Renal Glucosuria Clinical Presentation

Updated: Dec 10, 2018
  • Author: Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal); Chief Editor: Craig B Langman, MD  more...
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Medical history offers no clues for either primary or benign renal glucosuria. In cases associated with combined tubular defects or hyperglycemia (ie, diabetes mellitus), history is specific to the disease or syndrome.

Renal glucosuria is first noted on routine urinalysis. In cases of glucosuria associated with tubular disorders, a history of growth failure, polyuria, polydipsia, or dehydration may be noted.

Mutations of the SGLT-2 gene have not been associated with other clinical abnormalities such as hypoglycemia, tendency to develop diabetes mellitus, chronic kidney disease or higher rates of infection, especially urinary tract infections. [15] Age at diagnosis ranges from childhood to adulthood. Polyuria associated with sodium wasting and/or aminoaciduria has been reported when daily urinary excretion of glucose is high. [2, 25] Low levels of glycosylated hemoglobin (HbA1c) and insulin have been reported. [26]



No physical examination findings are relevant to renal glucosuria, unless associated with a secondary cause (eg, Fanconi syndrome, diabetes mellitus). Thus, FRG is considered a benign condition, more a phenotype than a disease.

In one patient with FRG polyuria, enuresis and later a mild growth and pubertal maturational delay were reported. Other findings reported in severe FRG include episodic dehydration and ketosis during pregnancy and starvation, [27] the presence of autoantibodies with evidence of autoimmune disease, [28] and increased incidence of urinary tract infections. [28] Activation of the renin-angiotensin-aldosterone system, secondary to natriuresis and possible extracellular volume depletion, has been seen. Hypercalcemia was identified in 5 of 7 male children, although the reason for this finding remains elusive. Several reports have described selective aminoaciduria, which has been postulated to be secondary to glucosuria and not a primary effect of SGLT2 mutation. [29, 30, 31] The proposed mechanism is that glucosuria is causing a depolarization and dissipation of the electric gradient of sodium-dependent amino acid transporters in the proximal renal tubule.

In cases associated with tubular disorders, signs or symptoms may include hypophosphatemic rickets, dehydration, short stature, muscle hypotonia, or ocular changes of cataracts or glaucoma (Lowe syndrome), or Kayser-Fleischer ring (Wilson disease).



The renal abnormality is specific to glucose and not other monosaccharides. The majority of case of inherited FRG are due to mutations in the sodium-glucose co-transporter 2 gene (SGLT2, OMIN:182381). However not all patients with heterozygous mutations show increased glucose excretion. The inheritance pattern is autosomal recessive, although autosomal dominance has been reported i.e. a codominant trait with variable penetrance. [32, 13, 14, 33] Glucosuria can be divided into 3 clinical scenarios, as follows:

  • Benign glucosuria: This condition has 3 variations and is generally discovered on routine urinalysis.

    • Type A is so-called classic glucosuria, with reduction in both renal glucose threshold and maximal glucose reabsorption rate.

    • In type B, a reduction in the glucose threshold, a normal reabsorptive rate, and an increased splay are observed.

    • Type O is defined by the complete absence of glucose reabsorption. Plasma glucose concentration, glucose tolerance testing, serum insulin concentrations, and glycosylated hemoglobin concentrations are normal. Other renal tubular abnormalities are absent. However, families with glucosuria and uricosuria in absence of other aspects of renal tubular dysfunction have been reported

  • FRG: The characterization of FRG into types A/B/O is surpassed by genotype-phenotype correlations in the vast majority of cases. [34] However, this is a difficult task because of the variable expressivity and because other genes may have an impact on overall renal glucose reabsorption. In general, patients with nonsense and missense mutations that are heterozygous for SGLT2 usually have mild glucosuria (< 10 g/1.73 m2/d). However, this does not occur in all carriers of such mutations because cases of severe glucosuria (>10 g/1.73 m2/d) with characteristic autosomal recessive inheritance with homozygosity or compound heterozygosity have been reported. [34, 14]

  • SGLT-1 gene mutations lead to low levels of glucosuria but patients suffer from glucose-galactose malabsorption in the gut, which may be associated with life-threatening severe diarrhea and dehydration unless a glucose- and galactose-free diet is instituted. [35]

  • Glucosuria with diabetes mellitus and pregnancy-induced diabetes mellitus: Obviously, patients have elevated plasma glucose concentration, abnormal glucose tolerance testing, and increased glycosylated hemoglobin concentrations.

  • Tubular dysfunction (Fanconi syndrome): This includes a large number of disorders characterized by presence of phosphaturia, bicarbonaturia, aminoaciduria, polyuria, renal tubular acidosis, growth failure, and rickets. Idiopathic, inherited, or acquired forms are observed. Therapy is directed to the tubular abnormality and disease state.



FRG is an entity considered to be a benign condition, more a phenotype than a disease.  Some of the following have been reported with this condition:

  • Polyuria and enuresis and later a mild growth and pubertal maturation
  • Episodic dehydration and ketosis during pregnancy and starvation [24]
  • Presence of several autoantibodies without clinical evidence of autoimmune disease [36]
  • An increased incidence of urinary tract infections [37]
  • Activation of the renin-angiotensin-aldosterone system, secondary to natriuresis and possible extracellular volume depletion
  • Hypercalciuria [38]
  • Selective aminoaciduria [39, 40]