Crystal-induced arthropathies: Recent investigative advances

Current Opinion in Rheumatology

Volumn 18, Issue 3, 2006, Pages 249-255

  Ellman, Michael H ^a   Becker, Michael A ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

ANKH gene; Calcium pyrophosphate deposition disease (pseudogout); Gout; Hyperuricemia; Urate transporter

Indexed keywords

ALLOPURINOL; AMLODIPINE; CLARITHROMYCIN; COLCHICINE; CORTICOSTEROID; FEBUXOSTAT; FENOFIBRATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDOMETACIN; LOSARTAN; MACROLIDE; MISOPROSTOL; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; PREDNISONE; PURICASE; TAMM HORSFALL GLYCOPROTEIN; URATE; URATE OXIDASE;

ALCOHOL CONSUMPTION; ANKH GENE; ARTHROPATHY; CARDIOVASCULAR DISEASE; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL; COMORBIDITY; CRYSTAL; DIET; DISEASE ASSOCIATION; FAMILIAL CALCIUM PYROPHOSPHATE DISEASE; FAMILIAL DISEASE; GENE; GENE MUTATION; GENETIC ASSOCIATION; GENETIC MARKER; GOUT; HUMAN; HYPERTENSION; HYPERURICEMIA; KIDNEY TUBULE; LESCH NYHAN SYNDROME; MEDULLARY SPONGE KIDNEY; METABOLIC SYNDROME X; PATHOGENESIS; PRIORITY JOURNAL; PSEUDOGOUT; REVIEW; SKIN DISEASE; UMOD GENE; URIC ACID NEPHROPATHY;

AGED; ARTHRITIS, GOUTY; CHONDROCALCINOSIS; HUMANS; HYPERURICEMIA; ORGANIC ANION TRANSPORTERS; URIC ACID;

EID: 33646704714     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.bor.0000218944.89365.dd     Document Type: Review

References (47)

