What is the appropriate evaluation and treatment for a 59-year-old with stage 2 hypertension (blood pressure 140‑150/90 mmHg) and an isolated elevated blood urea nitrogen of 34 mg/dL?

Management of Stage 2 Hypertension with Elevated BUN/Creatinine Ratio

Start dual antihypertensive therapy immediately with an ACE inhibitor (or ARB) plus a thiazide-like diuretic, and simultaneously investigate the elevated BUN/creatinine ratio to rule out renal artery stenosis or intrinsic kidney disease. 1

Blood Pressure Classification and Treatment Urgency

• Your patient has stage 2 hypertension (systolic 140-150 mmHg, diastolic ~90 mmHg), which mandates prompt pharmacological intervention within 1 month combined with lifestyle modification. 1
• The 2017 ACC/AHA guidelines explicitly recommend initiating two antihypertensive agents of different classes for stage 2 hypertension, particularly when systolic BP is ≥140 mmHg. 1
• At age 59, this patient requires a target BP <130/80 mmHg (ideally) or at minimum <140/90 mmHg. 1

Evaluation of the Elevated BUN/Creatinine Ratio

The BUN/creatinine ratio of 34 is significantly elevated (normal is 10-20) and requires immediate investigation before attributing hypertension solely to essential causes. 2

Critical Diagnostic Steps:

• Calculate eGFR using the CKD-EPI equation—a serum creatinine alone is insufficient to assess renal function, especially in a 59-year-old who may have reduced muscle mass. 2
• Obtain urinalysis with albumin-to-creatinine ratio to detect proteinuria or hematuria, which would suggest hypertensive nephropathy or primary renal disease. 2
• Check serum electrolytes (sodium, potassium) to screen for hyperaldosteronism or other electrolyte disturbances. 2
• Screen for secondary hypertension given the stage 2 severity: 2
  • Measure aldosterone-renin ratio if hypokalemia is present or BP remains resistant
  • Consider renal artery duplex ultrasound or CT/MR angiography if there are clinical clues (young age, abrupt onset, or worsening renal function)
  • Assess for obstructive sleep apnea if the patient has daytime sleepiness, snoring, or obesity

Interpretation of BUN/Creatinine Ratio:

• A ratio >20 suggests prerenal azotemia (volume depletion, heart failure, renal artery stenosis) or intrinsic renal disease. 2
• In the context of stage 2 hypertension, this could represent:
  • Hypertensive nephrosclerosis (chronic kidney damage from longstanding uncontrolled BP)
  • Renal artery stenosis (especially if BP is difficult to control or there is a sudden rise)
  • Volume depletion (less likely without diuretic use, but consider dietary factors)

Initial Pharmacological Therapy

First-Line Dual Therapy Regimen:

Start lisinopril 10 mg once daily PLUS chlorthalidone 12.5-25 mg once daily. 1, 3, 4, 5

• Lisinopril (ACE inhibitor): 5

  • Provides renin-angiotensin system blockade
  • Offers renal protection if early CKD is present
  • Starting dose: 10 mg once daily, titrate to 20-40 mg as needed
  • Monitor serum potassium and creatinine 2-4 weeks after initiation (risk of hyperkalemia and acute kidney injury, especially with concurrent diuretic use)

• Chlorthalidone (thiazide-like diuretic): 4

  • Superior 24-hour BP control compared to hydrochlorothiazide
  • Starting dose: 12.5-25 mg once daily
  • Maximum dose: 50 mg daily (doses >100 mg rarely add benefit)
  • Addresses volume-dependent hypertension
  • Monitor for hypokalemia, hyperuricemia, and glucose intolerance

Why This Combination?

