What is the optimal treatment plan for a female patient with incidentally detected hypertension, overt hypothyroidism (TSH 12 mIU/L), chronic kidney disease with proteinuria (UPCR 1.4), low potassium (3.3 mmol/L), mild concentric left‑ventricular hypertrophy and diastolic dysfunction, and no edema?

Optimal Treatment Plan for Hypertension with CKD, Hypothyroidism, and Proteinuria

This patient requires immediate thyroid hormone replacement with levothyroxine, aggressive blood pressure control targeting <130/80 mmHg using an ACE inhibitor or ARB as first-line therapy, potassium supplementation, and sodium restriction to <2 g/day. The hypothyroidism is likely contributing significantly to both the hypertension and the worsening renal function, and correction of the thyroid disorder should substantially reduce blood pressure, especially in younger patients. 1

Priority 1: Thyroid Hormone Replacement

Start levothyroxine immediately for the overt hypothyroidism (TSH 12 mIU/L). Correction of hypothyroidism typically results in substantial reduction in both systolic and diastolic blood pressure, and may improve the elevated creatinine and proteinuria. 1, 2 Hypothyroidism directly affects kidney function through hemodynamic alterations and can cause increased serum creatinine with reduced GFR; treatment often leads to normalization of GFR. 2, 3

• Initiate levothyroxine at an appropriate dose based on age and cardiovascular status, typically 1.6 mcg/kg/day for younger patients without cardiac disease, or 25-50 mcg/day if older or with cardiac concerns. 1
• Recheck TSH and free T4 in 6-8 weeks and adjust the dose to achieve euthyroidism before finalizing the antihypertensive regimen, as blood pressure may improve significantly with thyroid correction alone. 1, 2

Priority 2: Blood Pressure Management

Target Blood Pressure

Target blood pressure <130/80 mmHg given the presence of significant proteinuria (UPCR 1.42 g/g). 4, 5 This patient has CKD stage 3a (creatinine 1.45, estimated eGFR ~40-50 based on context) with overt proteinuria exceeding 1 g/day, which mandates aggressive blood pressure control. 5, 6

First-Line Antihypertensive Therapy

Initiate an ACE inhibitor (such as lisinopril 10 mg daily) or ARB (if ACE inhibitor not tolerated) immediately. 4, 5, 7 ACE inhibitors are strongly recommended for CKD stage 3 with albuminuria ≥300 mg/day. 5, 7, 6

• Titrate the ACE inhibitor to the maximum approved dose that is tolerated (lisinopril up to 40 mg daily) to achieve maximum renoprotective benefits. 5, 7, 6
• Check serum creatinine and potassium 2-4 weeks after starting or increasing the ACE inhibitor dose. 5, 7
• Continue the ACE inhibitor unless serum creatinine rises >30% within 4 weeks; a rise up to 30% is expected and reflects the intended hemodynamic effect. 5, 6

Second-Line Therapy

Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily preferred over hydrochlorothiazide) if blood pressure remains >130/80 mmHg after maximizing ACE inhibitor dose. 4, 5, 7 Thiazide-like diuretics provide superior cardiovascular event reduction compared to other second-line agents. 7

• A single-pill fixed-dose combination of ACE inhibitor plus thiazide diuretic is strongly recommended to improve adherence. 7
• Thiazide diuretics will also help correct the hypokalemia (K 3.34 mmol/L) through potassium-sparing effects when combined with ACE inhibitor therapy. 4

Third-Line Therapy

If blood pressure remains uncontrolled on ACE inhibitor plus thiazide diuretic, add a long-acting dihydropyridine calcium channel blocker (amlodipine 5-10 mg daily). 4, 5, 7 Most CKD patients with proteinuria require three or more antihypertensive agents to achieve target blood pressure. 5, 7

Critical Contraindication

Never combine an ACE inhibitor with an ARB (dual RAS blockade), as this increases the risk of hyperkalemia, hypotension, and acute kidney injury without added benefit. 4, 5, 7

Priority 3: Potassium Supplementation

Initiate potassium supplementation (potassium chloride 20-40 mEq daily) to correct the hypokalemia (K 3.34 mmol/L, previously 2.9 mmol/L). 4 The low potassium may be contributing to the hypertension and must be corrected.

