Acute kidney injury (AKI) is characterized by sudden (i.e., hours to days) impairment of kidney function. AKI is an increasingly common complication in hospitalized individuals around the world and is associated with markedly increased risk for morbidity, mortality, and healthcare expenditures. AKI is particularly common among individuals with preexisting chronic kidney disease (CKD). Severe AKI can also increase the risk for the subsequent development of CKD.
Keywordsacute kidney injury, epidemiology, incidence, mortality, outcomes, risk factors
Definition of Acute Kidney Injury, 684
Early Cohort Studies of Acute Kidney Injury, 685
Multicenter Cohort Studies of Acute Kidney Injury, 686
Large Database Studies of Acute Kidney Injury, 687
Epidemiology in Disease-Specific States, 688
Risk Factors for the Development of Acute Kidney Injury, 688
Risk Factors for Mortality Associated With Acute Kidney Injury, 693
Acute Kidney Injury in the Setting of Chronic Kidney Disease, 695
Long-Term Implications of an Episode of Acute Kidney Injury, 695
Acute Kidney Injury in the Developing World, 697
Acute kidney injury (AKI) is characterized by sudden (i.e., hours to days) impairment of kidney function. Descriptions of syndromes consistent with AKI date back to the ancient Greek period, when the diagnosis was possible only by observing a reduction in urine volume. Initial descriptions of AKI from the early 20th century centered around specific conditions such as crush injuries, war nephritis, and falciparum malaria. Sir William Osler in 1912 described several recognizable causes of AKI under the heading of “acute Bright’s disease,” including sepsis, pregnancy, burns, and toxins.
The modern-day conception of AKI has evolved alongside developments in pathology and clinical biochemistry that have permitted clinicopathological correlations and earlier diagnosis. AKI is not a single disease but rather a designation for a heterogeneous group of conditions that share common diagnostic features: specifically, an increase in the blood urea nitrogen (BUN) concentration, an increase in the serum or plasma creatinine concentration, a reduction in urine volume, or some combination of these. The causes of AKI have traditionally been divided into three broad categories: prerenal azotemia, intrinsic renal parenchymal disease, and postrenal obstruction. In prerenal azotemia, glomerular filtration falls as a result of inadequate kidney perfusion from hypovolemia, decreased cardiac output, or renal vasoconstriction. Prerenal azotemia is considered to be functional in nature and reversible with restoration of renal perfusion. Intrinsic renal diseases can be subdivided into those affecting the glomeruli (e.g., glomerulonephritis), tubules (e.g., acute tubular necrosis [ATN]), interstitium (e.g., acute interstitial nephritis), or blood vessels (e.g., thrombotic microangiopathy). Postrenal obstruction results from mechanical disturbance to the normal flow of urine from the kidneys to the ureter to the bladder and finally to the urethra for elimination.
Definition of Acute Kidney Injury
The specific quantitative criteria for diagnosing AKI—as defined by a rise in serum creatinine (SCr) concentration—ranges widely in the published literature, with more than two dozen definitions in use. An international panel of experts in nephrology and critical care medicine proposed a consensus definition of AKI in the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Acute Kidney Injury.
AKI is stratified into three stages, and each of the three stages can be reached either by a rise in SCr or a reduction in urine output. Stage 1 AKI can be reached by an increase in SCr of 0.3 mg/dL, 1.5 to 1.9 times the baseline SCr, or a reduction in urine output to <0.5 mL/kg/h for 6 to 12 hours. SCr-based definitions for stages 2 and 3 AKI can be reached by a doubling or tripling of baseline SCr, respectively. The urine output–based definitions for stage 2 are reached by sustaining <0.5 mL/kg/h for at least 12 hours, and for stage 3 they are reached with <0.3 mL/kg/h for at least 24 hours or anuria for at least 12 hours. The KDIGO criteria for the diagnosis of AKI are compared with other definitions of AKI in Table 45.1 .
