Modern facilities of pharmacological correction of hyperuricemia in rheumatic diseases: management of difficult clinical cases

The article presents clinical cases of management of patients with low compliance with treatment, suffering from rheumatic diseases and disorders of purine metabolism.Cases report 1. The first patient with advanced gout, after taking 100 mg of allopurinol, developed undesirable effects: sore throat, change in voice, cough, and therefore treatment was discontinued. After six months without therapy, the condition worsened and, in self-medication, the patient resumed taking allopurinol at a dose of 300 mg per day, which, as expected, resulted in a resumption of the allergic reaction and a serious exacerbation of gouty arthritis. In order to stop continuous relapses of arthritis, it became necessary to prescribe glucocorticoids. After stabilization of the state, constant administration of febucostat with positive clinical and laboratory dynamics was recommended.Cases report 2. The second patient with rheumatoid arthritis (RA) developed analgesic nephropathy, secondary hyperuricemia, and typical gouty attacks in the background of high activity of the underlying disease, existing kidney pathology and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs). Frequent exacerbations of arthritis prompted the patient to finally see a rheumatologist. The adjusted therapy made it possible to reduce RA activity, reach the recommended level of uric acid, and reduce the drug load on the kidneys with almost complete withdrawal of NSAIDs. Thus, in modern conditions, rheumatologists have in reserve all the necessary means for the pharmacological correction of hyperuricemia, even in difficult clinical cases. Febucostat is the drug of choice for correcting uric acid levels in case of intolerance to allopurinol, as well as in the development of secondary gout against the background of renal failure. In addition, it should be noted that the effectiveness of the treatment of rheumatic diseases largely depends on the patient’s compliance. To increase adherence to therapy, regular patient schools are recommended.

Tubular and interstitial disease

Tubulointerstitial diseases refer to a group of disorders in which inflammatory cell infiltrates within the kidney interstitium and/or tubular epithelium are seen on kidney biopsy. These disorders constitute an important group of kidney diseases with varying prevalences and presentations due to a number of causes. It is difficult to estimate the worldwide incidence of tubular and interstitial disease as it is a histological diagnosis and biopsy rates vary substantially around the world. Increasing incidence of tubulointerstitial nephritis has been related to polypharmacy, particularly in the older population. Tubulointerstitial nephritis may present acutely as an immunologically mediated hypersensitivity reaction to an inciting agent—typically a drug or infection—or chronically as a part of a disease process leading to chronic interstitial fibrosis and tubular atrophy. Allergic interstitial nephritis, analgesic nephropathy, nephrotoxic metals, hyperuricemia, Balkan nephropathy, Mesoamerican nephropathy, aristolochic acid nephropathy, and other rare causes of tubulointerstitial nephritis are covered in this section. Isolated defects of tubular function, tubular disorder-related nephropathies, and electrolyte derangements also constitute important aspects of tubulointerstitial diseases.

ANALGESIC NEPHROPATHY. A MODERN VIEW ON THE PROBLEM

Aim. To review Russian and foreign literature on modern methods of diagnosis and treatment of patients with analgesic nephropathy.Materials and methods. Russian and foreign literature sources published in recent years on the aforementioned problem were analyzed.Results. This article presents the concept of analgesic nephropathy (AN) and discusses causes and mechanisms of its development. The pathogenic effect of non-steroidal antiinfl ammatory drugs on renal tissue is indicated. Key stages of the disease and its clinical features are determined. An algorithm of diagnosis is proposed. The importance of a patient’s detailed medical history is emphasized, including the duration, multiplicity and reasons for taking analgesics. A particular attention is paid to questions of AN therapy and its prevention. Provided timely diagnosis and analgesics withdrawal, the possibility of reverting tubulointerstitial infl ammation is shown.Conclusion. It is shown that optimal solutions with regard to AN diagnosis and its treatment are yet to be found. A timely diagnosis inhibits the development of chronic renal failure, which early detection provides for a higher treatment effi ciency and improved prognosis.

NSAIDs and the Kidney

NSAIDs are among the most commonly prescribed medications in the United States. NSAID associated kidney disease presents in various ways including ischemic acute kidney injury, nephrotic syndrome, and analgesic nephropathy. Elderly patients and patients who are also on diuretics and/or renin angiotensin aldosterone system blockade are at higher risk of developing NSAIDs associated kidney disease. Additionally, NSAIDs negatively impact blood pressure. Unfortunately, there is no currently effective therapy for the prevention of NSAIDS associated kidney disease. Proposed preventative strategies are discussed.

Analgesic activity of allopurinol and febuxostat in experimental animals

Background: Currently, two classes of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are used to manage pain in different clinical situations. Chronic uses of these drugs have various adverse effects like gastric ulceration/bleeding, analgesic nephropathy and respiratory depression, physical dependence, addiction, respectively. Xanthine oxidase inhibitors, used for chronic gout, might have a role in alleviation of pain, as per literature survey. Hence, the present study was carried out to evaluate the potential analgesic activity of allopurinol and febuxostat in different experimental models.Methods: The analgesic activity of allopurinol and febuxostat was assessed by employing two different experimental pain models-tail flick latency model in rats for central analgesia and acetic acid induced writhing model in mice for peripheral analgesia and was compared with tramadol and aspirin.Results: Allopurinol and febuxostat produced significant central and peripheral analgesic effects as is evident from increase in reaction time in tail flick test and inhibition in number of writhes in acetic acid induced writhing test.Conclusions: The results of the present study demonstrate marked analgesic effect of allopurinol and febuxostat.