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

Bedeutung opioiderger Signalwege für die Modulation viszeraler Afferenzen bei funktionellen Magendarmerkrankungen

Funktionelle Erkrankungen des Magendarmtrakts sind überaus häufig. Sie sind charakterisiert durch Symptome wie Oberbauchschmerzen, Völlegefühl etc. sowie durch das Fehlen struktureller Läsionen oder biochemischer Abnormalitäten, die diese Symptome erklären. Die funktionelle Dyspepsie mit auf den Oberbauch bezogenen chronischen oder chronisch rezidivierenden Symptomen ist dabei eine der wichtigsten Erkrankungen, die in der Klinik Anlass gibt für endoskopische Untersuchungen. Hinsichtlich der Pathogenese der Symptome wird heute angenommen, dass neben Motilitätsstörungen vor allem Veränderungen der gastrointestinalen Sensorik eine zentrale Rolle einnehmen. So sind bei Patienten im Vergleich zu gesunden Probanden die Schwellen für die Wahrnehmung und das Auftreten von Beschwerden bei mechanischer Distension des Magens signifikant niedriger als bei gesunden Probanden . Neben Unterschieden hinsichtlich der Wahrnehmungsschwellen sind Patienten gekennzeichnet durch gestörte adaptive Veränderungen der Wahrnehmungsschwellen nach repetitiver mechanischer Stimulation oder einer mukosalen Schleimhautschädigung durch nicht-steroidale Antirheumatika (NSAR). Ziel der vorliegenden Untersuchung war es, den Einfluss opioiderger Bahnen für die Modulation viszeraler Wahrnehmungsschwellen zu erfassen und die Effekte bei Patienten mit funktioneller Dyspepsie und gesunden Probanden zu vergleichen. In Übereinstimmung mit anderen früheren Arbeiten findet sich bei Gesunden ein Anstieg viszeraler Wahrnehmungsschwellen nach repetitiver mechanischer Stimulation und Behandlung mit NSAR, während die Schwellen bei Patienten mit funktioneller Dyspepsie abnehmen. Die Gabe von Naloxon, einem unspezifischen Opioidantagonisten, bewirkt bei Gesunden einen signifikant stärker ausgeprägten Abfall viszeraler Wahrnehmungsschwellen als bei Patienten. Die Daten lassen insofern den Schluss zu, dass a) bei Patienten offensichtlich antinozizeptive Bahnen nur eingeschränkt funktionstüchtig sind; b) b) dies auf eine Störung opioiderg vermittelter antinozizeptiver Effekte zurückzuführen ist, was die verminderte Antwort auf intravenös appliziertes Naloxon bei Patienten nahe legt

Intravenous iron sucrose versus oral iron ferrous sulfate for antenatal and postpartum iron deficiency anemia: a randomized trial

OBJECTIVE: To compare oral iron to intravenous iron administration to women in late pregnancy and/or after labor to correct iron deficiency. METHODS: 271 anemic women (148 pregnant women and 123 women post lower segment caesarean section) with hemoglobin (Hb) levels below 110 g/L were enrolled over a two-year period and randomized to receive either two tablets FGF (ferrous sulfate with folic acid) or 400mg of intravenous iron sucrose plus folic acid 600 mg. Treatment effectiveness was assessed by measuring Hb and ferritin postpartum on day 1, day 14 and day 42. Transfusions of red blood cells and adverse drug reactions were recorded. RESULTS: Data of 214 women were available for analysis. Both forms of iron replacement therapy led to increased hemoglobin and ferritin levels over the testing period. Ferritin was significantly higher in the i.v. iron treatment group compared to the oral iron treatment group (p¼0.004) two weeks after delivery, while Hb values did not differ between the groups. No serious adverse drug reactions were observed. Red blood cell transfusion rate was low (1.9%), with equal rates observed in both treatment groups. CONCLUSION: Intravenous and oral irons were both effective in correcting peripartum anemia, although intravenous iron restored stores faster than oral iron.Bernd Froessler, Carmel Cocchiaro, Khaschayar Saadat-Gilani, Nicolette Hodyl and Gustaaf Dekke

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. Results: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors

Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide