Renal Glucosuria (Glycosuria with Normal Serum Glucose)
This patient most likely has familial renal glucosuria (FRG), a benign inherited condition caused by mutations in the SGLT2 gene that reduces the renal threshold for glucose reabsorption, requiring no treatment but warranting monitoring for associated metabolic abnormalities. 1, 2
Diagnostic Confirmation
Confirm the diagnosis by documenting:
- Persistent glycosuria on multiple occasions with consistently normal fasting and postprandial blood glucose levels (typically <100 mg/dL fasting) 1, 2
- Normal HbA1c (<5.7%) to exclude prediabetes or diabetes 3
- Normal oral glucose tolerance test if any diagnostic uncertainty exists 2
- Absence of other urinary abnormalities (no proteinuria, no hematuria, no other signs of proximal tubular dysfunction like aminoaciduria or phosphaturia) to distinguish FRG from generalized Fanconi syndrome 1, 2
Assess Renal Function Accurately
Calculate estimated GFR using the CKD-EPI equation rather than relying on serum creatinine alone, as normal-range serum creatinine can mask significantly reduced GFR, particularly in elderly patients, women, and those with lower muscle mass 4, 5. Up to 15.2% of patients with normal serum creatinine have GFR ≤50 mL/min/1.73 m², and this rises to 47.3% in those ≥70 years old 5.
Screen for glomerular hyperfiltration (eGFR above the age- and gender-specific 95th percentile), as this represents early reversible kidney damage that can occur even in prediabetes before albuminuria develops 6. If hyperfiltration is present, this suggests evolving diabetic kidney disease rather than benign FRG 6.
Rule Out Prediabetes and Early Diabetic Kidney Disease
Measure urine albumin-to-creatinine ratio (UACR) to exclude early diabetic nephropathy 3, 6. The presence of albuminuria (UACR >30 mg/g) with glycosuria strongly suggests prediabetes or diabetes with early kidney involvement rather than FRG 6.
If HbA1c is in the prediabetic range (5.7-6.4%), recognize that glomerular hyperfiltration and early renal dysfunction can occur before frank diabetes develops, representing a critical window for preventive intervention 6. The odds ratio for hyperfiltration increases progressively with rising HbA1c even within the prediabetic range 6.
Monitor for Associated Metabolic Abnormalities
Screen for clinical features that may accompany FRG, even though it is generally considered benign 1:
- Measure serum uric acid (often decreased due to increased renal uric acid excretion) 1
- Check 24-hour urine calcium excretion or spot urine calcium-to-creatinine ratio for hypercalciuria 1
- Monitor blood pressure, as altered systemic blood pressure has been reported in FRG patients 1
- Assess growth parameters in children, as lower body weight or height may occur 1
Ongoing Management Strategy
No glucose-lowering treatment is required for isolated FRG with confirmed normal glucose metabolism 1, 2. The condition is typically benign and asymptomatic 1, 2.
Reassess glucose metabolism annually with fasting glucose and HbA1c, as the distinction between benign FRG and early diabetic kidney disease is critical 3, 6. If glucose parameters drift upward into the prediabetic range, initiate lifestyle interventions immediately 3.
If eGFR is ≥30 mL/min/1.73 m² and prediabetes or diabetes is subsequently diagnosed, metformin becomes first-line therapy 3. Metformin is safe with eGFR ≥30 mL/min/1.73 m² but absolutely contraindicated when eGFR falls below 30 mL/min/1.73 m² 3, 7.
Critical Pitfalls to Avoid
Never assume glycosuria always indicates diabetes—FRG is a distinct genetic condition with normal glucose metabolism that mimics diabetes on urinalysis but requires no treatment 1, 2.
Never rely solely on serum creatinine to assess renal function, as it systematically underestimates kidney dysfunction, particularly in elderly patients, women, and those with lower muscle mass 4, 5. Always calculate eGFR using CKD-EPI equation 4.
Never dismiss glycosuria without documenting normal glucose metabolism on multiple occasions, as early diabetic kidney disease with hyperfiltration can present with glycosuria before significant hyperglycemia develops 6.
Never use MDRD equation for GFR estimation in patients with suspected normal or high GFR, as it systematically underestimates GFR in this range and was derived from populations with established renal insufficiency 4. Use CKD-EPI or Mayo Clinic Quadratic equation instead 4.