Hypouricemia

Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute kidney failure.{{cite journal|vauthors=Ito O, Hasegawa Y, Sato K, Mitsui H, Yuda F, Sato H, Ito S, Kudo K |title=A case of exercise-induced acute renal failure in a patient with idiopathic renal hypouricemia developed during antihypertensive therapy with losartan and trichlormethiazide |journal=Hypertens. Res. |volume=26 |issue=6 |pages=509–13 |date=June 2003 |pmid=12862209 |doi=10.1291/hypres.26.509 |doi-access=free }}{{cite journal|vauthors=Ohta T, Sakano T, Igarashi T, Itami N, Ogawa T | title = Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan| journal = Nephrol. Dial. Transplant.| volume = 19| issue = 6| pages = 1447–53|date=June 2004| pmid = 15150354| doi = 10.1093/ndt/gfh094| doi-access = free}}{{cite journal|vauthors=Mima A, Ichida K, Matsubara T, Kanamori H, Inui E, Tanaka M, Manabe Y, Iehara N, Tanaka Y, Yanagita M, Yoshioka A, Arai H, Kawamura M, Usami K, Hosoya T, Kita T, Fukatsu A | title = Acute Renal Failure After Exercise in a Japanese Sumo Wrestler With Renal Hypouricemia| journal = Am. J. Med. Sci.| volume = 336| issue = 6| pages = 512–514|date=December 2008| pmid = 19092327| doi = 10.1097/MAJ.0b013e318164717f}} There is also evidence that hypouricemia can worsen conditions such as rheumatoid arthritis, especially when combined with low Vitamin C uptake, due to free radical damage.{{cite journal|vauthors=Mahajan M, Kaur S, Mahajan S, Kant R |title=Uric acid a better scavenger of free radicals than vitamin C in rheumatoid arthritis.|journal= Indian Journal of Clinical Biochemistry| volume=24| issue=2| pages=205–207|date=April 2009| pmid=23105835| doi=10.1007/s12291-009-0038-6| pmc=3453227}}

Hypouricemia is often benign and not a medical condition, but it is a useful medical sign. It is known occasionally to result in a decreased ability to concentrate urine due to decreased hypertonicity of the renal medulla, and may contribute to hypotension when other risk factors are present. Hypotonicity of the renal medulla is considered normal in the fetus and in infants due to hypouricemia caused by low protein intake. {{cite web |last1=Chevalier |first1=Robert |title=Fetal and Neonatal Physiology (Fourth Edition), 2011 |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/kidney-concentrating-capacity |website=Science Direct |access-date=7 December 2023}} Hypouricemia is usually due to drugs and toxic agents, sometimes to diet or genetics, and, rarely, suggests an underlying medical condition.{{cn|date=November 2021}}

The majority of drugs that contribute to hypouricemia are uricosuric drugs that increase the excretion of uric acid from the blood into the urine.{{cite journal|vauthors=Ramsdell CM, Kelley WN | title = The clinical significance of hypouricemia| journal = Annals of Internal Medicine| volume = 78| issue = 2| pages = 239–42|date=February 1973| pmid = 4683752| doi = 10.7326/0003-4819-78-2-239}} Others include drugs that reduce the production of uric acid: xanthine oxidase inhibitors, urate oxidase (rasburicase), and sevelamer.{{cite journal |vauthors=Garg JP, Chasan-Taber S, Blair A, etal | title = Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial| journal = Arthritis and Rheumatism| volume = 52| issue = 1| pages = 290–5|date=January 2005| pmid = 15641045| doi = 10.1002/art.20781| doi-access = free}}

Hypouricemia is common in vegetarians and vegans due to the low purine content of most vegetarian diets.{{cite journal |vauthors=Siener R, Hesse A | title = The effect of a vegetarian and different omnivorous diets on urinary risk factors for uric acid stone formation | journal = Eur J Nutr | year = 2003 | volume = 42 | pages = 332–7| doi = 10.1007/s00394-003-0428-0 | pmid = 14673606 | issue = 6| s2cid = 25531908 }} Vegetarian diet has been found to result in mean serum uric acid values as low as 239 μmol/L (2.7 mg/dL).{{cite journal |vauthors=Szeto YT, Kwok TC, Benzie IF |title=Effects of a long-term vegetarian diet on biomarkers of antioxidant status and cardiovascular disease risk |journal=Nutrition |volume=20 |issue=10 |pages=863–6 |date=October 2004 |pmid=15474873 |doi=10.1016/j.nut.2004.06.006 }} While a vegetarian diet is typically seen as beneficial with respect to conditions such as gout, it may be associated with some other health conditions.{{Citation needed|date=December 2008}}

Transient hypouricemia sometimes is produced by total parenteral nutrition.{{cite journal |author=Koretz RL |title=Hypouricemia--a transient biochemical phenomenon of total parenteral nutrition |journal=Am. J. Clin. Nutr. |volume=34 |issue=11 |pages=2493–8 |date=November 1981 |pmid=6795918 |doi= 10.1093/ajcn/34.11.2493|doi-access=free }} Paradoxically, total parenteral nutrition may produce hypouricemia followed shortly by acute gout, a condition normally associated with hyperuricemia.{{cite journal|vauthors=Moyer RA, John DS | title = Acute gout precipitated by total parenteral nutrition| journal = J. Rheumatol.| volume = 30| issue = 4| pages = 849–50|date=April 2003| pmid = 12672211}}{{cite journal|vauthors=Derus CL, Levinson DJ, Bowman B, Bengoa JM, Sitrin MD | title = Altered fractional excretion of uric acid during total parenteral nutrition| journal = J. Rheumatol.| volume = 14| issue = 5| pages = 978–81|date=October 1987| pmid = 3123676}} The reasons for this are unclear.