|Acute Kidney Injury Network||Stage 1: increase of ≥0.3 mg/dL or 50% increase over baseline within 48 h |
Stage 2: ≥100% increase over baseline (doubling)
Stage 3: ≥200% increase over baseline or 0.5 mg/dL increase to at least 4 mg/dL
|Acute Dialysis Quality Initiative||RIFLE “R”: ≥50% increase over baseline |
RIFLE “I”: ≥100% increase over baseline (doubling)
RIFLE “F”: ≥200% increase over baseline or ≥0.5 mg/dL increase to at least 4 mg/dL
|Kidney Disease Improving Global Outcomes (KDIGO)||Stage 1: increase in SCr ≥0.3 mg/dL or ≥1.5 times; urine output <0.5 mL/kg/h for ≥6 h |
Stage 2: increase in SCr ≥2 times; urine output <0.5 mL/kg/h for ≥12 h
Stage 3: increase in SCr ≥3 times, or SCr >4 mg/dL, or initiation of renal replacement therapy; urine output <0.3 mL/kg/h for ≥24 h or anuria for ≥12 h
|International Ascites Club for AKI in Cirrhosis||Baseline SCr: stable SCr ≤3 mo ; if not available, a stable SCr closest to current one; if no previous SCr at all, use admission SCr |
Definition of AKI: increase in SCr ≥0.3 mg/dL ≤48 h, or increase of 50% from baseline
Stage 1: increase in SCr ≥0.3 mg/dL or increase in SCr ≥1.5–2 times baseline
Stage 2: increase in SCr >2.0–3 times baseline
Stage 3: increase in SCr >3 times baseline, SCr ≥4.0 mg/dL with increase ≥0.3 mg/dL, or initiation of renal replacement therapy
|Contrast nephropathy||≥0.5 mg/dL increase or 25% increase over baseline within 48 hours of receiving contrast|
There are several limitations of any SCr-based definition of AKI. First, the baseline SCr is often not known, making it impossible to gauge the absolute or percentage rise from baseline. Second, creatinine itself is an inadequate biomarker of kidney injury because of tubular secretion, the need for steady state determinations for accurate estimates of glomerular filtration rate (GFR), and the confounding influences of muscle mass and changes in volume of distribution, the latter particularly in the setting of acute illness. Assessment of GFR by gold standards such as iothalamate or inulin clearance is cumbersome and impractical in the acute setting but may be facilitated by technological developments. In patients with prerenal azotemia, creatinine may rise in the absence of any structural injury to the kidneys. In patients with severe parenchymal kidney injury, such as lupus nephritis, SCr may not rise at all.
Recent investigation into tubular injury biomarkers may herald a paradigm shift in the definition of AKI, similar to that seen over the past several decades in the definition of acute myocardial infarction (MI) (see Chapter 47 ). Acute MI is defined on the basis of myocardial injury markers, including troponin, without the requirement for a functional decrease in myocardial function such as cardiac output. It is possible that AKI may eventually be defined on the basis of sensitive injury biomarkers that rise well before the complex sequence of events and before an ultimate reduction in GFR, followed thereafter by a rise in SCr.
Early Cohort Studies of Acute Kidney Injury
Hou and colleagues in 1983 published one of the first chart review–based cohort studies of AKI. These investigators focused on hospital-acquired disease and therefore excluded patients with established AKI on admission. Over a 5-month period beginning in 1978, a total of 2216 consecutive medical and surgical admissions to Tufts Medical Center in Boston were followed for the development of AKI. The definition of AKI in this study was based on an absolute increase in SCr depending on the admission SCr: increase in SCr of greater than 0.5 mg/dL if admission SCr was less than 1.9 mg/dL; increase of greater than 1 mg/dL for admission SCr of 2 to 4.9; or an increase of greater than 1.5 mg/dL for admission SCr of greater than 5 mg/dL. Overall, 4.9% of patients met criteria for AKI. The major causes of hospital-acquired AKI were decreased renal perfusion (42%), major surgery (18%), contrast nephropathy (12%), and aminoglycoside antibiotics (7%). The crude in-hospital mortality rate was 32%, and the degree of kidney injury as assessed by change in SCr was noted to be important. In-hospital mortality was 3.8% in patients with an increase in SCr of 0.5 to 0.9 mg/dL and increased progressively to 75% in patients with a greater than 4 mg/dL increase who were not treated with renal replacement therapy. This study was also one of the first to establish the association between oliguria and mortality in patients with AKI (52% vs. 17% with and without oliguria, P < 0.01).
Shusterman and associates performed a case-control study of hospital-acquired AKI in patients admitted during 1 month to the Hospital of the University of Pennsylvania in Philadelphia in 1981. The definition of AKI was different from that employed by Hou et al. 4 years earlier. AKI was defined as a greater than 0.9 mg/dL increase in SCr with baseline SCr of less than 2 mg/dL, or a greater than 1.5 mg/dL increase in SCr with baseline SCr of greater than 2 mg/dL; the incidence was 1.9% among patients on medical, surgical, and gynecological services. The 34 AKI cases were matched to 57 controls without AKI. From this small group of cases and controls, the authors found volume depletion, aminoglycoside use, septic shock, congestive heart failure, and intravenous contrast administration as risk factors for AKI. They also found a 10-fold increased odds of death and a doubling of the length of stay among patients with AKI.
