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 



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 generalized proximal renal tubular dysfunction due to a reduction in the renal tubular reabsorption of glucose. The revised criteria for diagnosis of this condition includes: a normal oral glucose tolerance test in regard to plasma glucose concentration, normal plasma levels of insulin, free fatty acids, glycosylated hemoglobin, and relatively stable urinary glucose levels (10 to 100 g/d; except during pregnancy, when it may increase) with glucose present in all urine samples. The urine should contain glucose as the only source of carbohydrate, and individuals should have normal carbohydrate storage and use.

The inherited form of this disorder is called familial renal glucosuria (FRG) (PRG; OMIM #233100). FRG is a rare disorder due mainly to mutations in the sodium-glucose cotransporter 2 gene (SGLT2) that are responsible for the majority of cases.[1, 2, 3, 4]

To date over seventy mutations have been identified including missense mutations, nonsense mutations, small deletions and splicing mutations.  Most however are missense mutations. It is usually inherited in a co-dominant fashion with incomplete penetrance. Although the pattern of inheritance that best fits FRG is one of co-dominance, increased glucose excretion was not observed in all individuals with similar or identical mutations.  Heterozygosity for mutations suggest a role of nongenetic factors or other genes involved in renal glucose transport.[5]

The SGLT2 gene is localized to p11.2 on chromosome 16.  It consists of 14 separate exons spanning approximately 7.7kb of genomic DNA, and encodes the 672 amino acid protein SGLT2.  Glucosuria in these patients can range from < 1 to >150g/1.73m2 per day (normal value: range 0.03 to 0.3g/d). 


In general, renal glucosuria is a benign condition and does not require any specific therapy. Glucosuria may also be associated with tubular disorders such as Fanconi-de Toni-Debre 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 100g (556 mmol) per day.

The kidneys play an important role in glucose homeostasis. It helps to maintain glucose homeostasis by at least two mechanisms.[6]

  • Under normal circumstances, the kidney filters and reabsorbs 100% of glucose, approximately 180 g (1 mole) of glucose, each day. The glucose transporters expressed in the renal proximal tubule ensure that less than 0.5 g/day (range 0.03-0.3 g/d) is excreted in the urine of healthy adults. More water than glucose is reabsorbed resulting in an increase in the glucose concentration in the urine along the tubule. Consequently the affinity of the transporters for glucose along the tubule increases to allow for complete reabsorption of glucose from the urine.

  • It produces glucose by gluconeogenesis. The key enzymes of gluconeogenesis are phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These are expressed in the renal proximal tubule only and not the renal medulla. The kidneys produce between 2.0-2.5umol of glucose/kg/min thereby contributing about 20-25% of circulating glucose.[7]

Gluconeogenesis in the kidneys exceeds renal glucose consumption. It is important in the prevention of hypoglycemia, and its inappropriate increase in diabetic patients contributes to the development of hyperglycemia.

As plasma glucose concentration increases, there is concordant increase in the filtered load of glucose. As the rate of glucose entering the nephron rises above 260-350mg/1.73m2/min (14.5-19.5mmol/1.73m2/min), the excess glucose exceeds the reabsorptive capacity of proximal tubule and is excreted in the urine (i.e. glucosuria). In health individuals this equates to a blood glucose concentration of approximately 200mg/dL (11mmol/L), which is believed to be threshold for the appearance of glucosuria.[8]


Two means of glucose transport are noted: facilitative and secondary active transport. Facilitative transport occurs in essentially all cell types and is driven by the concentration gradient across cellular membranes. This form of glucose transport is predominantly mediated by members of the GLUT transporter family. Secondary active transport occurs in the intestine and the kidney tubules (predominantly proximal tubule) and is mediated by members of the SGLT transporter family. GLUTs are encoded by the SLC2 genes, and the SGLTs are encoded by the SLC5 genes.

Reabsorption of glucose predominantly occurs on the brush border membrane of the convoluted segment of the proximal tubule. Glucose enters at the luminal side of the proximal tubular cells by an active carrier-mediated transport process that requires energy provided by the sodium gradient between the intra- and extracellular compartments generated by sodium-potassium ATPase. Glucose enters the cell along with sodium, and sodium exits the cell at the basolateral side of the cell, which is sodium-independent and a facilitative transport requiring no energy.

There are two different families of glucose transporters expressed in the proximal tubule:

(i) The apical transporters are SGLT-1 (type 1) and SGLT-2. These transporters require energy and are sodium dependent.

(ii) The glucose carriers expressed in the basolateral domain are GULT-1 and GLUT-2 that do not require energy, sodium, or any other ion.

In the initial proximal tubule (termed S1), only SGLT-2 and GLUT-2 are expressed, whilst SGLT-1 and GLUT-1 are expressed in the distal medullary part of the proximal tubule (termed S3). The affinity of SGLT-2 is less than that for SGLT-1.  SGLT2 is a low-affinity, high-capacity glucose transporter.  It carries only one molecule of glucose whilst SGLT1 is a high-affinity, low capacity glucose transporter and carries two molecules of glucose. These transporters initially bind sodium, before binding glucose, and the electrochemical sodium gradient generated by the Na+/K+-ATPase is the driving force for the symporter activity. Under normal conditions the expression of these transporters does not vary and thus the capacity of the kidneys to reabsorb glucose is constant. Also, there are no hormones that impact on these transporters.

