Potassium Metabolism in Chronic Kidney Disease

Adaptive increases in renal and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with chronic kidney disease (CKD) as long as the glomerular filtration rate (GFR) remains >15-20mL/min. In these patients K+ balance is maintained by increased K+ secretion per functioning nephron, which is mediated in part by elevated plasma K+ concentration, aldosterone, increased flow rate, and enhanced Na+-K+-ATPase activity. Fecal losses of potassium also increase in CKD patients. These adaptive mechanisms are effective in preventing hyperkalemia, provided that urine output is in excess of 600mL/day. However, limits of adaptation render the CKD patient susceptible to hyperkalemia with even minor perturbations in these factors. Such is the case in patients with diabetes, where decreased mineralocorticoid activity is often an early finding caused by hyporeninemic hypoaldosteronism, or in patients primarily with renal tubular injury, as in tubulointerstitial renal disease. In these settings, hyperkalemia often develops with only mild or moderate reductions in GFR. Once the GFR falls to <15mL/min, an inflection point is reached whereby small incremental losses in renal function require progressively steeper rises in steady state S[K] to maintain total body K+ balance. Certain medications can impair potassium handling and excretion in CKD patients. At this level of renal function the impact of factors known to adversely affect K+ homeostasis is significantly magnified. In clinical practice hyperkalemia is usually the result of a combination of factors superimposed on renal dysfunction.