Glycosuria · What It Is, Causes, Signs and Symptoms, Treatment, and More

Glycosuria refers to the presence of reducing sugars (e.g., glucose, galactose, fructose) in the urine. Fructosuria (i.e., fructose in the urine) and galactosuria (i.e., galactose in the urine) can occur in the setting of an enzyme deficiency, however, these occurrences are relatively rare. Since glucose is the most common sugar found to be elevated in the urine, glycosuria is often synonymous with glucose in the urine.  

Normally, the glomerulus, which is a network of capillaries within the kidney, filters contents of blood (e.g., nitrogenous waste, electrolytes, glucose, amino acids) into the plasma filtrate of renal tubules and reabsorbs substances like electrolytes, glucose, and amino acids from the proximal tubule of the renal tubules back into the bloodstream. The proximal tubule contains sodium-glucose cotransporters (i.e., SGLT1, SGLT2), sodium-potassium-ATPase pumps, and glucose transporters (i.e., GLUT1, GLUT2) which facilitate sodium and glucose reabsorption across the tubular epithelium and back into the blood. Under normal physiological conditions, 100% of the filtered glucose is reabsorbed back to the blood, yet a  trace amount of glucose in the urine may still be regarded as physiologic. More than 25 milligrams per deciliter (mg/dl) of glucose in the urine is considered pathologic or abnormal, and it often occurs when the amount of filtered glucose exceeds the reabsorptive capacity of the proximal

Glycosuria can be caused by a variety of etiologies that either cause elevated blood sugar levels in the bloodstream or prevent glucose reabsorption in the renal tubules.   

Causes of elevated glucose levels include diabetes mellitus and gestational diabetes (i.e., diabetes mellitus diagnosed during pregnancy). Glycosuria in gestational diabetes is thought to occur from a physiologic increase in renal blood flow to the kidney, resulting in excess glucose filtration and a reduction in glucose reabsorption. Glucose reabsorption is facilitated by glucose transporters (e.g., SGLT1, SGLT2, GLUT2) which are present on the membranes. Mutations in these glucose transporters may cause glycosuria. For example, a mutation in SGLT1 is associated with glucose-galactose malabsorption, and a mutation in SGLT2 is associated with familial renal glucosuria (FRG).  

Another etiology of glycosuria due to dysfunctional glucose reabsorption despite normal blood sugar levels includes Fanconi syndrome. This is a rare form of renal glycosuria also known as type II proximal renal tubular acidosis, characterized by a defect in the proximal tubule of the kidney that prevents reabsorption of glucose and other solutes. Fanconi syndrome has several etiologies and can either be inherited, such as in Wilson disease (i.e., abnormal copper accumulation and deposition in the kidneys causing kidney damage); or acquired, like lead poisoning or  medication-induced (e.g., cisplatin, aminoglycosides). Additionally, some medications can prevent glucose reabsorption and cause glycosuria as an intended effect, such as diuretics (e.g., thiazides) used in hypertension, or SGLT2 inhibitors like canagliflozin used in type 2 diabetes mellitus. 

Increased age is a risk factor due to the increased risk of developing chronic disease conditions like diabetes mellitus and hypertension. These chronic conditions overwhelm the kidneys’ reabsorptive capacity but also increase the risk for renovascular damage, leading to subsequent leakage of glucose and proteins into the urine. 

Signs and symptoms of glycosuria typically reflect signs of excess blood glucose, including increased urination and frequency (i.e., polyuria), excessive thirst (i.e., polydipsia), and non-specific constitutional symptoms (e.g., fatigue, unintended weight loss due to polyuria). Individuals with elevated blood glucose with undiagnosed diabetes mellitus may also experience increased hunger since the body isn’t adequately utilizing glucose, and may also present with diabetic ketoacidosis, a medical emergency characterized by prolonged and extremely high blood sugar levels, as well as increased urine and blood ketone levels.  

Additionally, the presence of glucose in the urine may serve as a nutrient for bacteria, predisposing individuals to recurrent urinary tract infections. In some cases, glycosuria may not lead to any noticeable symptoms unless the underlying condition is severe.

Diagnosis of glycosuria begins with a thorough medical history and review of symptoms. Information pertaining to a family history of diabetes mellitus or Fanconi syndrome, and medication history should be elicited to identify the underlying cause of glycosuria. The diagnosis can be made using a urine dipstick test which can identify microscopic amounts of glucose, amino acids, and proteins. In cases where glycosuria is accompanied by elevated blood sugar levels on blood testing, a hemoglobin A1c blood test, which measures the average blood sugar levels over 3 months, can be used to assess for diabetes mellitus.  

Moreover, in Fanconi syndrome, there may be electrolyte abnormalities that can be detected with additional laboratory testing (e.g., comprehensive metabolic panel, or CMP). Due to the generalized defect of the proximal convoluted tubule in Fanconi syndrome, there may be hypophosphatemia with metabolic acidosis in the blood due to bicarbonate wasting and subsequently, phosphaturia, aminoaciduria, and glucosuria.

Management of glycosuria involves treating the underlying cause. For etiologies where glycosuria is a result of elevated blood sugar levels, strategies should be aimed at reducing glucose levels. These include lifestyle modifications, like exercise and a well-balanced diet; and pharmacologic modalities, such as glucose-lowering agents (e.g., insulin, metformin).  

In individuals with glycosuria that’s likely due to dysfunctional glucose reabsorption capabilities, treatment consists of supportive measures such as frequent hydration with electrolyte solutions and further avoidance of nephrotoxic medications. Individuals taking medications known to cause glycosuria as a side effect should be monitored for complications related to excess glucose in the urine (i.e., urinary tract infections). If the individual and the healthcare professional agree that the risks of the medication outweigh the benefits, the medication may be discontinued.