Glycosuria 

1️⃣ Definition

Glycosuria (Glucosuria) = Presence of glucose in urine.

Normally, urine contains no detectable glucose (or <25 mg/dL, below dipstick sensitivity).

It occurs when:

• Plasma glucose exceeds renal reabsorptive capacity
  OR
• Proximal tubular reabsorption is impaired

2️⃣ Renal Physiology of Glucose Handling

 Normal Physiology

• Glucose is freely filtered at the glomerulus
• Almost 100% reabsorbed in the proximal convoluted tubule (PCT)
• Transporters:
• SGLT2 → early PCT (S1 segment) – 90%
• SGLT1 → late PCT (S3 segment) – 10%
• Glucose exits via GLUT2/GLUT1 into bloodstream

 Renal Threshold & Transport Maximum (Tm)

When plasma glucose > 180 mg/dL → transporters saturate → glycosuria appears.

⚠ Important:
Threshold varies:

• Lower in pregnancy
• Lower in children
• Reduced in renal tubular disorders

3️⃣ Pathophysiology

Two Major Mechanisms

A. Overflow Glycosuria (Hyperglycemic Glycosuria)

Plasma glucose exceeds renal threshold.

Causes:

• Diabetes mellitus
• Stress hyperglycemia
• IV dextrose infusion
• Cushing syndrome
• Acute pancreatitis

B. Renal Glycosuria (Normoglycemic Glycosuria)

Plasma glucose normal but urine glucose present.

Cause: Proximal tubular defect.

Seen in:

• Fanconi syndrome
• Pregnancy
• Acute tubular injury
• Interstitial nephritis
• After kidney transplant
• SGLT2 inhibitor therapy

4️⃣ Causes of Glycosuria 

🔴 Hyperglycemic Causes

1. Diabetes mellitus (most common)
2. DKA / HHS
3. Stress (sepsis, trauma)
4. IV glucose
5. Endocrine disorders:
• Cushing syndrome
• Acromegaly
• Pheochromocytoma
• Thyrotoxicosis

🟢 Normoglycemic Causes

1. Familial renal glycosuria
2. Fanconi syndrome
3. Pregnancy
4. Proximal RTA
5. SGLT2 inhibitors
6. Acute tubular necrosis (recovery phase)

5️⃣ Important Clinical Entity: Diabetes Mellitus

In Diabetes mellitus:

• Hyperglycemia → filtered load exceeds Tm
• Glucose in urine → osmotic diuresis
• Leads to:
• Polyuria
• Polydipsia
• Dehydration
• Electrolyte loss

In DKA:

• Severe glycosuria
• Ketonuria
• Metabolic acidosis

6️⃣ Osmotic Diuresis – ICU Importance

Glucose in urine acts osmotically:

Water retained in tubular lumen → polyuria

Consequences:

• Volume depletion
• Hypernatremia
• Hypokalemia
• Prerenal AKI

ICU pearl:
Polyuria with high urine osmolality + glycosuria → think osmotic diuresis (not DI).

7️⃣ SGLT2 Inhibitor–Induced Glycosuria

Drugs:

• Empagliflozin
• Dapagliflozin
• Canagliflozin

Mechanism:
Block SGLT2 → reduce glucose reabsorption → therapeutic glycosuria

Benefits:

• ↓ HbA1c
• Weight loss
• CV mortality reduction
• Renal protection

Risks:

• Genital infections
• Euglycemic DKA
• Volume depletion

Exam point:
Normoglycemia with glycosuria in diabetic patient on SGLT2 → drug effect.

8️⃣ Familial Renal Glycosuria

Rare inherited disorder:

• SLC5A2 mutation
• Isolated glycosuria
• Normal blood sugar
• Benign

9️⃣ Fanconi Syndrome

Generalized proximal tubular dysfunction:

Loss of:

• Glucose
• Amino acids
• Phosphate
• Bicarbonate
• Uric acid

Causes:

• Multiple myeloma
• Drugs (tenofovir, ifosfamide)
• Heavy metals
• Cystinosis

🔟 Pregnancy & Glycosuria

Mechanisms:

• Increased GFR
• Lower renal threshold

Mild glycosuria common
BUT always rule out gestational diabetes.

1️⃣1️⃣ Diagnostic Approach

Stepwise Evaluation

Step 1: Confirm glycosuria

Urine dipstick

Step 2: Check plasma glucose

Step 3: If normoglycemic

Check:

• Serum bicarbonate
• Phosphate
• Urine amino acids
• Uric acid

→ Rule out Fanconi syndrome

1️⃣2️⃣ Laboratory Interpretation Pearls

Urine dipstick detects glucose ≥50–100 mg/dL

False positives:

• Oxidizing agents

False negatives:

• High vitamin C
• Dilute urine