What is the management plan for an adult patient with impaired renal function, proteinuria, and a history of hypertension or diabetes?

Management of Proteinuria in Adults with Impaired Renal Function and Hypertension or Diabetes

Start an ACE inhibitor or ARB immediately and uptitrate to the maximum tolerated dose, regardless of current blood pressure, as first-line therapy for any adult with proteinuria and impaired renal function. 1, 2

Initial Pharmacologic Intervention

• Initiate ACE inhibitor or ARB as first-line therapy for all patients with proteinuria ≥1 g/day, even if blood pressure is normal 2
• For proteinuria between 0.5-1 g/day, strongly consider starting ACE inhibitor or ARB therapy 2
• Uptitrate to maximum tolerated dose, not just to blood pressure control—the goal is proteinuria reduction, not merely BP normalization 1, 2

Critical Exception - When NOT to Start ACE Inhibitor/ARB

• Do not initiate ACE inhibitor or ARB in patients presenting with abrupt onset nephrotic syndrome, particularly if minimal change disease is suspected, as these drugs can precipitate acute kidney injury in this specific setting 1, 2
• Delay initiation in patients without hypertension who have podocytopathy expected to respond rapidly to immunosuppression 1

Blood Pressure Targets

• Target systolic BP <120 mmHg using standardized office measurement in most adult patients with proteinuria 1, 2
• In practice, achieving 120-130 mmHg systolic is acceptable in patients with glomerular disease 1
• Lower BP targets provide additional renoprotection in proteinuric patients beyond the effects of RAS blockade alone 3

Monitoring and Tolerating Expected Changes

Creatinine Elevation - Expected and Acceptable

• Accept up to 30% increase in serum creatinine after starting ACE inhibitor or ARB—this is a hemodynamic effect and reflects appropriate reduction in intraglomerular pressure 1, 2, 4
• Do not discontinue therapy for modest, stable creatinine increases up to 30% 1, 2
• This initial creatinine rise correlates with better long-term renal protection 5

When to Stop ACE Inhibitor/ARB

• Stop only if kidney function continues to worsen beyond 30% increase 1, 2
• Stop if refractory hyperkalemia develops despite management 1, 2

Monitoring Frequency

• Monitor serum creatinine, potassium, and proteinuria levels frequently when on ACE inhibitor or ARB therapy 1, 4

Essential Lifestyle Modifications (Synergistic with Pharmacotherapy)

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day)—this is mandatory, not optional, as sodium restriction enhances the antiproteinuric effect of ACE inhibitors 1, 2, 3
• Normalize weight through diet and exercise 1, 4
• Stop smoking 1
• Exercise regularly 1

Add-On Therapy for Persistent Proteinuria

If proteinuria remains elevated despite maximum-dose ACE inhibitor or ARB:

For Diabetic Patients

• Add SGLT2 inhibitor (dapagliflozin 10 mg daily, empagliflozin, or canagliflozin) if patient has diabetes with proteinuria >300 mg/g, regardless of glycemic control 3, 6
• SGLT2 inhibitors provide additive renoprotection to ARBs and reduce risk of eGFR decline, ESKD, cardiovascular death, and hospitalization for heart failure 6
• Can be used down to eGFR ≥25 mL/min/1.73 m² for renal protection (not for glycemic control) 6

For All Patients with Resistant Proteinuria

• Add thiazide-like diuretic (chlorthalidone or indapamide preferred) to RAS blocker 3
• Consider mineralocorticoid receptor antagonist (spironolactone 25-50 mg daily or eplerenone) for refractory cases, with careful potassium monitoring 1, 3
• Intensify dietary sodium restriction further in patients failing to achieve proteinuria reduction on maximal medical therapy 1

Managing Hyperkalemia to Continue RAS Blockade

• Use potassium-wasting diuretics and/or potassium-binding agents to normalize serum potassium, allowing continuation of RAS blockade 1, 4
• Treat metabolic acidosis (serum bicarbonate <22 mmol/L) as this contributes to hyperkalemia 1

Patient Education - Critical Safety Counseling

• Instruct patients to hold ACE inhibitor/ARB and diuretics during intercurrent illness with risk of volume depletion (vomiting, diarrhea, fever) to prevent acute kidney injury 1, 2, 4
• Consider transiently stopping RAS inhibitors during "sick days" 1

Treatment Goals

• Target proteinuria <1 g/day as the therapeutic goal 1, 2
• Aim for at least 30-50% reduction from baseline if <1 g/day cannot be achieved 3
• Proteinuria reduction is an independent target requiring aggressive treatment beyond blood pressure control alone 3

Additional Cardiovascular Risk Management

• Consider statin therapy for persistent hyperlipidemia, particularly in patients with nephrotic syndrome and other cardiovascular risk factors including hypertension and diabetes 1
• Assess ASCVD risk and align statin intensity accordingly 1

Common Pitfalls to Avoid

• Do not prematurely discontinue ACE inhibitors due to modest creatinine elevation—this removes critical renoprotection 2, 4
• Do not combine ACE inhibitor with ARB in most patients, as this increases adverse effects without additional benefit (exception: may consider in young adults without comorbidities) 1, 4
• Do not target proteinuria or blood pressure in isolation—both require simultaneous optimization 7
• Do not forget sodium restriction—pharmacotherapy alone is insufficient without dietary sodium reduction to <2 g/day 1, 2