The document discusses acute kidney injury (AKI) in critically ill patients, including: 1. AKI is common in ICU patients, with various causes like sepsis, ischemia, and nephrotoxins. Proper diagnosis involves assessing fluid status, urinary and serum markers, and biomarkers. 2. Prerenal AKI accounts for most ICU cases and results from reduced renal blood flow due to issues like dehydration. Sepsis is also a major cause through tissue hypoperfusion and endothelial damage. 3. Biomarkers like NGAL and KIM-1 can detect early kidney injury before rises in serum creatinine, but their use is limited by cost currently

1. Practical approach to detection and management of acute
kidney injury in critically ill patient
Dr. Kanika Chaudhary
REVIEW ARTICLE
Mohsenin V. Practical approach to detection and management of acute kidney injury in critically ill patient. J Intensive Care. 2017;5:57.
Published 2017 Sep 16. doi:10.1186/s40560-017-0251-y

2. Mohsenin V. Practical approach to detection and management of acute kidney injury in critically ill patient. J Intensive Care.
2017;5:57. Published 2017 Sep 16. doi:10.1186/s40560-017-0251-y
AUTHOR
Vahid Mohsenin
SOURCE
Journal of Intensive Care, September 2017

3. OVERVIEW
 INTRODUCTION
 CAUSES OF AKI
 DIAGNOSIS
 MANAGEMENT OF AKI
 CONCLUSION
 REFERENCES

4. INTRODUCTION
 Acute kidney injury (AKI) is a common complication among patients
with critical illness in the intensive care unit (ICU).
 The incidence of AKI is now significantly higher than previously
believed with over 50% of patients in the ICU developing AKI at some
point during the course of their critical illness.
 Mortality among ICU patients with AKI and multi-organ failure has
been reported to be more than 50%. Those that require renal
replacement therapy (RRT) mortality may be as high as 80%.

5.  AKI is characterized by a sudden decrease in kidney function over a
period of hours to days, resulting in accumulation of creatinine,
urea, and other waste products.
 A consensus definition of AKI and formulation of the RIFLE criteria—
acronym RIFLE stands for Risk, Injury, and Failure; and the two
outcome classes, Loss and End-Stage Renal Disease —is based on the
degree of rise of serum creatinine, decreased in glomerular filtration rate
(GFR), and urine output.
INTRODUCTION

6.  According to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO)
consensus guidelines, AKI is defined as
• An increase in the serum creatinine level of 0.3 mg/dL (26.5 μmol/L) or more within
48 h
• A serum creatinine level that has increased by at least 1.5 times the baseline value
within the previous 7 days
or
• A urine volume of less than 0.5 mL per kilogram of body weight per hour for 6 h.
INTRODUCTION

9. CAUSES OF AKI
Prerenal AKI
• Dehydration (vomiting, diarrhea)
• Bleeding or hypovolemia
• Heart failure
• Liver failure
• Narrowing of renal arteries
• Renal microangiopathy
• Exposure to vasoactive drugs

10. CAUSES OF AKI
Renal AKI
• Acute tubular injury/toxicity
• Drugs: Aminoglycosides, vancomycin, Amphotericin B, pentamidine,
Bisphosphonates, Cisplatin, ifosfamide, methotrexate (crystal nephropathy)
• Contrast dyes
• Tumor lysis syndrome
• Multiple myeloma
• Rhabdomyolysis (crush injury, cocaine, heroin, ketamine, methadone, and
methamphetamine)
• Tissue hypoperfusion, sepsis
• Acute interstitial nephritis
• Vancomycin, quinolones, rifampin, sulfonamides, β-lactams (penicillin,
cephalosporins), acyclovir (crystal nephropathy)
• NSAIDs
• Ifosfamide, carboplatin, Adriamycin, tyrosine kinase inhibitor

11. Post-renal AKI
 Postrenal AKI occurs when the normally unidirectional flow of urine is acutely
blocked either partially or totally, leading to increased retrograde hydrostatic pressure
and interference with glomerular filtration.
 Obstruction to urinary flow may be caused by functional or structural derangements
anywhere from the renal pelvis to the tip of the urethra.
CAUSES OF AKI

12. CAUSES OF AKI
Prerenal AKI
 Prerenal AKI including sepsis accounts for 60–70% of all AKI cases in critically ill
patients.
 Renal blood flow (RBF) autoregulation through its synchronized interplay of afferent
and efferent arterioles maintains a constant RBF and GFR within a wide range of mean
arterial blood pressure (80–180 mmHg). A decline in the GFR reflects a reduction in
blood pressure below the lower limit of the autoregulatory range. However, a significant
decline in blood pressure must occur to induce a sufficient reduction in GFR with
subsequent development of AKI.