SGLT1 and SGLT2 are members of the SLC5A gene family (also known as the sodium substrate symporter gene family [SSSF]). Twelve of these have been identified in the human genome, which has over 230 members; several of these (including SGLT1 and SGLT2) are associated with sodium glucose transport. SGLT members are multifunctional membrane-bound proteins. Apart from glucose, they also are involved in sodium-coupled transport of other sugars, monocarboxylates, amino acids, vitamins, ions, and osmolytes. They also exhibit sodium uniporter activity, channels for urea and water, glucose sensing, and tumor suppression.[9]

In addition to causing glycosuria, a defect of glucose reabsorption also affects the absorption of water and ions. A decrease in glucose reabsorption is associated with a loss of about 70% of water filtered at the glomerulus. As calcium reabsorption in the proximal tubule follows water reabsorption, glycosuria is generally associated with increased calcium excretion.

SGLT2 is the major contributor to renal glucose reabsorption. SGLT2 is a low-affinity sodium/glucose cotransporter responsible for the bulk of tubular reabsorption of filtered glucose. It is responsible for 80-90% of renal glucose reabsorption.[10] The SGLT2 gene encodes a sodium/glucose cotransporter protein that contains 672 amino acid residues. It is almost exclusively expressed in the luminal brush border of the early proximal tubule (termed S1) of the renal cortex and to a much lower degree in other organs such as the liver, brain, thyroid, muscle, and heart. It shares a 59% homology with SGLT-1 and has 14 putative transmembrane domains. It is localized to chromosome 6.

SGLT1 is a protein comprising 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, near the medullary proximal tubule (termed S3). It has a molecular weight of approximately 73 kDa and 13 transmembrane domains. It is responsible for reabsorption for the bulk of the remaining glucose. Despite the homology between the two, only one mutation is common: Arg137His. The human intestinal SGLT1 has been localized to chromosome 22.

Several other co-transporters in this family include SGLT4, SGLT5, SGLT6, and SMIT1 that are expressed in several tissues, including the kidneys. SGLT3 is a glucose-gated ion channel expressed in cholinergic neurons and the neuromuscular junction and may play a role in diet-trigged intestinal motility.

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.

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. The bulk of glucose is reabsorbed at the S1 segment by the high-capacity SGLT2 transporter, whereas the remaining glucose that enters the S3 segment is reabsorbed by the high-affinity SGLT1 transporter; together they minimize glucose loss in the urine.[11]

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

To date, only loss of function mutations have been identified in renal glucose transporters. Patients with FRG can be characterized according to the amount of glucose excreted in a 24-h urine collection, normalized for body surface: mild renal glucosuria for < 10 g/1.73 m2 per day and severe renal glucosuria for ≥10 g/1.73 m2 per day.[12]

Familial renal glycosuria (FRG) is a rare renal tubular disorder caused by mutations with the SLCA2 gene (FRG, McKusick 233100). This gene is mapped to chromosome 16p11.2. The first report of such a gene mutation was in 2000.[13] The mode of inheritance that best fits FRG has been suggested to be co-dominance with incomplete penetrance. Many heterozygous individuals display mild glycosuria (< 0.1 g/1.73 m2/24 h), others have varying degrees of glycosuria in the absence of hyperglycemia. Homozygous or compound heterozygous individuals usually have severe renal glycosuria in excess of 100 g/1.73 m2/24 h.[14, 15, 16]  Some mutations retain an 80% capacity of glucose transport, whilst others completely abolish protein expression.[17]

However, not all individuals with similar or identical mutations have the same degree of increased glucose excretion, suggesting a role of non-genetic factors or other genes that may play a role in glucose transport.[18] Also other SGLTs that are known to be expressed in the kidney and whose functions have not yet been clarified are candidates for modified genes in FRG. The role of other candidate genes is also supported by the finding of at least 3 patients with FRG in whom sequencing of the entire coding region of SLC5A2 showed no mutations.[19, 20]



United States

Depending on the screening criteria used, the incidence of renal glycosuria in the general population was approximately 0.29%.[21, 22]


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).


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


The disease has not been reported to occur in any increased frequency in either males or females.[23]


Although several reports describe younger patients, the condition can occur in all age groups.

Kidney Biopsy

Kidney biopsy in patients with FRG show normal kidney tissue using light microscopy, immunofluorescence and electron microscopy.


The prognosis is excellent with no recorded mortality and the only morbidity being polyuria and enuresis and later a mild growth and pubertal maturation delay observed during a follow-up period of 30 years.[24]   




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.

