If successful, this will be a significant milestone in laying the foundations for emissions trading in China. An important benefit of the carbon tax is the additional revenue generated. Domestic carbon taxes are easier and less controversial to impose compared to property taxes. If there is one aspect of U. Future Development. The Future Development blog informs and stimulates debate on key development issues.
This blog was first launched in September by the World Bank and the Brookings Institution in an effort to hold governments more accountable to poor people and offer solutions to the most prominent development challenges. Continuing this goal, Future Development was re-launched in January at brookings.
In a partial show of unity, G7 leaders agreed on conditions for recognizing and dealing with a future Taliban-led Afghan government, but there was palpable disappointment Biden could not be persuaded to extend the U. Yet, individual leaders offered less sanguine descriptions of the meeting as well as the state of affairs in Afghanistan, which have dramatically changed since the bloc last met in Britain in June.
At the time of that summit, Afghanistan had been almost an afterthought with the leaders more concentrated on the coronavirus pandemic, China and Russia. No commercial re-use. See rights and permissions.
Published by BMJ. Abstract Objective: There is a lack of standardisation in the terminology used to describe gout. Corticosteroids have been generally accepted as the safest option in most people with gout flares and concomitant CKD. The newer IL-1 antagonist therapies, such as canakinumab and anakinra, are not widely available, and there are no RCTs investigating their use in people with gout and CKD for which results are presented according to kidney function.
Data from case series and case reports are reassuring Essentially, these agents are widely used for a variety of conditions, but there is a relative paucity of data on their use in people with gout and CKD. In people without gout, the clearance of anakinra has been shown to be directly related to renal function and the drug is not cleared by dialysis Although the medications used for flare prophylaxis are the same as those used to treat flares, they are generally used at lower doses and for longer periods of time months rather than days or weeks.
Long-term use of colchicine in the general population has been associated with bone marrow suppression and neuromyotoxicity 50 , but whether these effects are increased in those with gout and CKD is unknown. Whereas short-term courses of glucocorticoids can be considered to have an acceptable risk—benefit profile, long-term use of glucocorticoids for flare prophylaxis can be associated with an increased risk of glucocorticoid-related adverse events, particularly infections, as seen in other rheumatic diseases 51 , This risk could be particularly concerning in a population that is already at high risk of severe infections, such as those with CKD.
Whether the gout flare rate when starting ULT is the same in those with CKD as in those without, and whether prophylaxis is always required, are unknown, although a recent study of incremental use of febuxostat suggested that prophylaxis might not be required when a dose-escalation approach is used The general issues identified as well as specific issues with individual drugs are discussed below and the G-CAN proposed research priorities are outlined in Box 4.
Does commencing allopurinol at a lower dose reduce the risk of allopurinol hypersensitivity syndrome AHS? Which are the most important risk factors for AHS, and can we more accurately predict who will get AHS-based risk factors? Does starting allopurinol at a low dose and gradually increasing the dose reduce the risk of flares and thus alleviate the need for flare prophylaxis?
Does allopurinol provide protection for the heart or kidneys in people with gout, chronic kidney disease CKD and cardiovascular disease? Is febuxostat neutral or associated with an increased risk of cardiovascular death in people with gout, CKD and cardiovascular disease? Is combination therapy with xanthine oxidase inhibitors safer or more effective than probenecid monotherapy?
What is the role of concomitant immunosuppression to avoid anti-drug antibodies in those with CKD? Is earlier tophaceous disease debulking in CKD, using recombinant PEGylate uricase therapy, a better approach than initial conventional oral urate-lowering therapy ULT? Because most large RCTs have excluded people with substantial renal impairment, there are few data from RCTs to inform decisions about when specific ULTs should not be used on the basis of kidney function.
No studies have specifically examined the risks and benefits of not treating gout in people with CKD with ULT, and all current guidelines recommend ULT treatment in this population. In many patients, but not all, untreated gout causes considerable morbidity in its own right, and in those with CKD the only option for treating flares might be long-term corticosteroids, which is associated with further morbidity. In general, two main reasons are given for avoiding ULT in people with CKD: lack of efficacy and an increased risk of adverse events.
Despite fewer data for febuxostat than for allopurinol, there has been more acceptance of using febuxostat in people with CKD, on the basis of the knowledge that febuxostat is mainly metabolized in the liver and is not dependent on renal function for excretion. Whether the combination of xanthine oxidase inhibitors XOIs; allopurinol or febuxostat with uricosurics such as probenecid is a viable strategy in people with gout and CKD is unknown as these combinations share the same limitations of uricosurics by themselves, and evidence that is even more limited.
Pegloticase is largely under-studied although the available data suggest it has similar efficacy and safety in those with impaired kidney function and those with normal kidney function As there are some data indicating that the frequency of gout flares decreases with advancing CKD and after dialysis, it is plausible that some patients with mild hyperuricaemia or normouricaemia and no flares will not require ULT There is a paucity of data on the safety and efficacy of ULT in people on haemodialysis, and even less in those on peritoneal dialysis.