13. GFR is controlled by adjusting Glomerular blood pressure through 3
mechanisms:
Autoregulati
on
(intrinsic)
Myogenic mechanism
( promote changing in blood pressure
by
stretching receptors)
Increase blood
pressure:
Afferent arteriole
vasoconstriction
and
Efferent arteriole
vasodilation
Decrease
glomerular
hydrostatic
pressure
Decrease
GFR
Decrease blood
pressure:
Afferent arteriole
vasodilation
And
moderate Efferent
arteriole
vasoconstriction
Increase
glomerular
hydrostatic
pressure
Increase
GFR
Tubuloglomerular
feedback mechanism
(promote changing in sodium
chloride concentration in Distal
tubules)
decrease resistance to blood flow in
the afferent arterioles → increase
glomerular hydrostatic pressure and
helps return GFR toward normal
increase renin release from the
juxtaglomerular cells of the afferent
and efferent arterioles → increase
angiotensin II → constrict efferent
arteriole and helps return GFR toward
normal
Hormonal
Regulation
Sympathetic
control
(extrinsic)
At rest: has no effect
In severe condition (such as
severe hemorrhage):
constriction of afferent arteriole
by releasing of vasoconstrictor
mediators
Decrease
GFR

14. Glomerular filtration rate (GFR): is the volume of plasma filtrate produced by both kidneys per
minute.
- The average per minute is: 125 ml/min (20% of renal plasma flow)
- The average per day is: 180 L/day (gallons)
- 99% will reabsorbed (178.5 L/day) from filtrate and only 1% will excreted (1.5 – 2
L/day)
So, most filtered water must be reabsorbed or death would ensue from water lost through
urination.
- These values varies with: kidney size, lean body weight and number of functional
nephrons
- The relation between GFR an Net Filtration Pressure:
• ↑ NFP → ↑GFR
• ↓ NFP → ↓ GFR
- Normally changes in GFR is a result from change of blood pressure.
If GFR is too high:
Fluid flows through tubules too rapidly to be
absorbed (will not absorbed very well). It will
lead to: 1- Urine output rises
2- Creates threat of dehydration and
electrolyte depletion
If GFR is too low:
Fluid flows sluggishly through tubules. It will leadto:
1 Tubules reabsorb wastes that should be eliminated
2 Azotemia develops (high levels of nitrogen-
containing
substances in the blood).

15.  In the tubuloglomerular feedback (TGF) mechanism through macula densa,
when blood pressure decreases, the vasodilators (vasodilator prostaglandins and
nitric oxide) are released with afferent arteriolar vasodilation and subsequent
stimulation of renin-angiotensin-aldosterone system (RAAS) . The opposite
occurs when blood pressure increases with generation of vasoconstrictor
mediators (vasoconstrictor ATP and adenosine), causing afferent arteriolar
vasoconstriction while the efferent arteriole dilates to stabilize RBF and GFR.
 The TGF mechanism and the myogenic activity of the afferent arteriole provide
an estimated 90% of the autoregulation capacity of RBF. Arterial blood pressure
alone cannot sustain GFR, so these important autoregulatory mechanisms
involving the TGF- and RAAS-mediated compensations are needed. Risk of AKI
increases when these mechanisms are inhibited through angiotensin converting
enzyme inhibitors (ACEI) and NSAID.

17. Renal/Intrinsic AKI
 The most common causes of intrinsic AKI are sepsis, ischemia, and
nephrotoxins
• SEPSIS-ASSOCIATED AKI
• ISCHEMIA-ASSOCIATED AKI
• NEPHROTOXIN-ASSOCIATED AKI
 In many cases, prerenal azotemia advances to tubular injury, termed as “acute
tubular necrosis

18. SEPSIS-ASSOCIATED AKI
 Sepsis and septic shock remain the most important causes of AKI in critically ill patients
and account for more than 50% of cases of AKI in the ICU.
 Tissue hypoperfusion and renal ischemia are the mechanisms of AKI in sepsis and
hyperdynamic septic shock.
 The hemodynamic effects of sepsis—arising from generalized arterial vasodilation,
mediated in part by cytokines that upregulate the expression of inducible NO synthase in
the vasculature—can lead to a reduction in GFR.

