Uric acid (capillary blood) in Leningradskaya Stanitsa

Detailed description of the study

Uric acid is a product of the metabolism of purine bases. This acid is formed from purines, which are synthesized in the body and also come from the food consumed: meat products, legumes.

Uric acid is produced in the liver. It is present in high concentrations in the blood as sodium salt.

Most uric acid is excreted from the body by the kidneys. The other part interacts with intestinal bacteria and is then excreted in the feces. Normally, the amount of synthesized and secreted acid is balanced.

If the concentration of uric acid exceeds the norm - 416.5 µmol/L in men and 339.2 µmol/L in women - this condition is called hyperuricemia. Reasons for increased concentration of uric acid in the blood:

1. Insufficient excretion of acid in the urine: kidney disease with impaired kidney function, prolonged fasting, drinking excessive amounts of alcohol or taking certain medications;
2. Increased acid synthesis in the body;
3. Excessive intake of purines from food: meat products, some alcoholic beverages;
4. For liver diseases that lead to increased breakdown of its cells (alcohol abuse, diseases of the hematopoietic system, antitumor therapy, etc.), since it is in the liver that uric acid is synthesized.

One of the most common diseases associated with hyperuricemia is gout. With this disease, there is a deposition of uric acid crystals in the soft tissues, where the formation of tophi occurs - nodules under the skin. The most typical places of damage are: the big toe of the lower limb, the ankle, the knee and elbow joint, the wrist, and the foot. Deposition of uric acid is also observed in the joints and kidneys, which provokes the development of the inflammatory process.

Predisposing factors to the development of gout are:

1. Hereditary disorders of purine metabolism;
2. Excess body weight;
3. Hypertonic disease;
4. Excessive alcohol consumption;
5. Excessive consumption of animal protein;
6. Taking certain medications (diuretics).

Gout is more common in men than in women. The peak incidence is observed at the age of 40-50 years. Treatment is lifelong and consists of taking anti-gout medications under the control of uric acid concentrations.

The main symptoms of gout are:

1. Redness of the skin in the area of ​​the affected joint;
2. Severe pain when touching the joint;
3. Inability to move the joint
4. Aching muscle pain.

According to modern clinical guidelines, there are a number of criteria for diagnosing gout. Among them, the most important is determining the level of uric acid in the blood.

Urolithiasis is another disease that develops due to impaired uric acid metabolism. As a result, the formation of stones in the organs of the urinary system is observed. Symptoms of urolithiasis include: pain in the lower back or abdomen, nausea, vomiting, frequent urination, and in some cases fever.

The development of diseases associated with the accumulation of uric acid in the body is usually preceded by long-term asymptomatic hyperuricemia. In view of this, in the presence of predisposing factors to gout or urolithiasis, periodic testing of uric acid levels for screening purposes is advisable.

This study helps the doctor assess the presence of hyperuricemia and monitor the treatment of gout and urolithiasis.

Treatment of gout in chronic kidney disease

In many patients, gout is accompanied by chronic kidney disease (CKD), which significantly complicates the choice of therapy in such cases. However, there are still no clear recommendations for the treatment of gout in patients with CKD based on data from large studies. Available national and international recommendations for the management of patients with gout are contradictory and not specific. The article discusses the possibilities and prospects for the use of urate-lowering drugs (febuxostat and allopurinol), as well as drugs prescribed for the relief and prevention of acute attacks of gouty arthritis (non-steroidal anti-inflammatory drugs, colchicine, glucocorticoids, interleukin 1 inhibitors).

Gout is a chronic rheumatic disease, the most common form of inflammatory arthritis, which most often develops in men over 40 years of age. The prevalence of the disease among adults ranges from

Decreased renal function is an important risk factor for the development of gout. Thus, the prevalence of hyperuricemia and gout increases with a decrease in glomerular function, regardless of other factors [5]. The results of this population-based study revealed that the relationship is not linear, and the threshold for an acute increase in the development of gout should be considered an estimated decline in glomerular filtration rate (eGFR) 2: with an eGFR of 2, 24% of adults have gout, compared with 2.9% with an eGFR > 90 ml/min/1.73 m2. CKD is even more common in people with hyperuricemia (HU): in stage 3 CKD, HC is observed in almost a third of cases (64%) [5].

