What adjustments should be made to the treatment plan for a patient with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), membranous nephropathy, and hypertension, currently on amlodipine, clonidine, and lisinopril, with persistent high blood pressure, and receiving Intravenous Immunoglobulin (IVIG) for CIDP?

Management of Resistant Hypertension in CIDP with Membranous Nephropathy

Add a thiazide-like diuretic (indapamide 2.5 mg or chlorthalidone 12.5-25 mg daily) as your third antihypertensive agent, and uptitrate lisinopril to the maximum tolerated dose while monitoring for hyperkalemia and renal function. 1

Blood Pressure Target and Current Status

• Your patient requires a systolic blood pressure target of <120 mmHg using standardized office measurement, as recommended by KDIGO 2021 guidelines for patients with CKD and proteinuria from membranous nephropathy 1
• The current regimen (amlodipine, clonidine, lisinopril) represents inadequate control and requires intensification 1

Medication Optimization Strategy

First Priority: Maximize ACE Inhibitor Therapy

• Uptitrate lisinopril to maximally tolerated dose (up to 40 mg daily) as first-line therapy for both hypertension and proteinuria in membranous nephropathy 1
• ACE inhibitors should be used at maximum allowed doses in patients with glomerular disease and proteinuria to reduce both blood pressure and protein excretion 1
• Monitor serum creatinine and potassium within 1-2 weeks after dose increases; accept up to 30% rise in creatinine if stable 1

Second Priority: Add Diuretic Therapy

• Add a thiazide-like diuretic as the third agent - either indapamide 2.5 mg daily or chlorthalidone 12.5-25 mg daily 1, 2
• Diuretics are the preferred agents for resistant hypertension in glomerular disease, particularly when combined with ACE inhibitors 1
• If single diuretic is insufficient, add mechanistically different diuretics (loop + thiazide) for synergistic effect 1

Third Priority: Consider Clonidine Replacement

• Clonidine is not a guideline-recommended agent for hypertension in CKD with proteinuria 1, 2
• Consider replacing clonidine with spironolactone 25-50 mg daily if blood pressure remains uncontrolled after adding thiazide diuretic, as spironolactone is particularly effective in resistant hypertension 2
• Use potassium-binding agents (patiromer or sodium zirconium cyclosilicate) if hyperkalemia develops, allowing continuation of RAS blockade 1

Critical Monitoring Parameters

Renal Function and Electrolytes

• Check serum creatinine, potassium, and bicarbonate within 1-2 weeks after any medication adjustment 1, 3
• Monitor for hyperkalemia risk factors: renal insufficiency, diabetes, concomitant potassium-sparing diuretics 3
• Treat metabolic acidosis if serum bicarbonate falls below 22 mmol/L 1
• Do not discontinue ACE inhibitor for creatinine increases up to 30% if stable 1

Volume Status and Blood Pressure

• Counsel patient to hold ACE inhibitor and diuretics during intercurrent illness with risk of volume depletion 1
• Monitor for symptomatic hypotension, particularly in patients receiving IVIG who may have volume shifts 3
• Reassess blood pressure after 2-4 weeks of treatment modification 2

Additional Laboratory Workup

Membranous Nephropathy Monitoring

• Measure anti-PLA2R antibodies to monitor immunologic activity and guide immunosuppressive therapy decisions 4
• Check 24-hour urine protein or spot urine protein-to-creatinine ratio to assess proteinuria severity 1
• Proteinuria >10 g/24 hours is associated with higher risk of progression to end-stage renal disease 5

Thromboembolism Risk Assessment

• Assess albumin level - membranous nephropathy with nephrotic syndrome carries high thromboembolism risk 1
• Consider prophylactic anticoagulation if albumin <2.5 g/dL or proteinuria >10 g/day, weighing bleeding risk 1

Infection Prophylaxis

• Ensure pneumococcal and influenza vaccination given nephrotic syndrome and IVIG therapy 1
• Consider trimethoprim-sulfamethoxazole prophylaxis if patient is on high-dose corticosteroids or other immunosuppression for membranous nephropathy 1

Supportive Care Measures

• Restrict dietary sodium to <2 g/day (<90 mmol/day or <5 g sodium chloride/day) 1
• Initiate statin therapy for dyslipidemia management given cardiovascular risk factors of hypertension and nephrotic syndrome 1
• Counsel on lifestyle modifications including weight management and physical activity as tolerated 1

Common Pitfalls to Avoid

• Do not combine ACE inhibitor with ARB - dual RAS blockade increases risks of hypotension, hyperkalemia, and acute kidney injury without proven benefit 3
• Do not stop ACE inhibitor prematurely for modest creatinine elevation; only discontinue if creatinine continues rising or refractory hyperkalemia develops 1
• Do not use potassium supplements or salt substitutes without careful monitoring given ACE inhibitor use and CKD 3
• Do not overlook IVIG-related volume effects - IVIG can cause volume expansion and may transiently worsen hypertension 3

When to Escalate Care

• Refer to nephrology/hypertension specialist if blood pressure remains ≥160/100 mmHg despite appropriate triple therapy 2
• Consider evaluation for secondary hypertension if resistant to four-drug regimen 2
• Urgent evaluation needed if acute kidney injury develops (>30% creatinine rise) or severe hyperkalemia (>6.0 mEq/L) occurs 1, 3