eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Renal Glucosuria

Author: Rajendra Bhimma, MB, ChB, MD, DCH (SA), FCP (Paeds)(SA), MMed (Natal), Associate Professor of Pediatrics, Principal Specialist, Department of Pediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa
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Updated: Feb 17, 2009

Introduction

Background

Renal glucosuria is the excretion of glucose in the urine in detectable amounts at normal blood glucose concentrations in the absence of any signs of general renal tubular dysfunction. In general, renal glucosuria is a benign condition and does not require any specific therapy. Glucosuria may be associated with tubular disorders such as Fanconi syndrome, cystinosis, Wilson disease, hereditary tyrosinemia, or oculocerebrorenal osteodystrophy (Lowe syndrome). Renal glucosuria has also been reported in patients with acute pyelonephritis in the presence of a normal blood glucose level. Glucose loss in the urine may vary from a few grams to more than 100 g (556 mmol) per day. Whereas mild renal glucosuria is relatively frequent, "heavy glucosuria" is extremely rare.

Pathophysiology

Glucose is freely filtered by the glomerulus with a fractional excretion of less than 0.1%. Adults excrete about 65 mg of glucose per day. Reabsorption of glucose predominantly occurs on the brush border membrane of the convoluted segment of the proximal tubule. Glucose enters the tubular cells by an active carrier-mediated transport process, which is sodium-dependent, and exits via the basolateral membrane by facilitated diffusion by a glucose transporter, which is sodium-independent.

The sodium-dependent glucose cotransporters are a family of glucose transporters found in the intestinal mucosa of the small intestine (SGLT1) and the proximal tubule of the nephron (SGLT2, predominantly, and SGLT1). They contribute to renal glucose reabsorption. SGLT1 and SGLT2 are members of the SLC5A gene family which has over 230 members. Several of these (including SGLT1 and SGLT2) are associated with sodium glucose transport.

SGLT2 is a low-affinity sodium/glucose cotransporter responsible for the bulk of tubular reabsorption of filtered glucose. The SGLT2 sodium/glucose cotransporter contains 672 amino acid residues and is almost exclusively expressed in the kidney. SGLT1 contains 664 amino acid residues and is a high amino acid cotransporter protein that is strongly expressed in the small intestine and, to some extent, in the kidney and is responsible for reabsorption for the bulk of the remaining glucose. These 2 cotransporters have significant homology; 59% of the amino acids are identical after alignment. Despite the homology between the two, only one mutation is common: Arg137His. 

The human intestinal SGLT1 has been localized to chromosome 22. SGLT1 is found in the straight segment of the proximal tubule. The other cotransporter is SGLT2, which is expressed in the S1 segment of the proximal tubule and is localized to chromosome 6. The facilitative glucose transporters have isoforms GLUT 1-5. GLUT2 is mainly associated with glucose transport in the convoluted portion of the proximal tubule. In segments with high reabsorptive rates (S1 and S2 segments), the carrier is high capacity, low affinity. At birth, a high-affinity, low-capacity pathway is also present to compensate for the reduced activity of the high-capacity, low-affinity pathway. 

Familial renal glycosuria (FRG) is a rare renal tubular disorder caused by mutations with the SLCA2 gene (FRG, McKusick 233100).¹ This gene is mapped to chromosome 16p11.2. The first report of such a gene mutation was in 2000.² The mode of inheritance that best fits FRG has been suggested to be codominance with incomplete penetrance. Many heterozygous individuals display mild glucosuria (<10 g/1.73 m²/24 h), whereas homozygous or compound heterozygous individuals usually have severe renal glycosuria in excess of 10 g/1.73 m²/24 h.³  

Glucose reabsorption is age dependent. In premature infants born at less than 30 weeks' gestation, glucosuria is quite common because the filtered load of glucose delivered to the kidney is often too high for the immature nephron to handle. Glucosuria normally occurs when the plasma glucose content is above 300 mg/dL, but some glucose may be seen in the urine at plasma glucose levels as low as 150 mg/dL because the glucose-handling capacity of individual nephrons widely varies. This variability arises from variation in the length of the proximal tubule and differences in glomerular size and location.

Tubular maximum for glucose (Tm glucose, mg/min/1.73 m²) corrected for the glomerular filtration rate (GFR) varies as a function of age. Tm glucose/GFR (mg/mL) presents as follows:

• Infants - 0.9-2.94 mg/mL
• Children - 1.82-2.94 mg/mL
• Adults - 2.31-2.70 mg/mL

The Tm glucose for children expressed in mg/min/1.73 m² is as follows:

• Premature infants - 25-190 mg/min/1.73 m²
• Term infants - 36-288 mg/min/1.73 m²
• Children - 254-401 mg/min/1.73 m² 

Frequency

United States

Incidence is estimated at 0.16-6.3%.

Mortality/Morbidity

Renal glucosuria is a benign condition, affected individuals do not have any complaints, and only very rarely a propensity to hypovolemia and hypoglycemia has been described.  However, morbidity is significant in Fanconi syndrome, Lowe syndrome, and cystinosis (see Differentials).

Race

To date, no predilection in any particular racial or ethnic group has been reported.

Sex

The disease has not been reported to occur in any increased frequency in either males or females.

Clinical

History

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.

Physical

No physical examination findings are relevant to renal glucosuria, unless associated with a secondary cause (eg, Fanconi syndrome, diabetes mellitus).

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).

Causes

The renal abnormality is specific to glucose and not other monosaccharides. The inheritance pattern is autosomal recessive, although autosomal dominance has been reported. 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 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.
• 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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