Seminars in nephrology最新文献

Intermittent hemodialysis (HD) is almost invariably performed with heparin, and thus HD patients are at risk of developing the immune-mediated adverse effect heparin-induced thrombocytopenia (HIT), caused by anti-platelet factor 4/heparin IgG, which strongly activates platelets. HIT patients develop hypercoagulability with greatly increased risk of thrombosis, both venous and arterial. Certain HIT-associated complications are more likely to develop among HD patients, including hemofilter thrombosis despite heparin, intravascular catheter and/or arteriovenous fistula-associated thrombosis, post-heparin bolus anaphylactoid/anaphylactic reactions, and thrombotic stroke and acute limb artery thrombosis (reflecting the high frequency of underlying arteriopathy in many patients with renal failure). Management of HIT in HD usually requires use of an alternative (non-heparin) anticoagulant; for example, danaparoid sodium (outside the USA) or argatroban (USA and elsewhere). Whether heparin-grafted hemodialyzers (without systemic heparin) can be used safely in acute HIT is unknown. The HIT immune response is remarkably transient and usually not retriggered by subsequent heparin administration. Accordingly, since renal failure patients often require long-term HD, there may be the opportunity-following seroreversion (loss of platelet-activating HIT antibodies)-to restart heparin for HD, a practice that appears to have a low likelihood of retriggering HIT.

An adequate knowledge of anticoagulants used to prevent clotting in the extracorporeal circuit is crucial to provide optimal hemodialysis. Drugs can potentially prevent extracorporeal circuit clotting, but administration, half-life, and potential side effects differ. However, there is a lack of concise recommendations to guide anticoagulation and to avoid side effects. Because of the development of newer anticoagulant agents, direct thrombin inhibitors, and heparinoids, some of the side effects related to heparin may be overcome, but a deeper knowledge of these newer drugs is necessary. Moreover, types of heparin used, routes of administration, and health care economics vary around the world. We performed an extensive review of the literature, and the present article focuses on available anticoagulant drugs, exploring doses, side effects, particular use in hemodialysis, mechanism of action, pharmacokinetic properties, and use in special situations. Classical anticoagulants are still the standard of anticoagulation, but many questions remain unanswered; for example, is there real superiority of one treatment over another in terms of efficacy, safety, and health care economics? Anticoagulant protocols for hemodialysis need to be standardized and further studies performed to answer all of these questions.

Cardiovascular diseases are highly prevalent among patients on dialysis. For these diseases, antiplatelets and antithrombotic therapies including heparin, vitamin K antagonists, and direct oral anticoagulants, are being used. However, the benefit-risk balance of these therapies could differ for dialysis patients compared with the general population. This review article focuses on the bleeding risk associated with the use of heparin, antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients receiving hemodialysis.

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly used to prevent clotting of the hemodialysis extracorporeal circuit and optimize hemodialysis adequacy. There is no consensus on the optimal dosing for UFH and LMWHs during hemodialysis. In clinical practice, semiquantitative clotting scoring of the dialyzer and venous chamber may help to guide UFH and LMWH dose adjustment. Laboratory monitoring has not been shown to improve clinical outcomes and is therefore not routinely indicated in most hemodialysis patients. It might, however, be considered in select patients, such as those with extremes of body weight or history of repeated clotting or bleeding. Methods for laboratory monitoring include the activated partial thromboplastin time, activated clotting time, and antifactor Xa assays for UFH and antifactor Xa assay for LMWHs. Target ranges for anticoagulation in hemodialysis have been suggested but not clearly defined. When utilizing these tests, issues such as availability, standardization, interfering factors, and interpretation must be considered. In this narrative review, we discuss the rationale and methods of monitoring anticoagulation in hemodialysis.

