Бессимптомная гиперурикемия

[ZSV]

Уважаемые коллеги! Прошу высказать свое мнение по поводу необходимости назначения лекарственной терапии пациенту.
Больной 33 лет обратился с жалобами на периодические ноющие боли в области правого подреберья, с иррадиацией в поясничную область справа. Ухудшение около 2 месяцев. В анамнезе - синдром Жильбера. 2 года назад проходил курс лечения фенобарбиталом по поводу желтухи, с положительным эффектом - билирубин вернулся в границы нормы. После обследования в настоящее время в биохимич. анализе крови обнаружено повыфшение уровня мочевой кислоты в 2 раза (850 ммоль\л), мочевина на верхней границе (6,2 ммоль\л), в ОАМ - ураты +++. На УЗИ органов брюшной полости, почек - изменений не выявлено. Клинически - жалоб на боли в суставах стоп, почек не было.
Необходимо ли назначение данному пациенту с бессимптомной урикемией аллопуринола, если отсутствуют клинические проявления? Данные в интернете по этому поводу противоречивы, одни авторы склоняются к его назначению, другие - к тому, что бы не назначать до клинических проявлений. Рекомендации Европейской антиревматической лиги по данному вопросу так же невнятны.
Заранне благодарен за ответ!

[Vipamuk]

Из UpToDate:
RECOMMENDATIONS — As stated above, in the absence of unequivocal evidence for a causal role of this chemical aberration in one or more of the non crystal deposition disorders listed above, it seems appropriate to maintain the view that hyperuricemia is not a disease. This view is strengthened by the fact that monosodium urate or uric acid crystal deposition, not urate itself, is the essential pathophysiologic link between hyperuricemia and clinical manifestations such as gouty arthritis, uric acid urolithiasis, and tophus formation [22]. Thus, hyperuricemia can be viewed as a necessary (although not usually sufficient) predisposing factor for the narrow range of clinical manifestations of gout.

Antihyperuricemic drug therapy for the great majority of individuals with asymptomatic hyperuricemia is not justifiable by risk/benefit analysis. As mentioned above, gouty arthritis is readily treatable and reversible if it occurs. Similarly prophylaxis against stone disease is not warranted in most individuals, but therapy should be started after discovery of a stone. The primary therapeutic modality in this setting is urinary alkalinization with potassium citrate or potassium bicarbonate, not allopurinol. (See "Uric acid nephrolithiasis".)

Three specific circumstances warrant at least consideration for the institution of antihyperuricemic treatment in asymptomatic subjects:

Persistent hyperuricemia in the infrequent patients with sustained serum urate concentrations greater than 13 mg/dL (773 micromol/L) in men and 10 mg/dL (595 micromol/L) in women. These high values may carry some nephrotoxic risk, perhaps related to the likelihood of some component of uric acid overproduction. (See "Prevention of recurrent gout", section on 'Indications'.)

This recommendation does not generally apply to patients with heart failure who may develop marked hyperuricemia due to renal hypoperfusion and reduced urate excretion. Such patients typically have advanced heart failure with limited life expectancy (unless they undergo transplantation) and are therefore at low risk for chronic urate nephropathy. (See "Diuretic-induced hyperuricemia and gout".)
Excretion of urinary uric acid in excess of 1100 mg (6.5 mmol) daily is associated with a 50 percent risk of uric acid calculi [17,23]. Management of these individuals should begin with dietary purine restriction. Allopurinol should be used if dietary restriction does not reduce uric acid excretion to less than 1000 mg/day (5.9 mmol/day). The dose should be adjusted to reduce uric acid excretion below 800 mg/day (4.8 mmol/day).
Patients about to receive radiotherapy or chemotherapy that is likely to result in extensive tumor cytolysis should be treated to prevent acute uric acid nephropathy and other manifestations of tumor lysis syndrome [11]. Preventive therapy in patients at risk includes intravenous hydration and either allopurinol or rasburicase (recombinant urate oxidase). These issues are discussed in detail elsewhere. (See "Tumor lysis syndrome", section on 'Prevention'.)

[ZSV]

В принципе, я так и сделал - отправил его с рекомендациями по диете с лабораторным контролем через 2 месяца. Кроме того, наличие Жильбера так же не симпатизирует к назначению медикаментозного лечения.

[Dr.Vad]

если нужно только снизить гиперурикемию, то можно воспользоваться результатами вот такой публикации:

Arthritis Care Res (Hoboken). 2011 Sep;63(9):1295-306.
Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials.
Juraschek SP, Miller ER 3rd, Gelber AC.
Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21224, USA.

Abstract
OBJECTIVE: To assess the effect of vitamin C supplementation on serum uric acid (SUA) by pooling the findings from published randomized controlled trials (RCTs).