The presence of CKD in patients with gout can have fatal consequences: in a large retrospective population-based cohort study, the hazard ratio (HR) for 5-year death from any cause in patients with gout with CKD compared with those without CKD in the age group ≥ 55 years was 1. 50 (95% CI 1.37–1.65). Moreover, in separately reviewed patients with gout younger than 55 years, the presence of CKD was equally harmful: the RR for death in this cohort was 1.65 (95% CI 1.01–2.71) [6]. The results of a prospective study showed that, along with serum C-reactive protein levels, family history of premature coronary heart disease, hypercholesterolemia and serum uric acid (UA) levels > 552 μmol/L, CKD stage 3 or more is an independent factor in cardiovascular death [7 ]. In addition, GFR is a factor contributing to the progression of gout, in particular the early development of subcutaneous tophi [8].

In addition to HU, one of the main causes of kidney damage in gout is the chronic inflammatory process caused by monosodium urate crystals, which directly affects the structure and function of the kidneys [9, 10]. Thus, a recent cross-sectional study by T. Bardin et al. demonstrated that in 36% of patients with untreated gout, renal ultrasonography revealed a hyperechoic structure of the Malpighian pyramids as a manifestation of interstitial nephritis, whereas such changes were not observed in patients without gout [11]. However, multivariate analysis showed that renal medulla hyperechogenicity was associated with the estimated duration of gout, the presence of subcutaneous tophi, urate arthropathy, double contour thickness according to joint ultrasonography, and decreased eGFR.

However, the authors did not find recommendations for the management of patients with gout that take into account the potential effect of drugs on renal function. This work analyzes the most significant data on the safety and effectiveness of drugs used for gout, taking into account their effect on the condition of the kidneys.

Drugs used to relieve attacks of gouty arthritis

The most complete effectiveness and safety of drugs used for the treatment of acute attacks of gouty arthritis in CKD were analyzed in a review by HL Pisaniello et al. [12]. Only those studies that recruited patients with gout, eGFR 2 (CKD stages 3–5) and treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs) and interleukin 1 inhibitors (ILs) as part of the study were selected for analysis. -1). Although the literature search covered the period from January 1, 1959 to January 31, 2018, a period of nearly 60 years, only 33 studies were reviewed, stratified by renal function, that analyzed the efficacy and/or safety of the following drugs: colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3) and GCs (n = 2), and 58 without stratification by renal function. Most studies excluded participants with severe CKD. According to the authors, it is difficult to draw any clear conclusions and the results of clinical trials cannot be extrapolated to patients with pre-existing CKD.

The use of NSAIDs in the presence of CKD is, in principle, limited, but, according to KS Tang and AD Shah, the question remains whether their short-term use is possible, at least based on the very limited arsenal of drugs for the treatment of pain in patients with CKD, especially in the terminal stage and with very limited evidence of the effect of NSAIDs on long-term outcomes of renal failure [13]. The review cited above [12] presented only three studies assessing kidney function over time, two of which described clinical cases [14] and one presented a report of two cases [15, 16] of acute kidney injury when using NSAIDs to relieve acute attack of gouty arthritis. These data are clearly insufficient to make a categorical judgment about the impossibility of using NSAIDs in patients with gout and CKD. Therefore, in the absence of an alternative, and given the excruciating pain that gout patients experience during an arthritic attack, even the presence of clinically significant CKD should not be an absolute contraindication to their short-term use.

A significant amount of data has been accumulated on the use of colchicine for CKD in patients with an acute attack of gouty arthritis, including randomized controlled trials (RCTs). However, none of them assessed the effect of the drug on renal function, despite mentioning varying levels of transient changes in renal function during colchicine use and after colchicine discontinuation [12]. Interestingly, in RCTs that assessed the effectiveness of colchicine at the then high dose of the drug (1 mg orally followed by 0.5 mg every two hours until signs of toxicity), the mean serum creatinine level in the 22 patients receiving colchicine was quite high – 0.14 ± 0.08 mmol/l, but no adverse effects from the kidneys were noted [17]. A study of the pharmacokinetics of colchicine revealed that its plasma concentrations were similar to those in hemodialysis patients and patients with normal and mild CKD, but were twice as high in moderate and severe renal failure [18]. On the one hand, the authors mention the presence of adverse events in four out of eight patients with end-stage CKD (diarrhea, headache), on the other hand, they report the absence of laboratory abnormalities associated with taking colchicine, without providing specific data. The subjects took 0.6 mg of the drug once.

Thus, recommendations for the use of colchicine in CKD remain largely empirical, and, as with NSAIDs, it is not rational to completely reject the use of colchicine in CKD in patients with gout. The threshold eGFR value for possible dose adjustment of the drug remains unclear.

