EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): study protocol for a multicentre, observational trial

IntroductionMore than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI.Methods and analysisEPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI.Ethics and disseminationEPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials.Trial registration numberNCT04165369

Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics

Introduction: Acute kidney injury (AKI) is a common complication in cardiac surgery patients and prevention is needed to improve clinical outcomes. Alpha-1-microglobulin (A1M) is a physiological antioxidant with strong tissue-protective and cell-protective properties that has demonstrated renoprotective effects. RMC-035, a recombinant variant of endogenous human A1M, is being developed for the prevention of AKI in cardiac surgery patients. Methods: In this phase 1b, randomized, double-blind, and parallel group clinical study, 12 cardiac surgery patients undergoing elective, open-chest, on-pump coronary artery bypass graft and/or valve surgery with additional predisposing AKI risk factors were enrolled to receive in total 5 intravenous doses of either RMC-035 or placebo. The primary objective was to evaluate the safety and tolerability of RMC-035. The secondary objective was to evaluate its pharmacokinetic properties. Results: RMC-035 was well tolerated. The nature and frequency of adverse events (AEs) were consistent with the expected background rates in the underlying patient population with no AEs reported as related to study drug. No clinically relevant changes were observed for vital signs or laboratory parameters except for renal biomarkers. Several established AKI urine biomarkers were reduced at 4 hours after first dose administration in the treatment group, indicating a reduced perioperative tubular cell injury following RMC-035 treatment. Conclusion: Multiple intravenous doses of RMC-035 were well tolerated in patients undergoing cardiac surgery. Observed RMC-035 plasma exposures were safe and in the range of expected pharmacological activity. Furthermore, urine biomarkers suggest reduced perioperative kidney cell injury, warranting further investigation of RMC-035 as a potential renoprotective treatment

Continuous Glucose Monitoring in Patients Undergoing Extracorporeal Ventricular Assist Therapy

<div><p>Background</p><p>Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino^® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock.</p><p>Methods</p><p>Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined.</p><p>Results</p><p>CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p<0.001). Mean error from standard was 15.0 mg/dl (11.9%). 44.2% of the readings were outside a 15% range around ABL-values. In one of 635 paired data-points, ABL revealed hypoglycemia (BG 32 mg/dl) whereas CGM did not show hypoglycemic values (132mg/dl).</p><p>Conclusions</p><p>CGM reveals minimally invasive BG-values in critically ill adults with dynamically impaired tissue perfusion. Because of potential deviations from standard, CGM-readings must be interpreted with caution in specific ICU-populations.</p></div

Clarke Error Grid Analysis.

<p>Zone A: Clinically accurate, Zone B: Benign, Zone C: Overcorrected, Zone D: Failure to detect, Zone E: Erroneus.</p

Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.

<p>Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.</p

Demographic data.

<p>Demographic data.</p

Iron Deficiency Caused by Intestinal Iron Loss—Novel Candidate Genes for Severe Anemia

The adult human body contains about 4 g of iron. About 1–2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient

A multinational observational study exploring adherence with the kidney disease : improving global outcomes recommendations for prevention of acute kidney injury after cardiac surgery

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] +/- 1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD +/- 1.1] vs 3.5 [SD +/- 1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice