PROTEINURIA 

1️⃣ Definition

Proteinuria = abnormal amount of protein in urine.

Normal urinary protein excretion:

• <150 mg/day (total protein)
• Albumin <30 mg/day

Anything above this is abnormal.

2️⃣ Normal Glomerular Filtration Barrier

The filtration barrier has 3 layers:

1. Fenestrated endothelium
2. Glomerular basement membrane (GBM)
3. Podocyte slit diaphragm

Mechanisms Preventing Protein Loss

• Size selectivity
• Charge selectivity (negative GBM repels albumin)
• Intact podocyte slit diaphragm (nephrin, podocin)

Loss of any component → proteinuria.

3️⃣ Classification of Proteinuria

A. By Quantity

B. By Mechanism

1️⃣ Glomerular Proteinuria (Most common)

Due to increased glomerular permeability.

Examples:

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Diabetic Nephropathy
• IgA Nephropathy

🔹 Mostly albumin
🔹 Can reach nephrotic range

2️⃣ Tubular Proteinuria

Defect in proximal tubular reabsorption.

Causes:

• Acute Tubular Necrosis
• Fanconi Syndrome
• Drug toxicity (aminoglycosides)

🔹 Usually <2 g/day
🔹 Low-molecular-weight proteins (β2-microglobulin)

3️⃣ Overflow Proteinuria

Excess circulating proteins overwhelm tubules.

Examples:

• Multiple Myeloma (Bence Jones proteins)
• Hemoglobinuria
• Myoglobinuria (rhabdomyolysis)

🔹 Urine dipstick may be negative (detects albumin only!)

4️⃣ Post-renal Proteinuria

Inflammation distal to kidney:

• UTI
• Stones
• Tumors

 Transient Proteinuria- Usually <1 g/day

Benign causes:

• Fever
• Exercise
• Stress
• Orthostatic proteinuria (young adults)

Orthostatic:

• Daytime proteinuria
• Normal early morning sample

4️⃣Clinical Spectrum

1️⃣ Asymptomatic Proteinuria

Found incidentally.

2️⃣ Nephrotic Syndrome

Criteria:

• Proteinuria >3.5 g/day
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• Lipiduria

3️⃣ Nephritic Syndrome

• Hematuria
• Hypertension
• Mild–moderate proteinuria

6️⃣ Evaluation of Proteinuria (Stepwise Approach)

STEP 1 — Confirm Presence

Urine Dipstick

Detects albumin.

Limitations:

• False negative in multiple myeloma
• False positive in concentrated urine

First positive dipstick?

🔹 Repeat urinalysis in 1–2 weeks
🔹 Ensure patient:

• Not febrile
• Not exercising heavily
• Not dehydrated

If repeat is negative → likely transient.

STEP 2 — Quantification

Preferred: Spot Urine Protein/Creatinine Ratio (UPCR)

• Correlates with 24-hour protein
• Easier & guideline preferred

Albumin/Creatinine Ratio (ACR)

KDIGO classification:

STEP 3 — Determine Cause

History

• Diabetes?
• SLE?
• Infections?
• Drugs?

Labs

• Serum creatinine
• Lipids
• ANA
• Complement
• HbA1c
• SPEP/UPEP (if suspected myeloma)

7️⃣ Indications for Renal Biopsy

• Unexplained proteinuria >1 g/day
• Nephrotic syndrome
• Proteinuria + hematuria
• Rapid decline in kidney function
• Suspected primary glomerular disease

Proteinuria in Specific Diseases

 Diabetic Kidney Disease

• Earliest sign: Microalbuminuria
• Progresses to overt proteinuria
• Often with retinopathy
• Managed with ACEi/ARB

 Lupus Nephritis

Associated with:

• Systemic Lupus Erythematosus
• Proteinuria + hematuria
• Low complement
• Biopsy essential

 Multiple Myeloma

• Multiple Myeloma
• Light chain proteinuria
• Dipstick may miss
• Confirm with UPEP

🔟 Management Principles (KDIGO-Aligned)

1️⃣ Treat Underlying Cause

• Diabetes → Tight glycemic control
• SLE → Immunosuppressives
• Myeloma → Hematology management

2️⃣ RAAS Blockade

ACE inhibitors / ARBs:

• Reduce intraglomerular pressure
• Reduce proteinuria independent of BP

3️⃣ SGLT2 Inhibitors

Now guideline-recommended for:

• CKD with albuminuria
• Diabetic & non-diabetic CKD

4️⃣ Blood Pressure Targets

• Target <130/80 mmHg in proteinuric CKD

5️⃣ Dietary Protein

• Moderate restriction (~0.8 g/kg/day in CKD)

 Complications of Persistent Proteinuria

• CKD progression
• Cardiovascular disease
• Hypercoagulability (nephrotic syndrome)
• Infections
• Malnutrition

 ICU Perspective

Proteinuria may occur in:

• Sepsis
• AKI
• Multi-organ failure

Transient but prognostic marker of severity.