Renal and systemic acid-base effects of chronic spironolactone administration

Abstract

Studies in dogs were carried out to investigate the effects of chronic administration of the mineralcorticoid antagonist spironolactone (15 mg/kg orally) on renal and systemic acid-base metabolism. In adrenalectomized dogs administered fixed mineralocorticoid and glucocorticoid replacement, spironolactone resulted in a definite renal antimineralocorticoid effect, as evidenced by natriuresis and chloruresis, and sustained metabolic acidosis and hyperkalemia due in part to impaired renal secretion of hydrogen and potassium. In adrenalectomized dogs receiving physiological glucocorticoid without mineralocorticoid, metabolic acidosis also occurred, but a marked stimulatory effect of spironolactone on net acid excretion occurred in association with increased urinary SO4-2 and total nitrogen excretion. Accordingly, spironolactone results in sustained renal tubular acidosis when administered in the presence of constant physiological levels of mineralocorticoid and glucocorticoid steroids. When administered under conditions of complete lack of mineralocorticoid activity, spironolactone exerts systemic and renal acid-base effects similar to those of a glucocorticoid steroid, namely, increased protein catabolism and sulfuric acid production with resultant extrarenal metabolic acidosis associated with increased net acid excretion.

Safety of Spironolactone in Dogs with Chronic Heart Failure because of Degenerative Valvular Disease: A Population‐Based, Longitudinal Study

“…The risk of renal dysfunction or hyperkalemia is similar in each group. These findings confirm the previous results obtained for plasma/serum sodium and potassium concentrations in healthy dogs , and dogs with MVD but without congestive HF and azotemia …”

“…Spironolactone (15 mg/kg/day for 9 days) administered to healthy dogs does not change plasma chloride, sodium, potassium, creatinine, or protein concentrations . Likewise, no consistent change in plasma sodium and potassium concentrations occurs when spironolactone is administered at 2, 10, and 20 mg/kg/day for 13 weeks .…”

Comprehensive characterization of the effect of mineralocorticoid receptor antagonism with spironolactone on the renin-angiotensin-aldosterone system in healthy dogs.

“…[23] Previous studies have demonstrated the biochemical safety of spironolactone in clinical canine patients [24] and in experimental models at doses as high as 15 mg/kg/day. [25] The data from this study also show that spironolactone was safe in healthy dogs at doses up to 4 mg/kg/day. No dog studied experienced an adverse event while on spironolactone at either dose and spironolactone treatment had no effect on the CBC and serum biochemistry pro le values or SAP in dogs in this study.…”

Aldosterone Regulates the Na-K-2Cl Cotransporter in Vascular Smooth Muscle

“…The increase in NKCC1 activity with spironolactone is consistent with a partial agonist effect that may occur with spironolactones. 20,21 To determine whether aldosterone increases the quantity of cotransporters, we stimulated aldosterone-treated aortas with phenylephrine. This ␣-adrenergic agent acutely stimulates NKCC1, 14 and we reasoned that an increase in cotransporter quantity would augment the stimulation by phenylephrine.…”