Nash and colleagues published a follow-up report of hospital-acquired AKI almost two decades later, using similar methodology and definitions to the earlier publication. Over a 4-month period in 1996, they prospectively followed 4622 medical and surgical admissions at Rush Presbyterian–St. Luke’s Medical Center in Chicago for the development of AKI, defined as in their earlier study. They identified 332 patients (7.2% of admissions) who developed AKI, higher than the 4.9% in the original study performed at a different institution. The in-hospital mortality rate of 19.4% was somewhat lower than the 25% reported previously. The most common causes of AKI remained decreased renal perfusion (39%; defined broadly to include congestive heart failure, cardiac arrest, and volume contraction), nephrotoxin administration (16%), contrast administration (11%), and major surgery (9%).
In 2016, Leaf and colleagues evaluated diagnostic testing for all adult inpatients who were admitted with or developed AKI during a single calendar year at Brigham and Women’s Hospital in Boston, defined using KDIGO criteria. A total of 70.8% of the patients experienced stage 1 AKI, 17.1% had stage 2 AKI, and 12.1% had stage 3 AKI. In a random subset of 100 AKI episodes, the most common underlying causes were ischemic ATN (24%), prerenal azotemia (21%), nephrotoxic ATN (10%), cardiorenal syndrome (8%), glomerulonephritis (5%), obstruction (3%), and hepatorenal syndrome (2%). Notably, the cause of AKI was unknown in 22% of episodes, and the remaining 5% included acute interstitial nephritis, rhabdomyolysis, and tumor lysis syndrome.
Multicenter Cohort Studies of Acute Kidney Injury
Initial cohort studies of AKI shed important light on the frequency, causes, and mortality associated with hospital-acquired AKI. No matter how carefully conducted, single-center studies are inherently limited in terms of sample size and external validity (i.e., generalizability to AKI at other medical centers). Recognizing this limitation, and the heterogeneity of causes of AKI at individual institutions, investigators have conducted multicenter epidemiological investigations of AKI.
Liano and Pascual conducted a prospective, 9-month study of all AKI episodes in 13 tertiary-care hospitals in Madrid, Spain, beginning in 1991. They defined AKI as a sudden rise in SCr of more than 2 mg/dL, excluding patients with preexisting chronic kidney disease (CKD; defined as SCr >3 mg/dL). Unlike the Hou et al. and Nash et al. studies, hospital- and community-acquired cases of AKI were included. Of the 748 episodes of AKI (representing 0.4% of admissions and 21 per 100,000 population), ATN was the most common cause (45%, defined to include diverse causes including surgery, nephrotoxin administration, sepsis, and renal hypoperfusion), followed by prerenal azotemia (21%, defined as the rapid recovery of kidney function after volume administration or restoration of cardiac output), acute-onset chronic renal failure (12.7%, not defined), and urinary tract obstruction (10%). The crude in-hospital mortality rate was 45% overall and as high as 65.9% in patients requiring dialysis (which constituted 36% of all cases of AKI). In a follow-up study, Liano and colleagues provided more details on the specific differences between AKI in and out of the intensive care unit (ICU). Compared with non-ICU patients, those admitted to the ICU were younger, more likely to die in hospital (71.5% vs. 31.5%), and more likely to have ATN from sepsis or renal hypoperfusion than from nephrotoxin administration.
Brivet and colleagues focused on AKI occurring in the ICU in a 20-center, prospective, 6-month study performed in France in 1991. They included all patients with a rise in SCr to at least 3.5 mg/dL or BUN to at least 100 mg/dL, or both, or a 100% increase if there was preexisting CKD. Patients with severe CKD (baseline SCr >3.5 mg/dL) were excluded. Overall, 7% of patients admitted to the ICU developed AKI or had AKI on admission. The major causes of AKI were attributed to sepsis (48%), hemodynamic alterations (32%), nephrotoxin administration (20%), and prerenal factors (17%). Overall in-hospital mortality was 58% and was higher in those with sepsis (73%) and delayed occurrence of AKI after admission (71%). Another group of French investigators performed a similar prospective observational study beginning in 1996. These authors found a 7.7% incidence of AKI in the ICU, defined as SCr of greater than 3.4 mg/dL or the need for dialysis. Overall in-hospital mortality was 66%, and 81% in patients with AKI that developed 1 week after admission to the ICU.
The Program to Improve Care in Acute Renal Disease (PICARD) performed a 31-month-long prospective observational cohort study of patients at five academic medical centers in the United States from 1999 to 2001. Eligible patients were those in the ICU for whom nephrology consultation was obtained; AKI was defined as an increase in SCr of greater than 0.5 mg/dL if baseline was less than 1.5 mg/dL or an increase of greater than 1 if baseline SCr was between 1.6 and 4.9. Unique to PICARD among AKI epidemiological studies to date was the extensive clinical detail captured (more than 800 data elements per patient, including details on dialysis procedures) and limited biological sample collection. A total of 618 patients were enrolled in PICARD. One of the most illustrative findings in PICARD was the degree of heterogeneity of patients with AKI across the five medical centers in terms of baseline characteristics, processes of care, and in-hospital mortality. Even across five academic medical centers, in-hospital mortality associated with AKI from ATN and nephrotoxins ranged from a low of 24% to a high of 62%. Substantial differences in process of care were also evident across the five sites in terms of dialysis modality. Despite the many differences, however, the presumed causes of AKI were relatively similar among institutions. Fifty percent of patients were labeled as having ATN with no specified precipitant. The next most common causes included nephrotoxin administration (26%), cardiac disease (20%, including MI, cardiogenic shock, and congestive heart failure), ATN from hypotension (20%), ATN from sepsis (19%), unresolved prerenal factors (16%), and liver disease (11%). The PICARD cohort has been the subject of subsequent epidemiological studies to derive prediction rules for mortality and to explore the associations between dialysis modality and timing of initiation and survival. The biological samples from subsets of PICARD participants have been used to study urea volume of distribution, insulin resistance, cytokine levels, , and oxidative stress in patients with AKI.
The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) investigators prospectively studied patients admitted to 54 ICUs across 23 countries over 15 months beginning in September 2000. The target population was patients with severe AKI: inclusion criteria were treatment with renal replacement therapy or AKI defined as oliguria (<200 mL in 12 hours) or BUN of greater than 84 mg/dL. Of 29,269 patients admitted to the ICUs, 1738 (5.7%) had AKI. The most common causes of AKI were septic shock (47.5%), major surgery (34%), cardiogenic shock (27%), hypovolemia (26%), and nephrotoxin administration (19%) (multiple causes were allowed on the data collection form, accounting for a total of more than 100%).
The overall in-hospital mortality rate in the BEST Kidney cohort study was 60.2%. As with PICARD, mortality varied widely across centers. Among countries contributing more than 100 patients to the cohort, in-hospital mortality ranged from 50.5% to 76.8%. A multivariable logistic regression model to identify independent correlates of in-hospital mortality yielded several previously identified risk factors also found in PICARD or the French Study Group, or both, including delayed AKI, age, sepsis, and a generic disease severity score that included BUN and urine output. Follow-up studies from the BEST Kidney multinational database have compared severity scoring systems for AKI-related mortality and investigated the relationship between diuretic administration and mortality.
Bagshaw and colleagues performed a retrospective interrogation of prospective data from the Australian New Zealand Intensive Care Society Adult Patient Database (ANZICS APD) to evaluate the incidence, risk factors, and outcomes associated with early AKI in septic ICU patients from January 2000 to December 2005. The patients were from 57 ICUs across Australia. Of the 33,375 patients with a sepsis-related diagnosis (27.8% of all patients admitted to the ICU), 42.1% had concomitant AKI. AKI was defined using a modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage kidney disease) criteria for risk (1.5 times SCr or <35 mL/h urine output), injury (2 times SCr or <21 mL/h urine output), and failure (3 times SCr or ≥0.5 mg/dL if baseline SCr >4.0 mg/dL or <4 mL/h urine output). They found that septic AKI had greater acuity of illness, lower blood pressures, worse pulmonary oxygenation, greater acidemia, and higher white blood cell counts than patients with nonseptic AKI. In addition, septic AKI was associated with greater severity of AKI and 60% increased odds of mortality in the ICU.
