Marie- Madeleine Couttenye

Background: Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications can occur. We performed a systematic review and meta-analysis to compare the efficacy and safety of citrate anticoagulation to heparin anticoagulation in critically ill patients treated with CRRT. Methods: Randomised controlled trials (RCTs) evaluating the safety and efficacy of citrate anticoagulation and heparin in CRRT were included. Articles not describing the incidence of metabolic and/or electrolyte disturbances induced by the anticoagulation strategy were excluded. The PubMed, Embase, and MEDLINE electronic databases were searched. The last search was performed on 18 February 2022. Results: Twelve articles comprising 1592 patients met the inclusion criteria. There was no significant difference between the groups in the development of metabolic alkalosis (RR = 1.46; (95% CI (0.52–4.11); p = 0.470)) or metabolic acidosis (RR = 1.71, (95% CI (0.99–2.93); p = 0.054)). Patients in the citrate group developed hypocalcaemia more frequently (RR = 3.81; 95% CI (1.67–8.66); p = 0.001). Bleeding complications in patients randomised to the citrate group were significantly lower than those in the heparin group (RR 0.32 (95% CI (0.22–0.47); p < 0.0001)). Citrate showed a significantly longer filter lifespan of 14.52 h (95% CI (7.22–21.83); p < 0.0001), compared to heparin. There was no significant difference between the groups for 28-day mortality (RR = 1.08 (95% CI (0.89–1.31); p = 0.424) or 90-day mortality (RR 0.9 (95% CI (0.8–1.02); p = 0.110). Conclusion: regional citrate anticoagulation is a safe anticoagulant for critically ill patients who require CRRT, as no significant differences were found in metabolic complications between the groups. Additionally, citrate has a lower risk of bleeding and circuit loss than heparin.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportionally affects frail, elderly patients and those with multiple chronic comorbidities. Whether patients on RRT have an additional risk because of their specific exposure and complex immune dysregulation is controversial. Methods: To describe the incidence, characteristics, and outcomes of SARS-CoV-2 infection, we conducted a prospective, multicenter, region-wide registry study in adult patients on RRT versus the general population from March 2 to May 25, 2020. This study comprised all patients undergoing RRT in the Flanders region of Belgium, a country that has been severely affected by coronavirus disease 2019 (COVID-19). Results: At the end of the epidemic wave, crude and age-standardized cumulative incidence rates of SARS-CoV-2 infection were 5.3% versus 2.5%, respectively, among 4297 patients on hemodialysis, and 1.4% versus 1.6%, respectively, among 3293 patients with kidney transplants (compared with 0.6% in the general population). Crude and age-standardized cumulative mortality rates were 29.6% versus 19.9%, respectively, among patients on hemodialysis, and 14.0% versus 23.0%, respectively, among patients with transplants (compared with 15.3% in the general population). We found no excess mortality in the hemodialysis population when compared with mean mortality rates during the same 12-week period in 2015–2019 because COVID-19 mortality was balanced by lower than expected mortality among uninfected patients. Only 0.18% of the kidney transplant population died of SARS-CoV-2 infection. Conclusions: Mortality associated with SARS-CoV-2 infection is high in patients on RRT. Nevertheless, the epidemic’s overall effect on the RRT population remained remarkably limited in Flanders. Calculation of excess mortality and age standardization provide a more reliable picture of the mortality burden of COVID-19 among patients on RRT.

A female hemodialysis patient with galactorrhea due to hyperprolactinemia was treated with different dialysis modalities to assess the effect on prolactin levels. A single session of both high-flux hemodialysis and hemodiafiltration resulted in decreased prolactin levels (16,6% and 77,2%, resp.). However, baseline prolactin levels measured immediately before the next dialysis session did not change markedly. After cabergoline treatment was started, prolactin levels normalized and galactorrhea disappeared. Thus, dopaminergic inhibition of prolactin secretion might be reduced in patients with end-stage renal disease. This dopaminergic resistance could be an important mechanism of hyperprolactinemia in hemodialysis patients and its subsequent treatment strategies.

Background Exercise intolerance is an important feature in patients with chronic kidney disease (CKD) and is prognostic for both increased morbidity and mortality. Little is known about the underlying mechanisms in predialysis CKD. This study aimed to gain more insight into the role of vascular dysfunction in the exercise intolerance of predialysis CKD. In addition, vascular-related microRNAs (miRNAs)—as epigenetic regulators of exercise capacity—were analysed. Methods Sixty-three patients with CKD stages 1–5 and 18 healthy controls were included. Peak oxygen consumption (VO₂peak) was determined by cardiopulmonary exercise testing, endothelial function by flow-mediated dilation (FMD) and arterial stiffness by carotid-femoral pulse wave velocity (PWV). Plasma miRNA levels (miR-21, miR-126, miR-146a, miR-150 and miR-210) were quantified by quantitative RT-PCR. Results VO₂peak was already impaired in mild CKD (stages 1–3A) and significantly correlated with estimated glomerular filtration rate (eGFR; r = 0.525, P < 0.001). Likewise, both FMD and PWV were significantly correlated with eGFR (r = 0.319, P = 0.007 and r = −0.365, P = 0.001, respectively). In multiple regression analysis, PWV remained one of the strongest independent determinants of VO₂peak (β = −0.301, P = 0.01). Of the studied miRNA, circulating levels of miR-146a and miR-150 correlated with eGFR, PWV and VO₂peak, but the association with the latter was lost when correcting for PWV. Conclusions Arterial stiffness contributes to the observed reduced aerobic capacity in predialysis CKD, independent of age, haemoglobin levels and endothelial function and represents a promising therapeutic target for improving exercise capacity in this population. Future work is required to elucidate why higher circulating levels of miR-146a and miR-150 are associated with impaired renal function and increased arterial stiffness.

Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD.

Introduction and Aims: Delayed graft function (DGF) (defined as the need for dialysis in the first week post-transplant) remains a common complication after renal transplantation (10-40%). The pre-transplant evaluation of the risk of DGF may influence the decision to accept or reject the graft and could also help to customize the initial immunosuppressive treatment, for instance by giving ATG induction with delayed calcineurin inhibitor administration. Here, we analyzed and compared the performance of 3 published DGF calculators that, based on pre-transplant donor, recipient, and procedure data, compute the theoretical risk of DGF for each patient.

Introduction and Aims: Exercise intolerance is an important feature in patients with CKD and an independent predictor of mortality. Limited data exist on underlying mechanisms in predialysis CKD. The contribution of vascular dysfunction, known to influence cardiovascular outcome in CKD, has not been studied before. The aim of this study was to gain more insight into the clinical (endothelial function and arterial stiffness), cellular (circulating vascular progenitor cells) and molecular (circulating microRNAs) determinants of exercise capacity in predialysis CKD.