Two kinds of genetic mutations are known to cause hypouricemia: mutations causing xanthine oxidase deficiency, which reduces the production of uric acid; and mutations causing abnormal kidney function that increases the excretion of uric acid. Collectively known as familial renal hypouricemia, the latter mutations are of two types, involving defects of presecretory and postsecretory reabsorption.{{cn|date=November 2021}}

A genetic mutation in Dalmatian dogs causes hypouricemia due to a kidney defect that interferes with reabsorption of uric acid. A similar mutation has been reported in a human brother and sister.{{cite journal|vauthors=Greene ML, Marcus R, Aurbach GD, Kazam ES, Seegmiller JE | title = Hypouricemia due to isolated renal tubular defect. Dalmatian dog mutation in man| journal = Am. J. Med.| volume = 53| issue = 3| pages = 361–7|date=September 1972| pmid = 5054729| doi = 10.1016/0002-9343(72)90181-7}}

In humans, loss-of-function mutations in the gene URAT1 are associated with presecretory reabsorption defects.{{cite journal|vauthors=Ichida K, Hosoyamada M, Kamatani N, Kamitsuji S, Hisatome I, Shibasaki T, Hosoya T | title = Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese| journal = Clin. Genet.| volume = 74| issue = 3| pages = 243–51|date=September 2008| pmid = 18492088| doi = 10.1111/j.1399-0004.2008.01021.x| s2cid = 205406749}}{{cite journal|vauthors=Takahashi T, Tsuchida S, Oyamada T, Ohno T, Miyashita M, Saito S, Komatsu K, Takashina K, Takada G | title = Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese| journal = Pediatr. Nephrol.| volume = 20| issue = 5| pages = 576–8|date=May 2005| pmid = 15772829| doi = 10.1007/s00467-005-1830-z | s2cid = 12711324}}{{cite journal| vauthors = Wakida N, Tuyen DG, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K| title = Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia| journal = J. Clin. Endocrinol. Metab.| volume = 90| issue = 4| pages = 2169–74| date = April 2005| pmid = 15634722| doi = 10.1210/jc.2004-1111| doi-access = free}}

Medical conditions that can cause hypouricemia include:

• Fanconi syndrome
• Hyperthyroidism
• Multiple sclerosis{{cite journal |vauthors=Toncev G, Milicic B, Toncev S, Samardzic G |title=Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood–brain barrier dysfunction |journal=Eur. J. Neurol. |volume=9 |issue=3 |pages=221–6 |date=May 2002 |pmid=11985629 |doi=10.1046/j.1468-1331.2002.00384.x |s2cid=7832500 }}
• Myeloma
• Nephritis
• Wilson's disease
• Purine nucleoside phosphorylase (PNP) deficiency{{Cite journal|last=Wilcox|first=W. D.|date=June 1996|title=Abnormal serum uric acid levels in children|journal=The Journal of Pediatrics|volume=128|issue=6|pages=731–741|issn=0022-3476|pmid=8648529|doi=10.1016/S0022-3476(96)70322-0}}

Uric acid clearance should also be performed, increase in clearance points to proximal tubular defects in the kidney, normal or reduced clearance points to a defect in xanthine oxidase.{{cn|date=November 2021}}

Idiopathic hypouricemia usually requires no treatment. In some cases, hypouricemia is a medical sign of an underlying condition that does require treatment. For example, if hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its risk of uric acid nephrolithiasis, the hyperuricosuria may require treatment.{{cite journal| vauthors = Martín Hernández E, Aparicio López C, Alvarez Calatayud G, García Herrera MA| title = [Vesical uric acid lithiasis in a child with renal hypouricemia]| language = es| journal = An. Esp. Pediatr.| volume = 55| issue = 3| pages = 273–6| date = September 2001| pmid = 11676906| url = http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0103&rev=37&vol=55&num=3&pag=273| access-date = 2008-12-25| archive-url = https://web.archive.org/web/20090327023934/http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0103&rev=37&vol=55&num=3&pag=273| archive-date = 2009-03-27| url-status = dead}}

• Inositol{{Citation needed|date=October 2008}}
• Antiuricosurics

In one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% of hospitalized men. (The definition was less than 0.14 mmol/L for women and less than 0.20 mmol/L in men.) {{cite journal |author=Crook M |title=Hypouricaemia in a hospital population |journal=Scand. J. Clin. Lab. Invest. |volume=53 |issue=8 |pages=883–5 |date=December 1993 |pmid=8140400 |doi= 10.3109/00365519309086502}}

• Hyperuricemia

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{{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}}

{{Clinical biochemistry blood tests}}

Category:Uric acid

Category:Abnormal clinical and laboratory findings for blood