Renal Glycosuria

Renal glycosuria is the excretion of glucose in the urine despite a normal blood glucose, caused by a reduced renal threshold for glucose reabsorption. Familial renal glycosuria is the commonest cause. It is a benign inherited condition of loss-of-function variants in SLC5A2, which encodes sodium-glucose cotransporter 2 in the proximal tubule.

Inheritance and severity:

• Autosomal recessive (homozygous or compound heterozygous): severe, with glycosuria above 10 to 150 g daily.
• Autosomal dominant or codominant with variable penetrance (heterozygous): mild, usually under 10 g daily.

Prevalence is about 1 in 500 people for any form. Familial renal glycosuria does not cause kidney disease, and long term outcomes are good.

Glycosuria also occurs in pregnancy (reduced threshold, in about 50%), in generalised proximal tubular dysfunction (Fanconi syndrome), in tubulointerstitial disease, and with SGLT2 inhibitor treatment (an expected pharmacological effect).

Pathophysiology. Glucose is filtered freely and reabsorbed almost completely in the proximal tubule through SGLT2 (about 90%) and SGLT1 (about 10%). When SGLT2 function is lost, filtered glucose is excreted at a lower plasma glucose than the normal threshold (about 10 mmol/L), and urine glucose rises. Fasting and postprandial blood glucose are normal.

• Asymptomatic: glycosuria on urinalysis in a person without diabetes, found on screening, pregnancy or insurance testing.
• Severe forms: polyuria, mild volume depletion, nocturia, salt craving, and enuresis in children; mild growth delay in a few.
• Ketosis during fasting, pregnancy or starvation (because of continued glucose loss) in severe forms.
• Genitourinary mycotic infection (candidal balanitis, vulvovaginitis) in some patients.
• Normal eGFR, no proteinuria, normal electrolytes.

Red flags

• Glycosuria with hyperglycaemia (diabetes).
• Glycosuria with phosphaturia, aminoaciduria, bicarbonate loss or low molecular weight proteinuria (Fanconi syndrome).
• Raised creatinine or proteinuria (tubulointerstitial disease or glomerular disease).
• Recurrent genital candidiasis or euglycaemic ketoacidosis in a person on an SGLT2 inhibitor.
• Weight loss, polyuria and thirst with glycosuria (diabetes).

• Fasting plasma glucose, HbA1c and, when needed, oral glucose tolerance test (2-hour glucose under 7.8 mmol/L excludes diabetes): normal values with glycosuria confirm renal glycosuria.
• Spot urine glucose and 24-hour urine glucose (over 0.5 g daily abnormal; familial dominant 1 to 10 g, recessive above 10 g daily).
• Creatinine, eGFR, electrolytes, bicarbonate, phosphate, calcium, uric acid, urine protein:creatinine ratio, urinary amino acids and urine beta-2 microglobulin to exclude generalised proximal tubular dysfunction.
• Medication history (SGLT2 inhibitors, topiramate, tenofovir, ifosfamide, cisplatin, outdated tetracyclines, heavy metals).
• Family testing: urine glucose in relatives.
• Genetic testing for SLC5A2 where needed (children with severe phenotypes, uncertain diagnosis).

Differential diagnosis

• Diabetes mellitus (including gestational), Fanconi syndrome (genetic, cystinosis, Dent disease, light chain, drug induced), heavy metal toxicity, tubulointerstitial nephritis, pregnancy, SGLT2 inhibitor effect, glucose galactose malabsorption (SGLT1 defect, with osmotic diarrhoea in infancy).

No treatment is required for isolated familial renal glycosuria; confirm the diagnosis and reassure.

• Explain that the condition is benign, does not progress to diabetes or kidney failure, and does not need drugs or dietary change.
• Avoid unnecessary diabetes treatment. Do not use urinary glucose to monitor glycaemia in affected people (use blood glucose or HbA1c).
• Severe forms (glycosuria above 100 g daily): increase water and salt intake to prevent dehydration and hypovolaemia (sodium chloride 6 to 10 g daily if no hypertension). Maintain carbohydrate intake during illness or fasting, and ensure small frequent meals in pregnancy.
• Treat candidal infections with clotrimazole 500 mg pessary once, or fluconazole 150 mg orally once (adjust eGFR below 50 mL/min/1.73 m²).
• Pregnancy: glycosuria is common. Screen for gestational diabetes with a 75 g oral glucose tolerance test at 24 to 28 weeks as usual. Maintain hydration, and check ketones when vomiting or fasting.
• SGLT2 inhibitors are not needed. If started for another indication, they cause the expected glycosuria (10 to 100 g daily).
• Dapagliflozin 10 mg daily and empagliflozin 10 mg daily (eGFR at least 25 and 20, respectively) need monitoring for genital infection, volume depletion and ketoacidosis. Stop 3 days before surgery.
• Generalised proximal tubular dysfunction: treat the cause and replace losses. Use sodium bicarbonate 500 mg to 1 g two to three times daily to bicarbonate at least 22 mmol/L; neutral phosphate 500 to 1000 mg elemental phosphate daily in divided doses; potassium chloride 40 to 120 mmol daily in divided doses; cholecalciferol 800 to 2000 units daily.

Monitoring. Yearly blood pressure, creatinine, eGFR, urine protein:creatinine ratio and fasting glucose or HbA1c. Review immediately if proteinuria, rising creatinine, polyuria or hyperglycaemia appears.

Referral and escalation. Nephrology or genetics when glycosuria is severe, familial with unexpected features, in a child with growth failure, or when other tubular abnormalities are present; urgent for ketosis or volume depletion.

Special groups

• Pregnancy: glycosuria in up to 50%; the usual diabetes screening applies; severe familial forms increase the risk of dehydration and ketosis.
• Children: usually asymptomatic; check growth; avoid unnecessary glucose testing.
• Athletes and people on low carbohydrate diets: ketosis risk is higher with severe forms.