How to manage a patient with hyperkalemia, impaired renal function, and poor diabetes control, presenting with dry eyes and mouth, on Empagliflozin (Empagliflozin) and Sitagliptin (Sitagliptin), Apixaban (Apixaban), and Clopidogrel (Clopidogrel)?

Management of Hyperkalemia, Impaired Renal Function, and Poor Glycemic Control with Sicca Symptoms

Stop empagliflozin immediately and address the dry eyes/mouth as likely Sjögren's syndrome or another autoimmune condition requiring urgent evaluation, while simultaneously managing the hyperkalemia with dietary restriction and close monitoring. 1

Immediate Assessment and Sicca Syndrome Evaluation

Your patient presents with a constellation of concerning findings: potassium 5.5 mEq/L, eGFR 54 mL/min (stage 3a CKD), HbA1c 93 mmol/mol (10.7%), and new-onset dry eyes/mouth on empagliflozin. The dry eyes and mouth are NOT typical side effects of empagliflozin or sitagliptin and warrant immediate investigation for Sjögren's syndrome or other autoimmune conditions. 1

• Check anti-SSA/Ro and anti-SSB/La antibodies, ANA, rheumatoid factor, and consider Schirmer test and salivary gland biopsy 1
• Evaluate for other autoimmune manifestations (joint pain, rash, fatigue) that may indicate systemic disease 1
• Discontinue empagliflozin immediately as SGLT2 inhibitors can exacerbate volume depletion and electrolyte abnormalities in patients with underlying autoimmune conditions 2, 3

Hyperkalemia Management in Stage 3a CKD

At potassium 5.5 mEq/L with eGFR 54 mL/min, this patient sits at the upper limit of the optimal range for stage 3 CKD (3.5-5.0 mEq/L for stage 1-2, but broader tolerance 3.3-5.5 mEq/L for stage 4-5). 4 However, given multiple risk factors (CKD, diabetes, likely on RAAS inhibitors given apixaban/clopidogrel suggesting cardiovascular disease), this potassium level requires intervention. 4

Medication Review and Adjustment

Do NOT discontinue any RAAS inhibitors if present—these provide mortality benefit in cardiovascular and renal disease. 1 Instead:

• Review for contributing medications: NSAIDs, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes 4
• Apixaban and clopidogrel suggest significant cardiovascular disease (likely prior MI, stroke, or atrial fibrillation), making RAAS inhibitor continuation critical 5
• Consider adding a loop diuretic (furosemide 40-80 mg daily) to increase urinary potassium excretion if adequate renal function present 1

Dietary Potassium Restriction

• Limit high-potassium foods: bananas, oranges, potatoes, tomatoes, processed foods 1
• Avoid salt substitutes containing potassium 1
• Evidence linking dietary potassium to serum levels is limited, but restriction remains prudent in this context 1

Potassium Binder Therapy

For potassium 5.0-6.5 mEq/L in patients on RAAS inhibitors, initiate an approved potassium-lowering agent while maintaining RAAS inhibitor therapy. 1

• Patiromer (Veltassa): Start 8.4 g once daily with food, titrate up to 25.2 g daily based on potassium levels; onset ~7 hours 1
• Sodium zirconium cyclosilicate (SZC/Lokelma): 10 g three times daily for 48 hours, then 5-15 g once daily for maintenance; onset ~1 hour 1
• Avoid sodium polystyrene sulfonate (Kayexalate) due to delayed onset, risk of bowel necrosis, and limited efficacy data 1

Diabetes Management After Stopping Empagliflozin

With HbA1c 93 mmol/mol (10.7%) and discontinuation of empagliflozin, glycemic control will worsen. Continue sitagliptin and intensify therapy:

• Sitagliptin is safe in stage 3a CKD (eGFR 54) and does not cause hyperkalemia 2
• Add basal insulin (e.g., insulin glargine 10 units at bedtime, titrate by 2 units every 3 days to fasting glucose 5-7 mmol/L) 1
• Alternatively, consider GLP-1 receptor agonist (e.g., semaglutide) for cardiovascular benefit, though monitor volume status given sicca symptoms 3
• Do NOT restart empagliflozin until sicca syndrome is fully evaluated and potassium is consistently <5.0 mEq/L 2, 3

Monitoring Protocol

Check potassium and renal function within 1 week of stopping empagliflozin and initiating potassium binder therapy. 1

• Weekly monitoring during dose titration phase 1
• Recheck at 1-2 weeks after achieving stable dose 1
• Then at 3 months, then every 6 months thereafter 1
• More frequent monitoring required given multiple comorbidities (CKD, diabetes, cardiovascular disease) 1

Critical Pitfalls to Avoid

• Do NOT ignore the sicca symptoms—these are NOT side effects of empagliflozin/sitagliptin and require urgent rheumatologic evaluation 1
• Do NOT discontinue RAAS inhibitors (if present) to manage hyperkalemia—use potassium binders instead 1
• Do NOT restart empagliflozin without addressing the underlying cause of sicca symptoms and stabilizing potassium 2, 3
• Do NOT use sodium bicarbonate unless metabolic acidosis is documented (pH <7.35, bicarbonate <22 mEq/L) 1
• Do NOT rely solely on dietary restriction—potassium binders are necessary at this level with multiple risk factors 1

Team Approach

Optimal management requires coordination between primary care, nephrology, rheumatology, and endocrinology. 1

• Nephrology: Manage hyperkalemia and CKD progression 1
• Rheumatology: Evaluate and treat sicca syndrome/autoimmune disease 1
• Endocrinology: Optimize diabetes control after stopping empagliflozin 1
• Ophthalmology: Assess dry eyes and initiate artificial tears/cyclosporine drops 1