METHODS: A total of 2,082 publications identified through systematic search were subjected to the following inclusion criteria: 1) RCTs conducted on human subjects, 2) reported end-trial SUA means and variance, 3) study design with oral vitamin C supplementation and concurrent control groups, and 4) trial duration of at least 1 week. Trials that enrolled children or patients receiving dialysis were excluded. Two investigators independently abstracted trial and participant characteristics. SUA effects were pooled by random-effects models and weighted by inverse variance.

RESULTS: Thirteen RCTs were identified in the Medline, EMBase, and Cochrane Central Register of Controlled Trials databases. The total number of participants was 556, the median dosage of vitamin C was 500 mg/day, trial size ranged from 8-184 participants, and the median study duration was 30 days. Pretreatment SUA values ranged from 2.9-7.0 mg/dl (Système International d'Unités [SI units]: 172.5-416.4 μmoles/liter). The combined effect of these trials was a significant reduction in SUA of -0.35 mg/dl (95% confidence interval -0.66, -0.03 [P = 0.032]; SI units: -20.8 μmoles/liter). Trial heterogeneity was significant (I(2) = 77%, P < 0.01). Subgroup analyses based on trial characteristics indicated larger reductions in uric acid in trials that were placebo controlled.

CONCLUSIONS: In aggregate, vitamin C supplementation significantly lowered SUA. Future trials are needed to determine whether vitamin C supplementation can reduce hyperuricemia or prevent incident and recurrent gout.

[ZSV]

Спасибо, Вадим Валерьевич, за интересную статью. Но применительно к данному больному - не спровоцирует ли камнеобразование введение аскорбиновой к-ты, учитывая большое количество уратов? Наверняка ведь многодневное введение С по 500 мг будет закислять мочу.

[Dr.Vad]

Насколько знаю, это общеизвестное заблуждение, основанное на прежних методиках определения оксалатов в моче, напр.:

Even though a certain part of oxalate in the urine derives from metabolized ascorbic acid (AA), the intake of high doses of vitamin C does not increase the risk of calcium oxalate kidney stones due to physiological regulatory factor: gastrointestinal absorption as well as renal tubular reabsorption of AA are saturable processes, and the metabolic transformation of AA to oxalate is limited as well. Older assays for urinary oxalate favored in vitro conversion of AA to oxalate during storage and processing of the samples. Recurrent stone formers and patients with renal failure who have a defect in AA or oxalate metabolism should restrict daily vitamin C intakes to approximately 100 mg. But in the large-scale Harvard Prospective Health Professional Follow-Up Study, those groups in the highest quintile of vitamin C intake (> 1,500 mg/day) had a lower risk of kidney stones than the groups in the lowest quintiles.
---
Ann Nutr Metab. 1997;41(5):269-82.
No contribution of ascorbic acid to renal calcium oxalate stones.
Gerster H.

поэтому в недавних публикациях витамин С рекомендуется как диетическое средство для снижения гиперурикемии:

Lifestyle and dietary recommendations for gout patients should consider overall health benefits and risk, since gout is often associated with the metabolic syndrome and an increased future risk of cardiovascular disease (CVD) and mortality. Weight reduction with daily exercise and limiting intake of red meat and sugary beverages would help reduce uric acid levels, the risk of gout, insulin resistance, and comorbidities. Heavy drinking should be avoided, whereas moderate drinking, sweet fruits, and seafood intake, particularly oily fish, should be tailored to the individual, considering their anticipated health benefits against CVD. Dairy products, vegetables, nuts, legumes, fruits (less sugary ones), and whole grains are healthy choices for the comorbidities of gout and may also help prevent gout by reducing insulin resistance. Coffee and vitamin C supplementation could be considered as preventive measures as these can lower urate levels, as well as the risk of gout and some of its comorbidities.

Curr Opin Rheumatol. 2010 Mar;22(2):165-72.
A prescription for lifestyle change in patients with hyperuricemia and gout.

[STc]

Остается добавить, что слабые органические кислоты не закисляют, а защелачивают мочу; аскорбиновая кислота используется, например, в защелачивающем тесте при дифдиагнозе с-мов Фанкони И Бартера.

[ZSV]

Да-да, уже "прошерстил" тему. Согласен с Вадимом Валерьевичем на счет ощеизвестного заблуждения. Порой сам себе поражаюсь, насколько школьное "вдалбливание" глубоко заседает. Даже мысли не возникает усомниться в чем - то!

[ZSV]

Пациент почти 3 месяца регулярно принимал аскорбиновую кислоту - с положительным эффектом. С 850 ммоль/л показатель снизился до 535,9 ммоль/л. Мочевина снизилась с 6,2 до 5,4 ммоль. Но не смотря на это мочевая к-та остается выше пределов нормы.
Уважаемые коллеги, как вы считаете, необходимо назначить ему аллопуринол, или нет?

[GIZA]

2012 Update on Diagnosis and Management of Gout
[Ссылки доступны только зарегистрированным пользователям ]

Currently, there is no evidence that treating asymptomatic hyperuricemia is beneficial and therefore it is not recommended.