ACUTE KIDNEY INJURY

Y Kandarini

Division of Nephrology & Hypertension

Department of Internal Medicine
Udayana School of Medicine/Prof Ngoerah General Hospital
2023
 Background
• AKI is part of a range of conditions summarized as acute kidney diseases and
disorders (AKD).
• AKI and AKD are a global concern.
• AKI can be cause by infections, hypovolaemic shock, related to sepsis, drugs
or invasive procedures
• The large spectrum of AKI implies diverse pathophysiological mechanisms
• Management in critical care settings is challenging, including appropriate
volume control, nephrotoxic drug management, and the timing and type of
kidney support.
• Long-term consequences of AKI and AKD include CKD and cardiovascular
morbidity
 Epidemiology of AKI

• Hoste EAJ, et al. Nature. 2018

Epidemiology of AKI
(High vs Low income countries)

• Hoste EAJ, et al. Nature. 2018

The Spectrum of Kidney Disease

• Hoste EAJ, et al. Nature. 2018

Severity of AKI and Long-term Kidney Outcome
• isi • The three stages of AKI
are defined by the extent
of renal function
impairment.
• Patients with AKI in which
structural damage causing
irreversible nephron loss
does not occur may fully
recover

• Kellum JA, et al. Nature. 2021

 Definition
• Acute kidney injury (AKI) is denoted by an abrupt decline in glomerular
filtration rate (GFR) sufficient to decrease the elimination of nitrogenous
waste products and other uremic toxins

2.1.1: AKI is defined as any of the following (Not Graded):

• Increase in SCr by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours; or

• Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to
have occurred within the prior 7 days; or
• Urine volume <0.5 ml/kg/h for 6 hours

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

KDIGO 2012
Diagnosis and staging of AKI

• KDIGO 2012
• Hoste EAJ, et al. Nature. 2018
 Comparison of Recent Consensus
•
AKI isi Urine Output KDGIO AKIN RIFLE
Stage 2012 2007 2003

1 <0.5 mL/kg/h for 6- Scr to 1.5-1.9 × baseline Scr to 1.5-2 × baseline Risk: Scr to ≥1.5 × increase
12 h over 7 d or ≥0.3 mg/dL or ≥0.3 mg/dL absolute Scr within 7 d, sustained for
absolute increase over 48 increase within 48 h ≥24 h
h
2 <0.5 mL/kg/h for Scr to 2.0-2.9 × baseline Scr to >2-3 × baseline Injury: Scr to ≥2 × increase
≥12 h
3 <0.3 mL/kg/h for Scr to ≥3.0 × baseline, or Scr to >3.0 × baseline, or Failure: Scr to ≥3.0 ×
≥24 Scr increase to ≥4.0 Scr increase to ≥4.0 mg/dL increase or Scr increase to
h or anuria for ≥12 h mg/dL or initiation of RRT (with increase of 0.5 mg/dL) ≥4.0 mg/dL (with
or initiation of RRT increase of 0.5 mg/dL) or
initiation of RRT
Loss: Complete loss of
kidney function for >4 wk
ESKD: ESKD for >3 mo

• AJKD 2018
Criteria for Defining AKI, AKD, CKD and NKD

• Kellum JA, et al. Nature. 2021

Risk factors for AKI

• Gameiro J, et al. J. Clin Med. 2020

Major Risk Factors for AKI

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Etiology of AKI
• isi

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Causes of AKI

• Gameiro J, et al. J. Clin Med. 2020

• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019
Causes of AKI in Hospital Setting

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Common Nephrotoxic Agents Leading to AKI
• Aminoglycosides (tobramycin, gentamycin)
• NSAIDs (ibuprofen, naproxen, ketorolac,
• isi
celecoxib)
• ACEi (captopril, lisinopril, benazepril,
ramipril)
• ARB (losartan, valsartan, candesartan,
irbesartan)
• Amphotericin
• Cisplatin
• Foscarnet
• Iodinated contrast
• Pentamidine
• Tenofovir
• Zolendronic acid

