Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

Background Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages. Methods This is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition. Results Two thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI95% [0.74–0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI95% [1.68–1.93], p < 0.001, non-adjusted and OR 1.37 CI95% [1.27–1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screatadm, pNGAL with a NRI of 0.27 CI95%(0.16–0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively). Conclusion Plasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission. Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011. Graphical abstract

Derivation and validation a risk model for acute kidney injury and subsequent adverse events after cardiac surgery: a multicenter cohort study

Background Acute Kidney Injury, a frequent complication in patients undergoing cardiac surgery, is associated with high mortality and poor quality of life. We aimed to establish a risk model for acute kidney injury and subsequent adverse events in Chinese cardiac patients. Methods This study included 11740 patients who had cardiac surgery at 14 institutions in China. Patients were randomly assigned to a derivation cohort (n = 8197) or a validation cohort (n = 3543). Variables ascertained during hospitalization were screened using least absolute shrinkage and selection operator and logistic regression to construct a nomogram model. Model performance was evaluated using C-statistic, calibration curve, and Brier score. The nomogram was further compared with the five conventional models: Mehta score, Ng score, AKICS score, SRI score, and Cleveland Clinic score. Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes criteria. Subsequent adverse events included mid-term outcomes: death from all causes and major adverse kidney events (defined as composite outcome of death from renal failure, dialysis, and advanced chronic kidney disease). Results Acute kidney injury occurred in 3237 (27.6%) patients. The model included 12 predictors. The nomogram achieved a C-statistic of 0.825 and 0.804 in the derivation and validation cohorts, respectively, and had well-fitted calibration curves. The model performance of the nomogram was better than other five conventional models. After risk stratification, moderate-risk or high-risk groups were associated with significantly higher rates of death from all causes and major adverse kidney events compared with low-risk group during 7-year follow-up. Conclusions The nomogram provided an effective tool for predicting acute kidney injury and evaluating its subsequent adverse events after cardiac surgery.

Effect of Restrictive Versus Liberal Fluid Management Strategies on Major Adverse Kidney Events in Critically Ill Adult Patients: A Protocol for a Systematic Review and Meta-Analysis

BackgroundIntravenous fluid therapy is ubiquitous in intensive care units (ICUs). There is increasing recognition of the value of restrictive fluid management strategies, including improved survival and renal function. However, these strategies have not been universally adopted. The purpose of this protocol is to outline our plan for investigating the current literature on the topic of restrictive versus liberal fluid management strategies in all critically ill adults and their associated outcomes, namely major adverse kidney events (MAKE). Methods We will conduct a systematic review and meta-analysis of randomized controlled trials evaluating fluid management strategies in critically ill adults. A search strategy was created with the help of medical librarians, using Ovid MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, and The Cochrane Library. Four independent researchers will perform study selection and data extraction in duplicate. The primary outcome of this study is detection of MAKE by 30 days. Secondary outcomes include reporting MAKE at 60 and 90 days; and mortality, new onset renal replacement therapy, and persistent renal dysfunction at 30, 60, and 90 days. If appropriate, we will perform a meta-analysis using a DerSimonian and Laird random-effects model. Subgroups will include patient type, ICU type, and study quality. Certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach.DiscussionThe results of this study will synthesize current evidence and better inform the optimal fluid management strategy in critically ill adults.Systematic review registration: Submitted to PROSPERO on June 16th, 2021.

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study

Background Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. Methods Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5–7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. Results Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. Conclusions In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.