In 2013, the FINNAKI study group performed a prospective, observational, multicenter cohort study of adult admissions exceeding 24 hours during a 5-month period in 17 Finnish ICUs. They first defined AKI by the Acute Kidney Injury Network (AKIN) criteria and second with the KDIGO criteria. They arrived at identical classification, and found that in 2901 eligible patients the incidence of AKI was 39.3% (17.2% for stage 1, 8.0% for stage 2, and 14.1% for stage 3). In logistic regression analyses, they found pre-ICU hypovolemia, diuretics, colloids, and CKD were independent risk factors for AKI. The hospital mortality for AKI patients was 25.6%, and the 90-day mortality for AKI patients was 33.7%.
Large Database Studies of Acute Kidney Injury
Medical administrative and claims databases afford investigators the opportunity to study AKI in large numbers of patients admitted to a wide spectrum of hospitals over multiple years, including patients not ordinarily represented in prospective cohort studies. The major limitation of most administrative databases is the lack of detailed clinical and laboratory information. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for acute renal failure (ARF) (584.x) and renal replacement therapies (39.95) have been found to be accurate for the identification of patients with severe AKI (defined as AKI requiring dialysis, or AKI-D) but less accurate for AKI not requiring dialysis.
Multiple studies to date have used large administrative or claims databases, or both, to study secular trends in the epidemiology of AKI in the United States. Waikar and colleagues used the Nationwide Inpatient Sample (NIS), a nationally representative database of hospital discharges, to study AKI from 1988 and 2002. Using ICD-9-CM codes to identify AKI, the study found a marked rise in the incidence and fall in the mortality associated with AKI and AKI-D. In the NIS, which includes patients younger than age 65, the incidence of AKI rose from 4 to 21 per 1000 discharges between 1988 and 2002. The study found a statistically significant decline in mortality, in contrast to the prevailing wisdom and a 2005 systematic review, which suggests that mortality rates have remained unchanged over decades.
Hsu and colleagues published studies on the regional and temporal variation in the incidence of AKI in the United States between 2007 and 2009. They found that the incidence of AKI-D was highest in the Midwest (523 cases/million person-years) and lowest in the Northeast (457 cases/million person-years). This incidence pattern differed from the regional variation in the incidence of end-stage renal disease (ESRD) patients requiring renal replacement therapy. Despite this incidence pattern, they found the in-hospital mortality associated with AKI-D was highest in the Northeast (25.9%) and lowest in the Midwest (19.4%). In their analysis of the NIS, Hsu et al. reported that the incidence of AKI-D increased from 222 to 553 cases/million person-years between 2000 and 2009. This increase was evident among all age, sex, and race subgroups evaluated. In addition, the total number of deaths associated with AKI-D more than doubled over this 10-year period. These findings are similar to their previous work reporting a rising incidence of AKI-D in a large integrated administrative and laboratory database from Kaiser Permanente of Northern California between 1996 and 2003. In another analysis of the NIS, Hsu and colleagues investigated the reasons for the increase in AKI-D incidence. They found that six diagnoses accounted for the temporal trend in AKI-D: septicemia, hypertension, respiratory failure, coagulation/hemorrhagic disorders, shock, and liver disease. Temporal changes in procedures commonly associated with AKI-D did not account for the increase in AKI-D rates.
A 2017 study evaluating the incidence of AKI and AKI-D was performed in patients admitted to the Mayo Clinic Hospital in Rochester, Minnesota, between 2006 and 2014 and found differing results. During the 9-year study period, the authors found no significant change in the annual AKI incidence rate, with a relative risk of 0.99 (95% confidence interval [CI], 0.97 to 1.01) for ICU patients and 0.993 per year (0.98 to 1.01) for general floor patients. They found similar results when using ICD-9 codes for the incidence of AKI-D and concluded that the incidence of AKI has been relatively stable over the last decade.
Epidemiology in Disease-Specific States
Estimates of the incidence of AKI and associated mortality have been performed in numerous conditions, including sepsis, contrast nephropathy, major surgery, and nephrotoxic antibiotic administration. Several of the largest studies are summarized in Table 45.2 . A striking and consistent finding across all causes studied to date is the marked increase in mortality associated with the development of AKI.
