University of Groningen
Acknowledging differences in Acute Kidney Injury Koeze, Jacqueline
DOI:
10.33612/diss.129582657
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Publication date:
2020
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Citation for published version (APA):
Koeze, J. (2020). Acknowledging differences in Acute Kidney Injury: a complex clinical syndrome in critically ill patients. University of Groningen. https://doi.org/10.33612/diss.129582657
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9
GENERAL INTRODUCTION
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11 General introduction
The global burden of critical illness is difficult to estimate because reasons for Intensive Care Unit (ICU) admission vary widely and ICU resources differ enormously worldwide.[1, 2] In the Netherlands every year approximately 80,000 patients, 1 in every 200 inhabitants, are admitted to an ICU. (https://www.stichting-nice.nl/datainbeeld/public) Reasons for ICU admission vary, and include scheduled admission after major surgery, admission after trauma, and admission with reduced consciousness due to a neurological condition or, with hemodynamic or respiratory instability caused by an infection. At the ICU patients can be monitored, the functioning of organs can be supported and interventions to treat the underlying cause(s) can be performed.
Depending on the need of admitted patients, the support or treatment consists of, fluids, antibiotics, vasopressors and mechanical support by means of mechanical ventilation or renal replacement therapy (RRT). This high level of patient care is labour intensive resulting in a high caregiver to patient ratio at ICU’s.
Despite all the interventions, ICU patients are at risk for dysfunction or failure of a single or multiple organ, e.g. multi-organ dysfunction syndrome (MODS). The kidneys are prone to dysfunction (acute kidney injury (AKI)) during ICU admission, as the reasons for admission such as shock and infection and their treatment are possible insults to the kidneys. Irrespective of the population studied and AKI definition used, the occurrence and severity of AKI are associated with increased risks of mortality ranging up to 50% in patients who need RRT during ICU admission.[3] In addition, AKI also leads to impaired recovery of kidney function and increased risk of mortality after ICU discharge even after mild AKI.[4–6]
This thesis focuses on the kidney. After an insult to the kidneys resulting in an acute decrease in glomerular filtration rate (GFR), serum creatinine accumulates in the serum over time. The degree of kidney failure is estimated by the rise in creatinine and the decrease in urine output.
Creatinine is a degradation product of creatine phosphate in muscle tissue. Under normal
circumstances, production and release of creatinine occur at a constant rate, filtration by the
glomerulus is complete and usually no reabsorption occurs.[7] Creatinine levels are dependent
on gender, muscle mass and diet.[8] Therefore, serum creatinine as a measure to monitor renal
function in individual patients is only reliable in so-called steady state conditions.(Figure 1)
Critically ill patients are not in a steady state condition and therefore, the use of serum creatinine
as a marker for kidney function may not be appropriate. First, critically ill patients are usually in
a catabolic state with wasting muscles. Second, fluid resuscitation in critically ill patients affects
serum creatinine levels. Third, some frequently used drugs, for example cotrimoxazol, influence
creatinine metabolism. Despite these issues, creatinine is still a key criterion in the definition of
AKI mainly because of the lack of a better criterion.