GCs are considered the safest option for treating an acute attack of arthritis in gout. Thus, according to RCT data, betamethasone 7 mg intramuscularly as a single dose was more effective than diclofenac sodium 75 mg twice a day with a lower incidence of adverse events. Although this study did not include patients with elevated serum creatinine levels, the development of adverse drug events from the kidneys was not recorded. Indeed, GCs could be given unconditional preference if not for the high likelihood of adverse events, such as increased blood pressure, hyperglycemia, myocardial ischemia, and relapses of arthritis [19].

When choosing the optimal treatment method, the individual patient’s own experience of using medications should also be taken into account. This may narrow the already limited list of anti-inflammatory therapy methods, but prescribing a obviously ineffective drug is pointless [20].

The use of IL-1 inhibitors: canakinumab and anakinra may be promising. Thus, only in one study out of seven reviewed by HL Pisaniello et al., the use of anakinra was identified with a decrease in renal function; the rest noted stable renal function during treatment with the drug, regardless of the initial presence of CKD [12]. However, there are prerequisites for limiting the use of anakinra, since the clearance of the drug depends on renal function and the drug is not excreted during dialysis. Therefore, it has been suggested that in patients with eGFR 2, anakinra should be administered every other day [21]. In turn, canakinumab, characterized by a long half-life and large molecular weight, is less dependent on renal excretion [22]. Data on the use of canakinumab indicate its high effectiveness in the treatment of attacks of gouty arthritis without any damage to renal function and an independent safety profile [23].

Drugs used to prevent attacks of gouty arthritis

To prevent attacks of arthritis when initiating therapy with urate-lowering drugs, the same drugs are used as for the treatment of acute attacks - colchicine, NSAIDs and GCs, but a distinctive feature is the longer (on average three to six months, rather than days or weeks) use of these drugs in low doses [20, 24].

There is no data on such long-term use of GCs in patients with reduced renal function for the prevention of attacks of arthritis, in contrast to colchicine and NSAIDs (naproxen), the use of which is most well studied for these purposes. A post hoc analysis of three RCTs of febuxostat in patients with gout who were also taking colchicine or naproxen to prevent arthritis attacks included patients with eGFR 2, and although the evolution of eGFR for participants by baseline renal function was not reported, adverse drug reactions were not reported. associated with decreased eGFR have not been reported [25]. In the study by M.N. Chikina et al. 28 of 97 patients with gout had an eGFR of 2, most of them taking colchicine, some taking various NSAIDs; an additional four patients had an eGFR of 2, all of whom were taking prednisolone [26]. Among the adverse events, none related to deterioration of renal function was also described.

Long-term use of colchicine is associated with a risk of bone marrow suppression and neuromyotoxicity [27], but it is unknown whether these life-threatening side effects are increased in patients with gout due to CKD.

Although clinical trial data are lacking, courses of GCs may be considered to have an acceptable risk-to-benefit ratio, but long-term use may be associated with an increased risk of various side effects, especially infections, such as in rheumatoid arthritis [28, 29]. .

An alternative method for preventing arthritis attacks may be to slowly titrate the dose of urate-lowering drugs [30], but it is unknown whether gradual escalation of the dose of urate-lowering drugs in patients with CKD will affect the frequency of arthritis attacks. In addition, it is unknown whether the frequency of arthritis attacks is the same in patients with gout in the first weeks and months of urate-lowering therapy with and without CKD.

Urate-lowering drugs

There are many unresolved issues regarding the use of urate-lowering drugs in patients with gout in CKD, and there is a consensus on the choice of a specific drug (allopurinol vs.

febuxostat), as well as the possibility of using high doses of allopurinol in patients with reduced renal function, which is confirmed by the contradictions in various recommendations for the treatment of gout [20, 24, 31, 32]. The question of at what eGFR value the use of urate-lowering drugs is completely contraindicated remains unresolved, especially since most large studies did not include patients with a significant decrease in renal function. Nevertheless, it can be assumed that complete refusal of urate-lowering therapy for patients with a significant decrease in renal function will lead to rapid progression of gout, and frequent attacks of arthritis will lead to the need for the use of symptomatic drugs, which in turn will entail a number of negative consequences.

The use of urate-lowering drugs in CKD is limited by their lower effectiveness and high risk of adverse events. However, various data have been accumulated on the effectiveness and safety of individual drugs, which allows us to draw certain conclusions.