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18. Doehner W, Anker SD. Uric acid in chronic heart failure. Semin Nephrol 2005; 24:61-66. This review emphasizes that chronic heart failure is more than a hemodynamic disorder but is a complex event that includes perturbations in urate and xanthine oxidase. High-dose allopurinol (≥300 mg/dl) was associated with less all-cause mortality than low-dose allopurinol (< 300 mg/dl).
19. Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int 2005; 67:1739-1742. Rat studies showing that hyperuricemia decreases serum nitric oxide, providing a mechanism for endothelial damage.
20. Sanchez-Lozada LG, Tapia E, Santamaria J, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005; 67:237-247. In normal rats made hyperuricemic, renal cortical vasoconstriction and glomerular hypertension occurred that was prevented by allopurinol treatment. In rats with preexisting renal disease, hyperuricemia increased renal vascular damage. The animal models documenting renal damage and hypertension with hyperuricemia are compelling.
21. Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004; 350:1093-1103.
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23. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med 2005;143:499-516. This comprehensive review of gout is part of the Annals of Internal Medicine's Physiology in Medicine series, linking medicine with science. This article does that admirably, bringing readers up to date about diet and urate levels, renal handling of urate, urate crystals and inflammation, etc. Their review of the basics of purine metabolism should be understandable to the nonrheumatologist.
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28. Hahn PC, Edwards NL. Management of hyperuricemia. In: Koopman, WJ, Moreland, LW, editors. Arthritis and allied conditions. 15th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. pp. 2341-2355. Also an excellent review.
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33. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum 2004; 51:321-325. This paper reinforces the notion that targeting serum urate levels to approximately 6.0 mg/dL will reduce the incidence of recurrent gouty arthritis. The authors found a direct linear correlation between gout attacks and increasing serum urate levels.
34. Becker M, Schumacher HR Jr, Wortmann RL, et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. Arthritis Rheum 2005; 52:916-923. This paper reports a phase 2 placebo-controlled 28-day trial demonstrating the short-term safety and urate-lowering efficacy of febuxostat (40 mg, 80 mg, or 120 mg daily) in patients with gout and serum urate levels of 8 mg/dl or greater.
35. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353:2450-2461. A phase 3 study starting with 762 patients with gout and serum urate concentrations of at least 8.0 mg/dl who received either febuxostat (80 mg or 120 mg) or allopurinol 300 mg daily for 52 weeks. Febuxostat at 80 or 120 mg was more effective than the standard dose of 300 mg allopurinol in lowering serum urate, but clinical outcomes (gout flare incidence and tophus size) were improved to similar degrees by both drugs at 52 weeks. Febuxostat will likely be a major therapeutic help to physicians treating patients with gout who are allergic or sensitive to allopurinol, and, hopefully, patients with moderate to severe chronic kidney disease. Febuxostat shares with allopurinol the propensity for precipitating gout flares, and prophylaxis should be used with medicines such as colchicine for as long as 6 months.
36. Mayer MD, Khosravan R, Vernillet L, et al. Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment. Am J Ther 2005; 12: 22-34. The story is still incomplete regarding the safety of febuxostat in patients with more than mild renal insufficiency, and febuxostat awaits further testing and experience in renal insufficiency.
37. Hung S, Chung W-H, Liou L-B, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005; 102:4134-4139. [Epub ahead of print] The association of this genetic marker and allopurinol and severe cutaneous reactions was striking, all of the patients with the adverse skin reactions carried the HLA-B*5801 allele! It will be important, of course, to confirm this link in other ethnic groups.
38. Liu CY, Sims-McCallum RP, Schiffer CA. A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy. Leuk Res 2005; 29:463-465. Multiple doses of rasburicase (an expensive medication) are often recommended in cancer patients with hyperuricemia and bulky tumors requiring immediate chemotherapy. Perhaps single doses and careful observation will suffice in many of the patients and will result in significant cost savings.
39. Sundy JS, Becker MA, Baraf HSB, et al. A phase 2 study of multiple doses of intravenous polyethylene glycol (PEG)-uricase in patients with hyperuricemia and refractory gout. Arthritis Rheum 2005; 52:3679. Forty-one patients were randomly assigned to receive doses of PEG-uricase administered intravenously every 2-4 weeks over 12 weeks of treatment. The mean plasma urate fell significantly; there were no reported anaphylactic reactions, but the dropout rate due to adverse events considered possible infusion reactions was high. Not unexpectedly, gout flares were frequent.
40. Bomalaski JS, Clark MA. Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase. Curr Rheumatol Rep 2004; 6:240-247.
41. Enomoto A, Endou H. Roles of organic transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol 2005; 9:195-205. An excellent review.
42. Ichida K, Hosoyamada M, Hisatome I, et al. Clinical and molecular analysis of patients with renal hypouricemia in Japan: influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol 2004; 15:164-173.
43. Habu Y, Yano I, Okudo M, et al. Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after hyperuricemia in the rat kidney. Biochem Pharmacol 2005; 69:993-999. In rats made hyperuricemic with rat chow containing uric acid and 5% oxonic acid, renal disease developed and OAT activity decreased but was reversible with restoration of normal urate levels. The recovery rate of the OAT was slower than that of the creatinine clearance, suggesting that OAT activity should be assessed when prescribing drug regimens in patients recovering from renal dysfunction.
44. Kang DH, Han L, Ouyang X, et al. Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol 2005; 25:425-433. The authors state that soluble urate stimulates vascular smooth muscle cell proliferation but the mechanism by which uric acid enters the cells is not known. They demonstrate in isolated rat tissue that voltage-sensitive and OAT pathways may have important roles in transporting urate in tissues other than renal epithelium. This, in turn, suggests a more expanded role for OATs.
45. Calado J, Gaspar A, Clemente C, Rueff J. A novel heterozygous missense mutation in the UMOD gene responsible for familial juvenile hyperuricemic nephropathy. BMC Med Genet 2005; 6:5. Not only is there new terminology to learn, but readers must recall Tamm-Horsfall protein from the recesses of memory. This autosomal dominant disorder leads to end-stage renal disease at young ages. The disease histologically resembles medullary cystic kidney disease and may represent a different facet of that disease.
46. Lens XM, Banet JF, Outeda P, Barrio-Lucia V. A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease. Am J Kidney Dis 2005; 46: 52-57. Further studies of the UMOD gene and uromodulin or Tamm-Horsfall protein, confirming that mutations of the gene are associated with the above clinically similar severe renal disorders.
47. - mice have abnormalities in intracellular and extracellular PPi and widespread soft tissue calcifications. This led to the discovery of abnormalities of the equivalent human gene (ANKH) and its association with familial chondrocalcinosis. This paper adds to the excitement of the ANK story by describing sporadic cases of chondrocalcinosis with a mutation in the ANKH gene.