Background. The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking. Methods. This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101).Results. There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103). Conclusions. In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.

Background Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. Methods This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV − AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. Results Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV − AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25–0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV − AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18–0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99–4.68). Conclusions In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Background: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk.Methods: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV+ AKI and COV− AKI, respectively), submitted to CRRT. Filter clotting risks in the first 72 hours were compared between groups.Results: Between January 2019 and July 2020, 248 patients were evaluated: 189 in the COV+ AKI group and 59 in the COV− AKI group. Filter clotting occurred during the first 72 hours of CRRT in 96 patients (38.7%). Heparin use conferred protection against filter clotting, resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV+ AKI patients than among the COV− AKI patients, although it was similar between the COV+ AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (6086 ng/ml). In the multivariate analysis, the protective effect of heparin against filter clotting persisted, whereas an elevated D-dimer level, high platelet count, and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was not a risk factor for filter clotting.Conclusions: In COV+ AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with low risk of complications.

BackgroundAcute kidney injury (AKI) is common in cirrhotic patients and is associated with negative outcomes. The aim of this study was to evaluate the presence of AKI and its progression according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria in cirrhotic patients admitted to the emergency department and to determine the association of AKI with hospital mortality.MethodsThis retrospective study included 258 cirrhotic patients admitted to the emergency department of a university hospital from March 2015 to February 2017. AKI was diagnosed and classified according to the KDIGO criteria.ResultsThe overall incidence of AKI in cirrhotic patients was 53.9%, and the overall hospital mortality was 28.4%. Mortality was associated with the presence, stage, and progression of AKI. Patients with AKI stage 1 and sCr < 1.5 mg/dl (KDIGO 1a) had a lower mortality rate than patients with AKI stage 1 and sCr > 1.5 mg/dl (KDIGO 1b). In the logistic regression analysis, three variables were independently associated with hospital mortality: cancer, AKI and progression of AKI.ConclusionsAccording to the data presented, a single measure of creatinine is not enough, and there is a need for meticulous follow-up of the renal function of patients with hepatic cirrhosis hospitalized in an emergency unit. In addition, this study reinforces the need for subclassification of KDIGO 1 in cirrhotic patients, since patients with acute renal injury and creatinine greater than 1.5 mg/dL present a worse clinical outcome.

Objectives The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. Trial design Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. Participants Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. Data Collection: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient’s age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. Exclusion criteria: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. Intervention and comparator Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. Main outcomes The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. Randomization RedCap→ randomization – 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. Blinding (masking) No blinding – Open label format Numbers to be randomized (sample size) Total number of patients 90 (45 per group) Trial Status Trial version 2.0 – ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 Trial registration Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990, registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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We report a case of purple urine bag syndrome, associated to Streptococcus agalactiae urinary tract infection, progressing to septic shock and death. We present a review of the literature on the subject and take the opportunity to attend readers about increasing incidence with population aging and its potential bad outcome.

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