19.  AKI can occur in the absence of overt signs of tissue hypoperfusion, suggesting that
other mechanisms may be at work.
 Sepsis may lead to endothelial damage, which results in microvascular thrombosis,
activation of reactive oxygen species, and leukocyte adhesion and migration, all of
which may injure renal tubular cells.
SEPSIS-ASSOCIATED AKI

20.  Healthy kidneys receive 20% of the cardiac output and account for 10% of resting
oxygen consumption, despite constituting only 0.5% of the human body mass.
 The kidneys are also the site of one of the most hypoxic regions in the body, the
renal medulla.
 The outer medulla is particularly vulnerable to ischemic damage because of the
architecture of the blood vessels that supply oxygen and nutrients to the tubules.
Enhanced leukocyte-endothelial interactions in the small vessels lead to
inflammation and reduced local blood flow to the metabolically very active S3
segment of the proximal tubule.
ISCHEMIA-ASSOCIATED AKI

21.  Clinically, AKI more commonly develops when ischemia occurs in the context of
limited renal reserve (e.g., chronic kidney disease or older age) or coexisting insults
such as sepsis, vasoactive or nephrotoxic drugs, rhabdomyolysis, or the systemic
inflammatory states associated with burns and pancreatitis.
ISCHEMIA-ASSOCIATED AKI

22. NEPHROTOXIN-ASSOCIATED AKI
 The kidney has very high susceptibility to nephrotoxicity due to extremely high blood
perfusion and concentration of circulating substances along the nephron where water is
reabsorbed and in the medullary interstitium; this results in high-concentration exposure
of toxins to tubular, interstitial, and endothelial cells.
 Nephrotoxic injury occurs in response to a number of pharmacologic compounds with
diverse structures, endogenous substances, and environmental exposures.

23.  All structures of the kidney are vulnerable to toxic injury, including the tubules,
interstitium, vasculature, and collecting system. As with other forms of AKI, risk
factors for nephrotoxicity include older age, chronic kidney disease (CKD), and
prerenal azotemia.
 Hypoalbuminemia may increase the risk of some forms of nephrotoxin-associated
AKI due to increased free circulating drug concentrations.
NEPHROTOXIN-ASSOCIATED AKI

24.  The pathophysiology of postrenal AKI involves hemodynamic alterations triggered by
an abrupt increase in intratubular pressures.
 An initial period of hyperemia from afferent arteriolar dilation is followed by intrarenal
vasoconstriction from the generation of angiotensin II, thromboxane A2, and
vasopressin, and a reduction in NO production. Reduced GFR is due to underperfusion
of glomeruli and, possibly, changes in the glomerular ultrafiltration coefficient.
Post-Renal AKI

26. Classification of the major causes of acute kidney injury. ACE-I, angiotensin-converting enzyme
inhibitor-I; ARB, angiotensin receptor blocker; NSAIDs, nonsteroidal anti-inflammatory drugs; TTP-
HUS, thrombotic thrombocytopenic purpura–hemolytic-uremic syndrome.

27. DIAGNOSIS
AKI is diagnosed when serum creatinine increases by ≥ 0.3 mg/dL
(≥ 26.5 μmol/L) within 48 h or increase in serum creatinine to ≥ 1.5 times
baseline within the previous 7 days or urine volume < 0.5 mL/kg/h for 6 h

28. A. Fluid volume assessment
 The real challenge is to determine the cause of AKI. The first order is to assess the fluid
volume status of the patient. This can be accomplished by estimating the fluid volume
balance in the preceding days, blood pressure trend, and assessment of intravascular
volume.
 Intravascular volume is not measured directly but can be inferred by the presence or
absence of fluid responsiveness. Echocardiography examining the inferior vena cava
diameter and its respiratory variation is becoming readily available in ICUs. More than
12% variation in the IVC diameter in mechanically ventilated patient with septic shock
had greater than 90% positive predictive value (PPV) for fluid responsiveness implying
intravascular volume deficit.

