RENAL MECHANISMS OF K DEPLETION IN METABOLIC ACIDOSIS

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The purpose of the proposed studies is to determine the role of aldosterone in the maintenance of potassium (K) depletion during chronic metabolic acidosis (CMA). Hypokalemia and K depletion are common findings both in clinical and experimental CMA. In K depletion induced by dietary K restriction, we have demonstrated a renal adaptation for K conservation using isolated perfused kidneys from rats. However, the adaptation for K conservation was not functioning when kidneys from rats with K depletion secondary to CMA were perfused at normal pH. This lack of K conservation in vitro could not be attributed to increased sodium excretion although an increase in sodium excretion and urine flow are likely the etiologies of the initial K loss which occurs in early CMA. Aldosterone levels are likely increased during CMA and this hormone is a potent stimulus of K secretion. In the present study, adrenalectomized (ADX) rats will be rendered acidotic while receiving dexamethasone and low or high doses of aldosterone replacement or no aldosterone replacement. The degree of K depletion and acidosis will be assessed in balance studies. Kidneys, from ADX rats replaced with aldosterone during CMA, will be perfused at normal pH. If an elevation in aldosterone mediates K loss during CMA, kidneys from acidosis rats on low aldosterone replacement should react normally to K depletion and conserve K. These studies will provide further understanding in renal handling of K and factors regulating K conservation.