Abstract
Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease VSports最新版本. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk of CKD, ESRD and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25. 8/100 person-years and 8. 6 per 100 person-years, respectively. Patients with AKI had higher risks of developing CKD (pooled adjusted hazard ratio 8. 8, 95% CI 3. 1-25. 5), ESRD (pooled adjusted HR 3. 1, 95% CI 1. 9-5. 0) and mortality (pooled adjusted HR 2. 0, 95% CI 1. 3-3. 1) than patients without AKI. The relationship between AKI and CKD or ESRD was graded depending on the severity of AKI and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, and death and other important non-renal outcomes.
Introduction
The incidence of acute kidney injury (AKI) has been increasing over time. 1, 2 Concurrently, the prevalence of CKD has also been increasing. 3 AKI has long been thought of as a completely reversible syndrome. However, over the past several years, a plethora of data from experimental animals and humans has been published that indicate that AKI more than likely results in permanent kidney damage (i. e. , CKD) and may also result in damage to non-renal organs. 4, 5 V体育平台登录.
Moreover, the proportion of patients surviving after AKI has also been increasing over time. 1, 6-8 Thus, if AKI indeed heightens the risk for CKD and other organ damage, then it could imply significant public health concerns in regards to the absolute number of persons developing incident CKD, progressive CKD, end-stage renal disease (ESRD), and cardiovascular events VSports注册入口.
Non-contemporary long-term follow-up studies of AKI were plagued by lacking follow-up of non-AKI patients, which did not permit the calculation of a relative risk or hazard ratio for the outcome of CKD in those with versus those without AKI. 9 However, over the past few years, several studies have attempted to estimate the incidence rate and relative hazards of the development of CKD both in survivors of AKI compared to populations without AKI V体育官网入口.
Thus, the goals of this systematic review and meta-analysis were to estimate the risk of CKD, ESRD, death, and other non-renal outcomes in persons with AKI versus those without AKI VSports在线直播. We also sought to determine whether pre-existing renal injury (decreased baseline GFR or pre-existing proteinuria) modified these associations.
Results
We identified 618 citations meeting our search criteria. After excluding 582 citations after reviewing the abstracts, 36 articles were selected for further review (Figure 1). Reasons for exclusion are shown in Figure 1. Finally, 13 studies (from 14 articles)10-22 were selected for inclusion into the systematic review. Study and patient characteristics from the selected articles are listed in Table 1. Eleven of the 13 studies followed more than 3000 patients and all were retrospective. One study included patients with HIV exclusively12 and two studies included hematopoietic stem cell transplant recipients V体育2025版. 13, 19.
Figure 1. Selection of Studies.
Table 1. Characteristics of Included Studies.
| First author, year of publication | Clinical Setting | No of pts | Years of enrollment | Mean age | Male (%) | White (%) | CKD | CKD progression | ESRD | Mortality |
|---|---|---|---|---|---|---|---|---|---|---|
| Hsu, 200910 | Hospitalized | 39805 | 1996-2003 | 66.6 | 56.6 | 73 | ✓ | ✓ | ||
| Lo, 200911 | Hospitalized | 3773 | 1996-2003 | 63.5 | 61 | 66.6 | ✓ | ✓ | ✓ | |
| Choi, 201012 | HIV | 17325 | 1975-1995 | 44 | 98 | 28 | ✓ | ✓ | ||
| Weiss, 200613 | HCT | 174 | 2002 | 54 | 67 | 83 | ✓ | ✓ | ||
| Newsome, 200814 | MI | 87094 | 1994-1995 | 77.1 | 51.5 | 87 | ✓ | ✓ | ||
| James(A), 201015, 23* | Coronary Angiography | 11249 | 2004 | 63.6 | 69.6 | NR | ✓ | ✓ | ✓ | ✓ |
| Wald, 200917 | ICU | 8855 | 2006 | 62 | 60 | NR | ✓ | ✓ | ||
| Lafrance, 201018 | CKD | 6862 | 2002 | 69.8 | 54 | NR | ✓ | ✓ | ||
| Ando, 201019 | HCT | 158 | 1987 | 31 | 61.3 | NR | ✓ | ✓ | ||
| James(B), 201016 | Hospitalized and Non-Hospitalized | 920985 | 2002 | 61 | 65 | NR | ✓ | ✓ | ✓ | |
| Ishani, 200920 | Hospitalized | 233803 | 2000 | 79.2 | 38.8 | 89 | ✓ | ✓ | ||
| Amdur, 200922 | Hospitalized | 113272 | 1999-2005 | 70.8 | 97.8 | 74 | ✓ | ✓ | ✓ | |
| Ishani, 201121 | Cardiac Surgery | 29388 | 1999-2005 | 65.4 | 98.8 | 84.4 | ✓ | ✓ | ✓ |
Abbreviations: HIV-Human immunodeficiency Virus, HCT-Hematopoietic stem cell transplant, VA-Veterans affairs, NR-Not reported ICU-Intensive care unit, MI-Myocardial infarction, CKD-Chronic kidney disease, ESRD- end stage renal disease; Y- Yes, N-No CKD definition was variable in different studies-It was CKD stage 4 in Lo11, Amdur22 and decrease in GFR>4 ml/min/year in James A15, decrease in GFR of at least 25% from baseline in Weiss13
Data is ascertained from two different manuscripts that referred to the same study population
The definitions of AKI varied substantially (Table 2). Maximum length of follow-up ranged from 6 months to 75 months. All 13 studies sufficiently met the quality criteria V体育官网.
Table 2. AKI definitions and Outcomes.
| First author, year of publication | AKI Definition Severity | Method of Ascertainment of AKI | Follow-up (mean or median in months) | Post-Discharge Mortality Overall (%) | Mortality Rate in AKI patients (per 100 person-yrs)† | Renal Outcomes In AKI patient (per 100 person-yrs)† | |
|---|---|---|---|---|---|---|---|
| CKD Rate | ESRD Rate | ||||||
| Hsu, 200910 | RRT | Labs and code for RRT | 6 | 19.7 | 43.7 | … | 28.1 |
| Lo, 200911 | RRT | Labs and code for RRT | 32.9 | 13.3 | 4.9 | 47.9 | … |
| Choi, 201012 | RIFLE | Labs | 68.4 | 48.5 | 9.9 | … | 0.6-5.6 |
| Weiss, 200613 | > 2 fold increase in Cr | Labs | 12 | 17.2 | … | 72.2 | … |
| Newsome, 200814 | Cr ↑0.3-0.5; 0.6-3.0 | Labs | 49.2 | 73.3 | 19.4 | … | 0.6 |
| James A, 201015, 23 | AKIN | Labs | 21.8 | 5.7 | 12.7-31.5 | 4.6-8.6† | 1.6-4.2† |
| Wald, 200917 | RRT | Diagnostic codes | 36 | 34.8 | 10.1 | … | 2.6 |
| Lafrance, 201018 | ↓ eGFR 25% & ≥5 ml/min | Labs | 19.4 | 15.3 | 9.4 | … | 12.1 |
| Ando, 201019 | >2 fold increase in Cr | Labs | 73.8 | 4.1 | … | ||
| James B, 201016 | ARF | Diagnostic codes | 35 | 3 | 1.0-12.4† | 0.03-15.8† | … |
| Ishani, 200920 | ARF | Diagnostic codes | 24 | 64 | 28.8 | … | 2.5 |
| Amdur, 200922 | ARF & ATN | Diagnostic codes | 75 | 44.7 | 7.8 | 22 | … |
| Ishani, 201121 | Class 1-4 | Labs | 61.2 | 23.1 | 4.1-6.6† | 6.6-10.5† | … |
Abbreviations: AKI- acute kidney injury; RRT- renal replacement therapy; RIFLE- Risk Injury Failure Loss End Stage Renal Disease classification; Cr- creatinine; eGFR- estimated glomerular filtration rate; AKIN- Acute Kidney Injury Network classification; ARF- acute renal failure; ATN- acute tubular necrosis
Range of rates is provided for studies that examined outcomes by differing severity of AKI.
Ishani21-AKI definition-Percent increase in creatinine post operatively for Class 1(1%-24% rise in creatinine), class 2(25%-49%), class 3(50%-99%), class 4(>100%)
Choi12-The rate of ESRD was 0.6/100 person years for those with mild AKI and 5.6/100 person years for those with moderate –severe AKI.
