What blood work tests are used to diagnose Familial Renal Glucosuria (FRG)?

Blood Work Tests for Familial Renal Glucosuria (FRG)

The diagnosis of Familial Renal Glucosuria does not rely on blood work tests but rather on demonstrating persistent isolated glucosuria in the presence of normal blood glucose levels. 1, 2, 3

Essential Diagnostic Approach

Blood Glucose Testing (Primary Requirement)

• Fasting plasma glucose (FPG) must be measured to confirm normoglycemia, with values <126 mg/dL (7.0 mmol/L) ruling out diabetes mellitus 4, 3
• Random plasma glucose should be <200 mg/dL (11.1 mmol/L) to exclude diabetes 4, 3
• HbA1c testing should be <6.5% to definitively exclude diabetes mellitus as the cause of glucosuria 4, 3
• Blood glucose measurements must be performed using laboratory enzymatic assay techniques on venous samples, not point-of-care testing 4

Confirmatory Testing Strategy

• If initial FPG is normal but clinical suspicion remains, perform an oral glucose tolerance test (OGTT) with 75g glucose load to exclude impaired glucose tolerance, with 2-hour values <200 mg/dL (11.1 mmol/L) confirming normal glucose metabolism 4, 5
• The OGTT is particularly valuable because it can detect subtle glucose metabolism abnormalities that fasting glucose alone might miss 5

Additional Blood Work to Exclude Other Conditions

Ruling Out Secondary Causes

• Serum creatinine and estimated GFR (eGFR) to assess kidney function and exclude chronic kidney disease as a cause of tubular dysfunction 4
• Serum electrolytes (sodium, potassium, bicarbonate) to rule out Fanconi syndrome or other proximal tubular disorders 2, 3
• Serum phosphate to exclude generalized proximal tubular dysfunction 3
• Venous blood gas or serum bicarbonate to rule out proximal renal tubular acidosis 3

Specialized Testing in Severe Cases

• Plasma renin and serum aldosterone levels may be elevated in patients with massive glucosuria (>65 g/1.73 m²/24h) due to volume depletion from associated natriuresis 2
• This testing is only relevant when glucosuria is exceptionally high and there are clinical signs of volume depletion 2

Genetic Confirmation

• Molecular genetic testing of the SLC5A2 gene is the definitive diagnostic test for FRG, identifying mutations in the SGLT2 transporter 1, 2, 6, 7
• Genetic testing should be pursued after excluding diabetes and other tubulopathies through the blood work outlined above 3, 6
• Most mutations are private (family-specific), with patients having either homozygous, compound heterozygous, or single heterozygous mutations 2, 7
• The condition follows codominant inheritance with incomplete penetrance 2, 7

Critical Pitfalls to Avoid

• Do not rely on point-of-care glucose meters for diagnosis, as they lack sufficient precision for diagnostic purposes 4
• Do not assume diabetes is excluded based on a single normal fasting glucose if glucosuria persists; confirm with HbA1c and consider OGTT 4, 5
• Do not overlook medications that can cause hyperglycemia (glucocorticoids, nicotinic acid) when interpreting glucose results 4, 5
• Ensure proper sample handling with plasma glucose samples spun and separated immediately after collection to prevent falsely low results 8