Purpose
Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, ...selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients.
Methods
The Acute Kidney Injury–Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge.
Results
A total of 1032 ICU patients out of 1802 57.3 %; 95 % confidence interval (CI) 55.0–59.6 had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95 % CI 0.890–3.169;
p
= 0.109), stage 2 = 2.945 (95 % CI 1.382–6.276;
p
= 0.005), and stage 3 = 6.884 (95 % CI 3.876–12.228;
p
< 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m
2
in 47.7 % (95 % CI 43.6–51.7) versus 14.8 % (95 % CI 11.9–18.2) in those without AKI,
p
< 0.001.
Conclusions
This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions.
Acute kidney injury (AKI) is a complication that occurs frequently in hospitalized patients. In this article, we provide an overview of the literature on the epidemiology of AKI in hospitalized ...patients.
The overview is restricted to hospitalized patients, and most emphasis is put on intensive care unit patients.
The population incidence of less severe AKI and AKI treated with renal replacement therapy is approximately 2,000-3,000 and 200-300 per million population per year, respectively. These numbers are comparable with the estimates for severe sepsis and acute lung injury. Approximately 4-5% of general intensive care unit patients will be treated with renal replacement therapy, and up to two thirds of intensive care unit patients will develop AKI defined by the RIFLE classification. The incidence of AKI is increasing. Intensive care unit patients with AKI have a longer length of stay and therefore generate greater costs. In addition, AKI is associated with increased mortality, even after correction for covariates. Increasing RIFLE class is associated with increasing risk of in-hospital death. Patients with AKI who are treated with renal replacement therapy still have a mortality rate of 50-60%. Of surviving patients, 5-20% remain dialysis dependent at hospital discharge.
AKI has a high incidence, comparable with acute lung injury and severe sepsis, and is associated with higher hospital mortality.
Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and ...survival.
To determine the optimal therapeutic dose, effect on kidney function, and adverse effects of a human recombinant alkaline phosphatase in patients who are critically ill with sepsis-associated AKI.
The STOP-AKI trial was an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study in 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI. Patients were enrolled between December 2014 and May 2017, and follow-up was conducted for 90 days. The final date of follow-up was August 14, 2017.
In the intention-to-treat analysis, in part 1 of the trial, patients were randomized to receive recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n = 31), 0.8 mg/kg (n = 32), or 1.6 mg/kg (n = 29) or placebo (n = 30), once daily for 3 days, to establish the optimal dose. The optimal dose was identified as 1.6 mg/kg based on modeling approaches and adverse events. In part 2, 1.6 mg/kg (n = 82) was compared with placebo (n = 86).
The primary end point was the time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC1-7 ECC). Incidence of fatal and nonfatal (serious) adverse events (SAEs) was also determined.
Overall, 301 patients were enrolled (men, 70.7%; median age, 67 years interquartile range {IQR}, 59-73). From day 1 to day 7, median ECC increased from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) in the recombinant alkaline phosphatase 1.6-mg/kg group vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2) in the placebo group (absolute difference, 9.5 mL/min 95% CI, -23.9 to 25.5; P = .47). Fatal adverse events occurred in 26.3% of patients in the 0.4-mg/kg recombinant alkaline phosphatase group; 17.1% in the 0.8-mg/kg group, 17.4% in the 1.6-mg/kg group, and 29.5% in the placebo group. Rates of nonfatal SAEs were 21.0% for the 0.4-mg/kg recombinant alkaline phosphatase group, 14.3% for the 0.8-mg/kg group, 25.7% for the 1.6-mg/kg group, and 20.5% for the placebo group.
Among patients who were critically ill with sepsis-associated acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly improve short-term kidney function. Further research is necessary to assess other clinical outcomes.
ClinicalTrials.gov Identifier: NCT02182440.
Recovery after Acute Kidney Injury Kellum, John A; Sileanu, Florentina E; Bihorac, Azra ...