James A15-The rate of incident CKD was 4.6/100 person-years and ESRD was 1.6/100 person years for those with mild AKI and 8.6/100 person-years and 4.2/100 person years respectively for those with moderate-severe AKI. The mortality rate was 12.7 and 31.5/100 person years respectively for those with mild AKI and with moderate-severe AKI.
James B16-The rate of CKD progression was 0.03/100 person years and mortality was 0.98/100person years for those with mild AKI and it was 15.8/100person years and 12.4/100 person years respectively for those with moderate-severe AKI.
Ishani21-The rate of incident CKD was 6.6/100 person years and mortality was 4.1/100 person years for those with mild AKI and 10.5/100 person years and 6.6/100 person years respectively for those with moderate-severe AKI.
Overall Analyses (VSports app下载)
The renal outcomes CKD and ESRD were calculated in person years. The pooled rate of CKD was 25.8 per 100 person years (range 3.4-72.2) and ESRD was 8.6 per 100 person years (range 0.63-28.1) (Table 2). The pooled adjusted HR for CKD for AKI vs. no AKI was 8.8 (95% CI 3.1-25.5; Figure 2a) and for ESRD was 3.1 (95% CI 1.9-5.0; Figure 2b). However, heterogeneity was very high (I2 > 75%). We were not able to reduce statistical heterogeneity to below 75% with deletion of studies from the pooled analyses.
Figure 2a. Pooled Adjusted Hazard Ratios for CKD after AKI.
Figure 2b. Pooled Adjusted Hazard Ratios for ESRD after AKI.
Outcomes by Severity of AKI
The outcomes of CKD and ESRD with varying degrees of AKI were reported in 6 out of 13 studies. The risk for CKD increased in a graded fashion with mild AKI (adjusted HR 2.0, 95% CI 1.4-2.8), moderate AKI (adjusted HR 3.3, 95% CI 1.7-6.2), and severe AKI (adjusted HR 28.2, 95% CI 21.1-37.5) (Table 3). The risk for ESRD also increased in a graded fashion with the severity of AKI: mild AKI (adjusted HR 2.3, 95% CI 1.7-3.3), moderate AKI (adjusted HR 5.0, 95% CI 2.6-9.8), and severe AKI (adjusted HR 8.0, 95% CI 1.3-48.6). However, heterogeneity was still high (I2 > 50%) for all subgroup analyses except for severe AKI and risk for CKD. Thus, we removed studies one at a time until heterogeneity fell below 25%. Statistical heterogeneity was reduced to 0% for the pooled analyses of moderate and severe AKI and the outcome of CKD, and mild and moderate AKI and the outcome of ESRD. In all cases where these more homogeneous estimates were created, the point estimate did not differ significantly from the inclusive analyses in any qualitative or quantitative fashion (Supplementary Table).
Table 3. Pooled HR for Outcomes of CKD and ESRD by Severity of AKI, Decreased Baseline GFR, and Pre-AKI Proteinuria.
