PDF
ePub
Citation
Print
Abstract
Gout is a disease that causes painful inflammatory arthritis related to hyperuricemia, due to the incorrect metabolism of uric acid. Decreased renal excretion of urate is thought to be the major hyperuricemic mechanism. Most genes responsible for the serum uric acid (SUA) level encode uric acid transporters or related regulatory proteins. The acquired effects can also modulate SUA level and uric acid excretion, which can result in acute gout. Interestingly, kidney related comorbidities in gout, such as hypertension, chronic kidney disease (CKD), and urolithiasis, all have a fairly high prevalence. Recent advancements in genetics and molecular physiology have greatly improved our understanding of renal reabsorption and secretion of filtered uric acid. Furthermore, the baseline SUA level appears to be established by a net balance between absorption and secretion through the epithelium of the kidneys and intestines. There have also been considerable progress in the management of gout patients with CKD. Increased prevalence of gout with CKD can be balanced by an expanded spectrum of treatment options for this important disease. Another issue is that lowering of the uric acid level can reduce the incidence of cardiovascular disease, renal disease, and urological complications. Basic research and clinical studies on these mechanisms might be helpful in determining the appropriate treatment for hyperuricemic patients. Based on currently existing literature, there have been improvements associated with medications that lower uric acid, particularly xanthine oxidase inhibitors. Here, we review the pathogenesis and epidemiology of hyperuricemia, specific diseases related to uric acid, and up-to-date perspectives on their management.
REFERENCES
1.McNaughton Collins M., Wilt T. Allopurinol for chronic prostatitis. Cochrane Database Syst Rev. 2000. 2:CD001041.
2.Zhu Y., Pandya BJ., Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011. 63:3136–41.
3.Hooper DC., Spitsin S., Kean RB., Champion JM., Dickson GM., Chaudhry I, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A. 1998. 95:675–80.
4.Spitsin S., Koprowski H. Role of uric acid in Alzheimerʼs disease. J Alzheimers Dis. 2010. 19:1337–8.
5.Ascherio A., LeWitt PA., Xu K., Eberly S., Watts A., Matson WR, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol. 2009. 66:1460–8.
6.Hershfield MS., Roberts LJ 2nd., Ganson NJ., Kelly SJ., Santisteban I., Scarlett E, et al. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo. Proc Natl Acad Sci U S A. 2010. 107:14351–6.
7.Latif W., Karaboyas A., Tong L., Winchester JF., Arrington CJ., Pisoni RL, et al. Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis population. Clin J Am Soc Nephrol. 2011. 6:2470–7.
8.Baldree LA., Stapleton FB. Uric acid metabolism in children. Pediatr Clin North Am. 1990. 37:391–418.
9.Al-Arfaj AS. Hyperuricemia in Saudi Arabia. Rheumatol Int. 2001. 20:61–4.
10.Conen D., Wietlisbach V., Bovet P., Shamlaye C., Riesen W., Paccaud F, et al. Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country. BMC Public Health. 2004. 4:9.
11.Anzai N., Jutabha P., Amonpatumrat-Takahashi S., Sakurai H. Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies. Clin Exp Nephrol. 2012. 16:89–95.
12.Perez-Ruiz F., Calabozo M., Erauskin GG., Ruibal A., Herrero-Beites AM. Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Rheum. 2002. 47:610–3.
13.Ichida K., Matsuo H., Takada T., Nakayama A., Murakami K., Shimizu T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012. 3:764.
14.Chou CT., Lai JS. The epidemiology of hyperuricaemia and gout in Taiwan aborigines. Br J Rheumatol. 1998. 37:258–62.
15.Trifirò G., Morabito P., Cavagna L., Ferrajolo C., Pecchioli S., Simonetti M, et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis. 2013. 72:694–700.
16.George J., Carr E., Davies J., Belch JJ., Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006. 114:2508–16.
17.Grams ME., Juraschek SP., Selvin E., Foster MC., Inker LA., Eckfeldt JH, et al. Trends in the prevalence of reduced GFR in the United States: a comparison of creatinine- and cystatin C-based estimates. Am J Kidney Dis. 2013. 62:253–60.
18.Jing J., Kielstein JT., Schultheiss UT., Sitter T., Titze SI., Schaeffner ES, et al. Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study. Nephrol Dial Transplant. 2015. 30:613–21.
19.Juraschek SP., Kovell LC., Miller ER 3rd., Gelber AC. Association of kidney disease with prevalent gout in the United States in 1988-1994 and 2007-2010. Semin Arthritis Rheum. 2013. 42:551–61.
20.Johnson RJ., Nakagawa T., Jalal D., Sánchez-Lozada LG., Kang DH., Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013. 28:2221–8.
21.Obermayr RP., Temml C., Gutjahr G., Knechtelsdorfer M., Ober-bauer R., Klauser-Braun R. Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 2008. 19:2407–13.
22.Kang DH., Nakagawa T., Feng L., Watanabe S., Han L., Mazzali M, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002. 13:2888–97.
23.Bellomo G., Venanzi S., Verdura C., Saronio P., Esposito A., Timio M. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010. 56:264–72.
24.Zoppini G., Targher G., Chonchol M., Ortalda V., Abaterusso C., Pichiri I, et al. Serum uric acid levels and incident chronic kidney disease in patients with type 2 diabetes and preserved kidney function. Diabetes Care. 2012. 35:99–104.
