What is the best management approach for a female patient with prediabetes, hypertension, hypothyroidism, chronic lymphocytic leukemia (CLL), and hyperlipidemia, who presents with impaired renal function and is currently on lisinopril 10 mg twice a day, with a blood pressure of 148/79 mmHg?

Optimal Management of Uncontrolled Hypertension in CKD Stage 4

This patient requires immediate intensification of her antihypertensive regimen by adding a second agent (loop diuretic or calcium channel blocker) and initiating an SGLT2 inhibitor for renoprotection, with a blood pressure target of <130/80 mmHg. 1

Blood Pressure Target and Current Status

• Target BP is <130/80 mmHg for patients with CKD (eGFR 27.6 = Stage 4), regardless of diabetes status, as this patient has high cardiovascular risk. 1
• Her current BP of 148/79 mmHg exceeds the systolic target by 18 mmHg, indicating inadequate control despite lisinopril 10 mg twice daily. 1
• The 2017 ACC/AHA guidelines specifically state that patients with CKD and hypertension are automatically assigned to high-risk category requiring treatment at BP ≥130/80 mmHg. 1

Immediate Medication Adjustments

Add a Second Antihypertensive Agent

• Add a loop diuretic (furosemide 20-40 mg daily) rather than a thiazide, as thiazide diuretics lose effectiveness when eGFR <30 mL/min/1.73m². 1
• Alternative option: Add a calcium channel blocker (amlodipine 5-10 mg daily) if loop diuretic is contraindicated or not tolerated. 1
• The 2017 ACC/AHA guidelines recommend initiating two antihypertensive agents when BP is >20/10 mmHg above target, which applies to this patient (18 mmHg above systolic target). 1

Continue Current ACE Inhibitor Therapy

• Continue lisinopril at current dose (10 mg twice daily = 20 mg total daily), as ACE inhibitors are first-line for CKD patients and provide renoprotection beyond BP lowering. 1
• The FDA label indicates no dose adjustment is needed for creatinine clearance >30 mL/min, and her eGFR of 27.6 is borderline but still acceptable. 2
• Monitor closely: Check creatinine, eGFR, and potassium within 1-2 weeks after adding the second agent, as combination therapy increases risk of hyperkalemia and acute kidney injury. 1

Critical Addition: SGLT2 Inhibitor for Renoprotection

• Initiate dapagliflozin 10 mg daily or empagliflozin 10 mg daily immediately, even though she has prediabetes (not overt diabetes), as SGLT2 inhibitors are indicated for CKD patients with eGFR ≥20 mL/min/1.73m². 1, 3, 4
• The 2019 ESC guidelines provide Class I, Level B evidence that SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) reduce renal endpoints in patients with eGFR 30 to <90 mL/min/1.73m². 1
• The CREDENCE trial demonstrated 30% relative risk reduction in composite renal outcomes (ESRD, doubling of creatinine, renal/CV death) with canagliflozin in patients with eGFR 30-90 and was stopped early for efficacy. 1
• Expect an initial eGFR dip of 3-5 mL/min within first 4 weeks, which is reversible and does not indicate harm—continue therapy unless eGFR drops >30% or patient becomes symptomatic. 3, 4

Monitoring Protocol

Within 1-2 Weeks After Medication Changes

• Check serum creatinine, eGFR, and potassium to assess for hyperkalemia (target K+ <5.5 mEq/L) and acute kidney injury. 1, 5
• Discontinue or reduce lisinopril dose if potassium >5.5 mEq/L or creatinine increases >30% from baseline. 1, 5
• Assess for volume depletion symptoms (dizziness, orthostatic hypotension) after starting loop diuretic and SGLT2 inhibitor. 3, 2

Monthly Follow-up Until BP Control Achieved

• The 2017 ACC/AHA guidelines recommend monthly evaluation of adherence and therapeutic response until BP target is achieved. 1
• Measure BP at each visit and titrate medications as needed—consider adding a third agent (calcium channel blocker if on loop diuretic, or vice versa) if BP remains >130/80 mmHg after 4 weeks. 1

Every 3 Months Once Stable

• Monitor eGFR, electrolytes, HbA1c (given prediabetes), and lipid panel. 1, 4
• Assess for progression to overt diabetes, as prediabetes with CKD carries high risk. 1

Additional Management Considerations

Lifestyle Modifications

• Sodium restriction to <2000 mg/day (ideally <1500 mg/day) to optimize antihypertensive efficacy and reduce volume overload. 3, 5
• Weight loss targeting BMI <25 (current BMI 27.6) through caloric restriction and aerobic exercise 90-150 minutes/week. 3
• These interventions provide additive BP reductions of 10-20 mmHg and directly slow CKD progression independent of medications. 3, 4

Cardiovascular Risk Reduction

• Initiate statin therapy (atorvastatin 40-80 mg daily) for ASCVD risk reduction, as patients with CKD Stage 4 are automatically high cardiovascular risk. 4, 5
• The 2019 ESC guidelines recommend statin therapy for all patients with CKD and diabetes/prediabetes. 1

Management of Comorbidities

• Continue levothyroxine for hypothyroidism at current dose (not specified but assumed stable). 1
• Monitor CLL status with hematology—elevated WBC (13,100 with 73% lymphocytes) is consistent with stable CLL and does not contraindicate any of the recommended antihypertensive agents. 1
• Optimize hyperlipidemia management with statin as noted above. 1, 4

Common Pitfalls to Avoid

• Do not use thiazide diuretics (hydrochlorothiazide, chlorthalidone) as they are ineffective when eGFR <30 mL/min/1.73m²—use loop diuretics instead. 1
• Do not combine ACE inhibitor with ARB, as this increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit. 1
• Do not delay SGLT2 inhibitor initiation until diabetes develops—the renoprotective benefit is independent of glucose lowering and applies to prediabetes patients. 1, 3
• Do not discontinue lisinopril when adding SGLT2 inhibitor—both provide complementary renal protection through different mechanisms and should be continued together. 1, 4
• Do not withhold SGLT2 inhibitor due to borderline low eGFR (27.6)—guidelines support use down to eGFR 20, and continuation even if eGFR drops below 20 during therapy. 1, 3

Referral Considerations

• Consider nephrology referral given Stage 4 CKD (eGFR 27.6) for co-management, discussion of renal replacement therapy planning, and optimization of CKD-mineral bone disorder management. 1
• Nephrology input is particularly important if BP remains uncontrolled on triple therapy or if eGFR continues to decline despite optimal management. 1