AJKD. 2018
William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019
Key Medications Requiring Dose Adjustment (or Cessation) in AKI
• Analgesics (morphine, meperidine, • Diabetic agents (sulfonylureas,
gabapentin, pregabalin) metformin)
• Antiepileptics (lamotrigine) • Allopurinol
• Antivirals (acyclovir, gancyclovir, • Baclofen
valgancyclovir) • Colchicine
• Antifungals (fluconazole) • Digoxin
• Antimicrobials (almost all antimicrobials • Lithium
need dose adjustment in AKI, with important
• Low-molecular-weight heparin
exceptions of azithromycin, ceftriaxone,
doxycycline, linezolid, moxifloxacin, nafcillin, • NOACs
rifampin)

• AJKD. 2018
Pathophysiology of AKI

• Kellum JA, et al. Nature. 2021

Evaluations and Continuum of Kidney Injury

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Evaluations of AKI
KIM-1 • A window of time exists in which kidney
NGAL
Cystatin C, injury goes undetected until serum
IL-8
creatinine concentrations rise (8 to 48
hours).
• Novel serum and urine biomarkers with
potential as early indicators of AKI.
• In AKI, preventing or delaying tubular
cell division may be a protective
Serum kreatinin
Volume urine
response to injury

William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Investigation and Workup of Suspected AKI
• isi

Anamnesis

Physical Examinations

Lab / Radiology

Biopsy

William JE et al. Comprehensive Clinical

Nephtology Sixth Ed. 2019
Sharfuddin A, et al. Acute Kidney Injury.
2015
 Evaluations of AKI
The pattern and timing of change in BUN and serum Lab Results
creatinine concentrations →
provide clues to the cause of AKI

Enhanced tubular rearbsoption of filtered urea → BUN / SC

Prerenal causes ratio >20 :1

increase in BUN parallels with SC→ ratio of approximately 10:1

Renal Causes maintained

The peak in serum creatinine level is generally within 5 to

Contrast agents 7 days post exposure

Aminoglycoside or cisplatin → often with delayed onset of AKI (7 to

Nephrotoxic agents 10 days)

• Sharfuddin A, et al. Acute Kidney Injury. 2015

• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019
Investigation and
Management of
Suspected AKI

William JE et al.
Comprehensive Clinical
Nephtology Sixth Ed.
2019
Urinary Sediment in Acute Kidney Injury
• isi

• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Systemic Effects of Acute Kidney Injury
• Hyperkalemia is a common and
potentially life-threatening complication
of AKI.
• Predictably, AKI is commonly complicated
by metabolic acidosis, typically with a
widening of the serum anion gap
• Mild hyperphosphatemia (5 to 10 mg/dL)
is a common consequence of AKI
• The injured kidney may prime and
activate leukocytes, which produce
proinflammatory cytokines that can
mediate remote organ injury.
• The lungs may be particularly vulnerable
from the combined effects of volume
overload, increased vascular permeability,
and proinflammatory environment.
Sharfuddin A, et al. Acute Kidney Injury. 2015
William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019
Complications of AKI
• Hyperkalemia is defined as a serum K+ level of >5.5
• isi mEq/L, and usually becomes symptomatic when serum
K+ is >6 mEq/L
• Pseudohyperkalaemia is where there is a red cell leak
of potassium in extracted blood
• Hyperkalemia can be asymptomatic, cause mild
symptoms, or be life threatening
• More severe hyperkalemia is associated with delayed
electrical conduction, resulting in an increased PR
interval and a widened QRS complex
• Hyperkalemia also has effects on noncardiac tissues.
Skeletal muscle cells are particularly sensitive to
hyperkalemia, causing generalized weakness. In patients
with severe hyperkalemia, diaphragmatic muscle
weakness may lead to respiratory failure.
• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019
• Molirotis B. Critical Care Nephrology. Remedica, 2005
• Harber M. Practical nephrology. Spinger. 2014
 Consequences of AKI on Kidney Lifespan

Severe AKI at an older age (pink lines) has a more immediate effect on the
remaining kidney lifespan than AKI at a younger age (blue lines).

