How to manage a patient with impaired renal function, hyperuricemia, dyslipidemia, well-controlled hypertension, and prediabetes on Lisinopril, metformin, chlorthalidone, and doxazosin?

Management of Declining Renal Function with Multiple Comorbidities

Immediate Medication Optimization

Add an SGLT2 inhibitor immediately as first-line therapy for cardiorenal protection, independent of glycemic control, given the eGFR of 58 mL/min/1.73 m² and prediabetes. 1, 2

• SGLT2 inhibitors provide Grade 1A evidence for cardiorenal protection in patients with CKD and should be prioritized over other glucose-lowering agents, even in prediabetes. 1, 2
• The American Diabetes Association and KDIGO recommend initiating SGLT2 inhibitors when eGFR ≥20-30 mL/min/1.73 m², continuing until dialysis or transplantation. 1
• SGLT2 inhibitors reduce serious hyperkalemia risk (hazard ratio 0.84), which is particularly relevant given this patient's elevated uric acid and thiazide use. 3
• Monitor for volume depletion in the first few weeks, especially given concurrent chlorthalidone use; consider temporarily reducing the diuretic dose. 3, 2
• A modest, reversible eGFR decline (hemodynamic) may occur initially but does not warrant discontinuation, as long-term eGFR preservation is well-documented. 3

Blood Pressure Management Considerations

Continue lisinopril 20 mg daily as the cornerstone of therapy for renal protection, despite the declining eGFR. 3

• ACE inhibitors like lisinopril have superior efficacy on urinary albumin excretion compared to other antihypertensive classes and should be maintained in patients with diabetes/prediabetes and CKD. 3
• No dose adjustment is required for lisinopril when creatinine clearance >30 mL/min (current eGFR 58). 4
• The current BP of 132/80 mmHg is acceptable; the 2017 ACC/AHA guideline supports targets <130/80 mmHg in high-risk patients, which this patient achieves. 3

Reassess the need for chlorthalidone given its contribution to hyperuricemia and the patient's gout history. 3

• While the 2017 ACC/AHA guideline acknowledges thiazides can increase uric acid, insulin resistance, and dyslipidemia, ALLHAT data showed chlorthalidone was unsurpassed in reducing CVD and renal outcomes compared to lisinopril, amlodipine, or doxazosin in patients with metabolic syndrome. 3
• Chlorthalidone caused only small increases in fasting glucose (1.5-4.0 mg/dL) without translating to increased CVD risk long-term. 3
• However, given the elevated uric acid (0.45) and gout history, consider switching to a lower dose (12.5 mg) or substituting with an alternative if BP remains controlled after SGLT2 inhibitor initiation. 3
• The SGLT2 inhibitor may provide additional natriuretic effects, potentially allowing diuretic dose reduction. 3

Consider discontinuing doxazosin based on ALLHAT trial evidence showing inferiority to chlorthalidone. 3, 5

• ALLHAT demonstrated doxazosin doubled the risk of congestive heart failure (RR 2.04) and increased combined CVD events (RR 1.25) compared to chlorthalidone, despite similar blood pressure control. 5
• Doxazosin showed higher stroke risk (RR 1.19) compared to chlorthalidone. 5
• If BP remains controlled on lisinopril and chlorthalidone (or reduced-dose chlorthalidone) plus SGLT2 inhibitor, doxazosin can be safely withdrawn. 3, 5

Lipid Management

Initiate atorvastatin 10-20 mg daily to achieve LDL <1.8 mmol/L given the 14% CVD risk. 1

• Current LDL of 2.1 mmol/L exceeds the target of <1.8 mmol/L for patients with elevated CVD risk. 1
• The National Lipid Association recommends statin therapy for all patients with diabetes/prediabetes and CKD. 1
• Statins are safe and effective across all stages of CKD without dose adjustment at eGFR 58. 1

Glycemic Management

Continue metformin 500 mg twice daily without dose adjustment at current eGFR of 58. 1, 2

• Metformin is safe when eGFR ≥30 mL/min/1.73 m² and should be continued. 1, 2
• Monitor eGFR every 3-6 months given the declining trend; metformin must be discontinued if eGFR falls below 30. 1, 2
• The excellent HbA1c of 46 indicates current therapy is effective. 1

Hyperuricemia Management

Maintain hydration and monitor uric acid; avoid initiating urate-lowering therapy unless symptomatic gout recurs. 3

• The elevated uric acid (0.45) is likely multifactorial: chlorthalidone contribution, declining renal function, and metabolic syndrome. 3
• Asymptomatic hyperuricemia does not require pharmacologic treatment. 3
• SGLT2 inhibitors may modestly reduce uric acid levels through increased urinary excretion. 3

Monitoring Plan

Establish a structured monitoring protocol given the multiple medication changes and declining renal function. 3, 1, 2

• Recheck eGFR, creatinine, potassium, and uric acid in 2-4 weeks after SGLT2 inhibitor initiation. 3, 2
• Monitor for SGLT2 inhibitor adverse effects: volume depletion, genital mycotic infections, and euglycemic DKA (rare). 3, 2
• Recheck lipid panel in 6-8 weeks after statin initiation to assess LDL goal achievement. 1
• Continue eGFR monitoring every 3-6 months given CKD stage G3a. 1, 2
• Monitor BP at each visit; if consistently <120/70 mmHg, consider reducing or discontinuing doxazosin first. 3

Common Pitfalls to Avoid

• Do not discontinue lisinopril due to declining eGFR unless it falls below 30 mL/min/1.73 m² or hyperkalemia develops. The renoprotective benefits outweigh risks at current kidney function. 3, 4
• Do not delay SGLT2 inhibitor initiation despite "prediabetes" label; cardiorenal benefits are independent of glycemic control and apply to patients with prediabetes. 1, 2
• Do not continue metformin if eGFR falls below 30 mL/min/1.73 m²; this is an absolute contraindication due to lactic acidosis risk. 2, 6
• Do not attribute all eGFR decline to medications; the fluctuating pattern (55-66 over time) suggests hemodynamic variability rather than progressive CKD, but continued monitoring is essential. 3, 4
• Do not add potassium supplements or potassium-sparing diuretics given lisinopril use and borderline hyperkalemia risk. 4