxine, CsA and thyroxine, or olive-oil vehicle. CsA resulted in an increase in BUN and serum K(+), along with a decrease in creatinine clearance, fractional excretion of potassium, and renal cortical Na(+), K(+) -ATPase activity, as compared with oil vehicle administration. Histochemical study showed reduced Na(+), K(+) -ATPase activity in the proximal tubular epithelial cells of the CsA-treated compared with the oil-treated rats. Histologically, isometric intracytoplasmic vacuolation, disruption of the arrangement and swelling of the mitochondria, and a large number of lysosomes in the tubular epithelium were characteristic of the CsA-treated rats. Co-administration of thyroxine prevented CsA-induced hyperkalemia and reduced creatinine clearance, Na(+), K(+) -ATPase activity, and severity of the histologic changes in the renal tubular cells when compared with the CsA-treated rats. Thyroxine increased the fractional excretion of potassium via the preservation of Na(+), K(+) -ATPase activity in the renal tubular cells. Thus, the beneficial effects of thyroxine may be suited to treatment modalities for CsA-induced hyperkalemia.

Keyword

Cyclosporin A; Hyperkalemia; Thyroxine; Renal Corex; Na(+); K(+)-ATPase

MeSH Terms

Animals
Cyclosporine/antagonists & inhibitors/*toxicity
Hyperkalemia/chemically induced/*drug therapy/metabolism/prevention & control
Immunosuppressive Agents/antagonists & inhibitors/*toxicity
Kidney Cortex/*drug effects/*enzymology/pathology
Male
Microsomes/enzymology
Potassium/blood/metabolism
Rats
Rats, Sprague-Dawley
Sodium-Potassium-Exchanging ATPase/*metabolism
Thyroxine/*pharmacology