Mutations of the SGLT-2 gene have not been associated with other clinical abnormalities such as hypoglycemia, tendency to develop diabetes mellitus, chronic kidney disease or higher rates of infection, especially urinary tract infections.[15] Age at diagnosis ranges from childhood to adulthood. Polyuria associated with sodium wasting and/or aminoaciduria has been reported when daily urinary excretion of glucose is high.[2, 25] Low levels of glycosylated hemoglobin (HbA1c) and insulin have been reported.[26]


No physical examination findings are relevant to renal glucosuria, unless associated with a secondary cause (eg, Fanconi syndrome, diabetes mellitus). Thus, FRG is considered a benign condition, more a phenotype than a disease.

In one patient with FRG polyuria, enuresis and later a mild growth and pubertal maturational delay were reported. Other findings reported in severe FRG include episodic dehydration and ketosis during pregnancy and starvation,[27] the presence of autoantibodies with evidence of autoimmune disease,[28] and increased incidence of urinary tract infections.[28] Activation of the renin-angiotensin-aldosterone system, secondary to natriuresis and possible extracellular volume depletion, has been seen. Hypercalcemia was identified in 5 of 7 male children, although the reason for this finding remains elusive. Several reports have described selective aminoaciduria, which has been postulated to be secondary to glucosuria and not a primary effect of SGLT2 mutation.[29, 30, 31] The proposed mechanism is that glucosuria is causing a depolarization and dissipation of the electric gradient of sodium-dependent amino acid transporters in the proximal renal tubule.

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).


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.


FRG is an entity considered to be a benign condition, more a phenotype than a disease.  Some of the following have been reported with this condition:

  • Polyuria and enuresis and later a mild growth and pubertal maturation
  • Episodic dehydration and ketosis during pregnancy and starvation [24]
  • Presence of several autoantibodies without clinical evidence of autoimmune disease [36]
  • An increased incidence of urinary tract infections [37]
  • Activation of the renin-angiotensin-aldosterone system, secondary to natriuresis and possible extracellular volume depletion
  • Hypercalciuria [38]
  • Selective aminoaciduria [39, 40]




Laboratory Studies

The following studies are indicated in renal glucosuria:

  • Urinalysis with microscopic analysis

  • Fasting blood glucose concentration

  • Serum electrolyte, bicarbonate, phosphorus, and uric acid levels

  • Glycosylated hemoglobin levels

  • A 24-hour urine collection for amino acids when other tubular abnormalities are present

  • Fractional excretion of phosphorus (< 15%), uric acid (< 15%, or uric acid per dL glomerular filtration rate [GFR] < 0.55), sodium (normal limit [NL] approximately 1-3%), potassium (< 25%), bicarbonate (NL < 15%)

Histologic Findings

To date, no direct evidence of SGLT2 heterozygous mutations in kidney tissue has been obtained.[41]



Medical Care

Benign renal glucosuria is a self-limiting process and requires no special medical care. If other associated findings suggest tubular disorders, then appropriate interventions are required. Selective inhibitors of SGLT2 such as dapagliflozin and canagliflozin are a new family of antidiabetic agents recently approved for lowering of blood sugar levels in patients with type 2 diabetes mellitus.[42] Dapagliflozin which is 1200-fold more selective for SGLT2 than SGLT1, either as monotherapy or in combination with other antidiabetic agents. SGLT2 inhibitors reduce blood glucose levels in patients with type 2 diabetes mellitus by inhibiting the glucose reabsorption pathway which results in glucosuria. Studies have also shown that SGLT2 inhibitors reduce body weight and systolic blood pressure, mainly due to its diuretic effect i.e. osmotic diuresis following loss of glucose but also mild urinary sodium loss.[42, 43, 44, 45]


Consultation with a pediatric nephrologist may be appropriate to exclude other forms of proximal tubulopathy.


No special dietary instructions are required. In a very rare case of extremely large amounts of urinary glucose, glucose or another carbohydrate may be required during episodes of great physical activity to prevent hypoglycemia.


No restriction of activity is necessary.



Medication Summary

No treatment is required for benign renal glucosuria.



Further Outpatient Care

See the list below:

  • Routine medical follow-up care with the primary care provider is required for patients with renal glucosuria.


No known complications to date.


See the list below:

  • Prognosis for benign renal glucosuria is excellent.

Patient Education

See the list below:

  • Benign renal glucosuria has no relationship to diabetes mellitus. Ensure that the patient and family understand this and the excellent prognosis.


Questions & Answers


What is renal glucosuria?

What is the role of glucose homeostasis in renal glucosuria?

What is the pathophysiology of renal glucosuria?

What is the role of SGLT2 protein in the pathophysiology of renal glucosuria?

What is the tubular maximum for glucose by age group?

What is familial renal glycosuria (FRG)?

What is the prevalence of renal glucosuria in the US?

What is the morbidity associated with renal glucosuria?

What are the racial predilections of renal glucosuria?

What are the sexual predilections of renal glucosuria?

Which age groups have the highest prevalence of renal glucosuria?

What are the biopsy findings characteristic of familial renal glycosuria (FRG)?

What is the prognosis of renal glucosuria?


Which clinical history findings are characteristic of renal glucosuria?

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What causes renal glucosuria?

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What are the differential diagnoses for Renal Glucosuria?


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How is renal glucosuria treated?

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