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

ABSTRACT:

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.

SUBMITTER: Flannery AH

PROVIDER: S-EPMC8364694 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSeveral biomarkers of AKI have been examined for their ability to predict AKI before serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research.MethodsSingle-center prospective study collecting blood and urine samples from critically ill patients with AKI Kidney Disease Improving Global Outcomes stage 2 or above, and matched controls from a single, tertiary care intensive care unit (ICU). Samples were collected at 24-48 hours after AKI diagnosis (patients) or ICU admission (controls), 5-7 days later, and 4-6 weeks after discharge for patients with AKI. The primary outcome of interest was MAKE at hospital discharge (MAKE-DC), consisting of the composite end point of death, RRT dependence, or a decrease in estimated glomerular filtration to <75% of baseline.ResultsSerum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE-DC compared with those not experiencing MAKE-DC. Additionally, serum/urinary NGAL and serum cystatin C measurements at the first time point remained significantly associated with MAKE events at 3, 6, and 12 months. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a logistic regression clinical prediction model of MAKE-DC (AUROC 0.94 and 0.87 versus 0.83; P=0.001 and P=0.02, respectively). Patients without MAKE-DC experienced a greater decline in serum NGAL from first to second measurement than those patients experiencing MAKE-DC.ConclusionsEarly measures of kidney biomarkers in patients who are critically ill are associated with MAKE-DC. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE-DC.

Project description:Klotho and Fibroblast Growth Factor (FGF)-23 were recently postulated as candidate biomarkers and/or therapeutic targets in acute kidney injury (AKI). We examined whether urine Klotho and serum intact FGF23 levels were differentially and independently associated with major adverse kidney events (MAKE) in critically ill patients with and without AKI. Single-center, prospective, case-control study. ICU in a tertiary medical center. 54 AKI patients and 52 controls without AKI admitted to the ICU. None. AKI was defined by KDIGO criteria and included only AKI stage ≥2. Controls were matched by age, gender, and baseline eGFR. Paired serum and urine samples were obtained 24-48h after AKI diagnosis (cases) or ICU admission (controls). The primary outcome was 90-day MAKE, which was the composite of all-cause death, dependence on renal replacement therapy or a 50% or higher decrease in eGFR from baseline. Forty-four (41.5%) patients developed MAKE-90. Patients who developed MAKE-90 had more comorbidity, higher acuity of illness scores and more prevalent AKI. Levels of urine Klotho adjusted by creatinine (Cr) were lower and serum intact FGF23 levels were higher in AKI patients vs. ICU controls. In adjusted models, the highest vs. lowest tertile of urine Klotho/Cr was independently associated with an overall 95% lower risk of MAKE-90 (81% lower risk in patients with AKI). The highest vs. lowest tertile of serum intact FGF23 was associated with >300% higher risk of MAKE-90. Urine Klotho/Cr levels were significantly lower and serum intact FGF23 levels significantly higher in critically ill patients with AKI vs. matched-controls without AKI. When measured in the first 48h of ICU admission or AKI diagnosis, urine Klotho/Cr independently associated with major adverse kidney events, particularly in patients with AKI. These results show promise for testing these biomarkers -individually or in combination- as part of novel risk-prediction models of renal outcomes in the ICU.

Project description:The aim of the present study was to investigate the incidence of adverse events (AEs) during intra-hospital transport (IHT) of critically ill patients and evaluate the risk factors associated with these events.This prospective multicenter observational study was performed in 34 intensive care units in China during 20 consecutive days from 5 November to 25 November 2012. All consecutive patients who required IHT for diagnostic testing or therapeutic procedures during the study period were included. All AEs that occurred during IHT were recorded. The incidence of AEs was defined as the rate of transports with at least one AE. The statistical analysis included a description of demographic and clinical characteristics of the cohort as well as identification of risk factors for AEs during IHT by univariate and multivariate logistic regression analyses.In total, 441 IHTs of 369 critically ill patients were analyzed. The overall incidence of AEs was 79.8% (352 IHTs). The proportion of equipment- and staff-related adverse events was 7.9% (35 IHTs). The rate of patient-related adverse events (P-AEs) was 79.4% (349 IHTs). The rates of vital sign-related P-AEs and arterial blood gas analysis-related P-AEs were 57.1% (252 IHTs) and 46.9% (207 IHTs), respectively. The incidence of critical P-AEs was 33.1% (146 IHTs). The rates of vital sign-related critical P-AEs and arterial blood gas analysis-related critical P-AEs were 22.9% (101 IHTs) and 15.0% (66 IHTs), respectively. All data collected in our study were considered potential risk factors. In the multivariate analysis, predictive factors for P-AEs were pH, partial pressure of carbon dioxide in arterial blood, lactate level, glucose level, and heart rate before IHT. Furthermore, the Acute Physiology and Chronic Health Evaluation II score, partial pressure of oxygen in arterial blood, lactate level, glucose level, heart rate, respiratory rate, pulse oximetry, and sedation before transport were independent influential factors for critical P-AEs during IHT.The incidence of P-AEs during IHT of critically ill patients was high. Risk factors for P-AEs during IHT were identified. Strategies are needed to reduce their frequency.Chinese Clinical Trial Register identifier ChiCTR-OCS-12002661. Registered 5 November 2012.