Calcium is a key clotting factor, and several inorganic molecules that bind to calcium have been found to reduce the clotting propensity of blood. Citrate, a calcium chelator, is used as inhibitor of the coagulation cascade in blood transfusion. Also, it is used as an anaticoagulant during dialysis to maintain patency of the extracorporeal circuit, known as regional citrate anticoagulation (RCA). The amount of citrate should be chosen such that ionized calcium concentrations in the extracorporeal circuit are reduced enough to minimize propagation of the coagulation cascade. The dialytic removal of the calcium-citrate complexes combined with reduced ionized calcium concentrations makes necessary calcium supplementation of the blood returning to the patient. This can be achieved in different ways. In classical RCA, citrate and calcium are infused in the afferent and efferent tubing, respectively, whereas the dialysate does not contain calcium. This setup has been shown to be highly efficacious with a very low clotting propensity. Strict monitoring of blood electrolytes is required. Alternatively, the use of a high-calcium dialysate leads to calcium loading, obviating the need for a separate calcium infusion pump. The main advantages are simplified delivery of RCA and less fluctuation of systemic calcium concentrations. Currently, citric acid is sometimes added to the acid concentrate as a replacement for acetic acid. Differences and similarities between RCA and citrate-containing dialysate are discussed. RCA is an excellent alternative to heparin for patients at high risk of bleeding.

Maintaining patency of the extracorporeal hemodialysis (HD) circuit is a prerequisite to perform HD. Unfractionated heparin and low-molecular-weight heparins are the most used anticoagulants in maintenance HD, but their administration comes with a major trade-off of bleeding complications. This narrative review article discusses technical factors impacting on HD circuit patency, such as tubings, dialyzer membranes, priming practices, and treatment settings. Strategies for monitoring extracorporeal circuit clotting during and after treatment are also reviewed, as these are essential tools for optimizing anticoagulation.

Infections are the second leading cause of death among patients with end-stage kidney disease, behind only cardiovascular disease. In addition, patients on chronic dialysis are at a higher risk for acquiring infection caused by multidrug-resistant organisms and for death resulting from infection owing to their likelihood of requiring treatment that involves invasive devices, their frequent exposure to antibiotics, and their impaired immunity. Vascular access is a major risk factor for bacteremia, hospitalization, and mortality among hemodialysis (HD) patients. Catheter-related bacteremia is the most severe central venous catheter (CVC)-related infection and increases linearly with the duration of catheter use. Given the high prevalence of CVC use and its direct association with catheter-related bacteremia, which adversely impacts morbidity and mortality rates among HD patients, several prevention measures aimed at reducing the rates of CVC-related infection have been proposed and implemented. As a result, a large number of clinical trials, systematic reviews, and meta-analyses have been conducted to assess the effectiveness, clinical applicability, and long-term adverse effects of such measures. Peritoneal dialysis chronic treatment without the occurence of peritonitis is rare. Although most cases of peritonitis can be treated adequately with antibiotics, some cases are complicated by hospitalization or a temporary or permanent need to abstain from using the peritoneal dialysis catheter. Severe and long-lasting peritonitis can lead to peritoneal membrane failure, requiring the treatment method to be switched to HD. Some measures as patients training, early diagnosis, and choice of antibiotics can contribute to the successful treatment of peritonitis. Finally, medical directors are key leaders in infection prevention and are an important resource to implement programs to monitor and improve infection prevention practices at all levels within the dialysis clinic.

Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.

Individuals, societies, and the environment are affected by neglected and emerging diseases. These diseases result in a variety of severe outcomes, including permanent disabilities, chronic diseases such as chronic kidney disease, and even mortality. Consequences include high health care expenditures, loss of means of support, social stigma, and social exclusion. The burden of these diseases is exacerbated in low- and middle-income countries owing to poverty, inadequate fundamental infrastructure, and the absence of health and social protection systems. The World Health Organization is committed to promoting the following public health strategies to prevent and control neglected tropical diseases: preventive chemotherapy; intensive case management; vector control; provision of safe drinkable water, sanitation, and hygiene; and veterinary public health. In addition, it promotes a One Health strategy, which is a collaborative, multisectoral, and interdisciplinary approach to achieving the greatest health outcomes by recognizing the interdependence of human beings, animals, plants, and their shared environment. This article provides knowledge and strategies for the prevention and treatment of neglected and emerging diseases, with a particular concentration on kidney diseases, as part of a comprehensive approach to One Health.