How to manage an elderly patient with type 2 diabetes (T2D) and hypertension, impaired renal function, and elevated blood pressure despite being on amlodipine, valsartan, and furosemide, with current medications including gluconorm (gliclazide), dapagliflozin, and metformin?

Management of Uncontrolled Hypertension in Elderly Patient with T2D and CKD

Immediate Blood Pressure Management Priority

Add spironolactone 25mg daily as the fourth antihypertensive agent, as this patient has resistant hypertension (SBP 169 mmHg despite triple therapy with amlodipine, valsartan, and furosemide) and spironolactone is the evidence-based fourth-line agent. 1

Rationale for Spironolactone Addition

• The 2024 ESC guidelines explicitly recommend spironolactone as the preferred fourth-line agent when BP remains uncontrolled on a three-drug combination of RAS blocker + calcium channel blocker + diuretic 1
• This patient meets criteria for resistant hypertension: BP ≥140/90 mmHg despite adherence to three antihypertensive medications including appropriate doses of a calcium channel blocker (amlodipine), ARB (valsartan), and diuretic (furosemide) 2
• The PATHWAY-2 trial demonstrated spironolactone's superiority as fourth-line therapy for resistant hypertension 2

Critical Monitoring Requirements with Spironolactone

• Check serum potassium and creatinine within 1-2 weeks after initiating spironolactone, then monthly for 3 months, as the combination of ARB + spironolactone significantly increases hyperkalemia risk 1, 2
• Hold spironolactone if potassium rises above 5.5 mmol/L or if creatinine increases significantly 2
• Start with spironolactone 25mg daily; can increase to 50mg if BP remains uncontrolled and potassium remains safe 1

Alternative Fourth-Line Agents if Spironolactone Not Tolerated

• If spironolactone causes hyperkalemia or is not tolerated, consider amiloride, doxazosin, eplerenone, clonidine, or beta-blocker as alternatives 1
• Beta-blockers should only be added if there are compelling indications (angina, post-MI, heart failure, or rate control needs) 1

Blood Pressure Target for This Patient

• Target systolic BP 120-129 mmHg given this patient has both diabetes and CKD with eGFR 35-55 mL/min/1.73 m² 1
• The 2024 ESC guidelines specifically recommend this intensive target for patients with diabetes receiving BP-lowering drugs, if tolerated 1
• For patients with moderate-to-severe CKD and eGFR >30 mL/min/1.73 m², the same 120-129 mmHg systolic target applies 1

Diabetes Medication Optimization

Continue Dapagliflozin - Critical for Cardiorenal Protection

• Continue dapagliflozin 10mg daily as it provides cardiovascular and renal protection independent of glycemic control, which is essential given this patient's CKD and cardiovascular risk 1
• SGLT2 inhibitors are specifically recommended in hypertensive patients with CKD and eGFR >20 mL/min/1.73 m² to improve outcomes in the context of their modest BP-lowering properties 1
• Dapagliflozin reduces risk of hospitalization for heart failure in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors 3
• The patient's eGFR of 35-55 mL/min/1.73 m² is above the 20 mL/min/1.73 m² threshold where dapagliflozin remains indicated for CKD protection 1, 3

Reassess Metformin Safety

• Consider reducing metformin dose or discontinuing it entirely, as the patient's eGFR of 35-55 mL/min/1.73 m² approaches the safety threshold and increases lactic acidosis risk 4
• Metformin is contraindicated with eGFR <30 mL/min/1.73 m², and initiation is not recommended with eGFR 30-45 mL/min/1.73 m² 4
• If eGFR falls below 45 mL/min/1.73 m², assess benefit-risk of continuing metformin 4
• Monitor eGFR at least every 3-6 months given borderline renal function and elderly status 4

Gliclazide (Gluconorm) Considerations

• Continue gliclazide but monitor closely for hypoglycemia, especially if adding spironolactone causes any hemodynamic changes 1
• With A1C 7.4%, glycemic control is reasonable, so aggressive intensification is not needed 1

Renal Function Monitoring Strategy

SGLT2 Inhibitor Effects on eGFR

• Expect a small transient reduction in eGFR (typically 5-10 mL/min) within the first 1-4 weeks of dapagliflozin therapy, which represents hemodynamic adjustment rather than kidney injury 5, 6, 7
• This initial eGFR decline is due to post-glomerular vasodilation and reduced glomerular hyperfiltration, which is actually renoprotective long-term 6
• eGFR typically returns toward baseline by 24 weeks and remains stable with continued therapy 7
• Do not discontinue dapagliflozin for this expected initial eGFR dip unless eGFR falls below 20 mL/min/1.73 m² 1, 3

Monitoring Schedule

• Check eGFR, creatinine, and potassium 1-2 weeks after adding spironolactone 1, 2
• Recheck these parameters monthly for first 3 months, then every 3-6 months thereafter 4, 2
• More frequent monitoring warranted given elderly status, CKD, and multiple medications affecting renal function 4

Albuminuria Management

• The urine ACR of 49.29 mg/mmol (approximately 435 mg/g) indicates moderately increased albuminuria 1
• The current regimen of ARB (valsartan) + SGLT2 inhibitor (dapagliflozin) provides optimal antiproteinuric therapy 1
• Recheck urine ACR in 3-6 months to assess response to therapy 1

Volume Status Assessment

• Before adding spironolactone, assess for volume depletion, as elderly patients on triple therapy including furosemide are at higher risk 1, 3
• Check orthostatic vital signs: measure BP after 5 minutes sitting/lying, then 1 and 3 minutes after standing 1
• If orthostatic hypotension present (SBP drop ≥20 mmHg or DBP drop ≥10 mmHg), address volume status before intensifying BP therapy 1
• Consider whether furosemide dose can be optimized or if switching to a thiazide-like diuretic (chlorthalidone or indapamide) would be more appropriate for hypertension management 1, 8

Lifestyle Modifications to Reinforce

• Sodium restriction to <2g/day (5g salt/day) provides additive BP reduction of 5-10 mmHg 1, 2
• Weight loss if overweight (target BMI 20-25 kg/m²) 1
• Regular aerobic exercise as tolerated 1
• Alcohol limitation to <100g/week 1
• These lifestyle measures are particularly important in resistant hypertension and can reduce need for additional medications 2, 8

Medication Adherence Verification

• Confirm medication adherence before labeling as resistant hypertension, as non-adherence is the most common cause of apparent treatment resistance 9, 2
• Consider pill counts, pharmacy refill records, or directly observed therapy if adherence uncertain 2
• Simplify regimen with single-pill combinations where possible to improve adherence 1

When to Refer to Hypertension Specialist

• If BP remains ≥160/100 mmHg despite four-drug therapy at optimal doses 1
• If multiple drug intolerances occur 9
• If secondary hypertension suspected (sudden onset, young age, resistant to therapy, hypokalemia) 1, 2
• If eGFR continues to decline despite optimization 1

Critical Pitfalls to Avoid

• Do not combine two RAS blockers (ACE inhibitor + ARB) - this increases adverse events without benefit 1
• Do not add beta-blocker as fourth agent unless compelling indication exists (angina, post-MI, heart failure, rate control) 1
• Do not discontinue dapagliflozin for initial eGFR dip - this is expected hemodynamic effect, not kidney injury 6, 7
• Do not ignore hyperkalemia risk with ARB + spironolactone combination - monitor potassium closely 1, 2
• Do not continue metformin without regular eGFR monitoring given borderline renal function 4