|Author, Year (Reference)||Setting||Definition of AKI||Incidence||In-Hospital Mortality|
|Rangel-Frausto et al., 1995||ICU admissions with sepsis/SIRS ( n = 2527)||Acute SCr increase to >2 mg/dL, need for dialysis, or doubling of SCr||AKI: 9% for SIRS, 51% for culture + septic shock||3%–46%, depending on severity |
AKI mortality not reported
|Neveu et al., 1996||ICU admissions with AKI and sepsis ( n = 345)||100% increase in SCr to ≥3.5 mg/dL or BUN ≥100 mg/dL, or 100% increase in BUN or SCr||Not reported; 46% of all AKI was in the setting of sepsis||AKI from sepsis: 74% |
Nonseptic AKI: 45%
|Hoste et al., 2003||Surgical ICU admissions with sepsis ( n = 185)||SCr rise from ≤1 to ≥2 mg/dL||AKI: 30% |
|No AKI: 28% |
|Yegenaga et al., 2004||ICU admissions with sepsis/SIRS ( n = 217)||SCr increase to >2 mg/dL||AKI: 13% |
|No AKI: 24% |
|Bagshaw et al., 2008||ICU admissions with sepsis ( n = 33,375)||Modification of RIFLE criteria, restricted to initial 24 h of admission||AKI: 42.1% |
RIFLE “F”: 9.6%
|No AKI: 12.6% |
RIFLE “F”: 35.8%
|Lopes et al., 2010||Septic ICU admissions ( n = 426)||RIFLE criteria||Not reported||No AKI: 15.6%, |
|Pereira et al., 2017||ICU admission with sepsis/septic shock ( n = 457)||RIFLE, AKIN, and KDIGO criteria||RIFLE “R”: 18.2%, “I”: 23.0%, |
AKIN stage 1: 18.2%, stage 2: 30.0%, stage 3: 56.6%
KDIGO stage 1: 21.3%, stage 2: 23.3%, stage 3: 48.3%
|Percutaneous Coronary Intervention (PCI)|
|McCullough et al., 1997||PCI ( n = 1826)||Increase in SCr >25%||AKI: 14% |
|No AKI: 1% |
|Rihal et al., 2002||PCI ( n = 7586)||Increase in SCr ≥0.5 mg/dL||AKI: 3.3% |
|AKI: 22% |
No AKI: 1%
|Marenzi et al., 2004||ST-elevation acute MI treated with primary PCI ( n = 208)||Increase in SCr >0.5 mg/dL||AKI: 19% |
|AKI: 31% |
No AKI: 0.6%
|Mehran et al., 2004||PCI ( n = 8357)||Increase in SCr ≥25% or ≥0.5 mg/dL||AKI: 13%||Not reported|
|Harjai et al., 2008||PCI ( n = 985)||Increase in SCr >0.5 mg/dL||AKI: 5.2% |
|AKI: 40.9% |
No AKI: 10.2%
|Brown et al., 2016||PCI ( n = 3,633,762)||ICD-9 reported AKI and AKI-D||AKI: 19.6% (2001) to 9.2% (2011) |
AKI-D: 28.3% (2001) to 19.9% (2011)
|Marenzi et al., 2016||PCI ST-elevation MI ( n = 3772)||Increase in SCr by 25% (AKI-25), ≥0.3 mg/dL (AKI-0.3), ≥0.5 mg/dL (AKI-0.5)||AKI-25: 15% |
|IV Contrast for Radiological Examination|
|Mitchell & Kline, 2007||CT angiography to rule out pulmonary embolism in the emergency department ( n = 1224)||Increase in SCr >25% or 0.5 mg/dL within 7 days||AKI: 4% of entire cohort, 12% of those with two SCr measurements |
|Weisbord et al., 2008||Baseline eGFR <60, nonemergent CT with IV contrast||Increase in SCr ≥25%||AKI: 6.5% |
|No difference in 30-day mortality for AKI vs. no AKI|
|Chertow et al., 1997||CABG or valvular surgery ( n = 43,642)||Need for dialysis||AKI: not reported |
|(30-day mortality) |
No AKI: 4.3%
AKI: not reported
|Mangano et al., 1998||CABG or valvular surgery ( n = 2222)||Increase in SCr ≥0.7 mg/dL to at least 2 mg/dL||AKI: 7.7% |
|No AKI: 0.9% AKI: 19% AKI-D: 63.8%|