• Kellum JA, et al. Nature. 2021

 Preventive and
Treatment
Strategies for
• isi AKI

• Gameiro J, et al. J.
Clin Med. 2020
Management of AKI
• isi

• KDIGO 2012
Fluid Management in Acute Kidney Injury
• isi

• Kellum JA, et al. Nature. 2021

 Prevention of Contrast-Induced Acute Kidney Injury

• The Prevention of CI-AKI Consensus Working Panel recommends that measures to

reduce the AKI risk should be implemented in patients with a baseline estimated GFR
(eGFR) below 60 ml/min/1.73 m2
• For prevention of CI-AKI, patients at risk should receive intravenous hydration
• The KDIGO AKI guidelines recommend either isotonic sodium chloride or sodium
bicarbonate solutions in patients at risk for CI-AKI unless there are contraindications
to volume expansion
• Iodinated contrast can be categorized. The KDIGO AKI guidelines recommend either
iso-osmolar or low-osmolar iodinated contrast for patients at risk for CI-AKI.
• The volume of contrast administered is also an independent predictor of CI-AKI and
should be reduced as much as possible

• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Serial Case of CI-AKI/CIN
PIT PERNEFRI 2021
No Mehran Tindakan CIN-AKI CHART SC PASIEN
5
1 13 Elective PCI Tidak
4

2 12 Elective PCI Tidak 3

mg/dL
2
CT Scan
3 13 Tidak
Kontras 1

0
CT Scan BASELINE 12 JAM 24 JAM 48 JAM 72 JAM
4 15 Tidak
Kontras WAKTU

1 2 3 4 5 6 7 8 10
5 19 Primary PCI Ya
PRODUKSI URIN PASIEN
6 18 Primary PCI Ya 1.4
1.2
7 11 Primary PCI Tidak

CC/KG BERAT BADAN

1
8 11 Arteriografi Tidak 0.8
0.6
Tidak 0.4
9 11 Venografi
Dievaluasi 0.2
0
24 JAM 48 JAM 72 JAM 96 JAM
CT Scan
10 12 Tidak WAKTU
Kontras
1 2 3 4 5 6 7 8 9 10

• The recommendation in this serial case, is the approach in patient

management with High Risk of CIN is an individual approach with a
look at the background and condition of the disease. The experience
of the clinicians plays a role in decision making about the therapeutic
plan and procedures in each patient
Management of CI-AKI/CIN

• Faggioni M, Mehran R. Preventing Contrast-induced Renal Failure: A Guide. ICR; Interv Cardiol Rev. 2016
 Dialysis Interventions for Treatment of AKI

• 5.1.1: Initiate RRT emergently when life-threatening changes in fluid,

electrolyte, and acid-base balance exist.
• 5.1.2: Consider the broader clinical context, the presence of conditions
that can be modified with RRT, and trends of laboratory tests—rather
than single BUN and creatinine thresholds alone—when making the
decision to start RRT.

• KDIGO. 2012
 Algorithm for Initiation of
Acute RRT
• isi • ARRT should be initiated for life-
threatening hyperkalemia or acidosis
refractory to medical treatment, uremic
features such as pericarditis or coma
and refractory hypervolemia causing
end-organ complications (e.g.,
pulmonary edema).
• ARRT should be initiated if the burden of
fluid and solute derangements is
increasing and anticipated to result in
complications, rather than waiting for
them.
• ARRT should probably be initiated
earlier in patients who are less able to
resolve fluid and solute derangements

• William JE et al. Comprehensive Clinical Nephtology Sixth Ed. 2019

Advantages and Disadvantages of CRRT, IHD, SLED, and PD

• isi

• KDIGO. 2012
Potential applications for RRT
• isi

• KDIGO. 2012
Summary
• AKI is associated with increased morbidity and mortality and adverse
long-term patient and kidney outcomes
• The large spectrum of AKI implies diverse pathophysiological mechanisms
• Improvements in AKI diagnosis and treatment remain unmet medical
needs
• AKI is potentially treatable and reversible, and treatment is often specific
to the underlying condition
• AKI management in critical care settings is challenging, including
appropriate volume control, nephrotoxic drug management, and the
timing and type of kidney support