• Increase dietary potassium intake to 3500-5000 mg/day through fruits and vegetables. 4
• Recheck serum potassium 2-4 weeks after starting ACE inhibitor and potassium supplementation, as ACE inhibitors raise potassium levels. 5, 7
• Adjust potassium supplementation based on follow-up levels; the ACE inhibitor may provide sufficient potassium retention once at therapeutic doses. 5

Priority 4: Lifestyle Modifications

Restrict dietary sodium to <2 g/day (<5 g salt), as this is critical for blood pressure control and enhances the antiproteinuric effects of ACE inhibitor therapy in patients with proteinuria. 4, 5, 6

Restrict protein intake to 0.8 g/kg/day given CKD stage 3 (eGFR ~40-50). 4, 5 Avoid high-protein diets >1.3 g/kg/day. 4, 5

Encourage weight loss if overweight (target at least 1 kg reduction), moderate-intensity physical activity 90-150 minutes per week, and alcohol moderation (≤1 drink per day for women). 4, 5

Implement a DASH-like diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated and total fat. 4

Priority 5: Monitoring Protocol

Schedule clinic visits every 6-8 weeks until blood pressure target <130/80 mmHg is achieved. 5, 7

Check basic metabolic panel (serum creatinine, potassium, bicarbonate) 2-4 weeks after each medication adjustment. 5, 7

Implement home blood pressure monitoring during medication titration to prevent hypotension (systolic <110 mmHg). 5

Once blood pressure is controlled, follow up every 3-6 months with monitoring of serum creatinine, eGFR, potassium, and urine albumin-to-creatinine ratio. 5, 7

Reassess TSH and free T4 every 6-8 weeks until euthyroid, then annually. 1, 2

Priority 6: Management of Left Ventricular Hypertrophy and Diastolic Dysfunction

The mild concentric LVH and stage 2 diastolic dysfunction are consequences of chronic hypertension and will improve with aggressive blood pressure control and correction of hypothyroidism. 4, 1 No specific additional therapy is required beyond optimal blood pressure management. 4

The mild pulmonary hypertension (TR Vmax PG 28.47 mmHg) is likely secondary to diastolic dysfunction and will also improve with blood pressure control. 4

Priority 7: Patient Education (Sick-Day Management)

Instruct the patient to hold or reduce antihypertensive doses during acute illnesses with vomiting, diarrhea, or reduced oral intake to prevent volume depletion and acute kidney injury. 5, 7

Teach the patient to watch for symptoms of hypotension such as fatigue, light-headedness, or dizziness. 5, 7

Expected Outcomes and Treatment Goals

Evidence of proteinuria improvement should be apparent by 3 months, with at least 50% reduction by 6 months. 6 Target UPCR <500-700 mg/g by 12 months. 6

Correction of hypothyroidism should result in substantial blood pressure reduction within 2-3 months, potentially reducing the number of antihypertensive medications required. 1, 2

Aggressive blood pressure control to <130/80 mmHg will slow progression of CKD and reduce cardiovascular risk. 4, 5, 7

Common Pitfalls to Avoid

Do not delay thyroid hormone replacement; hypothyroidism is directly contributing to both hypertension and renal dysfunction. 1, 2, 3

Do not discontinue the ACE inhibitor for a creatinine rise <30%; this reflects the intended hemodynamic effect. 5, 6

Do not accept a blood pressure of <140/90 mmHg as adequate; this patient requires <130/80 mmHg given the proteinuria. 5, 7

Do not use beta-blockers as first-line therapy; they are not indicated unless there are compelling indications such as coronary artery disease or heart failure. 4, 7

Inadequate diuretic dosing leads to fluid retention and poor blood pressure control, while excessive dosing causes volume contraction and worsening renal function. 7