Hypouricemia Explained

Hypouricemia should not be confused with Hyperuricemia.

Hypouricemia

Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men.[1] Hypouricemia usually is benign and sometimes is a sign of a medical condition.

Presentation

Complications

Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute kidney failure.[2] [3] [4] 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.[5]

Causes

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. [6] Hypouricemia is usually due to drugs and toxic agents, sometimes to diet or genetics, and, rarely, suggests an underlying medical condition.

Medication

The majority of drugs that contribute to hypouricemia are uricosuric drugs that increase the excretion of uric acid from the blood into the urine.[7] Others include drugs that reduce the production of uric acid: xanthine oxidase inhibitors, urate oxidase (rasburicase), and sevelamer.[8]

Diet

Hypouricemia is common in vegetarians and vegans due to the low purine content of most vegetarian diets.[9] Vegetarian diet has been found to result in mean serum uric acid values as low as 239 μmol/L (2.7 mg/dL).[10] 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.

Transient hypouricemia sometimes is produced by total parenteral nutrition.[11] Paradoxically, total parenteral nutrition may produce hypouricemia followed shortly by acute gout, a condition normally associated with hyperuricemia.[12] [13] The reasons for this are unclear.

Genetics

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.

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.[14]

In humans, loss-of-function mutations in the gene URAT1 are associated with presecretory reabsorption defects.[15] [16] [17]

Medical conditions

Medical conditions that can cause hypouricemia include:

Diagnosis

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.

Treatment

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.[20]

Drugs and dietary supplements that may be helpful

Prevalence

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.) [21]

See also

Notes and References

  1. Chizyński K, Rózycka M . [Hyperuricemia] . pl . Pol. Merkur. Lekarski . 19 . 113 . 693–6 . November 2005 . 16498814 .
  2. Ito O, Hasegawa Y, Sato K, Mitsui H, Yuda F, Sato H, Ito S, Kudo K . A case of exercise-induced acute renal failure in a patient with idiopathic renal hypouricemia developed during antihypertensive therapy with losartan and trichlormethiazide . Hypertens. Res. . 26 . 6 . 509–13 . June 2003 . 12862209 . 10.1291/hypres.26.509 . free .
  3. Ohta T, Sakano T, Igarashi T, Itami N, Ogawa T . Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan. Nephrol. Dial. Transplant.. 19. 6. 1447–53. June 2004. 15150354. 10.1093/ndt/gfh094. free.
  4. 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 . Acute Renal Failure After Exercise in a Japanese Sumo Wrestler With Renal Hypouricemia. Am. J. Med. Sci.. 336. 6. 512–514. December 2008. 19092327. 10.1097/MAJ.0b013e318164717f.
  5. Mahajan M, Kaur S, Mahajan S, Kant R . Uric acid a better scavenger of free radicals than vitamin C in rheumatoid arthritis.. Indian Journal of Clinical Biochemistry. 24. 2. 205–207. April 2009. 23105835. 10.1007/s12291-009-0038-6. 3453227.
  6. Web site: Chevalier . Robert . Fetal and Neonatal Physiology (Fourth Edition), 2011 . Science Direct . 7 December 2023.
  7. Ramsdell CM, Kelley WN . The clinical significance of hypouricemia. Annals of Internal Medicine. 78. 2. 239–42. February 1973. 4683752. 10.7326/0003-4819-78-2-239.
  8. Garg JP, Chasan-Taber S, Blair A, etal . Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Arthritis and Rheumatism. 52. 1. 290–5. January 2005. 15641045. 10.1002/art.20781. free.
  9. Siener R, Hesse A . The effect of a vegetarian and different omnivorous diets on urinary risk factors for uric acid stone formation . Eur J Nutr . 2003 . 42 . 332–7. 10.1007/s00394-003-0428-0 . 14673606 . 6. 25531908 .
  10. Szeto YT, Kwok TC, Benzie IF . Effects of a long-term vegetarian diet on biomarkers of antioxidant status and cardiovascular disease risk . Nutrition . 20 . 10 . 863–6 . October 2004 . 15474873 . 10.1016/j.nut.2004.06.006 .
  11. Koretz RL . Hypouricemia--a transient biochemical phenomenon of total parenteral nutrition . Am. J. Clin. Nutr. . 34 . 11 . 2493–8 . November 1981 . 6795918 . 10.1093/ajcn/34.11.2493. free .
  12. Moyer RA, John DS . Acute gout precipitated by total parenteral nutrition. J. Rheumatol.. 30. 4. 849–50. April 2003. 12672211.
  13. Derus CL, Levinson DJ, Bowman B, Bengoa JM, Sitrin MD . Altered fractional excretion of uric acid during total parenteral nutrition. J. Rheumatol.. 14. 5. 978–81. October 1987. 3123676.
  14. Greene ML, Marcus R, Aurbach GD, Kazam ES, Seegmiller JE . Hypouricemia due to isolated renal tubular defect. Dalmatian dog mutation in man. Am. J. Med.. 53. 3. 361–7. September 1972. 5054729. 10.1016/0002-9343(72)90181-7.
  15. Ichida K, Hosoyamada M, Kamatani N, Kamitsuji S, Hisatome I, Shibasaki T, Hosoya T . Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese. Clin. Genet.. 74. 3. 243–51. September 2008. 18492088. 10.1111/j.1399-0004.2008.01021.x. 205406749.
  16. Takahashi T, Tsuchida S, Oyamada T, Ohno T, Miyashita M, Saito S, Komatsu K, Takashina K, Takada G . Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese. Pediatr. Nephrol.. 20. 5. 576–8. May 2005. 15772829. 10.1007/s00467-005-1830-z . 12711324.
  17. 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. Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia. J. Clin. Endocrinol. Metab.. 90. 4. 2169–74. April 2005. 15634722. 10.1210/jc.2004-1111. free.
  18. Toncev G, Milicic B, Toncev S, Samardzic G . Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood–brain barrier dysfunction . Eur. J. Neurol. . 9 . 3 . 221–6 . May 2002 . 11985629 . 10.1046/j.1468-1331.2002.00384.x . 7832500 .
  19. Wilcox. W. D.. June 1996. Abnormal serum uric acid levels in children. The Journal of Pediatrics. 128. 6. 731–741. 0022-3476. 8648529. 10.1016/S0022-3476(96)70322-0.
  20. Martín Hernández E, Aparicio López C, Alvarez Calatayud G, García Herrera MA. [Vesical uric acid lithiasis in a child with renal hypouricemia]]. es. An. Esp. Pediatr.. 55. 3. 273–6. September 2001. 11676906. 2008-12-25. 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. 2009-03-27. dead.
  21. Crook M . Hypouricaemia in a hospital population . Scand. J. Clin. Lab. Invest. . 53 . 8 . 883–5 . December 1993 . 8140400 . 10.3109/00365519309086502.

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