A Historical Perspective on Uremia and Uremic Toxins.

Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney's function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells.

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25-30 ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.

Chronic kidney disease in inflammatory bowel disease, a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) is associated with various immune mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis and uveitis. Chronic kidney disease (CKD) is defined by a reduction in kidney function (eGFR less than 60ml/min/1.73m2) and/ or damage markers that are present for at least three months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, utilizing a random effect model. The systematic review was registered in PROSPERO (RD42023381927). Fifty-four articles were included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients (n = 102,230) vs. healthy populations (n = 762,430). Of these, diagnosis of CKD was based on ICD codes in five studies vs. on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59 (95%CI 1.31-1.93), without any difference between studies using diagnostic coding (OR 1.70 95%CI 1.33-2.19) vs. diagnosis based on eGFR (OR 1.36 95%CI 1.33-1.64). IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research.

Extracorporeal Techniques in Kidney Failure.

During the last decades, various strategies have been optimized to enhance clearance of a variable spectrum of retained molecules to ensure hemodynamic tolerance to fluid removal and improve long-term survival in patients affected by kidney failure. Treatment effects are the result of the interaction of individual patient characteristics with device characteristics and treatment prescription. Historically, the nephrology community aimed to provide adequate treatment, along with the best possible quality of life and outcomes. In this article, we analyzed blood purification techniques that have been developed with their different characteristics.

Avoiding Systemic Heparinization During Hemodialysis: How the Dialysis Setup Might Help.

Heparin is the most widely used anticoagulant for maintaining patency of the extracorporeal blood circuit during intermittent hemodialysis. Inadvertently, this leads to systemic heparinization of the patient. Repeated intermittent heparinization during hemodialysis has been associated with increased bleeding risks and metabolic and immunologic effects. Alternative strategies for minimizing systemic anticoagulation encompass dilution methods, regional citrate anticoagulation, priming of the extracorporeal circuit, and modifications to dialyzer membranes and dialysate composition. The effectiveness of these alternatives in maintaining patency of the extracorporeal circuit varies substantially. Although most studies have focused on particular changes in the hemodialysis setup, several combined interventions for adapting the hemodialysis setup are now being studied. This narrative review aims to present an overview of the current landscape of hemodialysis setup strategies aimed at limiting or avoiding systemic anticoagulation during treatment. Additionally, this review intends to shed light on the underlying pathophysiological mechanisms that contribute to variations observed in reported outcomes.

Regional Citrate Anticoagulation: A Tale of More Than Two Stories.

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.