Key result
Treatment with triamterene in SGK1-deficient mice led to severe, eventually lethal body weight loss and increased plasma aldosterone, urea, and K+ concentrations compared to wild-type mice.
Why the study?
Does SGK1 deficiency alter the response to diuretic treatment in mice?
Does SGK1 deficiency alter the response to diuretic treatment in mice?
SGK1 is required for diuretic tolerance to triamterene, highlighting its role in renal Na+ reabsorption mechanisms beyond ENaC.
SGK1 deficiency heightens triamterene risk in mice; leaves open its relevance to human diuretic safety and renal Na+ handling.
BACKGROUND/AIMS: Serum- and glucocorticoid-inducible kinase 1 (SGK1) stimulates the epithelial sodium channel (ENaC), renal outer medullary K(+) channel 1, Na(+)/K(+)-ATPase and presumably the Na(+)-Cl(-) cotransporter (NCC). SGK1-deficient mice (sgk(-/-)) show a compensated salt-losing phenotype with secondary hyperaldosteronism. The present experiments explored the role of SGK1 in the response to diuretics. METHODS: sgk1(-/-) mice and their wild-type littermates (sgk1(+/+)) were treated with the ENaC blocker triamterene (200 mg/l), the Na(+)-K(+)-2Cl(-) cotransport inhibitor furosemide (125 mg/l), the NCC blocker hydrochlorothiazide (400 mg/l) and the mineralocorticoid receptor blocker canrenoate (800 mg/l) for 8 days. Renal SGK1 expression was studied using quantitative RT-PCR and immunofluorescence. RESULTS: Diuretic treatment increased SGK1 mRNA and protein expression in the kidney of wild-type sgk1(+/+) mice. The responses to furosemide, hydrochlorothiazide or canrenoate were not different between sgk1(+/+) and sgk1(-/-) mice, and were accompanied by moderate increases in plasma aldosterone and urea concentrations. However, treatment with triamterene in sgk1(-/-) mice (but not in sgk1(+/+) mice) led to severe, eventually lethal, body weight loss as well as increases in plasma aldosterone, urea and K(+) concentrations. CONCLUSIONS: SGK1 is required for diuretic tolerance to triamterene. The observations confirm the impaired kaliuretic potency of sgk1(-/-) mice and point to a role of SGK1 in renal Na(+) reabsorption by mechanisms other than ENaC.
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Artunç et al. (2009) studied SGK1 deficiency. Diuretic treatment (triamterene, furosemide, hydrochlorothiazide, canrenoate) vs. wild-type littermates (sgk1+/+) was evaluated on Response to diuretics (body weight, plasma aldosterone, urea, K+ concentrations). Treatment with triamterene in SGK1-deficient mice led to severe, eventually lethal body weight loss and increased plasma aldosterone, urea, and K+ concentrations compared to wild-type mice.
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