NORD gratefully acknowledges Julie Rice, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Renal (kidney) glycosuria is a rare condition in which too much of the simple sugar glucose is removed through the urine. This happens even though there are normal or low levels of glucose in the blood. When the kidney is working correctly, glucose is only removed into the urine when there is too much in the blood. However, in people with renal glycosuria, glucose is removed in the urine when it should not be because the renal tubules in the kidneys are not working properly. The renal tubules are the part of the kidney that cleans the blood. Most affected people have no symptoms (asymptomatic). When renal glycosuria occurs by itself, the condition can be inherited in an autosomal dominant or autosomal recessive pattern.
In people with renal glycosuria, glucose is removed in the urine even though there are normal or low levels of glucose in the blood. As blood flows through the kidneys, glucose and other substances are cleaned from the liquid portion of the blood. The newly cleaned blood then moves through tubes in the kidneys (renal tubules). Helpful substances, including glucose, sodium, and wate, are reabsorbed and returned to the bloodstream. Unwanted substances are removed from the bloodstream through the urine. When the kidney is working, glucose is only removed into the urine when there is too much sugar in the blood. However, in people with renal glycosuria, extra glucose is removed and/or, the kidney is unable to reabsorb glucose as quickly as it should. (For more, see “Causes” below.)
Most people with renal glycosuria have no obvious symptoms (asymptomatic). Sometimes, glycosuria can cause excess urination (polyuria), extreme thirst
(polydipsia), and other symptoms. Involuntary urination (enuresis) and mild delays in growth and maturation during puberty have been reported in rare cases. When a person with renal glycosuria is pregnant or starving, this may cause low levels of fluid in the body (dehydration). It can also cause a tissue build-up of certain chemical substances (ketone bodies). Fluids also build up due to too much breakdown of fats (ketosis).
Renal glycosuria is an inherited problem of membrane transport (i.e., an abnormal renal transport syndrome). Membrane transport disorders are marked by problems with the movement (i.e., transport) of one or more compounds across the outer layer of the cell (cell membranes). They are thought to result from harmful genetic changes (mutations) that cause certain membrane proteins to not be made correctly.
Because the renal tubules are not working well, there is a reduction in the levels of glucose in the blood. The body begins to accept this lower level as the new normal and interprets normal levels of glucose as excess, causing the body to remove glucose through urine when levels are not increased (low renal threshold for glucose). In some people, there is a reduction in the maximum rate at which glucose may be reabsorbed into the bloodstream (reduced transport maximum [tubular maximum for glucose or “TmG”]). Renal glycosuria is divided into two major subtypes. Type A has a low renal threshold, and reduced TmG. Type B has a low renal threshold and normal TmG. In addition, there is renal glycosuria type 0, in which there is no renal tubular glucose reabsorption.
The primary cause of renal glycosuria is a harmful change (mutation) in a gene known as “SLC5A2” (also called the renal sodium-glucose cotransporter gene).
Many inheritance patterns have been reported for renal glycosuria, and more research is needed to clarify the pattern of inheritance. Renal glycosuria can be inherited autosomal recessive manner. Recessive genetic conditions occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Autosomal dominant inheritance with reduced penetrance has also been reported. Reduced penetrance means that someone with a genetic mutation may or may not develop symptoms. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
People who inherit two copies of a gene for renal glycosuria (homozygosity) may have more severe symptoms, as do those who inherit one copy of a gene mutation for renal glycosuria and a second copy with a different gene mutation for renal glycosuria in the same gene (compound heterozygotes). Based on such evidence, a codominant inheritance pattern with reduced penetrance has been recently proposed as the best fit. Codominance occurs when both copies of the gene are equally expressed, with neither being dominant or recessive.
Renal glycosuria types A and B have occurred in members of the same family. In such cases, both parents may be normal or may have abnormal renal tubular transport of glucose. Such evidence leads experts to suggest that other genetic or non-genetic factors may be involved in causing renal glycosuria.
Renal glycosuria occurs in about 1/33,000 people in the general population and affects males and females equally. Most people with renal glycosuria have no symptoms (asymptomatic). Less commonly, serious symptoms (e.g., dehydration, ketosis) may be seen. This happens most often under certain conditions such as pregnancy or starvation.
Renal glycosuria is diagnosed based upon laboratory tests of urine and blood. They are looking for glucose in the urine and normal or low levels of glucose in the blood. (Usually, people cannot eat the night before the testing.) Once someone has this diagnosis, they may go on to have genetic testing for changes (mutations) in the SLC5A2 gene to determine risks for family members.
Treatment is not needed for most people with this condition. However, some people with renal glycosuria may develop diabetes mellitus. (For more information, please see the “Related Disorders” section above.) so people with this condition should have testing to rule out diabetes. People with renal glycosuria should have routine medical care with a primary care provider and treatment is based on symptoms.
Genetic counseling will help affected people and their families.
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Porter R. et al., eds. The Merck Manual. 20th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2018.
Jameson JL, et al., eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw-Hill Companies, Inc; 2018.
Djeddi D, Cauliez A, Oulebsir A, Hureaux M, Vanrenterghem A, Vargas-Poussou R. Persistently high urine glucose levels caused by familial renal glycosuria. Arch Pediatr. 2020;27(7):386-387. doi:10.1016/j.arcped.2020.07.002
Lee JH, Kim SA, Jo CH, Lee CH, Kim GH. Urinary concentration defect and renal glycosuria in cyclosporine-treated rats. Electrolyte Blood Press. 2020;18(1):1-9. doi:10.5049/EBP.2020.18.1.1
Li S, Yang Y, Huang L, Kong M, Yang Z. A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature. Mol Med Rep. 2019 May;19(5):4364-4376. doi: 10.3892/mmr.2019.10110. Epub 2019 Apr 1. PMID: 30942416; PMCID: PMC6472135.