|Ryckwaert et al., 2002||CABG or valvular surgery ( n = 591)||Increase in SCr ≥20% within 3 days of surgery||AKI: 15.6% |
|No AKI: 1% |
|Bove et al., 2004||Cardiopulmonary bypass/CABG (including valve replacement) ( n = 5068)||Increase in SCr ≥100%||AKI: 3.4% |
|No AKI: 2.7% |
|Loef et al., 2005||CABG or valvular surgery ( n = 843)||Increase in SCr ≥25% within 7 days of surgery||AKI: 17.2% |
|No AKI: 1.1% |
|Thakar et al., 2005||Open-heart surgery ( n = 18,838)||Need for dialysis||AKI: not reported |
|Mehta et al., 2006||Cardiac surgery ( n = 449,524)||Need for dialysis||AKI: not reported |
|No AKI-D: 2.3% |
|Brown et al., 2006||Patients undergoing CABG (without valve replacement) ( n = 1391)||Increase in SCr <25%, 25%–49%, 50%–99%, |
|25%–49%: 16% |
|(90-day mortality) Increase in SCr: 25%–49%: 0.5% |
|Robert et al., 2010||Cardiac surgery ( n = 25,086)||AKIN and RIFLE criteria||AKIN: No AKI: 1.3%, stage 1: 4.1%, stage 2: 14.2%, stage 3: 36.8%; RIFLE: No AKI: 1.4%, |
“R”: 3.3%, “I”: 11.1%, “F”: 36.4%
|Leehey et al., 1993||Aminoglycosides ( n = 243)||Increase in SCr = 0.5 mg/dL and 100% over baseline||AKI: 20.6% |
|Wingard et al., 1999||Amphotericin B for aspergillosis ( n = 239)||Increase in SCr ≥100%||AKI: 53% |
|No AKI-D: 57% |
|Bates et al., 2001||Amphotericin B ( n = 707) (64 received liposomal preparation)||Increase in SCr ≥50% to at least 2 mg/dL (severe: peak SCr ≥3 mg/dL)||AKI: 30% |
Severe AKI: 13%
|No AKI: 14% |
|Fowler et al., 2006||Daptomycin ( n = 124) or gentamicin + penicillin or vancomycin ( n = 126)||Decrease in CrCl to <50 mL/min, or decrease in CrCl of 10 mL/min if <50 at baseline||AKI, daptomycin: 11% AKI, gentamicin: 26.3%||Not reported|
|Rocha et al., 2015||Amphotericin B ( n = 160)||AKI-binary criteria (≥2 times baseline, ≥0.3 mg/dL or 1.5 times baseline) |
|No AKI: 21.4% |
AKI (≥0.3mg/dL or 1.5 times baseline): 44.4%
KDIGO: No AKI: 23.9%,
stage 1: 18.0%,
stage 2: 30.0%,
stage 3: 73.3%
|No AKI: 23.9% |
|Aortic Aneurysm Repair|
|Godet et al., 1997||Thoracic or thoracoabdominal aortic surgery ( n = 475)||Increase in SCr to >1.7 mg/dL or 30% over baseline||AKI: 25% |
|AKI (no dialysis): 38% |
|Ryckwaert et al., 2003||Infrarenal aortic abdominal surgery ( n = 215)||Increase in SCr ≥20%||AKI: 20% |
|No AKI: 1.2% |
|Prinssen et al., 2004||Open ( n = 174) or endovascular ( n = 171) AAA repair||Increase in SCr ≥20%||AKI: 13% (both groups) |
AKI-D: not reported
|Piffaretti et al., 2012||Endovascular TAA ( n = 171)||RIFLE||No AKI: 4% AKI: 29%||Not reported|
Risk Factors for the Development of Acute Kidney Injury
AKI that occurs in the hospital or outpatient setting can be predicted with limited accuracy. For AKI caused by ischemic or toxic ATN, the severity of injury—for example, duration of hypotension, dose, or duration of nephrotoxin exposure—is an obvious risk factor for AKI. Specific predisposing demographic and clinical variables associated with a heightened risk for AKI have been investigated in a number of studies to help clinicians stratify patients according to the probability of AKI ( Table 45.3 ).
