Proteinuria

BASICS

Definition: Proteinuria = urinary protein excretion >150 mg/day
Nephrotic-range: ≥3.5 g/day (adults); >1,000 mg/m²/day (children)
Pediatrics: Normal up to 100 mg/m²/day (neonates up to 300 mg/m²/day)
Pregnancy: >20 weeks—think preeclampsia/eclampsia; <20 weeks—suggests underlying renal disease

Normal filtration: ≤150 mg/day (mostly albumin ~20 mg)
Glomerular proteinuria: Increased capillary permeability (primary: minimal-change, membranous, FSGS, MPGN, IgA; secondary: DM, HTN, lupus, amyloid, infection, malignancy, drugs)
Tubulointerstitial: Impaired proximal tubular reabsorption (e.g., NSAIDs, aminoglycosides, ATN, Fanconi, interstitial nephritis, toxins)
Overflow: Excess filtered LMW proteins (e.g., multiple myeloma, hemoglobinuria, myoglobinuria)
Benign/transient: Fever, exercise, orthostatic (postural), dehydration, stress

Control weight, BP, and glucose to lower risk of proteinuric kidney disease

Frothy/foamy urine, swelling, hematuria, recent infection, changes in urine output, UTI, DM, CHF, lupus, pregnancy symptoms (headache, visual changes, swelling)

Urinalysis (UA): Initial screen (sensitive for albumin, not LMW proteins)
- 1+ = 30 mg/dL, 2+ = 100 mg/dL, 3+ = 300 mg/dL, 4+ = 1,000 mg/dL
- False +: alkaline, concentrated urine, hematuria, drugs
- False -: dilute urine, low albumin, non-albumin proteins
If trace–2+: Repeat UA to rule out transient causes
If persistent/3+–4+: Quantify with spot urine protein:creatinine ratio (P/C) (preferred over 24-hr collection)
- P/C ratio (mg/mg or g/g): Correlates to g/24h
- Orthostatic: <0.3 supine, >0.3 upright
If P/C >0.3: Further labs: CBC, LFT, lipids, ferritin, ESR, coags, autoimmune serologies, viral (HIV, hepatitis), complement, SPEP/UPEP (MM), antiphospholipase A2R (membranous)
Imaging: Renal US if persistent/proteinuria unexplained

Pregnancy: Proteinuria >20 weeks—screen for preeclampsia (BP, platelets, LFTs)

Treat underlying disease
BP goal (diabetic/nondiabetic): ≤140/90 mm Hg
- If albuminuria: ≤130/80; if >1g/24h: ≤125/75
Proteinuria goal: <0.5 g/day

ACEi: Titrate to max tolerated, even if normotensive (preferred)
ARBs: If ACEi not tolerated; do NOT combine ACEi+ARB
Loop diuretics: For edema and BP/proteinuria
- Continue ACEi/ARB up to 30% rise in creatinine

β-Blockers: Cardio- and renoprotective
Non-dihydropyridine CCBs: (verapamil/diltiazem) if additional antiproteinuric effect needed
Aldosterone antagonists: Spironolactone, eplerenone

Corticosteroids: For steroid-responsive disease (e.g., minimal change, especially in children)
Anticoagulation: Consider if nephrotic-range proteinuria (risk of thrombosis)

Transient/orthostatic proteinuria: benign
Persistent: depends on cause; higher levels predict CKD progression, MI, mortality
Nephrotic-range: risk hypercholesterolemia, hypercoagulability, infection