Fishman B, Shlomai G, Twig G, et al. Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents. Cardiovasc Diabetol. 2019; 18: 124 https://doi.org/10.1186/s12933-019-0929-7
Ishigaki K, Kato I, Murakami T, et al. Renal dysfunction is rare in Fukuyama congenital muscular dystrophy. Brain Dev. 2019;41(1):43-49. doi:10.1016/j.braindev.2018.07.012
Fishman B, Shlomai G, Twig G, et al. Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents. Cardiovasc Diabetol. 2019;18(1):124. Published 2019 Sep 25. doi:10.1186/s12933-019-0929-7
Samodelov SL, Visentin M, Gai Z, Häusler S, Kullak-Ublick GA. Renal glycosuria as a novel early sign of colistin-induced kidney damage in mice [published online ahead of print, 2019 Oct 7]. Antimicrob Agents Chemother. 2019;63(12):e01650-19. doi:10.1128/AAC.01650-19
Urakami T, Yoda M, Yoshida K, Mine Y, Aoki M, Suzuki J. Renal glucosuria in schoolchildren: Clinical characteristics. Pediatr Int. 2018;60(1):35-40. doi:10.1111/ped.13456
Gu X, Chen M, Xu Y, Wang Y. Acquired renal glucosuria in an undifferentiated connective tissue disease patient with a SLC5A2 heterozygous mutation: A case report. Medicine (Baltimore). 2018;97(50):e13664. doi:10.1097/MD.0000000000013664
Tada H, Kawashiri MA, Sakata K, et al. Renal glucosuria is not associated with atherosclerotic cardiovascular disease outcome in a general Japanese community. Atherosclerosis. 2017;261:111-116. doi:10.1016/j.atherosclerosis.2017.02.015
Gong S, Guo J, Han X, et al. Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria. J Clin Endocrinol Metab. 2017;102(5):1548-1556. doi:10.1210/jc.2016-2332
Ottosson-Laakso E, Tuomi T, Forsén B, et al. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time. PLoS One. 2016;11(1):e0146114. Published 2016 Jan 6. doi:10.1371/journal.pone.0146114
Aires I, Fila M, Polidori D, Santos AR, Costa AB, Calado J. Determination of the renal threshold for glucose excretion in Familial Renal Glucosuria. Nephron. 2015;129(4):300-304. doi:10.1159/000381677
Prié D. Familial renal glycosuria and modifications of glucose renal excretion. Diabetes Metab. 2014;40(6 Suppl 1):S12-S16. doi:10.1016/S1262-3636(14)72690-4
Chino Y, Samukawa Y, Sakai S, et al. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos. 2014;35(7):391-404. doi:10.1002/bdd.1909
Toka HR, Yang J, Zera CA, Duffield JS, Pollak MR, Mount DB. Pregnancy-associated polyuria in familial renal glycosuria. Am J Kidney Dis. 2013;62(6):1160-1164. doi:10.1053/j.ajkd.2013.05.018
Rohfleisch A, Nseir G, Chehade H, Noverraz MG, Venetz JP, Barbey F. Glucosurie rénale [Renal glucosuria]. Rev Med Suisse. 2013;9(378):636-640.
Mauricio D. Inhibidores SGLT-2: de la corteza del manzano y la glucosuria familiar al tratamiento de la diabetes mellitus tipo 2 [Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus]. Med Clin (Barc). 2013;141 Suppl 2:31-35. doi:10.1016/S0025-7753(13)70061-7
Lee H, Han KH, Park HW, Shin JI, Kim CJ, Namgung MK, Kim KH, Koo JW, Chung WY, Lee DY, Kim SY, Cheong HI. Familial renal glucosuria: a clinicogenetic study of 23 additional cases. Pediatr Nephrol. 2012 Jul;27(7):1091-5. doi: 10.1007/s00467-012-2109-9.
Yu L, Lv JC, Zhou XJ, Zhu L, Hou P, Zhang H. Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients. Hum Genet. 2011;129(3):335-344. doi:10.1007/s00439-010-0927-z
Limsuwat C, Prabhakar SS. Reversible renal glycosuria in acute interstitial nephritis. Am J Med Sci. 2012;344(3):245-247. doi:10.1097/MAJ.0b013e318254bd71
Santer R, Calado J. Familial Renal Glucosuria and SGLT2: From a Mendelian Trait to a Therapeutic Target. Clinical Journal of the American Society of Nephrology. 2010;5(1):133-141. doi:https://doi.org/10.2215/CJN.04010609.
Kanai Y, et al. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest. 1994;93:397-404.
Oemar BS, et al. Complete absence of tubular glucose reabsorption; a new type of renal glucosuria. Clin Nephrol. 1987;27:156-60.
De Marchi S, et al. Close genetic linkage between HLA and renal glycosuria. Am J Nephrol. 1984;4:280-86.
De Marchi S, et al. Renal glycosuria: dominant or recessive autosome anomaly? Mode of hereditary transmission based on the analysis of a 3-generation family tree. Minerva Med. 1983;74:301-06.
Elsas LJ, et al. Autosomal recessive inheritance of renal glycosuria. Metabolism. 1971;20:968-75.
Elsas LJ, et al. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J Clin Invest. 1969;48:1845-54.
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD.Updated 10/24/20. Available at: https://omim.org/entry/233100 Accessed October 5, 2021.
Bhimma R. Renal Glucosuria. Medscape. Updated: Dec 10, 2018. https://emedicine.medscape.com/article/983678-overview Accessed October 5, 2021.
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