| Grouping | Comparison | Outcome | # Studies | References | HR | CI | I2 |
|---|---|---|---|---|---|---|---|
| Overall | AKI vs. No AKI | CKD | 7 | 11, 13, 15, 16, 19, 21, 22 | 8.8 | 3-25.5 | 99% |
| AKI vs. No AKI | ESRD | 7 | 10, 12, 14, 15, 17, 18, 20 | 3.1 | 1.9-5.0 | 98% | |
| Dose response | Mild AKI vs. No AKI | CKD | 2 | 15, 21 | 2.0 | 1.4-2.8 | 74% |
| Moderate AKI vs. No AKI | 3 | 13, 15, 21 | 3.3 | 1.7-6.2 | 63% | ||
| Severe AKI vs. No AKI | 2 | 11, 13 | 28.2 | 21.1-37.5 | 0% | ||
| Mild AKI vs. No AKI | ESRD | 4 | 12, 14, 15, 18 | 2.3 | 1.7-3.3 | 84% | |
| Moderate AKI vs. No AKI | 3 | 12, 14, 15 | 5.0 | 2.6-9.8 | 88% | ||
| Severe AKI vs. No AKI | 2 | 12, 17 | 8.0 | 1.3-48.6 | 98% | ||
| Effect modification by decreased baseline GFR | AKI on decreased GFR vs. No AKI and decreased GFR | CKD | 2 | 11, 16 | 24.4 | 15.3-38.9 | 89% |
| AKI on normal GFR vs. No AKI and normal GFR | 2 | 11, 16 | 38.8 | 21.9-68.9 | 81% | ||
| AKI on decreased GFR vs. No AKI and decreased GFR | ESRD | 3 | 12, 17, 20 | 1.9 | 1.6-2.3 | 0% | |
| AKI on normal GFR vs. No AKI and normal GFR | 3 | 12, 17, 20 | 9.2 | 4.1-20.3 | 93% | ||
| Effect modification by pre-existing proteinuria | AKI with proteinuria vs. No AKI and proteinuria | CKD | 1 | 16 | 106.9 | 76.3-149.8 | NA |
| AKI without proteinuria vs. No AKI without proteinuria | 1 | 16 | 30 | 24.3-37 | NA | ||
| AKI with proteinuria vs. No AKI with proteinuria | ESRD | 1 | 12 | 1.4 | 0.9-2.2 | NA | |
| AKI without proteinuria vs. No AKI without proteinuria | 1 | 12 | 3.7 | 2.4-5.7 | NA |
Abbreviations: AKI- acute kidney injury; CKD- chronic kidney disease; ESRD- end stage renal disease; HR- hazards ratio; CI- confidence interval
Only one study stratified AKI by recovery status.12 Choi et al. found that the adjusted risk for ESRD was not present in those with mild AKI that recovered (adjusted HR 0.9, 95% CI 0.6-1.4 vs. HR 2.2, 95% CI 1.5-3.1 in those without recovery) and was markedly attenuated in those with moderate-severe AKI that recovered (adjusted HR 2.5, 95% CI 1.3-4.7 vs. HR 10.6, 95% CI 5.0-22.6 in those without recovery).12
VSports手机版 - Effect Modification by Decreased Baseline GFR and Pre-existing Proteinuria before AKI
The presence of baseline decreased GFR modified the relationship between AKI and both progressive CKD and ESRD. In the 2 studies11, 16 that reported both the risk for CKD after AKI in those with and without decreased baseline GFR, the risk of CKD was higher in patients without decreased baseline GFR (adjusted HR 38.8, 95% CI 21.9-68.7) than those with decreased baseline GFR (adjusted HR 24.4, 95% CI 15.3-38.9). Similarly, in the 3 studies12, 17, 20 that reported both the risk for ESRD those with and without decreased baseline GFR, the risk of ESRD was higher in those with AKI and without decreased baseline GFR (adjusted HR 9.1, 95% CI 4.1-20.3) compared to those with decreased baseline GFR (adjusted HR 1.9, 95% CI 1.6-20.3; Table 3)
Two studies compared the association of AKI with either CKD12 or ESRD16 in patients with varying degrees of underlying baseline proteinuria. Patients with AKI who had pre-existing proteinuria (and normal baseline GFR) had higher risk of CKD (defined as doubling of creatinine or ESRD) compared to patients without any proteinuria (HR 106.9, 95% CI 76.3-149.8) compared to HR 30.0 (95% CI 24.3-37), respectively.16 The modifying effect of pre-existing proteinuria was less robust for the outcome of ESRD alone (adjusted HR 3.7, 95% CI 2.4-5.7 with no proteinuria vs. adjusted HR 1.4, 95% CI 0.9-2.2 with proteinuria;12 Table 3).
AKI and Mortality (V体育ios版)
The overall post-discharge pooled mortality was 24.2% (3-73.3%). The mortality rate in patients with AKI was 16.8 per 100 person years (range 0.98-43.7). The adjusted risk for death was 2.0 (95% CI 1.3-3.1) for those with AKI compared to those without AKI (Figure 3). When we eliminated the study by James et al. due to a very high risk of death for AKI vs. no AKI, the pooled adjusted HR became 1.6 (95% CI 1.3-2.1),16 however, this did not reduce statistical heterogeneity.