25.Goicoechea M., de Vinuesa SG., Verdalles U., Ruiz-Caro C., Ampuero J., Rincón A, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010. 5:1388–93.
26.Siu YP., Leung KT., Tong MK., Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006. 47:51–9.
27.Whelton A., MacDonald PA., Chefo S., Gunawardhana L. Preservation of renal function during gout treatment with febuxostat: a quantitative study. Postgrad Med. 2013. 125:106–14.
28.Hosoya T., Kimura K., Itoh S., Inaba M., Uchida S., Tomino Y, et al. The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study. Trials. 2014. 15:26.
29.Maalouf NM., Cameron MA., Moe OW., Sakhaee K. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens. 2004. 13:181–9.
30.Daudon M., Traxer O., Conort P., Lacour B., Jungers P. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol. 2006. 17:2026–33.
31.Lieske JC., de la Vega LS., Gettman MT., Slezak JM., Bergstralh EJ., Melton LJ 3rd, et al. Diabetes mellitus and the risk of urinary tract stones: a population-based case-control study. Am J Kidney Dis. 2006. 48:897–904.
32.Pak CY., Sakhaee K., Moe O., Preminger GM., Poindexter JR., Peterson RD, et al. Biochemical profile of stone-forming patients with diabetes mellitus. Urology. 2003. 61:523–7.
33.Daudon M., Lacour B., Jungers P. Influence of body size on urinary stone composition in men and women. Urol Res. 2006. 34:193–9.
34.Ekeruo WO., Tan YH., Young MD., Dahm P., Maloney ME., Mathias BJ, et al. Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients. J Urol. 2004. 172:159–63.
35.Sakhaee K., Adams-Huet B., Moe OW., Pak CY. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int. 2002. 62:971–9.
36.Abate N., Chandalia M., Cabo-Chan AV Jr., Moe OW., Sakhaee K. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int. 2004. 65:386–92.
37.Fellström B., Danielson BG., Karlström B., Lithell H., Ljunghall S., Vessby B. The influence of a high dietary intake of purine-rich animal protein on urinary urate excretion and supersaturation in renal stone disease. Clin Sci (Lond). 1983. 64:399–405.
38.Pak CY., Sakhaee K., Peterson RD., Poindexter JR., Frawley WH. Biochemical profile of idiopathic uric acid nephrolithiasis. Kidney Int. 2001. 60:757–61.
39.Reddy ST., Wang CY., Sakhaee K., Brinkley L., Pak CY. Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis. 2002. 40:265–74.
40.Preminger GM. Pharmacologic treatment of uric acid calculi. Urol Clin North Am. 1987. 14:335–8.
41.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.
42.Odvina CV. Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol. 2006. 1:1269–74.
43.Krieger JN., Egan KJ., Ross SO., Jacobs R., Berger RE. Chronic pelvic pains represent the most prominent urogenital symptoms of “chronic prostatitis”. Urology. 1996. 48:715–21. discussion 721-2.
44.McNaughton Collins M., Barry MJ. Epidemiology of chronic prostatitis. Curr Opin Urol. 1998. 8:33–7.
45.Moon TD. Questionnaire survey of urologists and primary care physicians' diagnostic and treatment practices for prostatitis. Urology. 1997. 50:543–7.
46.Nickel JC., Nigro M., Valiquette L., Anderson P., Patrick A., Mahoney J, et al. Diagnosis and treatment of prostatitis in Canada. Urology. 1998. 52:797–802.
47.Roberts RO., Lieber MM., Rhodes T., Girman CJ., Bostwick DG., Jacobsen SJ. Prevalence of a physician-assigned diagnosis of prostatitis: the Olmsted County Study of Urinary Symptoms and Health Status Among Men. Urology. 1998. 51:578–84.
48.Persson BE., Ronquist G. Evidence for a mechanistic association between nonbacterial prostatitis and levels of urate and creatinine in expressed prostatic secretion. J Urol. 1996. 155:958–60.
49.Kurkar A., Elderwy AA., Awad SM., Abulsorour S., Aboul-Ella HA., Altaher A. Hyperuricemia: a possible cause of hemospermia. Urology. 2014. 84:609–12.
50.Nickel JC., Siemens DR., Lundie MJ. Allopurinol for prostatitis: where is the evidence? Lancet. 1996. 347:1711–2.
51.Yamanaka H. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids. 2011. 30:1018–29.
Table 1.
Drugs that affect uric acid levels
| Name | Effect on serum uric acid level | Magnitude of effect (%) | Mechanism of action |
|---|---|---|---|
| Losartan | Down | 20-25 | Uricosuric effect |
| Diuretics | Up | 6-19 | Uric acid reabsorption in proximal tubule |
| Beta-blockers | Up | 6-9 | Unclear |
| ACE inhibitors | Stationary (but attenuates rise | - | Uricosuric effect |
| caused by diuretics) | |||
| Calcium channel blockers | Down | 3-10 | Uricosuric effect |
| Alpha blockers | Stationary | - | - |
| HmG CoA reductase inhibitorsa) | Down | 3.6-12.0 | Uricosuric effect |
| Fenofibrate | Down | 20 | Presumed inhibition of URAT 1 transporter |
| Acetylsalicylic acid | Up at low doses, down at higher doses | 6 with low doses | Low dose: uric acid retention |
| High doses: uricosuric |
XML Download