Pros and cons of antithrombotic therapy in end-stage kidney disease: a 2019 update

Burlacu, Alexandru; Genovesi, Simonetta; Ortíz, Alberto; Combe, Christian; Basile, Carlo; Schneditz, Daniel; Sande, Frank van der; Popa, Grigore T.; Morosanu, Cornel; Covic, Adrian

doi:10.1093/ndt/gfz040

Cited by 24 publications

(16 citation statements)

References 88 publications

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“…However, these doses are based solely on pharmacodynamic studies in patients with ESKD without clinical outcome data. 109 In retrospective claims analyses, rivaroxaban had an insignificantly decreased risk of ischemic stroke, but major bleeding was lower in the rivaroxaban group (HR, 0.68; 95% CI, 0.47-0.99) than in the warfarin group. 110 The majority of ESKD experience has been with apixaban.…”

Section: Ckd and Eskdmentioning

confidence: 96%

Role of direct oral anticoagulants in patients with kidney disease

Derebail

Rheault

Kerlin

2020

Kidney International

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The anticoagulation field is experiencing a renaissance that began with regulatory approval of the direct thrombin inhibitor dabigatran, a direct oral anticoagulant (DOAC), in 2010. The DOAC medication class has rapidly evolved to include the additional approval of 4 direct factor Xa inhibitors. Commensurately, DOAC use has increased and collectively account for the majority of new anticoagulant prescriptions. Despite exclusion of patients with moderateto-severe kidney disease from most pivotal DOAC trials, DOACs are increasingly used in this setting. An advantage of DOACs is similar or improved antithrombotic efficacy with less bleeding risk when compared with traditional agents. Several post hoc analyses, retrospective studies, claims data studies, and meta-analyses suggest that these benefits extend to patients with kidney disease. However, the lack of randomized controlled trial data in specific kidney disease settings, with their unique pathophysiology, should be a call to action for the kidney community to systematically study these agents, especially because early data suggest that DOACs may pose less risk of anticoagulant-related nephropathy than do vitamin K antagonists. Most DOACs are renally cleared and are significantly protein bound in circulation; thus, the pharmacokinetics of these drugs are influenced by reduced renal function and proteinuria. DOACs are susceptible to altered metabolism by P-glycoprotein inhibitors and inducers, including drugs commonly used for the management of kidney disease comorbidities. We summarize the currently available literature on DOAC use in kidney disease and illustrate knowledge gaps that represent important opportunities for prospective investigation.

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Section: Ckd and Eskdmentioning

confidence: 96%

Role of direct oral anticoagulants in patients with kidney disease

Derebail

Rheault

Kerlin

2020

Kidney International

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“…While clinical experience and expert opinion can, of course, be criticized and must be analysed, we greatly believe that their significance cannot be completely dismissed [ 63 ]. For instance, in the absence of clear evidence in some areas (such as antithrombotic therapy in end-stage renal disease), expert opinion is still very welcome so that nephrologists are not left alone when facing difficult and sometimes risky clinical and therapeutic decisions for which supporting evidence is lacking [ 44 ]. All these ethical/philosophical/practical dilemmas actually extend to most areas within general nephrology ( Table 2 ), causing nephrologists to struggle to choose between passivity (adopting a ‘wait and see’ approach and deciding to act only when Level 1 evidence becomes available) and an exceedingly proactive attitude based on long-lasting ‘beliefs’ that sometimes are not confirmed [ 66 , 67 ].…”

Section: Ethical Considerationsmentioning

confidence: 99%

Evidence in chronic kidney disease–mineral and bone disorder guidelines: is it time to treat or time to wait?

Bover

Ureña-Torres

Mateu

et al. 2020

Clinical Kidney Journal

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Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and ‘living’ guidelines), highlight some of the current important CKD–MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the ‘best available evidence’), which may prove useful in the face of the uncertainty over the decision whether ‘to treat’ or ‘to wait’.

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“…Experimentally, clopidogrel, which inhibits platelet aggregation by selectively inhibiting adenosine diphosphate binding to P2Y 12 receptors on platelets, has been found to protect the microvasculature of tracheal transplants [38]. However, drugs such as aspirin and clopidogrel are difficult to manage in transplant recipients [39].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Platelets: Mechanistic and Diagnostic Significance in Transplantation

2020

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Purpose of Review In addition to their function in coagulation, platelets recently have been recognized as an important component of innate immune responses. This review relates salient immune functions of platelets to transplants. Recent Findings Platelets are critical bridges between vascular endothelium and leukocytes. Real-time imaging of platelets has demonstrated that platelets rapidly adhere to vascular endothelium and form a nidus for attachment of neutrophils and then monocytes. However, the majority of platelets subsequently release from endothelium and return to the circulation in an activated state. These recycled platelets have the potential to transport proteins and RNA from the graft to the recipient. Some of the platelets that return to the circulation are attached to leukocytes. Summary Platelets have the potential to modulate many elements of the graft and the immune response from the time of organ retrieval through ischemia-reperfusion to acute and chronic rejection. Beyond mechanistic considerations, assays that detect changes in platelet protein or RNA expression could be used to monitor early inflammatory responses in transplants.

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Pros and cons of antithrombotic therapy in end-stage kidney disease: a 2019 update

Cited by 24 publications

References 88 publications

Role of direct oral anticoagulants in patients with kidney disease

Role of direct oral anticoagulants in patients with kidney disease

Evidence in chronic kidney disease–mineral and bone disorder guidelines: is it time to treat or time to wait?

Platelets: Mechanistic and Diagnostic Significance in Transplantation

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