How to manage patients with stage 3 hypertension and proteinuria?

Management of Stage 3 Hypertension with Proteinuria

Start an ACE inhibitor or ARB immediately and uptitrate to the maximum tolerated dose, target systolic blood pressure <120 mmHg, and restrict dietary sodium to <2.0 g/day. 1

First-Line Pharmacologic Management

ACE inhibitors or ARBs are mandatory first-line therapy for patients with both hypertension and proteinuria. 1 The key is aggressive uptitration—do not stop at the dose that merely controls blood pressure, but push to the maximum tolerated or FDA-approved daily dose for optimal antiproteinuric effect. 1, 2, 3

• For losartan specifically, uptitrate to 100 mg daily to achieve approximately 30% reduction in proteinuria. 2, 4
• Monitor serum creatinine and potassium within 2-4 weeks after initiation or dose increase. 1, 5, 3
• Continue therapy even if serum creatinine rises up to 30% within 4 weeks of initiation—this modest increase is acceptable and expected. 1, 5
• Stop the ACE inhibitor/ARB only if kidney function continues to worsen beyond 30% or if refractory hyperkalemia develops. 1

Blood Pressure Target

Target systolic blood pressure <120 mmHg using standardized office measurements. 1 This aggressive target is specifically recommended for patients with proteinuria and has been validated in the KDIGO guidelines. 1, 2 In practical terms, achieving 120-130 mmHg is acceptable in most patients with glomerular disease. 1, 2

Dietary Sodium Restriction

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) in all patients. 1, 2, 3 This is not optional—sodium restriction is synergistic with ACE inhibitor/ARB therapy and significantly enhances the antiproteinuric effect. 5, 2 Intensify sodium restriction further in patients who fail to achieve proteinuria reductions despite maximally tolerated medical therapy. 1

Diuretic Therapy

Add diuretics as the preferred second-line agent if blood pressure remains uncontrolled or volume overload is present. 1 Thiazide-like diuretics are preferred over thiazides due to superior cardiovascular outcomes data. 3

• If diuretic response is insufficient, add mechanistically different diuretics (e.g., loop diuretic with thiazide). 1
• Monitor closely for hyponatremia, hypokalemia, GFR reduction, and volume depletion. 1

Management of Hyperkalemia

Use potassium-wasting diuretics and/or potassium-binding agents to reduce serum potassium to normal, allowing continued use of RAS blockade. 1, 5, 2, 3 This strategy is critical—do not discontinue the ACE inhibitor/ARB prematurely due to hyperkalemia when it can be managed with adjunctive therapy. 1, 5

• Treat metabolic acidosis if serum bicarbonate is <22 mmol/l, as this contributes to hyperkalemia. 1

Resistant Proteinuria Management

If proteinuria persists despite maximized ACE inhibitor/ARB and blood pressure control, add a mineralocorticoid receptor antagonist (spironolactone 25-50 mg daily). 1, 2, 3 Monitor potassium carefully when adding this agent. 2, 3

Monitoring Strategy

• Check labs every 2-4 weeks initially: serum creatinine, eGFR, potassium, and urine protein-to-creatinine ratio. 2, 3
• Target proteinuria reduction of ≥25% by 3 months, ≥50% by 6 months. 2
• Ultimate goal: proteinuria <1 g/day or complete clinical response (UPCR <500-700 mg/g by 12 months). 1, 2, 3

Critical Patient Counseling

Counsel patients to hold ACE inhibitor/ARB and diuretics during intercurrent illnesses or when at risk for volume depletion. 1 This is essential to prevent acute kidney injury during sick days. 1

Additional Lifestyle Modifications

• Normalize weight. 1, 2
• Stop smoking. 1, 2
• Exercise regularly. 1, 2

Cardiovascular Risk Management

Consider statin therapy for persistent dyslipidemia, particularly in patients with other cardiovascular risk factors including hypertension. 1, 5, 3 Lifestyle modifications are important in all patients with persistent dyslipidemia and glomerular disease. 1

Common Pitfalls to Avoid

• Do not combine ACE inhibitor with ARB (dual RAAS blockade) unless in young adults with specific glomerular diseases—this increases adverse events without additional benefit in most patients. 1, 5
• Do not start ACE inhibitor/ARB in patients with abrupt onset nephrotic syndrome (e.g., minimal change disease), as these drugs can cause acute kidney injury in this setting. 1, 3
• Do not stop ACE inhibitor/ARB prematurely for modest creatinine increases up to 30%—this is expected and acceptable. 1, 5