Project description:BackgroundWhether early fluid accumulation is a risk factor for adverse renal outcomes in septic intensive care unit (ICU) patients remains uncertain. We assessed the association between cumulative fluid balance and major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or sustained renal dysfunction, in such patients.MethodsWe performed a multicenter, retrospective observational study in 1834 septic patients admitted to five ICUs in three hospitals in Stockholm, Sweden. We used logistic regression analysis to assess the association between cumulative fluid balance during the first two days in ICU and subsequent risk of MAKE30, adjusted for demographic factors, comorbidities, baseline creatinine, illness severity variables, haemodynamic characteristics, chloride exposure and nephrotoxic drug exposure. We assessed the strength of significant exposure variables using a relative importance analysis.ResultsOverall, 519 (28.3%) patients developed MAKE30. Median (IQR) cumulative fluid balance was 5.3 (2.8-8.1) l in the MAKE30 group and 4.1 (1.9-6.8) l in the no MAKE30 group, with non-resuscitation fluids contributing to approximately half of total fluid input in each group. The adjusted odds ratio for MAKE30 was 1.05 (95% CI 1.02-1.09) per litre cumulative fluid balance. On relative importance analysis, the strongest factors regarding MAKE30 were, in decreasing order, baseline creatinine, cumulative fluid balance, and age. In the secondary outcome analysis, the adjusted odds ratio for dialysis or sustained renal dysfunction was 1.06 (95% CI 1.01-1.11) per litre cumulative fluid balance. On separate sensitivity analyses, lower urine output and early acute kidney injury, respectively, were independently associated with MAKE30, whereas higher fluid input was not.ConclusionsIn ICU patients with sepsis, a higher cumulative fluid balance after 2 days in ICU was associated with subsequent development of major adverse kidney events within 30 days, including death, renal replacement requirement, or persistent renal dysfunction.

Project description:BACKGROUND:Acute kidney injury (AKI) is a common problem in critically ill patients and associated with high rates of morbidity and mortality. Recently, Major Adverse Kidney Events (MAKE) were introduced as important kidney endpoints. If these endpoints can be predicted, then it may help the physicians to identify high-risk patients and provide the opportunity to have targeted preventive therapy. The objective of this study was to create a simplified scoring system to predict MAKE within 28 days among AKI patients in ICU. METHODS:This is a prospective web-based multicenter cohort study that was conducted in adults who were admitted to the ICU in 17 centers across Thailand from 2013 to 2015. A predicting score was derived from the regression equation with Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic test and produce predictive models. Internal validation was obtained using the bootstrapping method. RESULTS:From 5071 cases, 2856 (56%) had AKI. Among those with AKI, 1749 (61%) had MAKE. Among those that have MAKE, there were 1175 (41.4%) deaths, 414 (14.4%) were on dialysis and 1154 (40.7%) had non-recovery renal function. The simplified score points of low Glasgow coma scale was 3, tachypnea was 1, vasopressor use was 1, on mechanical ventilation was 2, oliguria was 2, serum creatinine rising ≥ 3 times was 5, high blood urea nitrogen was 3, low hematocrit was 2, and thrombocytopenia was 1. The area under ROC curve for optimism corrected performance was 0.80 (0.78, 0.81). When the cut-off value was 7, the sensitivity, specificity, positive likelihood ratio, and positive predictive values were 0.75, 0.76, 3.10, and 0.84, respectively. When the scoring system was calibrated, the α intercept and β slope were 1.001 and 0, respectively. CONCLUSIONS:SEA-MAKE scoring system is a new simplified clinical tool that can be used to predict major adverse kidney events in AKI patients. The simplicity of the scoring system is highly likely to be used in resource-limited settings. However, external validation is necessary before widespread use.

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