Figure 3. Pooled Adjusted Hazard Ratios for Mortality after AKI.
"VSports在线直播" AKI and Non-renal Outcomes
We also examined the association between AKI and non-renal outcomes, when available (Supplementary Table). Mild AKI was associated with increased occurrence of CHF in two studies (HR 1.4, 95% CI 1.1-1.7, I2 = 10%) and risk of cardiovascular disease (HR 1.2, 95% CI 0.8-1.8, I2 = 80%).12, 23 Moderate-severe AKI was also associated with an increased risk for CHF and cardiovascular disease (HR 2.2, 95% CI 1.6-3.0 for CHF, I2 = 0%; HR of 1.3, 95% CI 0.9-1.8, I2 = 0% for cardiovascular disease).12, 15 In the only study that reported these outcomes, AKI was associated with future hospitalization for AKI (mild AKI HR 2.3, 95% CI 1.7-3.0 and moderate-severe AKI 5.1, 95% CI 3.4-7.6) but was not associated with hospitalization for cerebrovascular accidents (HR 1.2; CI 0.43-3.2) or for other hospitalizations (HR 0.8, 95% CI 0.6-1.1).23
Meta-regression
We formally examined the relationship between 5 study level continuous variables and the risk for each of CKD and ESRD via meta-regression. Although there was a trend towards longer length of follow-up being associated with less risk for CKD, and higher proportion of females and older age being associated with greater risk for ESRD, none of the study level variables were statistically associated with the risk for the outcome.
Discussion
This is the first systematic review and meta-analysis summarizing the association of AKI with CKD and ESRD. The data suggest that patients who survive AKI have a greater risk of CKD, ESRD, and other adverse outcomes compared to patients without AKI after adjustment for several important confounding variables. The relationship between AKI and CKD or ESRD was graded, with a greater risk associated with increasing severity of AKI. The risk for ESRD was modified by baseline GFR and the risk for CKD was modified by pre-existing proteinuria. Recovery of AKI diminished the relationship between AKI and ESRD.
These findings that AKI increases the risk for both CKD and ESRD are not surprising. However, this meta-analysis provides an opportunity to systematically estimate the associated absolute and relative risk of these outcomes after AKI. One finding that is potentially counterintuitive is that patients with normal GFR prior to AKI had a higher relative risk for the development of ESRD compared to those with AKI in the setting of decreased baseline GFR. For example, in the study by Wald et al., the absolute risk for ESRD without AKI and decreased baseline GFR was 9.8% and increased to 18.4% for those with AKI and decreased baseline GFR (approximately 2-fold higher). For those with normal baseline GFR, the absolute risks for ESRD were 4.6% and 0.4% (more than 10-fold) for those with and without AKI, respectively. While the absolute risk for ESRD was lower in those without decreased baseline GFR and AKI than those with AKI and decreased baseline GFR, the relative risk (hazard ratio) for ESRD was greater in those with normal GFR because of the extremely low probability (denominator) of ESRD in those without AKI or decreased baseline GFR.
The reasons why AKI would increase the risk of CKD, ESRD, and other adverse outcomes remain unknown. Data from experimental animals suggests that AKI can induce renal fibrosis, and also that it can affect other organs in a deleterious fashion, such as the lungs, heart, and liver.4, 5, 24 Thus, despite the fact that AKI is typically reversible in nature, by the standard of serum creatinine concentrations, there may be subclinical renal and extra-renal damage that persists and mediates these outcomes.
However, despite all of the fact that all studies performed multivariable adjustments to derive the adjusted point estimates for the hazard ratios via a substantial number of demographic, physiologic and clinical variables, there still remains the possibility that the “independent relationship” between AKI and the outcomes is still biased by residual confounding due to unmeasured variables or imprecise measurement of known confounders. For example, several studies included in this systematic review11, 14, 16, 17, 20, 22 used ICD-9 codes for ascertainment of important confounders such as CKD, diabetes, hypertension, and heart disease. Administrative codes have been shown to under-report co-morbidities.25 Furthermore, claims provide nothing in the context of the severity of the co-morbidity (e.g., diet-controlled type 2 diabetes vs. severe type 2 diabetes requiring high doses of insulin with or without adequate glycemic control). Thus, in the absence of a randomized, controlled trial of an intervention that reduces AKI which in turn reduces the incidence of CKD, ESRD, or any other of the outcomes potentially related to AKI, then it is challenging to deduce causality with absolute confidence.
