Gout

Naomi Schlesinger, Peter E Lipsky

• Publisher: Elsevier
• Year: 2018
• ISBN:
  9780323548243
• Topic: Medizin
• Subtopic: Rheumatologie, Orthopädie & Prothetik

Concise and clinically focused, Gout, by Drs. Naomi Schlesinger and Peter E. Lipsky, provides a one-stop overview of recent developments regarding this common form of inflammatory arthritis. Impacting an estimated 8.3 million people in the U.S. alone, gout is seen frequently by both primary care physicians as well as rheumatologists. This resource provides detailed coverage of the epidemiology, causes, diagnosis, management, and treatment of patients with both acute and chronic gout.

• Addresses key topics such as genetics, hyperuricemia, comorbidities of gout, treatment guidelines for acute and chronic gout, classification and diagnosis, and imaging.
• Discusses future outlooks for improving pharmacological and nonpharmacological treatment options, including an overview of drugs in the pipeline.
• Consolidates today's available information on this timely topic into one convenient resource.

Chapter 1

Hyperuricemia and the Silent Deposition of Monosodium Urate Crystals

Mariano Andres, MD, PhD, and Jose-Antonio Bernal, MD, PhD

Abstract

Hyperuricemia is a prevalent condition in Western countries. Although definitions vary across the literature according to differing criteria, hyperuricemia is closely linked with cardiovascular and renal disorders. However, whether it behaves as an independent risk factor or just a bystander is still to be elucidated. The presence of hyperuricemia is required for the formation of monosodium urate crystals and the development of gout. In recent years and owing to advances in musculoskeletal imaging, such as ultrasound and dual-energy computed tomography, accumulating evidence indicates that a significant number of subjects with asymptomatic hyperuricemia may have deposits of monosodium urate crystals at the joints and periarticular tissues without experiencing the manifestations of gout. The relevance of this silent deposition remains to be clarified, but it has certainly led to a redefinition of “hyperuricemia-gout” disorder.

Keywords

DECT; hyperuricemia; monosodium urate crystal; silent crystal deposition; ultrasound; Uric acid

Definition of Hyperuricemia

Hyperuricemia (HU) is the elevation of serum uric acid levels and is a necessary condition for the development of monosodium urate (MSU) crystals and gout. Uric acid is an end product of the metabolism of purines. In nonprimate mammals, uric acid is metabolized to allantoin by uricase, whereas in primates (including humans) purine metabolism stops with uric acid due to a nonfunctional enzyme. The biology and potential advantages of this are reviewed in other chapters of the present work.

Despite general agreement that HU depends on raised serum urate (SU) levels, to date there is no consensus regarding the boundaries of HU. Undoubtedly the risk of gout increases with a rise in SU levels.¹ SU levels tend to vary in the same person over time in relation to dietary intake or weight; also, during gout flares, SU often decreases.² The definition of HU may significantly differ regarding one’s point of view.

Population-based studies have shown variations in SU levels according to gender, ethnicity, and local lifestyles, leading to differing boundaries for normal levels. Women generally show lower SU levels in relation to the uricosuric effect of estrogens—indeed, after menopause, SU levels tend to increase.³ However, gout is based on MSU crystal formation and deposition, a phenomenon strictly linked to uric acid properties; its saturation point is estimated as 6.8 mg/dL (0.40 mmol/L) under physiologic conditions of pH and temperature.⁴ With regard to gout, this seems like a more appropriate boundary between normouricemia and HU. In terms of gout management, a SU target of 6 mg/dL (0.36 mmol/L) is often used as the target for determining when urate-lowering agents should be prescribed.^5,6 Some authors would consider gout patients with SUs above this level as having HU,⁷ whereas others claim that the SU target should be individualized and discussed with the patient according to his or her characteristics so as to ensure the dissolution of MSU crystals.⁸

Consequences of Hyperuricemia

The main consequence of HU is SU crystallization and deposition in joint and periarticular tissues and, as a result, the development of gout. HU is an essential precursor to gout, but not every subject with HU will suffer from the disease. Data show that approximately 80% to 90% of patients with HU will not develop gouty symptoms, and only 22% of asymptomatic patients with SU ≥ 9 mg/dL (0.54 mmol/L) will develop gout in the following 5 years.¹ But, as to be discussed, some of patients with asymptomatic HU will develop MSU deposits without any symptoms of gout. In the process of crystallization, uric acid must be at persistently high levels and likely protein fibers such as collagen acting as templates for crystal formation.⁹ After the first MSU crystal is formed, crystal formation and growth will continue as long as HU persists.

There is a close relationship between HU-gout and kidney function, as indicated by the physiology of uric acid: 70% of the daily production of uric acid is eliminated by the kidneys¹⁰; for example, the National Health and Nutrition Examination Survey (NHANES)¹¹ showed that 61% of patients with HU and 71% of patients with gout suffered from stage 2 or higher chronic kidney disease (CKD). This relationship between HU and the kidney is indeed bidirectional, because renal impairment causes HU by decreasing urate filtration and/or impairing tubular transportation; at the same time, HU may itself cause renal impairment.¹² One of the mechanisms behind this is acute urate nephropathy, also called acute tumor lysis syndrome, due to the precipitation of MSU crystals in distal tubules, collecting ducts, and ureters secondary to a high and rapid increase in SU levels after massive cell lysis in patients with hematologic malignancies. Another consequence of HU for the kidney is uric acid nephrolithiasis, affecting approximately 12% of patients with HU. Such patients’ likelihood of developing stones is directly correlated with their SU levels.¹¹ Another mechanism is chronic urate nephropathy, which is probably the most frequent consequence of HU affecting the kidney. Here the decrease in renal function may be due to a complex pathogenesis that includes (1) glomerulosclerosis and MSU crystal deposition in the renal interstitium, leading to an inflammatory response and secondary interstitial fibrosis; (2) HU-induced vascular change...