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0 1 2 3 4 5 6 30
350
0 50
100 150 200 250 300
Ser um c rea tini ne (μ m ol/ l)
70
0 60 50 40 30 20 10
GFR (ml /mi n/1 .7 3m
2Time (days after kidney insult)
Detection by RIFLEPossible baseline values for creatinine
Detection by AKIN & KDIGO window for biomarkers to early detect AKI
Improvement of kidney function
Persistent kidney damage and CKD
Figure 1. Hypothetical serum creatinine and GFR course over time in an ICU patient
Graphic representation of the acute decline in kidney function, glomerular filtration rate (GFR) (blue) and the delayed rise in serum creatinine (green) in an ICU patient. The orange lines show the delay in timing of detection using different definitions (boundaries for RIFLE, AKIN and KDIGO). The blue bar shows the possible window for biomarkers in detecting AKI. The dotted lines indicate the possible long term course of kidney function. Figure adapted from Thomas et al.[9]
As stated above AKI is a syndrome defined by a rise in serum creatinine and/or a decrease in urine output.[10] The initiative to define AKI was driven by the need to compare studies regarding renal failure in critically ill patients. This AKI definition evolved over time and the criteria are applied variably.[9, 11, 12] Current studies in critically ill patients show incidences of AKI ranging from 15 to 40%.[3–6, 13–16] The incidences differ due to different populations studied (general ICU populations, selected – surgical – populations) and the use of different AKI definitions. The difference in definition is not only associated with a difference in AKI incidence, but also influences the severity of AKI. AKI is graded based on the extent of serum creatinine rise compared with levels in the previous 48 hours or seven days, depending on the definition used.(Table 1) When recent serum creatinine values are unknown, surrogates like serum creatinine from the past year or calculated levels of serum creatinine based on an assumed normal kidney function are used.
AKI is not only defined by an increase in serum creatinine. The Risk Injury, Failure, End-Stage (RIFLE), the Acute Kidney Injury Network (AKIN) and the Kidney Disease Improving Global Outcomes (KDIGO) definitions of AKI also include urine output criteria that are based on a decrease in hourly
Chapter 1
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13 urine output.(Table 1) [10–12] For severity based on the urine output criteria the amount and duration of the decreased urine output (normal range 1.5 – 2 L/day; approximately 1 ml/kg/h for a person of 80kg) is used.(Table 1) As well as the serum creatinine criteria the urine output criteria are applied variously in research concerning AKI, either hourly data or averaged data over 6 or even 24 hours are used. The different definitions and criteria with different references or applications lead to difficulty in interpreting the results of studies.[9] This means there is still a need for a better way to define AKI.
Table 1. AKI definitions and criteria
RIFLE = Risk, Injury, Failure, Loss and End-Stage-Kidney-Disease [12]. GFR = glomerular filtration rate.
RRT = renal replacement therapy AKIN = Acute Kidney Injury Network [11] KDIGO = Kidney Disease Improving Global Outcomes [10]
The exact mechanisms underlying the development of AKI are unknown, but mechanisms are multifactorial with hypoperfusion and a subsequent inflammatory response as the central cause.
[17, 18] This inflammatory response can be triggered by breakdown products of cells (Damage Associated Molecular Patterns (DAMP’s)), activated immune cells, bacterial endotoxins (Pathogen Associated Molecular Patterns (PAMP’s)) in sepsis, reduced renal perfusion, or toxic substances
RIFLE definition [12] AKIN definition [11] KDIGO definition
[10] All [10–12]
Severity Serum creatinine criteria Urine output
criteria
1 or Risk
creatinine *1.5 Or GFR decrease >25%
creatinine + ≥ 26.4 µmol/l Or creatinine 150-200% (*1.5-2.0)
creatinine *1.5-1.9 Or creatinine + ≥ 0.3 mg/dl (26.5 µmol/l)
<0.5 ml/kg/h
≥ 6 hours
2 or Injury
creatinine *2 Or GFR decrease >50%
creatinine 200-300% (*>2.0-3.0) creatinine * 2.0-2.9 <0.5 ml/kg/h
≥ 12 hours
3 or Failure
creatinine *3 Or
creatinine ≥ 4 mg/dl (350 µmol/l) with acute increase ≥ 0.5 mg/dl
(44 µmol/l) Or GFR decrease 75%
creatinine >300% (*>3.0) Or
creatinine ≥ 4 mg/dl (354 µmol/l) with acute increase ≥ 0.5 mg/dl (44
µmol/l) Or RRT
creatinine *3 Or creatinine ≥ 4 mg/dl
(354 µmol/l) Or RRT
< 0.3 ml/kg/h
≥ 24 hours Or Anuria ≥ 12
hours
Reference
creatinine < 1-7 days < 48 hours < 7 days