American journal of respiratory and critical care medicine,
03/2017, Letnik:
195, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Little is known about how acute kidney injury (AKI) resolves, and whether patterns of reversal of renal dysfunction differ among patients with respect to ultimate recovery.
We sought to examine ...different patterns for AKI reversal that are found in patients and assess how they relate to postdischarge outcomes.
We studied 16,968 critically ill patients with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI, using an electronic database. Reversal of AKI was defined as alive and no longer meeting criteria for even stage 1. Recovery was defined as reversal at hospital discharge.
We observed five patterns. The most common (4,508; 26.6%) was early reversal that was sustained through discharge, but almost as many patients (4,496; 26.5%) had no reversal at all. The remaining patients had late reversal after Day 7 (9.7%); early reversal with one or more relapses, but with ultimate recovery (22.5%); and relapsing without recovery (14.7%). Outcomes for patients with these phenotypes were quite different, with age-adjusted 1-year survival varying from more than 90% for early reversal to less than 40% for patients never reversing. Relapses are common (37.3%), especially in the first 72 hours after reversal, and are associated with a fivefold increased risk for death by 1 year compared with early sustained reversal.
We have identified five distinct recovery phenotypes on the basis of the clinical course over the first week after AKI manifestation. These phenotypes may identify patients amenable to therapeutic intervention. Long-term outcomes are associated with recovery status at hospital discharge.
Critical care represents a large percentage of healthcare spending in developed countries. Yet, little is known regarding international variation in critical care services. We sought to understand ...differences in critical care delivery by comparing data on the distribution of services in eight countries.
Retrospective review of existing national administrative data. We identified sources of data in each country to provide information on acute care hospitals and beds, intensive care units and beds, intensive care admissions, and definitions of intensive care beds. Data were all referenced and from as close to 2005 as possible.
United States, France, United Kingdom, Canada, Belgium, Germany, The Netherlands, and Spain.
Not available.
None.
No standard definition existed for acute care hospital or intensive care unit beds across countries. Hospital beds varied three-fold from 221/100,000 population in the United States to 593/100,000 in Germany. Adult intensive care unit beds also ranged seven-fold from 3.3/100,000 population in the United Kingdom to 24.0/100,000 in Germany. Volume of intensive care unit admissions per year varied ten-fold from 216/100,000 population in the United Kingdom to 2353/100,000 in Germany. The ratio of intensive care unit beds to hospital beds was highly correlated across all countries except the United States (r = .90). There was minimal correlation between the number of intensive care unit beds per capita and health care spending per capita (r = .45), but high inverse correlation between intensive care unit beds and hospital mortality for intensive care unit patients across countries (r = -.82).
Absolute critical care services vary dramatically between countries with wide differences in both numbers of beds and volume of admissions. The number of intensive care unit beds per capita is not strongly correlated with overall health expenditure, but does correlate strongly with mortality. These findings demonstrate the need for critical care data from all countries, as they are essential for interpretation of studies, and policy decisions regarding critical care services.
Purpose
To evaluate equations for estimation of glomerular filtration rate (GFR) and measured urinary creatinine clearance, compared to measured GFR in critically ill patients.
Methods
GFR was ...measured using inulin clearance. Multiple blood samples were collected per patient for determination of serum creatinine, cystatin C and inulin. GFR was estimated by the use of the following estimation equations (eGFR): four commonly used creatinine-based equations Cockcroft–Gault, Modification of Diet in Renal Disease (both the short and long formula) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), five cystatin C based estimation equations (Hoek, Larsson, Filler, Le Bricon, CKD-EPIcys) and one equation combining cystatin C and serum creatinine (CKD-EPIcr-cys). In addition we measured urinary creatinine clearance. Bias, precision and accuracy of all estimates were compared to those of the inulin clearance.
Results
Data were collected from 83 patients, of whom 68 were considered evaluable. The median age was 58 years interquartile range (IQR) 39–68. The median inulin clearance was 80 mL/min/1.73 m
2
(IQR 31–114). Equations based on creatinine had much bias and poor precision and accuracy. Measured urinary creatinine clearances overestimated GFR. Equations based on cystatin C were free of bias, but also had limited precision and accuracy.
