An extrarenal mechanism of potassium adaptation

Alexander, E. A.; Levinsky, Norman G.

doi:10.1172/jci105769

Cited by 137 publications

(46 citation statements)

References 13 publications

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“…Furthermore, our data suggest that in these segments Na-K-ATPase is involved in K+ adaptation regardless of the mineralocorticoid status of the animals. Thus, our data are consistent with a model of K+ secretion that involves Na-K-ATPase in the basolateral membrane and passive K+ movement in the apical membrane ofthe CCD (24,25) Adaptation to a dietary K+ load also involves certain extrarenal mechanisms such as the secretion of K+into the colon (28)(29)(30). These processes are probably dependent on aldosteronestimulated Na-K-ATPase in the colonic mucosa.…”

Section: Discussionsupporting

confidence: 89%

Renal adaptation to potassium in the adrenalectomized rabbit. Role of distal tubular sodium-potassium adenosine triphosphatase.

Garg¹,

Narang²

1985

J. Clin. Invest.

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Potassium secretion and sodium-potassium adenosine triphosphatase (Na-K-ATPase) activity in the distal nephron segments are known to be influenced by the dietary intake of KV. This has been attributed to a change in the plasma aldosterone level, which also influences K+ secretion and Na-K-ATPase activity in the distal nephron. To investigate whether or not dietary K+ can modulate Na-K-ATPase activity in the distal nephron independently of aldosterone, we determined Na-K-ATPase activity in four distinct nephron segments of adrenalectomized (adx) rabbits given four specific diets for 1 wk before experimentation. Na-K-ATPase activity was determined by a fluorometric microassay in which ATP hydrolysis is coupled to NADH oxidation. The nephron segments examined were the distal convoluted tubule (DCI), the connecting tubule (CNT), the cortical collecting duct (CCD), and the outer medullary collecting duct (MCD). All diets were similar in composition except for their K+ contents, which were 100, 300, 500, and 700 meq/kg in groups 14, respectively. In these adx animals, Na-K-ATPase activity increased >200% in the CCD as the dietary intake of K+ increased. There was a linear relationship between K+ excretion and the enzyme activity in this segment. There was a 50% increase in Na-K-ATPase activity in the CNT as the dietary intake of K+ increased in adx animals. However, there were no significant differences in Na-K-ATPase activities in the DCT and MCD among the four treatment groups. It is concluded that dietary K+ intake can influence Na-K-ATPase activity in the CCD and CNT independently of plasma aldosterone levels.

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Section: Discussionsupporting

confidence: 89%

Renal adaptation to potassium in the adrenalectomized rabbit. Role of distal tubular sodium-potassium adenosine triphosphatase.

Garg¹,

Narang²

1985

J. Clin. Invest.

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“…This observation confirms the finding ofYoung and Paulsen (32) that potassium excretion may be maintained at normal levels in spite of a significant reduction in plasma potassium concentration provided mineralocorticoid levels are appropriately elevated. The observed reduction in plasma potassium concentration is most likely due to an aldosterone-induced shift of potassium into extrarenal tissues (32)(33)(34). Some potassium depletion may also have occurred during the 10-d pretreatment period with the high aldosterone infusion (9).…”

Section: Resultsmentioning

confidence: 99%

“…As a consequence, kaliuresis after an acute infusion of KCI may be attenuated in that the infused KC1 would be retained within body cells until potassium balance is restored (17, 18). It is also known that an increase in aldosterone shifts potassium into cells (32)(33)(34)36). Accordingly, the infused KC1 may move preferentially into the intracellular compartment.…”

Section: Resultsmentioning

confidence: 99%

Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

Stanton¹,

Pan²,

Deetjen³

et al. 1987

J. Clin. Invest.

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We examined the independent effects of a high potassium diet and increased aldosterone levels on the development of renal potassium adaptation. This condition is defined by the increased ability of the kidneys to excrete an acute infusion of potassium. Rats were adrenalectomized (ADX) and received aldosterone at basal levels (0.5 Asg/100 g * d) or at high levels (2.0 ;g/100 go d) for 10 d. In each experimental group, animals received either a control diet or a high potassium diet. In ADX animals with basal aldosterone levels, a high potassium intake increased but did not completely restore the ability to excrete potassium and induced proliferation of the basolateral membrane of principal cells in the collecting tubule (i.e, morphologic adaptation). In contrast, increased aldosterone did not induce functional adaptation. Elevated aldosterone and dietary potassium intake were required to produce functional potassium adaptation indistinguishable from that in potassium-loaded, adrenal-intact animals.

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“…Overall, these findings suggest that extrarenal potassium homeostasis was responsible for the different levels of extracellular potassium between the groups. Some animal and human studies support the role of aldosterone in extrarenal potassium handling through gastrointestinal secretion or transcellular shifts (24)(25)(26)(27), but a trial in anephric patients failed to identify a significant effect of exogenous mineralocorticoid on extracellular potassium (28). Angiotensin II may have varying effects on distal renal potassium channels, but effects of ARB on these channels in other tissues and extrarenal potassium homeostasis are unknown (29).…”

Section: Discussionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.Design, setting, participants, & measurements In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.Results Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P,0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P,0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.Conclusion Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

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An extrarenal mechanism of potassium adaptation

Cited by 137 publications

References 13 publications

Renal adaptation to potassium in the adrenalectomized rabbit. Role of distal tubular sodium-potassium adenosine triphosphatase.

Renal adaptation to potassium in the adrenalectomized rabbit. Role of distal tubular sodium-potassium adenosine triphosphatase.

Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

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