Důsledky hyperurikémie

Asymptomatic hyperuricemia

• Most patients with asymptomatic hyperuricemia never develop gout or stones
• Pharmacologic treatment for asymptomatic hyperuricemia carries some risk
• Is not considered beneficial or cost-effective
• Generally is not recommended [8]
• Patients can be advised on lifestyle changes
• Changes in diet
• Reduction in alcohol intake
• Exercise [8]
• Patients receiving cytolytic treatment
• May receive prophylaxis against acute uric acid nephropathy [8]
• Uric acid levels can be elevated ten to 15 years before clinical manifestations of gout [9]
• Hyperuricemia does not represent a disease or a specific indication for therapy
• Majority of patients with elevated uric acid require no long term therapy
• Patient may give a history of a purine rich diet or alcohol consumption
• Specifically beer
• Current medications should be reviewed [9]
• 18.8% of patients with HUE developed gout during a 5-year follow-up period [11]

USA

• 21% of the general population
• 25% of hospitalized patients
• Most common complication gout
• In 3.9% of the U.S. population [9]

Taiwan

• 42.1% men
• 27.4% women [10]

Arthritis uratica - dna - ghout - podagra - pakostnice

• Závažné kloubní onemocnění
• Hlavním příznakem velmi bolestivé akutní záchvaty v kloubech
• Acute monoarthritis
• Most commonly in the great toe
• Less frequently in the tarsal joint, knee, and other joints [8]
• Acute polyarticular involvement may happen in:
• Post menopausal women
• Hypertensive male with alcohol abuse may present with [20]
• Nemá jednotnou příčinu
• Několik odchylek metabolismu purinů
• Nejčastější a nejběžnější příčinou
• Defekt v synthese PRPP
• Hromadí se velké množství kyseliny močové v měkkých tkáních
• Vznikají tzv. tofy
• Nephrolithiasa [1]
• Urátová lithiáza
• Možné ledvinné selhání [2]
• Akutní nebo chronická [2]
• V 90 % postihuje muže
• Nejčastěji ve 4.–5. dekádě
• ženy
• Téměř výhradně po menopauze
• Ztráta urikosurického účinku estrogenů [3]

Primární (idiopatická) dna

• Cca 90 % případů

Sekundární dna

• Symptomem jiného onemocnění
• Leukémie
• Onemocnění ledvin
• Buněčného rozpadu při léčbě cytostatiky
• Leschův-Nyhanův syndrom aj.

May mimic rheumatoid arthritis

• Symmetric small-joint involvement
• Tophaceous deposits on extensor tendon surfaces
• Resemble rheumatoid nodule [9]
• 30 % of patients with tophaceous gout also have low titers of rheumatoid factor
• Postmenopausal women who are receiving diuretic therapy
• Have a tendency to form tophi in osteoarthritic joints of the hands
• Mimicking inflammatory “erosive osteoarthritis” [9]

Tophaceous disease

• More likely to occur in patients with:
• Poly-articular presentation
• Serum urate higher than 9.0 mg per dL (535 µmol per L)
• Younger age at disease onset 40.5 years or younger [9]

hs CRP

• Levels are positively associated with the prevalence of hyperuricemia [8]

Rozklad ve tkáních

• Elevated serum UA can decompose and generate free radicals in various conditions
• Leading to increased oxidative stress
• Inflammation
• Cell proliferation
• And angiotensin II production [12]

Hyperuricosuria

• uric acid levels that exceed
• 800 mg/day in men
• 750 mg/day in women [9]
• Most commonly associated with increased dietary intake
• Uric acid stones are 5% to 10% of all urinary stones [9]

Kardio-metabolické onemocnění

• Arteriální hypertenze (60 %)
• Hypertriacylglycerolémie (80 %) [3]
• obesity [10]
• Hypertension [10]
• Type 2 diabetes [10]
• Nonalcoholic fatty liver disease [10]
• Coronary artery disease [10]
• Stroke [10]
• MSU crystals augment platelet aggregation
• Enhances the risk of coronary thrombosis [20]
• Hyperurikemie strongly associated with endothelial dysfunction
• Lowering serum uric acid improves endothelial dysfunction markedly in different clinical situations [20]
• HUE is a strong risk factor for
• Atherosclerosis
• Hypertension
• Metabolic syndrome [11]
• May include obesity, hyperlipidemia, and diabetes mellitus [11]

