Management of Severe Hypertension with Nephrotic-Range Proteinuria
This patient requires immediate aggressive blood pressure control with intravenous antihypertensives to prevent end-organ damage, followed by initiation of maximally-dosed ACE inhibitor or ARB therapy once blood pressure is stabilized, combined with loop diuretics for volume management and strict sodium restriction.
Immediate Management of Hypertensive Emergency
Blood pressure 223/134 mmHg constitutes a hypertensive emergency requiring immediate reduction to prevent stroke, myocardial infarction, and progressive renal injury 1.
Initiate intravenous antihypertensive therapy (labetalol, nicardipine, or clevidipine) to reduce blood pressure by approximately 20-25% within the first hour, avoiding precipitous drops that could compromise renal perfusion 1.
Target systolic blood pressure should ultimately be <120 mmHg using standardized office measurement in patients with glomerular disease and proteinuria 1.
Critical Caveat Before Starting ACE Inhibitor/ARB
Do NOT immediately start ACE inhibitor or ARB if this represents abrupt onset nephrotic syndrome, particularly if minimal change disease is suspected, as these drugs can cause acute kidney injury in this setting 1.
However, given the documented history of proteinuria >3 g/dL previously, this likely represents chronic glomerular disease rather than abrupt onset, making ACE inhibitor/ARB appropriate once blood pressure is controlled 2.
Transition to Long-Term Renin-Angiotensin System Blockade
Once blood pressure is stabilized, initiate ACE inhibitor or ARB and uptitrate to maximally tolerated or FDA-approved dose (not just to blood pressure control), as this provides blood pressure-independent antiproteinuric effects 1, 2, 3.
The goal is dual: achieve systolic blood pressure <120 mmHg AND reduce proteinuria to <1 g/day 1, 2, 3.
Accept up to 30% increase in serum creatinine after starting ACE inhibitor/ARB, which represents expected hemodynamic changes and is not a reason to discontinue therapy 1, 2.
Only stop ACE inhibitor/ARB if kidney function continues to worsen beyond 30% increase or refractory hyperkalemia develops 1.
Essential Adjunctive Diuretic Therapy
Initiate loop diuretics (furosemide or bumetanide) for volume management, as nephrotic-range proteinuria typically causes significant edema and volume overload 1.
Loop diuretics can be given as bolus or continuous infusion; consider combination with intravenous albumin in diuretic-resistant cases 1.
For persistent volume overload despite loop diuretics, add thiazide-like diuretic (chlorthalidone or indapamide) for synergistic effect 3, 4.
Mandatory Lifestyle Modifications
Restrict dietary sodium to <2.0 g/day (<90 mmol/day), which is non-negotiable and enhances the antiproteinuric effect of ACE inhibitor/ARB therapy 1, 2, 3, 4.
Implement weight normalization through diet and exercise if overweight, smoking cessation, and regular physical activity 1.
Add-On Therapy for Resistant Proteinuria
If proteinuria remains elevated despite maximized ACE inhibitor/ARB and diuretic therapy, consider adding low-dose spironolactone (25-50 mg daily) or eplerenone with careful potassium monitoring 1, 3, 4.
If the patient has diabetes, add SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin) regardless of glycemic control for additive renoprotection 3, 4.
Critical Monitoring Parameters
Check serum creatinine, eGFR, potassium, and urine protein-to-creatinine ratio every 2-4 weeks initially 2, 3.
Target proteinuria reduction of ≥25% by 3 months and ≥50% by 6 months, aiming for absolute proteinuria <1 g/day 3.
Monitor for hyperkalemia, particularly when combining ACE inhibitor/ARB with spironolactone; use potassium-wasting diuretics or potassium-binding agents as needed 1.
Additional Cardiovascular Risk Management
Consider statin therapy for persistent dyslipidemia, particularly given the cardiovascular risk factors of hypertension and nephrotic syndrome 1, 3.
Assess for diabetes if not already done, as diabetic nephropathy is a common cause of nephrotic-range proteinuria 5.
Common Pitfalls to Avoid
Do not discontinue ACE inhibitor/ARB prematurely due to modest creatinine elevation, as this removes critical renoprotection 1, 2.
Do not combine ACE inhibitor with ARB, as this increases adverse effects without additional benefit in most patients 1.
Counsel patient to hold ACE inhibitor/ARB and diuretics during intercurrent illnesses with risk of volume depletion (sick day rules) 1, 2.
Avoid precipitous blood pressure reduction that could compromise renal perfusion and worsen kidney function 1.
Underlying Etiology Considerations
Given the history of nephrotic-range proteinuria and severe hypertension, consider renal biopsy if not previously performed to establish the underlying glomerular disease and guide immunosuppressive therapy if indicated 1.
Proteinuria >3 g/dL with severe hypertension may represent hypertensive nephrosclerosis, diabetic nephropathy, focal segmental glomerulosclerosis, or other glomerular diseases 6, 7.