Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.
Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.
Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that characteristically causes joint inflammation and damage. In addition, many patients develop extraarticular manifestations which may cause significant comorbidity and premature mortality.Some respiratory tract involvement of the upper and lower airways and parenchymal disease features are unique to RA, including cricoarytenoid arthritis and RA pulmonary nodulosis, and others, especially the interstitial parenchymal involvement, occur in many other idiopathic and autoimmune diseases. The pathophysiology of lung disease is not well understood. Rheumatoid lung disease may even predate the onset of joint disease, and could be triggered by chronic airway and alveolar epithelial injury. Chronic systemic inflammation and risk factors such as cigarette smoking, infection, host genetics, and immune dysregulation are contributors. Treatment of the respiratory disease is directed at reducing the systemic inflammation of RA. Less well understood is the management of the interstitial lung disease of RA, for which antifibrotic and immune suppressive agents may be helpful. The management of RA-related lung disease is perhaps the major remaining hurdle in reduction of the disease burden related to extraarticular manifestations of this disease.
This study does not support the hypothesis that an environmental agent, caused by dust pollution related to earthquake damage, has a causative role in the pathogenesis of AAV.
Objectives The aim was to evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULTs) for people with gout and chronic kidney disease (CKD) stages 3–5. Methods PubMed, The Cochrane Library and EMBASE were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of <60 ml/min and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for whom we did include case reports. Results There were 36 reports with an analysis of efficacy and/or safety based upon renal function: allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5) and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function: allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3) and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of <30 ml/min). For allopurinol, in particular, there was significant variability in the dose of drug used and the efficacy in terms of urate lowering, across all levels of renal impairment. Conclusion There is a lack of evidence regarding the efficacy and/or safety of currently used ULTs according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.
IntroductionRheumatoid arthritis (RA) affects approximately 0.5%–1% of the general population. Clinically significant interstitial lung diseases (ILD) develops in just under 10% of people with RA, and subclinical disease is more common. Little is known about RA-ILD in New Zealand (NZ), or the number of persons with RA in Canterbury, NZ. This study aims to determine: (1) incidence and prevalence of RA, (2) incidence and prevalence of RA-ILD, (3) clinical characteristics and risk factors for the development of RA-ILD, (4) long-term outcomes of RA-ILD, in the population resident within the Canterbury District Health Board (CDHB) catchment area.Methods and analysisPersons aged 18 years of age and older, and resident in the region covered by the CDHB with RA as well as RA-ILD will be identified by retrospective review of medical records. Prevalent as well as incident cases of RA between 1 January 2006 and 31 December 2008 and between 1 January 2011 and 31 December 2013 will be identified, and followed until 30 June 2019. Existing as well as incident cases of RA-ILD during this time will be identified. The association between the development of ILD and clinical characteristics and environmental exposures will be examined using Cox-proportional hazard models. Kaplan-Meier methods will be used to estimate survival rates for patients with RA-ILD. Mortality for people with RA and RA-ILD will also be compared with the general population of the CDHB.Ethics and disseminationData will be obtained by retrospective review of medical records. Deidentified patient data will be stored in a secure online database. Data on individual patients will not be released, and all results will only be published in aggregate. Ethical approval has been obtained from the University of Otago Human Research Ethics Committee (REF HD18/079). Results will be published in peer-reviewed medical journals and presented at conferences.Trial registration numberACTRN12619001310156; Pre-results.
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