We evaluated renal handling and plasma potassium (K) and aldosterone (PA) responses to acute oral K loading in 11 patients with tubulointerstitial renal disease (creatinine clearance 32 +/- 5 ml/min [SE] ) and 13 control subjects (creatinine clearance 123 +/- 5). After 4 days of a 10 mEq Na, 50 mEq K diet, the subjects received 0.5 mEq KCl/kg body weight. Prior to KCl there were no differences between the groups in plasma K or urinary K excretion (UKV). In the 4 hr following KCl, less of the load (13 +/- 4%) was excreted by patients than control subjects (54 +/- 5%; P less than 0.001). Plasma K at 3 hr post KCl, and the amount of retained potassium translocated into the intracellular compartment (patients 14 +/- 3; control subjects 7 +/- 2 mEq; P less than 0.05) were significantly higher in the patients than in control subjects. After KCl, PA levels increased in both groups, and the increments in the patients tended to exceed those of controls; patients with hypoaldosteronism, however, transferred less K into cells and had an even greater impairment of renal K excretion than those with normal baseline PA. The results indicate that the impaired response to an acute oral potassium load in chronic renal failure is related primarily to defective renal rather than extrarenal mechanisms.

The literature regarding the various conditions associated with hyperkalemia and impaired tubular excretion of potassium is confusing. We propose a classification of these disorders based on clinical findings and, when possible, pathophysiology. We suggest the term ‘renal tubular hyperkalemia’ (RTH) to designate these conditions and define RTH as hyperkalemia disproportionate to any decrement in glomerular filtration rate and not due primarily or solely to mineralocorticoid deficiency or the effect of medications impairing either mineralocorticoid action or potassium transport. The classification provides an organizational framework to help the clinician evaluate patients with chronic unexplained hyperkalemia.

Clinically important hyperkalemia occurred in 2 patients receiving a single small dose of potassium chloride by mouth. In spite of normal or near normal renal function, both subjects manifested abnormalities predisposing to impaired potassium homeostasis including hypoaldosteronism, autonomic dysfunction, or diabetes mellitus. It is suggested that in this type of patient the oral dose of potassium be as small as possible, taken with meals or given as a slow-release preparation.

The renin-aldosterone system and tubular responsiveness to exogenous mineralocorticoid administration was evaluated in 2 hyperkalemic patients with obstructive uropathy. Both patients manifested marked renal sodium wasting and a modest inability to lower urine pH despite systemic acidosis. None of the abnormalities was corrected with supraphysiologic doses of mineralocorticoid. In addition, plasma renin and aldosterone levels were inappropriately low. Thus, both hypoaldosteronism and renal tubular resistance to mineralocorticoids coexisted in these patients. It is likely that an association between these abnormalities is more frequent than previously recognized.