What causes renal glucosuria?

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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Answer

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.


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