Glycosuria

Glycosuria is the term for glucose present in urine, in amounts that can be detected by the usual techniques.

Pathogenesis

The concentration of glucose in plasma is held within narrow limits (4-10 mmol/L). The kidneys play a role in glucose homeostasis by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane¹ .

Virtually all the glucose that is filtered through the glomeruli is reabsorbed by the proximal renal tubule and so glycosuria represents an abnormal state. The amount of glucose not reabsorbed by the kidneys is usually less than 0.1%. Adults excrete about 65 mg of glucose per day and standard techniques do not detect this level.

There are two basic causes of glycosuria. One cause of glycosuria is that the level of blood glucose is so high that the renal tubules are unable to reabsorb all that is presented. The other is a failure of the tubules to reabsorb all glucose at a level where this should be possible. The latter is called renal glycosuria.

The level of blood glucose at which it spills into the urine is called the renal threshold. Under normal circumstances this is around 10 mmol/L.

Diastix® and Medi-Test® are plastic strips carrying glucose oxidase and a colour indicator, usually o-toluidine. They are specific and unlikely to give positive results for substances other than glucose. Glucose oxidase strips have superseded older reagents for reducing substances.

Elevated blood glucose

• If glycosuria occurs because a normal renal threshold has been exceeded, this is usually indicative of impaired glucose tolerance or frank diabetes.

• Glycosuria can occur in a person who doesn't have diabetes if a substantial amount of food high in sugar is consumed and transiently overwhelms the insulin response, causing hyperglycaemia.

• Other conditions which may cause hyperglycaemia include:
  

  • Thyrotoxicosis.

  • Acromegaly.

  • Cushing's syndrome (including administration of corticosteroid drugs).

  • Severe anxiety states.

• Very rapid gastric emptying, as in dumping syndrome after surgery for peptic ulcers, can raise blood glucose above the threshold.

• Stress hormones elevate blood glucose and in the severely ill patient they may elevate glucose beyond the renal threshold.

Renal glycosuria

Pregnancy

Pregnancy is associated with a reduced renal threshold. This results from increased renal blood flow so that the tubules are presented with a greater volume each minute. Glycosuria in pregnancy, however, must not be dismissed, as it may be the first sign of gestational diabetes.

Urine glucose dipstick analysis is not useful in the detection of gestational diabetes because of its low sensitivity and negative predictive value.

The National Institute for Health and Care Excellence (NICE) has published guidance for testing for gestational diabetes mellitus (GDM)² .

Fanconi's syndrome

Inadequate proximal renal tubular resorption of glucose occurs in Fanconi's syndrome. There may be a history of growth failure, rickets, polyuria, polydipsia or dehydration. This may be idiopathic, inherited or acquired.

Renal glycosuria

This is also known as benign glycosuria, familial renal glycosuria, primary renal glycosuria and nondiabetic glycosuria.

Renal glycosuria is a rare inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. Renal glycosuria is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule³ .

Renal glycosuria occurs in males and females. Renal glycosuria is diagnosed based upon laboratory tests that confirm the presence of glucose in the urine in association with normal or low blood glucose levels. It is usually asymptomatic.

In most affected individuals, no treatment is required. However, some individuals with renal glycosuria may develop diabetes mellitus.

Other causes of renal glycosuria

Some secondary causes of renal glycosuria are:

• Sodium-glucose co-transporter-2 (SGLT2) drugs can lead to a dose-dependent glycosuria⁴ .

• Oculo-cerebro-renal dystrophy (Lowe's syndrome).

• Cystinosis.

• Wilson's disease.

• Interstitial nephritis.

• Hereditary tyrosinaemia.

• Heavy metal poisoning, such as lead, mercury or after use of out-of-date tetracycline.

• Intestinal glucose-galactose malabsorption (where the defective sodium-dependent glucose co-transporter protein is also present in the renal tubules).

Exclusion of these (by appropriate testing) should only be carried out if otherwise clinically indicated.

Misleading results

Testing sticks using glucose oxidase are specific for glucose. Other substances do not cause it to change. The small amounts of glucose normally excreted by the kidneys are usually below the sensitivity range of this test but on occasions may produce a colour between the negative and the lowest positive and may be interpreted by the observer as positive.