29.  Central venous pressure (CVP) dynamic changes or arterial pulse pressure variation
during respiratory cycle can also provide information about intravascular volume
deficit. A drop of ≥ 1 mmHg in CVP during spontaneous inspiration or mechanical
breath had a PPV of 84% and negative predictive value of 94% for fluid
responsiveness in a mixed medical and surgical ICU. In arterial pulse pressure
variation of > 13% during respiratory cycle, the respective values were 94% and 96%
A. Fluid volume assessment

30. B. Urinary and serum biochemical measurements
 Urinary diagnostic indices can have confirmatory value. Concentrated
urine with urine-specific gravity > 1.020, BUN/Cr > 20:1, urine Na
< 20 mEq/L, or low FeNa < 1.0% are consistent with fluid volume
deficit or renal hypoperfusion denoting a prerenal AKI. On the other
hand, rising serum creatinine with FeNa > 2.0% highly suggests renal
AKI.

32. C. Biomarkers of kidney injury
 The current definition and classification of AKI tell nothing about whether the
dysfunction is purely functional or completely structural—these two extremes likely
do not exist.
 Serum creatinine is the defining indicator of AKI in KDIGO guideline. But it has
been shown, serum creatinine, to be a lagging indicator of AKI development and it is
easily influenced by many factors, including gender, muscle mass, and some
medications.

33.  The search for early identification of AKI has led to the development of multiple
biomarkers of AKI capable of detecting kidney injury at its early stage. A series of
molecules have been evaluated over the years, and significant advances have been made
in the field.
 Several biomarkers categorized as functional (e.g., serum creatinine, serum cystatin
C) and damage (e.g., NGAL, neutrophil gelatinase-associated lipocalin; KIM-1,
kidney injury molecule-1; TIMP2, tissue inhibitor of metalloproteinases 2;
IGFBP3, insulin-like growth factor-binding protein 3) markers in combination to
improve the diagnostic categorization of AKI and permit more guided interventions.
C. Biomarkers of kidney injury

34.  Cystatin C
• Small protein produced by nucleated cells
• Eliminated by GFR
• Behaves similar to serum creatinine but is less dependent on muscle mass
• In ICU patients, cystatin C will detect AKI 1–2 days earlier before the rise of serum
creatinine
• Its costly measurement limits its routine use
C. Biomarkers of kidney injury

35.  NGAL and KIM-1
• Some capacity to detect an injury to the kidney well before the rise of serum creatinine
• Measurement of serum or urine NGAL has been shown to be a good diagnostic test for
AKI and prognostic indicator of RRT need and mortality in patients with shock
• Routine use of NGAL in clinical setting is limited due to its increase in both serum
and urine which may be related to the presence of a systemic inflammatory state
including sepsis and not necessarily the development of AKI
C. Biomarkers of kidney injury

36.  A simple product of biomarker levels (TIMP-2 × IGFBP7) expressed in (ng/mL)2/1000,
launched as a final commercial product, known as NephroCheck
 The cutoffs of > 0.3 and > 2 (ng/mL)2/1000 were associated with a progressively
increased risk of AKI and major adverse kidney events (death, the need of RRT or
persistent renal dysfunction)
 NephroCheck of < 0.3 (ng/mL)2/1000 had a negative predictive value of 96%
following adjustment for the prevalence of AKI
C. Biomarkers of kidney injury

37. D. Urine microscopy
 Urine sediments can not only help to differentiate prerenal AKI
from renal AKI but can also provide insight as to the site of nephron
injury.

40. E. Radiologic evaluation
 Postrenal AKI should always be considered in the differential diagnosis of AKI
because treatment is usually successful if instituted early.
 Simple bladder catheterization can rule out urethral obstruction. Imaging of the
urinary tract with renal ultrasound or CT should be undertaken to investigate
obstruction in individuals with AKI unless an alternate diagnosis is apparent.
 If a high clinical index of suspicion for obstruction persists despite normal imaging,
antegrade or retrograde pyelography should be performed.
 Vascular imaging may be useful if venous or arterial obstruction is suspected.
 MRI with gadolinium-based contrast agents should be avoided if possible in
severe AKI due to the possibility of inducing nephrogenic system fibrosis, a rare but
serious complication seen most commonly in patients with end-stage renal disease.

41. F. Kidney biopsy
 If the cause of AKI is not apparent based on the clinical context, physical
examination, laboratory studies, and radiologic evaluation, kidney biopsy should be
considered.
 The kidney biopsy can provide definitive diagnostic and prognostic information
about acute kidney disease and CKD
 Kidney biopsy is associated with a risk of bleeding, which can be severe and organ-
or life-threatening in patients with thrombocytopenia or coagulopathy

42. MANAGEMENT OF AKI
A. Fluid volume expansion
 If clinical assessment points toward intravascular volume deficit, optimization of the
hemodynamic status and correction of any volume deficit should have a salutary effect
on kidney function and help to minimize further extension of the kidney injury.
 Fluid resuscitation should be done while monitoring urine output, blood pressure, or
CVP dynamic changes as endpoints to avoid excessive fluid administration.