It has been suggested that haemodialysis should reduce serum urate concentration such that specific ULT is no longer required 58 , However, this is not a universal finding It has also been reported that serum urate is at the target concentration less often in those on haemodialysis than in those on peritoneal dialysis, perhaps due to the intermittent rather than continuous removal of urate through dialysis The data for use of allopurinol and febuxostat in patients undergoing haemodialysis are predominantly limited to case reports and case series 61 , 62 , 63 , 64 , For allopurinol, detailed information about the effect of haemodialysis on plasma concentrations of oxypurinol the active metabolite of allopurinol indicates that it is effectively dialysed 66 and suggests that allopurinol should be given after haemodialysis.
On the basis of primarily case series and a retrospective case—control study 67 , there is general agreement that the starting dose of allopurinol should be low and increased slowly, although no prospective trial data are available to prove or disprove the rationale that such an approach will reduce the risk of AHS. Both allopurinol and febuxostat have been associated with hypersensitivity reactions, which can be severe with either drug 71 , As might be expected with any life-threatening reaction, mortality is higher in those with pre-existing CKD Oxypurinol concentration, which is influenced by allopurinol dose, the presence of diuretics and renal function, might have a role in the pathophysiology of AHS.
In vitro studies have shown allopurinol hypersensitivity to be mediated by an oxypurinol-specific T cell response, and drug concentration is an important factor in T cell sensitization 74 , However, there is no evidence that a specific oxypurinol concentration precipitates AHS, as many individuals tolerate high concentrations and AHS has been reported in some with low concentrations, indicating that other factors must be involved.
Currently, treatment of AHS is supportive. The combined evidence that those with CKD and high oxypurinol concentrations have a poorer outcome and that oxypurinol is readily dialysed begs the question as to whether early dialysis can improve outcomes in people with AHS.
There are no data about CKD or renal function and the risk of drug reaction with eosinophilia and systemic symptoms DRESS associated with febuxostat treatment. CARES was a large RCT in people with gout and pre-existing CVD conducted in the USA that found no increased risk related to treatment with febuxostat compared with allopurinol for the primary end point, which was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or unstable angina with urgent revascularization HR 1.
However, pre-specified secondary analyses revealed an increased risk of cardiovascular-related death HR 1. Although there are a number of issues with the CARES study 79 , it raised issues about the relative safety of allopurinol and febuxostat in people with gout and CVD and led to a black box warning for febuxostat use. Febuxostat was non-inferior to allopurinol for the primary end point a composite of hospitalization for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death.
Overall, fewer deaths occurred in the febuxostat group than in the allopurinol group Whether CKD modulates this risk or whether febuxostat has a better cardiovascular safety profile than allopurinol in this population remains to be determined. Combination therapy with a XOI and a uricosuric can be very effective, and if uricosuric toxicity is a consequence of urate concentration within renal tubules then combination therapy could theoretically ameliorate such toxicity.
However, as uricosuric treatment is usually not considered for patients with advanced CKD this approach is largely untested. This Consensus Statement highlights where knowledge regarding the management of gout in people with CKD remains incomplete, and proposes a research agenda to address the most important areas of uncertainty, which includes a better understanding of the natural history of gout in people with CKD. A greater knowledge of the safety of treatments used for the management of gout flares, as well as the requirement for flare prophylaxis in this population, is also needed.
Additional investigation is required to determine the safe dosing of allopurinol in people with CKD, as well the prediction and management of AHS. Further research is also required to help determine whether febuxostat is associated with increased cardiovascular risk or is in fact risk-neutral, and whether febuxostat is safer to use than allopurinol in people with gout and CKD.
The safety and efficacy of uricosuric medications at different levels of renal function is another area where further research would be of benefit. Evidence regarding the use of pegloticase in people with gout and CKD is limited. From the standpoint of treating or preventing gout flares, the knowledge gaps are also substantial and revolve around the safe use and dosing of colchicine, the safety and efficacy of IL-1 inhibitors and the absolute indication for prophylactic therapy in all patients in whom ULT is being initiated.
In order to resolve these issues, it is important that researchers include patients with all stages of CKD in clinical trials of gout management wherever possible, and undertake pre-specified analyses of safety and efficacy according to renal function, using standardized outcome measures.
Kuo, C. Global epidemiology of gout: prevalence, incidence and risk factors. Article Google Scholar. Chen-Xu, M. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends; The National Health and Nutrition Examination Survey, Arthritis Rheumatol.
Zhu, Y. Roughley, M. Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies. Arthritis Res. Dalbeth, N. Reduced creatinine clearance is associated with early development of subcutaneous tophi in people with gout.
BMC Musculoskelet. Lu, C. Clinical characteristics of and relationship between metabolic components and renal function among patients with early-onset juvenile tophaceous gout. Krishnan, E. Busso, N. Mechanisms of inflammation in gout. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra.
Mihai, S. Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome. Kato, S. Aspects of immune dysfunction in end-stage renal disease. Akchurin, O. Update on inflammation in chronic kidney disease. Blood Purif. Krane, V. Statins, inflammation and kidney disease. Bardin, T. A cross-sectional study of patients found a diffuse hyperechoic kidney medulla pattern in patients with severe gout.
Kidney Int. Sellmayr, M. Only hyperuricemia with crystalluria, but not asymptomatic hyperuricemia, drives progression of chronic kidney disease. Bursill, D. Kumar, S. A survey of indications, results and complications of surgery for tophaceous gout.
Becker, M.
0コメント