Potassium Binding for Conservative and Preservative Management of Chronic Kidney Disease

Deborah J. Clegg; Biff F. Palmer

Disclosures

Curr Opin Nephrol Hypertens. 2020;29(1):29-38. 

In This Article

Potassium Homeostasis in Chronic Kidney Disease

Hyperkalemia is uncommon in patients with CKD until the glomerular filtration rate falls below 15–20 ml/min. The ability to maintain a relatively normal plasma K+ concentration despite a significant reduction in renal mass is because of an adaptive increase in the secretory rate of K+ in remaining nephrons.[7] Increased K+ secretion occurs in association with structural changes characterized by cellular hypertrophy, increased mitochondrial density, and proliferation of the basolateral membrane in cells in the distal nephron and principal cells of the collecting duct.[8,9] Additionally, there is an increase in gastrointestinal (primarily in the colon) K+ secretion, which plays a progressively important role in the maintenance of total body K+ content with advancing CKD (Figure 2). Decreased colonic secretion likely explains the development of hyperkalemia reported in anephric dialysis patients following the administration of RAASi.[10]

Figure 2.

Cell model of K+ secretion in the colon demonstrating increased expression of the BK channel in chronic kidney disease. BK, big potassium, also known as Maxi-K+; CLC2, chloride channel protein 2; NKCC, Na+-K+-Cl cotransporter.

Despite adaptations that occur in the kidney and gastrointestinal tract, the ability to further augment K+ secretion is extremely limited in advanced CKD, and hyperkalemia can result from even modest increases in K+ intake and/or use of drugs, such as RAASi blockers. Once the GFR falls to less than 15–20 ml/min steady state plasma K+ concentration rises steeply with each incremental loss in kidney function.[11,12]

Hyperkalemia is also common in kidney transplant patients where tubular injury and/or impaired release of renin along with administration of drugs, such as trimethoprim and RAASi blockers play contributory roles.[13,14] Additionally, calcineurin inhibitors further increase the risk of hyperkalemia in the kidney transplant population again resulting in suboptimal dosing of these critical therapeutics. Calcineurin normally exerts a dephosphorylating effect on the Na+-Cl cotransporter in cells of the initial collecting duct (DCT1). Inhibition of calcineurin leads to unopposed phosphorylation of the co-transporter resulting in increased activity. The reduction in delivery of Na+ and flow to the aldosterone-sensitive distal nephron impairs K+ secretion. The clinical result is development of hyperkalemia and hypertension with decreased circulating levels of renin and aldosterone.

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