What is the best treatment approach for a patient with hypertension and impaired renal function, as indicated by elevated creatinine and decreased Glomerular Filtration Rate (GFR), but without proteinuria or diabetes?

Management of Hypertension with Impaired Renal Function (Without Proteinuria or Diabetes)

First-Line Antihypertensive Selection

In a hypertensive patient with impaired renal function (eGFR 62 ml/min/1.73m², Stage 2 CKD) but WITHOUT proteinuria or diabetes, you should start with standard antihypertensive therapy rather than mandating ACE inhibitors or ARBs as first-line agents. 1

The key distinction here is the absence of proteinuria—this fundamentally changes your treatment approach:

• ACE inhibitors or ARBs are NOT mandatory first-line therapy when there is no albuminuria, even with reduced eGFR 1
• The KDIGO 2021 Blood Pressure Guideline explicitly states it "may be reasonable" (Practice Point, not a recommendation) to treat patients with CKD and no albuminuria with RASi, but this is optional 1
• Without proteinuria, the primary renoprotective benefit of RAS blockade is lost, as these agents work predominantly by reducing intraglomerular pressure and proteinuria 2, 3

Blood Pressure Target

Target systolic blood pressure <130 mmHg and diastolic <80 mmHg using standardized office measurement. 4

• This target applies to all patients with CKD Stage 2-4, based on cardiovascular and mortality benefits demonstrated in the SPRINT trial 4
• The more aggressive target of <120 mmHg systolic is primarily beneficial in patients with significant proteinuria, which this patient lacks 5

Rational Drug Selection Strategy

Start with any effective antihypertensive class based on comorbidities and tolerability—thiazide-like diuretics, calcium channel blockers, ACE inhibitors, or ARBs are all appropriate initial choices. 1, 4

Practical Algorithm:

1. If blood pressure is ≥150/90 mmHg: Consider initiating two antihypertensive medications simultaneously for more effective control 4

2. Preferred initial combinations:

   • Thiazide-like diuretic (chlorthalidone or indapamide preferred) + calcium channel blocker 4
   • ACE inhibitor or ARB + thiazide-like diuretic 1
   • ACE inhibitor or ARB + calcium channel blocker 2

3. If monotherapy is chosen: Select based on patient-specific factors:

   • Thiazide-like diuretic if volume-dependent hypertension suspected 1
   • Calcium channel blocker (dihydropyridine) for isolated systolic hypertension or elderly patients 2
   • ACE inhibitor or ARB if borderline proteinuria develops or for additional cardiovascular protection 1

Monitoring Requirements

Check serum creatinine and potassium within 2-4 weeks after initiating or uptitrating any RAS blocker (if used). 1, 4

• Accept up to 30% increase in serum creatinine after RAS blocker initiation—this reflects hemodynamic changes, not progressive damage 1, 4
• Stop ACE inhibitor/ARB if creatinine rises >30% or if refractory hyperkalemia develops 1
• Monitor for hyperkalemia risk, especially if combining RAS blockers with other potassium-retaining agents 6

Critical Caveat: When NOT to Use ACE Inhibitors/ARBs

Avoid dual RAS blockade (combining ACE inhibitor + ARB, or adding aliskiren) as this increases risks of hyperkalemia, acute kidney injury, and hypotension without additional benefit. 6

• The VA NEPHRON-D trial demonstrated that combining lisinopril with losartan in diabetic nephropathy increased adverse events without improving outcomes 6
• This prohibition applies even more strongly in non-proteinuric patients where dual blockade has no theoretical benefit 1

Lifestyle Modifications

Restrict dietary sodium to <2 g/day (<90 mmol/day) to enhance antihypertensive medication effectiveness. 1, 4

Additional measures include:

• Weight normalization if BMI >25 4
• Regular physical activity (≥150 minutes/week moderate-intensity) 4
• Smoking cessation 1

Management of Resistant Hypertension

If blood pressure remains uncontrolled on three medications (including a diuretic), add low-dose spironolactone (25-50 mg daily) with careful potassium monitoring. 4, 5

• Mineralocorticoid receptor antagonists are highly effective for resistant hypertension but carry significant hyperkalemia risk with eGFR <60 ml/min/1.73m² 1, 5
• Monitor potassium within 1 week of initiation and regularly thereafter 5

Key Distinction from Proteinuric CKD

The absence of proteinuria in this patient means:

• No mandatory indication for RAS blockade (unlike patients with albuminuria ≥30 mg/g where ACEi/ARB are strongly recommended) 1
• No need for maximum-dose RAS inhibitor titration (which is specifically indicated for antiproteinuric effects) 5
• Primary goal is blood pressure control rather than proteinuria reduction 1, 4

Monitor urine albumin-to-creatinine ratio annually—if proteinuria develops (≥30 mg/g), transition to RAS blocker-based therapy becomes strongly indicated 1, 5