Conclusions
In this cohort of patients, estimates of GFR had low accuracy and precision. Cystatin C based formulas, especially CKD-EPIcr-cys, showed limited bias; however, the accuracy and precision of these estimates were still insufficient. Measured urinary creatinine clearance overestimates GFR, but may provide a cheap alternative, when this is taken into account.
In intensive care unit (ICU) patients, acute kidney injury treated with renal replacement therapy (AKI-RRT) is associated with adverse outcomes. The aim of this study was to evaluate variables ...associated with long-term survival and kidney outcome and to assess the composite endpoint major adverse kidney events (MAKE; defined as death, incomplete kidney recovery, or development of end-stage renal disease treated with RRT) in a cohort of ICU patients with AKI-RRT.
We conducted a single-center, prospective observational study in a 50-bed ICU tertiary care hospital. During the study period from August 2004 through December 2012, all consecutive adult patients with AKI-RRT were included. Data were prospectively recorded during the patients' hospital stay and were retrieved from the hospital databases. Data on long-term follow-up were gathered during follow-up consultation or, in the absence of this, by consulting the general physician.
AKI-RRT was reported in 1292 of 23,665 first ICU admissions (5.5 %). Mortality increased from 59.7 % at hospital discharge to 72.1 % at 3 years. A Cox proportional hazards model demonstrated an association of increasing age, severity of illness, and continuous RRT with long-term mortality. Among hospital survivors with reference creatinine measurements, 1-year renal recovery was complete in 48.4 % and incomplete in 32.6 %. Dialysis dependence was reported in 19.0 % and was associated with age, diabetes, chronic kidney disease (CKD), and oliguria at the time of initiation of RRT. MAKE increased from 83.1 % at hospital discharge to 93.7 % at 3 years. Multivariate regression analysis showed no association of classical determinants of outcome (preexisting CKD, timing of initiation of RRT, and RRT modality) with MAKE at 1 year.
Our study demonstrates poor long-term survival after AKI-RRT that was determined mainly by severity of illness and RRT modality at initiation of RRT. Renal recovery is limited, especially in patients with acute-on-chronic kidney disease, making nephrological follow-up imperative. MAKE is associated mainly with variables determining mortality.
The lack of a standard definition for acute kidney injury has resulted in a large variation in the reported incidence and associated mortality. RIFLE, a newly developed international consensus ...classification for acute kidney injury, defines three grades of severity--risk (class R), injury (class I) and failure (class F)--but has not yet been evaluated in a clinical series.
We performed a retrospective cohort study, in seven intensive care units in a single tertiary care academic center, on 5,383 patients admitted during a one year period (1 July 2000-30 June 2001).
Acute kidney injury occurred in 67% of intensive care unit admissions, with maximum RIFLE class R, class I and class F in 12%, 27% and 28%, respectively. Of the 1,510 patients (28%) that reached a level of risk, 840 (56%) progressed. Patients with maximum RIFLE class R, class I and class F had hospital mortality rates of 8.8%, 11.4% and 26.3%, respectively, compared with 5.5% for patients without acute kidney injury. Additionally, acute kidney injury (hazard ratio, 1.7; 95% confidence interval, 1.28-2.13; P < 0.001) and maximum RIFLE class I (hazard ratio, 1.4; 95% confidence interval, 1.02-1.88; P = 0.037) and class F (hazard ratio, 2.7; 95% confidence interval, 2.03-3.55; P < 0.001) were associated with hospital mortality after adjusting for multiple covariates.
In this general intensive care unit population, acute kidney 'risk, injury, failure', as defined by the newly developed RIFLE classification, is associated with increased hospital mortality and resource use. Patients with RIFLE class R are indeed at high risk of progression to class I or class F. Patients with RIFLE class I or class F incur a significantly increased length of stay and an increased risk of inhospital mortality compared with those who do not progress past class R or those who never develop acute kidney injury, even after adjusting for baseline severity of illness, case mix, race, gender and age.
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