Renal glucosuria E74.8

After it could be shown in studies that in humans the i.v. injection of the plant glucoside phlorizin leads to the excretion of the entire filtered amount of glucose, the so-called gliflozines(SGLT2 inhibitors) were developed for therapeutic purposes (Ghezzi 2018). In Germany, the first drug to be launched was dapagliflozin in 2012 (Schwabe 2017).

Renal glucosuria is a selective disorder of renal glucose reabsorption (Muntau 2018) in which - despite normal blood glucose levels - there is increased urinary excretion of glucose and other tubular disorders are not detectable (Schärer 2002).

Familial renal glucosuria (FRG) is one of the tubulopathies (Muntau 2018).

It is differentiated between 3 different types:

• Type A: This type results from a defect of the glucose transporter SGLT2, which is responsible for the reabsorption of glucose in the 1st half of the proximal tubule. In this case, both the tubular reabsorption maximum for glucose and the minimal renal threshold are decreased (Muntau 2018). The latter is normally around 180 mg / dl of glucose in the blood (Liman 2021).
• Type B: In type B, a defect of the glucose transporter SGLT1 is found at the end of the proximal tubule. The renal threshold for glucose is decreased, but the tubular reabsorption maximum is only limited at high glucose concentrations. Additionally, there is malabsorption for glucose and galactose (Muntau 2018).
• Type O: In type O, renal reabsorption for glucose is almost completely absent (Lentze 2008).

Very rarely occurring (Herold 2020). More detailed figures can be found in a study by Fishman (2019). Here, of 2,506,830 conscripts, 0.044% (n=1,108) had renal glucosuria.

In a 2018 Japanese study, glucosuria was detected in 0.1% of 3,309,631 school children in which 70.3% were due to renal glucosuria. The sex ratio (boys: girls) was 50.3%: 49.7% (Urakami 2018).

FRG is usually inherited in a codominant manner with incomplete penetrance (Ottoss-Laakso 2016). The disease is caused by a mutation of the SLC5A2 gene, which leads to a defect in the sodium-glucose cotransporter (Herold 2020).

The mode of inheritance is incomplete autosomal recessive (Lentze 2008 / Muntau 2018).

SGLT2 is the major glucose co-transporter, responsible for 90% of renal reabsorption of glucose, while the more distal glucose co-transporter SGLT1 is responsible for only 10% (Ottosson- Laakso 2016).

Renal glucosuria is asymptomatic and will usually be discovered incidentally during laboratory testing (Rebelo 2012).

In addition to the laboratory tests mentioned below, the diagnosis is made by:

DNA analysis: mutations of the SLC5A2 gene (Herold 2020)

Determination of the renal glucose reabsorption maximum: This shows a reduced reabsorption of glucose (Muntau 2018).

Sonography

The kidneys are unremarkable (Rebelo 2012).

Urinalysis:

• Glucosuria (Herold 2020)
• pH value inconspicuous (Rebelo 2012)

Blood test:

• Normoglycaemia (Herold 2020)
• HbA1C- value in normal range
• Glucose tolerance test normal (Rebelo 2012)

Glucosuria along with hyperglycemia:

• Diabetes mellitus

Glucosuria in the absence of hyperglycemia:

• Renal trauma
• Infection of the kidney
• Cystinosis and other metabolic disorders
• Fanconi- Bickel- syndrome (additionally hepatomegaly and disturbances of liver function [Schatz 2006])
• Fanconi- de- Toni- Debré- syndrome (additionally transport disorders for amino acids, bicarbonate and phosphate [Schatz 2006])
• Fanconi syndrome (predominantly genetic)
• Disruption of renal tubules in terms of Fanconi syndrome by drugs (Rebelo 2012) such as:
  • Aminoglycoside antibiotics
  • Cisplatin
  • Deferasirox
  • Sodium valproate
  • Tenofovir (Hall 2013)
• Amyloidosis (transport defect caused by peritubular deposits)
• Collagenoses
• Vasculitides (Schatz 2006)

No therapy is required (Muntau 2018).

FRG is considered a benign condition, although urinary glucose loss can be as high as 150 g / 1.73 m² (Ottosson- Laakso 2016).

A Finnish study Ottosson- Laakso 2016 demonstrated that renal glucosuria has no effect on BMI and on any glucose tolerance (Lentze 2008).

However, a 2019 Israeli study showed that renal glucosuria is more commonly associated with lower body weight and less commonly associated with elevated systolic blood pressure levels (Fishman 2019).

In siblings, a urine strip test is sufficient to detect glucosuria, as a diagnosis made with certainty is sufficient (Lentze 2008).

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