The effectiveness of allopurinol in patients with even a moderate decrease in eGFR is very low, and the achievement of the target serum UA level (in most recommendations is 2 [34, 35]. Whether this approach is rational is a controversial issue. Thus, in patients with reduced renal function, the likelihood of adverse reactions increases, in particular, allopurinol hypersensitivity syndrome, which is often fatal.36 Although the risk of hypersensitivity syndrome depends on the starting dose, even with a dose of ≤ 100 mg/day in patients with CKD, it almost doubled (RR 1, 88; 95% CI 1.17–3.02) In addition, titrate the dose of allopurinol to achieve the target serum UA level (starting from 50–100 mg/day and then increasing the dose by no more than 100 mg/day every 2 –4 weeks, maximum permissible dose – 900 mg/day) often takes a long time, during which the disease continues to progress.

Another widely used drug for the treatment of gout, the selective xanthine oxidase inhibitor febuxostat, unlike allopurinol, is mainly metabolized in the liver and its excretion is much less dependent on renal function. 96 patients with gout and CKD (eGFR ml/min/1.73 m2) were randomized to receive febuxostat 30 mg twice daily, 40/80 mg once daily, or placebo. 68.8% of patients receiving febuxostat at a daily dose of 60 mg/day and 45.2% receiving 40/80 mg/day achieved serum sUA levels

According to A. Whelton et al., based on an analysis of long-term, up to 48 months, administration of febuxostat at a dose of 80 or 120 mg/day in 551 patients with gout, a persistent decrease in serum sUA levels led to maintenance of eGFR on average 1.15 ml/min [39].

Current data based on the results of the FAST (Febuxostat versus Allopurinol Streamlined Trial) trial showed that febuxostat was noninferior to allopurinol for the primary endpoint (a composite of hospitalization for nonfatal myocardial infarction or biomarker-positive acute coronary syndrome; nonfatal stroke or cardiac death). vascular diseases). Moreover, the total number of deaths in the febuxostat group was less than in the allopurinol group [40]. These data challenge the notion that febuxostat increases cardiovascular risk, but it is unclear whether febuxostat has a superior cardiovascular safety profile compared with allopurinol in patients with severe kidney disease. However, the recommendations of the French Association of Rheumatology in patients with gout and eGFR from 30 to 60 ml/min/1.73 m2 suggest the use of febuxostat as an alternative to allopurinol, and in case of eGFR from 2 doses, avoid allopurinol and give preference to febuxostat [32].

It follows from the above that more in-depth knowledge is needed about the safety of treatment methods related to both the relief of acute attacks of exacerbation of gouty arthritis and their prevention, and urate-lowering therapy in patients with gout with reduced renal function. Nevertheless, the existing, albeit limited, data allow us to make an informed choice when prescribing therapy for a particular patient.

Important Notes

Material for research

Capillary blood.

Children under 7 years of age: venous blood/capillary blood (for special indications). Children over 7 years of age and adults: venous blood. Capillary blood collection for research is carried out only for children under 7 years of age (for special indications)! According to GOST R 53079.4-2008, indications for taking capillary blood are possible: in newborns, in patients with very small or hard-to-reach veins, with large-area burns, and in severely obese patients.

Symptoms

Gout usually develops after years of accumulation of uric acid crystals in the joints and surrounding tissues. Symptoms include:

• Increased local temperature, pain, swelling, and severe tenderness in the joint, usually the big toe joint. This is a classic manifestation of gout. Sometimes a similar pattern can develop in another joint, such as the ankle or knee.
• There may be discoloration around the injured joint (bright red or purplish)
• The pain usually begins during the night and is so intense that even a light touch is very painful.
• Rapid onset of discomfort over several hours and then gradual regression over the next few days.
• Limited movement in the damaged joint.
• After a gout attack subsides, the skin around the damaged joint returns to normal and itching may persist.
• Some people may have gout without attacks, called chronic gout. Chronic gout in older age groups may not be very painful and is often confused with other types of arthritis.
• Gout may first appear as nodules (tophi) on the hands, elbows, or ears. In such cases, there may not be the classic symptoms of a gout attack.

Diagnostics

The most reliable confirmation of gout is the analysis of synovial fluid obtained by arthrocentesis. But if there is inflammation in the joint area (redness, pain), it is not advisable to perform a puncture. In such cases, the diagnosis is made based on a blood test for uric acid.

The diagnosis of gout is made based on medical history and blood and urine tests for uric acid.

X-ray is informative only in the late stages of gout and is necessary for differential diagnosis with other types of arthritis.

Expert Research

Specialists at the Mayo Clinic in the USA conducted a study that made it possible to identify the first signs of the disease. This research center is one of the largest private medical and research centers in the world. According to them, gout is characterized by the development of swelling, redness of the skin and pain in the joints - often the joints at the base of the big toe. Symptoms may come and go. But it is possible to control them. You need to visit a doctor who will draw up a treatment regimen and tell you exactly how to relieve the discomfort.