43.  Buffered crystalloids with low-chloride content may be associated with a
decreased risk of AKI as unphysiologic chloride concentration (154 mEq/L) in
normal saline can cause renal vasoconstriction, decreased glomerular filtration,
and metabolic acidosis
 Colloid solutions such albumin can be used in patients with hypoalbuminemia in
the setting of fluid volume deficit, hypotension, and AKI. Albumin infusion is also
indicated in patients with liver cirrhosis with AKI in the form of hepatorenal
syndrome in conjunction with vasopressors.
A. Fluid volume expansion

44. B. Vasopressors
 In septic shock with AKI norepinephrine is the vasopressor of choice with target mean
arterial pressure of 65–70 mmHg.
 In patient with chronic hypertension, a higher target mean arterial pressure of 80–
85 mmHg is recommended.
 The target mean arterial blood pressure of 65–70 mmHg is also applicable in patients
with hepatorenal syndrome In hepatorenal syndrome, all vasoconstrictors should include
cotherapy with albumin.

45. C. Diuretics
 Diuretics may be used to relieve hypervolemia among patients with AKI who are not
anuric. Loop diuretics are the preferred agents as they provide a greater natriuretic
effect than thiazide diuretics.
 Dosing of loop diuretics varies inversely with GFR. Hence, high (or maximum)
doses of diuretics may be needed for patients with impaired GFR

47.  In diuretic-naïve patients, we start with 80 mg of intravenous (IV) furosemide, or
equivalent, and assess for response. Patients who were on diuretics prior to the onset of
AKI should receive a dose that is at least double their prior (home) dose.
 If there is no definite augmentation in the urine output within two hours of an IV
diuretic dose, then we administer double the initial dose (maximum of 200 mg in a
single dose of IV furosemide or equivalent). Addition of a thiazide diuretic such
as chlorothiazide (500 to 1000 mg IV) is sometimes given in conjunction with
furosemide to augment urine output. Lack of response to a 200 mg dose of IV
furosemide or equivalent, with or without a thiazide diuretic, may suggest the
need for extracorporeal removal of excess volume.
C. Diuretics

48. D. Renal Replacement Therapy
Accepted urgent indications for RRT in patients with AKI generally include:
 Refractory fluid overload
 Severe hyperkalemia (plasma potassium concentration >6.5 mEq/L) or rapidly
rising potassium levels
 Signs of uremia, such as pericarditis, encephalopathy, or an otherwise
unexplained decline in mental status
 Severe metabolic acidosis (pH <7.1)
 Certain alcohol and drug intoxications

49.  Early initiation of RRT within 8 h of KDIGO stage 2 AKI significantly reduced
90-day mortality (39.3%) compared with delayed initiation of RRT.
 In the early RRT group, renal function recovery was faster with shorter ICU stay
compared with the delayed RRT group
D. Renal Replacement Therapy

50.  AKI is prevalent in critically ill patients in ICU. The most common etiologies of AKI in
these patients are due to fluid volume deficit or kidney hypoperfusion and ATN due
to shock, inflammatory state, or nephrotoxic drugs.
 Early recognition of pathophysiology of AKI by careful review of patient’s history and
hospital course and intravascular volume assessment complemented by urine
biochemical analysis and urine microscopy should guide management strategy in order
to reduce further progression of AKI and mortality.
CONCLUSION

51. REFERENCES
1. Harrison’s Principles of Internal Medicine 19th ed
2. Current Medical Diagnosis and Treatment 2019
3. Mohsenin V. Practical approach to detection and management of acute kidney
injury in critically ill patient. J Intensive Care. 2017;5:57. Published 2017 Sep 16.
doi:10.1186/s40560-017-0251-y
4. Mark D Okusa, MD Mitchell H Rosner, MD.Overview of the management of acute
kidney injury (AKI) in adults. Uptodate Nov 2020.
5. Paul M Palevsky, MD Renal replacement therapy (dialysis) in acute kidney injury
in adults: Indications, timing, and dialysis dose. Uptodate July 2020.

52. THANK YOU