How to manage hyperkalemia in a patient with Chronic Kidney Disease (CKD)?

Management of Hyperkalemia in Chronic Kidney Disease

For patients with CKD and hyperkalemia, immediately implement dietary potassium restriction to <3 g/day, review and adjust RAAS inhibitors, and initiate newer potassium binders (patiromer or sodium zirconium cyclosilicate) to maintain target potassium of 4.0-5.0 mEq/L while preserving cardioprotective and renoprotective medications. 1, 2

Immediate Assessment and Risk Stratification

• Obtain an ECG immediately to assess for hyperkalemia-related changes including peaked T waves, widened QRS, or PR prolongation, as these indicate cardiac membrane instability requiring urgent intervention 1
• Patients with CKD stage 4-5 have a broader optimal potassium range (3.3-5.5 mEq/L), but levels >5.5 mEq/L still require intervention to reduce mortality risk 1
• The presence of heart failure, diabetes, or concurrent RAAS inhibitor use dramatically increases mortality risk at elevated potassium levels 1

Dietary Management

Limit dietary potassium to <3 g/day (approximately 77 mEq/day) by restricting high-potassium foods: bananas, oranges, potatoes, tomatoes, processed foods, and salt substitutes. 1, 2

• Refer to a renal dietitian for culturally appropriate dietary counseling, as dietary modification alone may be sufficient for mild cases 3
• Implement an individualized approach that includes dietary and pharmacologic interventions while considering associated comorbidities and quality of life 3
• Provide advice to limit intake of foods rich in bioavailable potassium, particularly processed foods, for CKD G3-G5 patients with history of hyperkalemia 3
• Presoaking root vegetables, including potatoes, effectively lowers potassium content by 50% to 75% 3
• Foods containing <100 mg or <3% daily value are considered low in potassium; foods containing 200-250 mg or >6% daily value are considered high in potassium 3
• Salt substitutes containing potassium may cause life-threatening hyperkalemia and are inappropriate for people who need to limit both salt and potassium 3

Medication Review and Adjustments

If on mineralocorticoid receptor antagonists (MRAs), halve the dose immediately when potassium >5.5 mEq/L (e.g., reduce spironolactone from 50mg to 25mg daily). 1

• Discontinue NSAIDs and COX-2 inhibitors immediately, as these cause sodium retention, worsen renal function, and dramatically increase hyperkalemia risk 1
• Review and eliminate contributing medications including potassium supplements, salt substitutes, and herbal supplements that can raise potassium (alfalfa, dandelion, horsetail, Lily of the Valley, milkweed, and nettle) 3, 2
• For patients with potassium >6.5 mEq/L, discontinue or reduce RAAS inhibitors temporarily 2
• Consider adjustments to diet or concomitant medications to mitigate hyperkalemia before discontinuing RAAS inhibitors 3
• Strategies to achieve normal potassium levels include dietary adjustments, adjusting diuretic doses, and/or utilizing SGLT2 inhibitors 3

Pharmacologic Management with Potassium Binders

Patiromer (Veltassa) is the preferred first-line agent for chronic hyperkalemia in CKD patients requiring continued RAAS inhibitor therapy. 1, 2

• Starting dose: 8.4 g once daily for potassium 5.1-5.5 mEq/L; 16.8 g once daily for potassium 5.5-6.5 mEq/L 2
• Sodium zirconium cyclosilicate (ZS-9/Lokelma) is an alternative with faster onset (~1 hour): starting dose 10 g three times daily for 48 hours, then 5-15 g once daily for maintenance 1, 2
• Administer potassium binders at least 3 hours before or 3 hours after other oral medications; patients with gastroparesis may require 6-hour separation 4
• Sodium polystyrene sulfonate (SPS) should be avoided for chronic management due to limited efficacy data and serious gastrointestinal adverse effects including intestinal necrosis 2, 4
• The availability of newer potassium binders enables optimization of RAAS inhibitor therapy in more patients with hyperkalemia 1

RAAS Inhibitor Optimization

Continue RAAS inhibitors whenever possible in CKD patients with hyperkalemia, as these medications slow CKD progression and improve cardiovascular outcomes. 1, 2

• For patients with potassium 5.0-6.5 mEq/L on RAAS inhibitors, initiate an approved potassium-lowering agent (patiromer or SZC) and maintain RAAS inhibitor therapy unless an alternative treatable cause is identified 2
• For patients with potassium >6.5 mEq/L, discontinue or reduce RAAS inhibitor temporarily, initiate potassium-lowering agent when levels >5.0 mEq/L, and restart RAAS inhibitor at lower dose once potassium <5.0 mEq/L with concurrent potassium binder therapy 2
• The choice of a nonsteroidal MRA should prioritize agents with documented kidney or cardiovascular benefits 3
• Monitor potassium at 1 month after initiation of finerenone and then every 4 months 3

Monitoring Protocol

Recheck potassium and renal function within 72 hours to 1 week after initiating dietary restriction and medication adjustments. 1, 2

• Continue weekly monitoring during dose titration phase until potassium stabilizes in target range of 4.0-5.0 mEq/L 1, 2
• Check potassium at 1-2 weeks after achieving stable dose, at 3 months, then every 6 months thereafter 2
• More frequent monitoring required in patients with heart failure, diabetes, or history of hyperkalemia 2
• Be aware of variability of potassium laboratory measurements as well as factors that may influence potassium measurement including diurnal and seasonal variation, plasma versus serum samples, and medication actions 3

Target Potassium Range

Maintain serum potassium between 4.0-5.0 mEq/L to minimize mortality risk in CKD patients. 1, 2

• Patients with advanced CKD (stage 4-5) have a broader optimal range of 3.3-5.5 mEq/L, but maintaining 4.0-5.0 mEq/L minimizes mortality risk 1, 2

Addressing Non-Dietary Causes

When hyperkalemia persists despite strict adherence to dietary potassium restriction, investigate non-dietary causes including spurious values, hemolysis, metabolic acidosis, other exogenous potassium sources, constipation, inadequate dialysis, and medications. 3

• Renal potassium excretion typically is maintained until GFR decreases to <10-15 mL/min/1.73 m² 3
• Risk of hyperkalemia is increased by urinary obstruction, rhabdomyolysis, hemolysis (blood transfusions and tumor lysis), acidosis, or treatment with potassium-sparing diuretics, ACE inhibitors, or ARBs 3
• Monitor treatment for metabolic acidosis to ensure it does not result in serum bicarbonate concentrations exceeding the upper limit of normal and does not adversely affect BP control, serum potassium, or fluid status 3

Common Pitfalls to Avoid

• Failing to check magnesium levels, as hypomagnesemia can make hyperkalemia resistant to correction 3
• Not addressing metabolic acidosis, which is a major risk factor for hyperkalemia 5
• Discontinuing RAAS inhibitors prematurely without attempting potassium binder therapy first 1, 2
• Using sodium polystyrene sulfonate chronically due to risk of intestinal necrosis 4
• Not separating potassium binder administration from other medications by at least 3 hours 4