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

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.

Cyclosporine metabolic side effects: association with the WNK4 system

“…In our study, blood pressure rose from 128·0 ± 2·3 in controls to 162·0 ± 3·6 mmHg in cyclosporine‐treated rats. In another study, rats treated by cyclosporine 25 mg kg −1 for 30 days showed an increase in blood potassium from 4·5 to 5·2 mEq L −1 [26], which is very similar to the hyperkalemia that we have found. Hypercalciuria of similar degree to that observed by us was found in rats treated by 50 mg kg −1 cyclosporine [27].…”

Effect of Triclosan on the Renal Cortex of Adult Male Albino Rats and the Possible Protective Role of Ellagic Acid: Histological and Biochemical Study

“…U.S Food and Drug Administration [34] reported that TCS induced renal changes by ROS damaging of variety of transport proteins including Na/K ATPase [35]. Reduced Na+, K+-ATPase activity in the proximal tubular epithelial cells resulted in intracytoplasmic vacuolation, disruption of the arrangement and swelling of the mitochondria and large number of lysosomes [36]. Previous studies reported that sloughing of the nonviable cells into the tubular lumen induced formation of casts which cause luminal obstruction leading to decrease in glomerular filtration [37].…”

Up-Regulation of Local TGF-β Contributes to a Decrease in Renal Tubular Na<sup>+</sup>-K<sup>+</sup> ATPase and Hyperkalemia in a Mouse Model of Crush Syndrome

“…Activation levels of this pomp likely determine a predisposition to hyperkalemia. For example, cyclosporin-A suppresses Na + -K + -ATPase production in a culture of renal tubular cells [31], while forced induction of this pump by thyroxine leads to the attenuation of hyperkalemia in a rat model of cyclosporin-A-induced AKI [19]. Inversely, inhibition of this pump by drugs underlies the mechanism of their toxicity, including hyperkalemia [32] [33].…”

“…Renal Na + -K + -ATPase activity was visualized, as reported [19]. In brief, renal tissues were perfused with 2% polyvinyl pyrrolidone, 0.8 mM CaCl 2 and 100 mM histidine (pH 7.3) for 20 min and refrigerated in dry ice acetone.…”