The strengths of this systematic review are the following: adequate length of follow-up in the studies (most over 2 years), all studies reported parameter estimates of the hazard ratio adjusted for confounders, four studies examined outcomes associated with differing severities of AKI. The limitations include a high-degree of statistical heterogeneity among the primary analyses which may limit the validity of the point estimates and confidence intervals. However, we were able to demonstrate stable associations when more homogeneous studies were pooled. Part of the heterogeneity was related to different definitions of AKI (and of CKD). However, the outcomes of ESRD and death are less prone to bias.
Since this review demonstrates an unequivocal association between AKI and CKD in a number of large, well-performed studies, we would encourage the medical community to focus efforts on determining whether this relationship is modifiable or simply a prognostic factor that serves as a barometer and predictor of ongoing and future risk. Only elegant studies in experimental animals and randomized trials in humans of interventions to prevent AKI prior to its occurrence or given after AKI to ameliorate the severity and duration of injury or interfere with subsequent organ injury will be able to address this question.
Methods
This study was performed in accordance with published guidelines for systematic review, analysis, and reporting for meta-analyses of observational studies.
Studies Eligible for Review
A study published from January 1985 onward was eligible for inclusion if it conducted at least 6 months of follow-up of patients after a defined episode of AKI and reported the incidence of at least 1 of the following outcomes: (1) End stage renal disease (ESRD), (2) CKD or (3) progression of CKD. We excluded studies that contained fewer than 50 participants in the initial cohort and studies that exclusively focused on “AKI syndromes” (e.g., rapidly progressive glomerulonephritis, hemolytic-uremic syndrome, hepato-renal syndrome) and studies that reported only mortality. Studies were required to include a control group without AKI.
"V体育官网" Literature Review and Study Selection
We searched the MEDLINE and EMBASE (January 1985 to February 2011) databases using the following terms: acute renal insufficiency, acute kidney injury, acute kidney failure, chronic kidney disease, chronic renal failure, chronic renal insufficiency, End stage renal disease; progression (explode), treatment outcome, risk. An additional search was performed through the Scopus and references of all selected articles were reviewed to identify any eligible studies. The search was restricted to humans only. Each article chosen by the primary reviewer (SS) was reviewed by a second reviewer to confirm eligibility (SGC).
Data Collection
Two reviewers (SS and SGC) extracted data by using a standardized data extraction form. The reviewers extracted data about characteristics of participants (number, age, and sex), clinical setting, type of study (prospective versus retrospective), dates of enrollment, definition and severity of AKI, definition of CKD, and incidence of the outcomes in participants with and without AKI. Severity of AKI was grouped in the “mild”, “moderate” and “severe”, when possible. Mild AKI roughly represented the equivalent of Stage 1 AKIN or RIFLE R AKI. Moderate AKI roughly represented Stage 2 AKIN or RIFLE I AKI. Severe AKI roughly represented AKIN Stage 3 or RIFLE F AKI or dialysis-requiring AKI. Incident CKD was defined as per the study investigators, representing stage 4 CKD in 2 studies,11, 22 CKD stage 3,19 doubling of creatinine or ESRD,16 and GFR decline > 4 ml/min/year.15 Progressive CKD was defined as having pre-existing decreased GFR (eGFR < 60 ml/min) prior to AKI and meeting the definition of stage 4 CKD11 or doubling in creatinine/ESRD.16 Method quality was assessed by using criteria adapted from Hayden et al.26 Any discrepancies about data extraction or quality score were resolved by a third reviewer.