• The ACE inhibitor + thiazide diuretic combination is guideline-recommended for non-Black patients with stage 2 hypertension. 1, 3
• This regimen targets two complementary mechanisms: renin-angiotensin blockade and volume reduction. 3
• Thiazide diuretics enhance the efficacy of ACE inhibitors and are more affordable than other agents. 1
• Critical caveat: If the patient is Black, consider starting with a calcium channel blocker (amlodipine 5-10 mg) + thiazide diuretic instead, as this combination is more effective in Black populations. 1, 3

Monitoring and Follow-Up

Short-Term (2-4 Weeks):

• Recheck BP to assess response to therapy—aim for at least a 20/10 mmHg reduction initially. 3
• Repeat serum creatinine, eGFR, and potassium to detect any worsening renal function or hyperkalemia from the ACE inhibitor. 1, 2, 5
• Obtain urinalysis with albumin-to-creatinine ratio if not already done. 2
• Confirm medication adherence—non-adherence is the most common cause of apparent treatment resistance. 3, 2

Medium-Term (3 Months):

• Target BP <130/80 mmHg should be achieved within 3 months of therapy initiation. 1, 3
• If BP remains ≥140/90 mmHg despite dual therapy, add a calcium channel blocker (amlodipine 5-10 mg daily) to create guideline-recommended triple therapy. 3, 6
• If BP remains uncontrolled on triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent for resistant hypertension. 3, 6

Long-Term (6-12 Months):

• Monitor for hypertension-mediated organ damage: 2
  • Annual urinalysis and eGFR
  • ECG to detect left ventricular hypertrophy
  • Fundoscopy if BP was ever >180/110 mmHg or if diabetes is present
• Reassess cardiovascular risk using SCORE2 or ACC/AHA Pooled Cohort Equations to guide statin therapy if indicated. 2

Lifestyle Modifications (Adjunctive to Pharmacotherapy)

Lifestyle changes can lower systolic BP by 10-20 mmHg and are mandatory alongside drug therapy. 1, 3, 2

• Sodium restriction to <2 g/day (≈5 g salt)—yields 5-10 mmHg systolic reduction and enhances ACE inhibitor and diuretic efficacy. 3, 2
• DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat)—reduces BP by ~11/5.5 mmHg. 3, 2
• Weight loss if BMI ≥25 kg/m²—losing ~10 kg reduces BP by ~6/4.6 mmHg. 3, 2
• Regular aerobic exercise (≥30 minutes most days, ≈150 minutes/week moderate intensity)—lowers BP by ~4/3 mmHg. 3, 2
• Limit alcohol to ≤2 drinks/day for men, ≤1 drink/day for women. 3, 2

Common Pitfalls to Avoid

• Do not delay treatment intensification when BP remains ≥140/90 mmHg—stage 2 hypertension requires prompt action within 2-4 weeks to reduce cardiovascular risk. 1, 3
• Do not rely on monotherapy dose escalation (e.g., increasing lisinopril to 40 mg before adding a second agent)—combination therapy is more effective than monotherapy dose increases for stage 2 hypertension. 1, 3
• Do not combine an ACE inhibitor with an ARB (dual RAS blockade)—this increases the risk of hyperkalemia and acute kidney injury without additional cardiovascular benefit. 3, 6
• Do not add a beta-blocker as the second or third agent unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation)—beta-blockers are less effective than calcium channel blockers or diuretics for stroke prevention in uncomplicated hypertension. 3, 6
• Do not ignore the elevated BUN/creatinine ratio—this could represent renal artery stenosis, hypertensive nephrosclerosis, or intrinsic kidney disease, all of which require specific management. 2, 7
• Do not assume treatment failure without first confirming adherence and ruling out secondary causes of hypertension (primary aldosteronism, renal artery stenosis, obstructive sleep apnea, medication interference). 3, 2

When to Refer to a Hypertension Specialist

• BP remains ≥160/100 mmHg despite triple therapy at optimal doses (resistant hypertension). 3, 2
• Suspected secondary hypertension (e.g., primary aldosteronism, renal artery stenosis, pheochromocytoma). 2
• Worsening renal function (rising creatinine, declining eGFR) after initiating ACE inhibitor therapy—may indicate bilateral renal artery stenosis. 2, 5
• Multiple drug intolerances or contraindications to standard therapy. 3