|Author, Year (Reference)||Clinical Setting||N |
(% With AKI Outcome)
|AKI Definition||Identified Risk Factors in Multivariable Models|
|Davidson et al., 1989||Diagnostic cardiac catheterization||1162 (6%)||Increase in SCr ≥0.5 mg/dL||Older age and baseline SCr ≥1.2|
|Rich & Crecelius, 1990||Cardiac catheterization, age ≥70, including percutaneous coronary intervention||183 (11%)||Increase in SCr ≥0.5 mg/dL||Contrast volume ≥200 mL, serum albumin <3.5 mg/dL, DM, serum sodium <135 mmol/L, SCr >1.5, NYHA class III or IV|
|Lautin et al., 1991||Femoral arteriography||394 (22%)||Increase in SCr >0.3 mg/dL and 20% over baseline||Diabetes, baseline SCr >1.5 mg/dL|
|McCullough et al., 1997||Percutaneous coronary intervention||1826 (0.77%)||Need for dialysis||Lower baseline CrCl, diabetes, contrast volume|
|Godet et al., 1997||Thoracoabdominal aortic surgery||475 (25%)||Increase in SCr to at least 1.7 mg/dL or ≥30% increase if preexisting CKD||Age >50, preoperative SCr >1.3, ischemia duration >30 min, use of cell saver, >5 units pRBC transfusion|
|Chertow et al., 1998||Established AKI (placebo arm of RCT)||256 (57%)||Need for dialysis or death||Oliguria, low serum albumin, acute MI, mechanical ventilation, arrhythmias|
|Chertow et al., 1998||Cardiac surgery||42,773 (1.1%)||Need for dialysis||Valve surgery, lower preoperative CrCl, IABP, prior heart surgery, NYHA class IV, PVD, LVEF <35%, pulmonary rales, COPD, SBP ≥160 (CABG only)|
|Gruberg et al., 2001||Percutaneous coronary intervention||7690 (0.66%)||Need for dialysis||Non–Q-wave MI, saphenous vein graft intervention, peak postprocedural SCr, IABP, contrast volume, lower baseline CrCl|
|Rihal et al., 2002||Percutaneous coronary intervention||7586 (3.3%)||Increase in SCr ≥0.5 mg/dL||Older age, higher baseline SCr, CHF, DM, shock, MI, PVD, contrast volume|
|Hoste et al., 2003||Sepsis||185 (16%)||Increase in SCr to at least 2 mg/dL||pH <7.3 and SCr >1 mg/dL on day of sepsis diagnosis|
|Mehran et al., 2004||Percutaneous coronary intervention||8357 (13.1%)||Increase in SCr ≥25% or ≥0.5 mg/dL||Hypotension, IABP, CHF, CKD, DM, age >75, anemia, contrast volume|
|Yegenaga et al., 2004||Sepsis||257 (11%)||Increase in SCr to at least 2 mg/dL or urine output <400 mL/24 h||Older age, higher SCr, higher CVP, serum bilirubin >1.5 mg/dL|
|Marenzi et al., 2004||Percutaneous coronary intervention for acute MI||208 (19%)||Increase in SCr >0.5 mg/dL||Age ≥75, or older anterior acute MI, time to reperfusion ≥6 h, contrast volume, IABP|
|Thakar et al., 2005||Cardiac surgery||33,217 (1.7%)||Need for dialysis||Female, CHF, IABP, COPD, insulin-requiring diabetes, previous cardiac surgery, emergency/valve surgery, higher preoperative SCr|
|Chawla et al., 2005||Sepsis||194 (18%)||>75% increase in SCr (baseline ≤2 mg/dL) or >50% increase (baseline >2 mg/dL)||Low serum albumin, high A-a gradient, active cancer|
|Chertow et al., 2006||Established AKI||618 (64%)||Need for dialysis||Younger age, oliguria, higher BUN, liver failure|
|Mehta et al., 2006||Cardiac surgery||449,524 (1.4%)||Need for dialysis||Higher preoperative SCr, older age, type of surgery (±valve), diabetes, recent MI, nonwhite race, chronic lung disease, prior CABG, NYHA class IV, cardiogenic shock|
|Wijeysundera et al., 2007||Cardiac surgery||20,131 (1.3%–2.2%)||Need for dialysis||Lower preoperative eGFR, diabetes, lower LVEF; previous cardiac surgery, procedure (±valve), urgency, and preoperative IABP|
|Kheterpal et al., 2009||General surgery||75,952 (1%)||Need for dialysis||Age ≥56 or older man, emergency surgery, intraperitoneal surgery, DM, congestive heart failure, ascites, hypertension, CKD|
|Plataki et al., 2011||Septic shock||390 (61%)||>50% increase in SCr, 2 times SCr, or urine output <0.5 mg/kg/h × 12 h||Delay to initiate antibiotics, intraabdominal sepsis, blood product transfusion, use of ACEI/ARB, BMI|
|Soto et al., 2012||ICU—ARDS||751 (62%)||>25% decrease in eGFR or SCr × 1.5||BMI|
|Darmon et al., 2015||ICU—hematological malignancies||1009 (67%)||≥0.3 mg/dL or 50% increase over baseline within 48 h||Older age, nonrenal SOFA, hypertension, tumor lysis syndrome, nephrotoxic agents, myeloma|