"VSports app下载" Outcome Measures
Primary outcome measures were the adjusted hazard ratios (HR) for incident or progressive CKD, and ESRD in survivors of AKI compared to those without AKI. Progressive CKD was only evaluated in a subgroup analysis of the 2 studies11, 16 that reported this outcome separately for those with and without decreased baseline GFR. The adjusted HR for long-term mortality, cardiovascular events, and hospitalizations were secondary outcomes. We also assessed unadjusted incidence rates for each of these end points, defined by the number of events in survivors beyond hospitalization or other relevant short-term period (28 or 30 days) divided by patient-years of follow-up. We assessed method quality of the studies by using the criteria of Hayden et al.: 1) representative study sample; 2) lack of study attrition; 3) adequate measurement of prognostic factor of interest (AKI); 4) adequate measurement of study outcome; 5) accounted for important potential confounders; 6) utilized appropriate statistical analyses.26
"VSports在线直播" Statistical Analysis
Random effects meta-analysis was conducted to estimate the magnitude of risk associated with AKI for each outcome, as measured by the combined adjusted HRs with 95% confidence intervals. Adjusted risk estimates included those published in final multivariate models for each study, which considered confounding from sociodemographic and clinical covariates, such as age, gender, race, co-morbidities, medications, and laboratory values. Inverse variance-weighted averages of logarithmic HRs were calculated for each of the endpoints. We formally assessed heterogeneity of effects between studies with the Cochran Q and the I2 statistic. We evaluated the association of AKI with the outcomes in the following pre-specified subgroups: 1. Dose response by severity of AKI; 2. Presence of decreased baseline GFR; 3. Presence of pre-existing proteinuria. All pooled analyses were conducted using Review Manager 5.0.25 (Cochrane Collaboration, Copenhagen). We also performed meta-regression using SAS 9.1 (Cary, NC) on 5 study-level variables (duration of follow-up, year of publication, overall mortality rate, proportion of males, and mean age) to determine the relationship between these variables expressed continuously and the natural log of the relative risk of CKD and ESRD.
Supplementary Material
Supplementary Table. Sensitivity Analyses- attempt to reduce Heterogeneity (< 25%)
Abbreviations: AKI- acute kidney injury; CKD- chronic kidney disease; ESRD- end stage renal disease; HR- hazards ratio; CI- confidence interval
Acknowledgments
We would like to thank Mark Gentry, Yale University School of Medicine Library, for his assistance with our search of the medical literature.
Footnotes
Disclosure: Dr. Coca is funded by the career development grant K23DK08013 from the National Institutes of Health. Dr. Parikh is funded by R01HL-085757 and UO1-DK082185 from the National Heart, Lung, and Blood Institute.
References
- 1.Xue JL, Daniels F, Star RA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol. 2006;17:1135–1142. doi: 10.1681/ASN.2005060668. [DOI] [PubMed] [Google Scholar]
- 2.Hsu CY, McCulloch CE, Fan D, et al. Community-based incidence of acute renal failure. Kidney Int. 2007;72:208–212. doi: 10.1038/sj.ki.5002297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–2047. doi: 10.1001/jama.298.17.2038. [DOI] [PubMed] [Google Scholar]
- 4.Basile DP. Rarefaction of peritubular capillaries following ischemic acute renal failure: a potential factor predisposing to progressive nephropathy. Curr Opin Nephrol Hypertens. 2004;13:1–7. doi: 10.1097/00041552-200401000-00001. [DOI] [PubMed] [Google Scholar]
- 5.Basile DP, Donohoe D, Roethe K, et al. Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol. 2001;281:F887–899. doi: 10.1152/ajprenal.2001.281.5.F887. [DOI (V体育平台登录)] [PubMed] [Google Scholar]
- 6.Waikar SS, Curhan GC, Wald R, et al. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17:1143–1150. doi: 10.1681/ASN.2005091017. [DOI] [PubMed] [Google Scholar]