Korejská populace

• Positively associated with hyperuricemia
• In both sexes
• obesity, metabolic syndrome, renal impairment, and low-grade inflammation
• Only in women
• Alcohol consumption, education, and current smoking status [25]

Urate crystals

• Can engage an intracellular pattern recognition receptor
• The macromolecular NALP3 (cryopyrin) inflammasome complex

NALP3 inflammasome

• May result in interleukin 1 (IL-1) beta production
• Incites an inflammatory response

Inhibition of this pathway

• Targeted as a treatment for hyperuricemia-induced crystal arthritis
• Efficacy of the IL-1 inhibitors for preventing gout flares during the initiation of allopurinol therapy
• Canakinumab
• Rilonacept [8]

Neurologické příznaky u kojenců

Osteoarthritis of the knee

• Positively associated with osteoarthritis of the knee in a cohort of Chinese women [8]

Renální poškození

• Krystalky se ukládají v kanálcích
• Později přestupují do intersticia
• Vede k hydronefróze
• Tlaková atrofie ledviny ze stagnující moči
• Nefropatie
• urolithiáza
• Intersticiální dnavá nefritida
• Akutní ledvinné selhání [3]

Urátové konkrementy

• Nejčastěji tvořeny čistou kyselinou močovou
• Někdy urátem sodným
• V mírně alkalické moči
• Se mohou vytvořit konkrementy z urátu amonného
• Zpravidla za přítomnosti močové infekce spojené se štěpením močoviny
• Z krystalků kyseliny močové (uricit)
• Z močanu amonného

Krystalky urátu sodného v intersticiu ledvin

• Zánětlivou reakci (chronická intersticiální nefritida)

Akutní renální selhání

• Poměrně vzácné
• Při náhlém vzestupu kyseliny močové v krvi
• Cytostatická léčba u leukemií
• Pokud je současně koncentrovaná moč (dehydratace) o kyselém pH
• Akutní urátová nefropatie [4]

Symotomy

• Hematuria
• Pain in the flank, abdomen, or inguinal region
• And/or nausea and vomiting [8]
• 0

Lowering the blood concentration of uric acid

• May permit any existing crystals of uric acid to be gradually dissolved into the blood
• Should reduce the formation of new crystals
• Xanthine oxidase inhibitors
• Uricosurics [7]

Risk of stroke incidence and mortality

• Meta-analysis by Kim et al
• Hyperuricemia may modestly increase the risk of stroke incidence and mortality [8]
• Authors reviewed 16 studies
• Together included 238,449 adults
• Studies that adjusted for known risk factors
• RR for stroke in patients with hyperuricemia was 1.47
• 4 studies; 95% confidence interval [CI] 1.19, 1.76
• RR for mortality was 1.26
• 6 studies; 95% CI 1.12, 1.39 [8]

Nežádoucí účinky standardní terapie

• Aneb proč má smysl snažit se o porzumění a řešit to i jinak
• Citace:
• "Uricosuric drugs (i.e., probenecid and benzbromarone) that reduce the serum uric acid concentration (SUA) by increasing the renal excretion of uric acid and xanthine oxidase inhibitors (i.e., allopurinol) that decrease serum uric acid by inhibiting uric acid synthesis have been the mainstays of conventional HUE treatment. Although these treatments have very good results as hypouricemic agents, they may be associated with gastrointestinal reactions, liver and kidney damage, and other adverse effects, and, in rare cases, allopurinol has been associated with reactive hepatitis and fulminant hepatic failure. Therefore, long-term treatment may not be advisable." [11]
• Citace závěru metanalýzy efektivity a bezpečnosti TČM:
• "The results indicate that Chinese medicinal herbs have a positive therapeutic effect with fewer adverse drug reactions." [11]