What to do in a patient with Type 2 Diabetes Mellitus (DM-2), chronic kidney disease (CKD), and hypertension (HTN) whose diabetes and hypertension are controlled, already on Angiotensin Receptor Blocker (ARB) and Empagliflozin (Jardiance) with evidence of proteinuria?

Management of Persistent Proteinuria in Controlled DM-II, CKD, and HTN on ARB and SGLT2i

Add a nonsteroidal mineralocorticoid receptor antagonist (finerenone) to your current regimen of ARB and empagliflozin, as this triple therapy provides superior proteinuria reduction compared to dual therapy alone in patients with persistent albuminuria despite standard treatment. 1

Optimize Current Medications First

Before adding new agents, ensure your patient is receiving maximum benefit from existing therapy:

• Uptitrate the ARB to the highest approved tolerated dose if not already maximized, as proven renoprotective benefits were achieved in trials using maximum doses 2
• Accept up to 30% increase in serum creatinine after ARB uptitration—this is an expected hemodynamic effect, not a reason to reduce the dose 2
• Continue empagliflozin even if eGFR falls below 20 ml/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 2
• Monitor serum creatinine, potassium, and blood pressure within 2-4 weeks after any dose adjustment 2

Add Finerenone for Persistent Proteinuria

The KDIGO 2024 guidelines suggest adding a nonsteroidal MRA (finerenone) for adults with type 2 diabetes, eGFR >25 ml/min/1.73 m², normal serum potassium, and albuminuria >30 mg/g despite maximum tolerated RAS inhibitor dose (Grade 2A). 2

The evidence supporting this recommendation is compelling:

• The recent CONFIDENCE trial (2025) demonstrated that combination therapy with finerenone plus empagliflozin reduced albuminuria 32% more than empagliflozin alone and 29% more than finerenone alone in patients already on RAS blockade 1
• Finerenone can be safely added to ARB plus SGLT2i therapy without unexpected adverse events 2, 1
• This triple therapy is most appropriate for patients at high risk of CKD progression, as demonstrated by persistent albuminuria despite standard-of-care therapies 2

Dosing: Start finerenone 10 mg daily if eGFR 25-60 ml/min/1.73 m² or 20 mg daily if eGFR >60 ml/min/1.73 m² 1

Critical Monitoring for Hyperkalemia

To mitigate hyperkalemia risk with triple therapy:

• Select patients with consistently normal potassium levels before initiating finerenone 2
• Check potassium within 4 weeks of starting finerenone, then regularly thereafter 2
• Manage hyperkalemia with potassium-lowering measures rather than immediately stopping medications: use potassium-wasting diuretics, potassium binders, moderate dietary potassium intake, or treat metabolic acidosis with sodium bicarbonate if serum bicarbonate <22 mmol/L 2
• Reduce or discontinue finerenone only as a last resort if hyperkalemia remains refractory despite these interventions 2

Intensify Blood Pressure Control

Even though hypertension is "controlled," target systolic blood pressure <120 mmHg using standardized office measurement in patients with CKD and albuminuria, as lower targets provide additional renoprotection beyond antiproteinuric effects alone 2, 3

If additional blood pressure lowering is needed:

• Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) as these enhance antiproteinuric effects of RAS blockade 3, 4
• Consider adding a dihydropyridine calcium channel blocker if further blood pressure reduction is required 2

Mandate Dietary Sodium Restriction

Restrict dietary sodium to <2.0 g/day (<90 mmol/day or <5 g sodium chloride/day), as sodium restriction synergistically enhances the antiproteinuric effects of ARBs and is as important as medication optimization 2, 3, 4, 5

This intervention is often overlooked but critical—intensify dietary sodium restriction in patients who fail to achieve proteinuria reductions despite maximally tolerated medical therapy 2

Additional Lifestyle Modifications

• Achieve weight normalization through diet and exercise, as obesity independently worsens proteinuria 3
• Counsel smoking cessation if applicable 2
• Counsel the patient to temporarily hold ARB, empagliflozin, and finerenone during intercurrent illnesses with risk of volume depletion (diarrhea, vomiting, excessive sweating) to prevent acute kidney injury 2, 4

Monitoring Parameters and Goals

• Monitor urine albumin-to-creatinine ratio every 3-6 months, aiming for reduction to <300 mg/g or at least 30-50% reduction from baseline 3, 4
• Check serum creatinine, eGFR, and potassium within 2-4 weeks after adding finerenone, then regularly 2
• Continue all three agents (ARB, empagliflozin, finerenone) even if eGFR falls below 30 ml/min/1.73 m², unless refractory hyperkalemia or symptomatic hypotension develops 2

Common Pitfalls to Avoid

• Do not discontinue ARB prematurely due to modest creatinine elevation (<30% increase), as this removes critical renoprotection 2
• Do not add an ACE inhibitor to the ARB—combination ACEi/ARB therapy is harmful and explicitly contraindicated in CKD patients with or without diabetes (Grade 1B) 2, 4
• Do not withhold finerenone solely due to fear of hyperkalemia in patients with normal baseline potassium—proactive potassium management allows continuation of renoprotective therapy 2