- 7.Bagshaw SM, George C, Bellomo R, et al. Changes in the incidence and outcome for early acute kidney injury in a cohort of Australian intensive care units. Crit Care. 2007;11:R68. doi: 10.1186/cc5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Swaminathan M, Shaw AD, Phillips-Bute BG, et al. Trends in acute renal failure associated with coronary artery bypass graft surgery in the United States. Crit Care Med. 2007;35:2286–2291. doi: 10.1097/01.ccm.0000282079.05994.57. [DOI] [PubMed] [Google Scholar]
- 9.Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961–973. doi: 10.1053/j.ajkd.2008.11.034. [DOI (V体育ios版)] [PMC free article] [PubMed] [Google Scholar]
- 10.Hsu CY, Chertow GM, McCulloch CE, et al. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol. 2009;4:891–898. doi: 10.2215/CJN.05571008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Lo LJ, Go AS, Chertow GM, et al. Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int. 2009;76:893–899. doi: 10.1038/ki.2009.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Choi AI, Li Y, Parikh C, et al. Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney Int. 2010;78:478–485. doi: 10.1038/ki.2010.171. ["V体育2025版" DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Weiss AS, Sandmaier BM, Storer B, et al. Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant. 2006;6:89–94. doi: 10.1111/j.1600-6143.2005.01131.x. [DOI] [PubMed] [Google Scholar]
- 14.Newsome BB, Warnock DG, McClellan WM, et al. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med. 2008;168:609–616. doi: 10.1001/archinte.168.6.609. [DOI] [PubMed] [Google Scholar]
- 15.James MT, Ghali WA, Tonelli M, et al. Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function. Kidney Int. 2010;78:803–809. doi: 10.1038/ki.2010.258. ["V体育官网入口" DOI] [PubMed] [Google Scholar]
- 16.James MT, Hemmelgarn BR, Wiebe N, et al. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet. 2010;376:2096–2103. doi: 10.1016/S0140-6736(10)61271-8. [DOI] [PubMed] [Google Scholar]
- 17.Wald R, Quinn RR, Luo J, et al. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA. 2009;302:1179–1185. doi: 10.1001/jama.2009.1322. [DOI] [PubMed] [Google Scholar]
- 18.Lafrance JP, Djurdjev O, Levin A. Incidence and outcomes of acute kidney injury in a referred chronic kidney disease cohort. Nephrol Dial Transplant. 2010;25:2203–2209. doi: 10.1093/ndt/gfq011. [DOI] [PubMed] [Google Scholar]
- 19.Ando M, Ohashi K, Akiyama H, et al. Chronic kidney disease in long-term survivors of myeloablative allogeneic haematopoietic cell transplantation: prevalence and risk factors. Nephrol Dial Transplant. 2010;25:278–282. doi: 10.1093/ndt/gfp485. [DOI (V体育官网入口)] [PubMed] [Google Scholar]
- 20.Ishani A, Xue JL, Himmelfarb J, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009;20:223–228. doi: 10.1681/ASN.2007080837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Ishani A, Nelson D, Clothier B, et al. The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med. 2011;171:226–233. doi: 10.1001/archinternmed.2010.514. [DOI] [PubMed] [Google Scholar]
- 22.Amdur RL, Chawla LS, Amodeo S, et al. Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis. Kidney Int. 2009;76:1089–1097. doi: 10.1038/ki.2009.332. [DOI] [PubMed] [Google Scholar]
- 23.James MT, Ghali WA, Knudtson ML, et al. Associations Between Acute Kidney Injury and Cardiovascular and Renal Outcomes After Coronary Angiography. Circulation. 2011;123:409–416. doi: 10.1161/CIRCULATIONAHA.110.970160. [DOI] [PubMed] [Google Scholar]
- 24.Kelly KJ. Distant effects of experimental renal ischemia/reperfusion injury. J Am Soc Nephrol. 2003;14:1549–1558. doi: 10.1097/01.asn.0000064946.94590.46. ["V体育ios版" DOI] [PubMed] [Google Scholar]
- 25.Quan H, Parsons GA, Ghali WA. Validity of information on comorbidity derived rom ICD-9-CCM administrative data. Med Care. 2002;40:675–685. doi: 10.1097/00005650-200208000-00007. [DOI] [PubMed] [Google Scholar]
- 26.Hayden JA, Côté P, Bombardier C. Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med. 2006;144:427–437. doi: 10.7326/0003-4819-144-6-200603210-00010. [DOI] [PubMed] [Google Scholar]
"V体育2025版" Associated Data
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Supplementary Materials
Supplementary Table. Sensitivity Analyses- attempt to reduce Heterogeneity (< 25%)
Abbreviations: AKI- acute kidney injury; CKD- chronic kidney disease; ESRD- end stage renal disease; HR- hazards ratio; CI- confidence interval