ACUTE KIDNEY

INJURY

DR. MONDAY ZACCHEAUS

REGISTRAR, DEPT OF INTERNAL MEDICINE, UPTH.
OUTLINE
 Introduction
 Epidemiology
 Aetiology
 Pathophysiology
 Clinical presentation
 Diagnosis/Investigations
 Treatment/Complications
 Prevention/Prognosis
 Conclusion
 Reference
INTRODUCTION
 Acute Kidney Injury (AKI) was first
described by John Abercombie in 1821
formerly known as Acute renal failure.
 It is characterized by:
 Rapid decline in GFR (hours to days)
 Retention of nitrogenous waste products
 Abnormalities of:
• ECF volume

• Electrolyte

• Acid-base homeostasis
 DEFINITIONS
• It was in 2004 that nephrologists ,
dialysis groups, critical care physicians
and other interest groups came together
in an attempt to provide a universally
acceptable and evidence based definition
of AKI
• The Acute dialysis Quality
initiative(ADQI) Group initiated the
process via International consensus
conference.
DEFINITIONS
After a careful study of the acute renal
failure problem came up with the following:
Designation of ARF to AKI
A universally acceptable definition of AKI.
Staging /classification of AKI according to.
The severity.
• The development of Guideline for the
management of AKI
UNIVERSAL DEFINITION
OF AKI (KDIGO)
A clinical syndrome characterised by
sudden deterioration in kidney functions
within a period of hours or days
leading to the failure to excrete
nitrogenous waste products and to
maintain fluid and electrolyte
UNIVERSAL DEFINITION
OF AKI
• Objectively determined as

• i). Based on urine out put: Urine

volume less than 0.5ml/kg/hr for
more than 6hr.

• ii).Based on Serum creatinine level:

Increase in Scr >1.5 -2 fold from
baseline.
RIFLE CRITERIA FOR AKI
 AKIN GRADING OF AKI
• In 2005, the Acute Kidney Injury Network

(AKIN) reviewed the RIFLE Criteria. Several

challenges noted by clinicians with the use of

the RIFLE criteria were considered.

• The network proposed several modifications to

the RIFLE criteria and these came to be known

as the AKIN criteria.

AKIN
AKIN stage
CRITERIA
Serum creatinine
FOR AKI
Urine output
Stage 1 1.5–1.9 times baseline <0.5 ml/kg/h for
OR 6–12 hours
>0.3 mg/dl (>26.5
umol/l) increase
Stage 2 2.0–2.9 times baseline <0.5ml/kg/hr >12 hours
Stage 3 3.0 times baseline <0,3ml/kg/hr for >24 hrs.
OR OR :
Increase in serum Anuria for >12 hrs
creatinine to
>4.0 mg/dl (>353.6
mmol/l)
OR
Initiation of renal
replacement therapy
OR, In patients <18
years, decrease in
eGFR to <35 ml/min per
1.73 m
 KDIGO CRITERIA FOR AKI
• In 2012, the Kidney Disease Improving Global

Outcomes (KDIGO) workgroup on AKI reviewed the

state of knowledge on AKI.
• The group pointed to the advantages and
disadvantages of each of the RIFLE and AKIN
criteria.
• They proposed a new set of criteria that essentially
was a merger of the RIFLE and AKIN criteria.
• The resulting criteria became known as the KDIGO
criteria for diagnosis and classification of AKI
KDIGO Diagnostic Criteria
Increase in serum creatinine by
>0.3g/dl (>26.5µmol/L) within 48hours
OR

Increase in serum creatinine to >1.5

times the baseline which is
known or presumed to have occurred
within the preceding 7days
OR

Urine output <0.5mL/Kg/hour for 6hrs

KDIGO CLASSIFICATION OF AKI
1. Anatomic 3. Urine output
2. – Prerenal – Oliguric
– Non-oliguric
3. – Intrinsic renal 4. Prior Kidney status
4. – Post renal – In the setting of
prior normal kidney
5. 2. Setting of function
Acquisition – In the setting of
prior impaired kidney
6. – Community function
acquired 5. Epidemiology: HIC,
LMIC
– Hospital acquired 6. Clinical setting
 EPIDEMIOLOGY
•Global phenomenom.
• All racial groups, all age groups,
both Gender.
• Globally, the mean age of patients with AKI
is 60 years, (67years in HICs and 50years
in LMIC).
• Incidence and prevalence vary widely due
to differences in definition, causes and
 EPIDEMIOLOGY
 60% of patients with AKI are men and this
is independent of the socioeconomic status
of the region.
 AKI is more prevalent in individuals of
lower socioeconomic class.
 In the USA, the risk of pregnancy-related
AKI was considerably higher in Black women
than in white women.
 In Asia, the risk of AKI after cardiac
surgery was higher in India and Malaysia
than in China.
 EPIDEMIOLOGY
• The pattern of epidemiology AKI can be
broadly divided into two, that seen in:
• • High-income countries
• Low and middle-income countries
High income countries (HIC)
• Susantitaphong et al. in a meta-analysis of
154 studies that:
• ➢Defined AKI according to the KDIGO
 EPIDEMIOLOGY
 ➢Included 3,585,911 individuals (84%
from HIC)
 Reported the rates of AKI to be
➢8.3% in the community
➢20.0 – 31.7% in hospitalized patients
 Mortality rate was
• Average pooled = 23%
• Up to 49.4% in those requiring dialysis
• Low and middle income countries:
• Data from LMICs is both less robust and
reliable.
 EPIDEMIOLOGY
• Mehta et al. in another worldwide meta-
analysis that:
• Adopted the same definitions and inclusion
and exclusion criteria to those by
Susantitaphong et al.
• Included 765 studies and 77,393,454
patients.
• Estimated the overall rates of AKI to be 21%
• Mortality rates:
• 21% overall.
• Up to 46% in those requiring dialysis
EPIDEMIOLOGY: SOME NIGERIAN DATA
Parameter UPTH(6yrs) UCH(3yrs) LUTH(10yrs) IUTH(19yrs)
N 121 40 175 113
% Med adm. 1.9 NA NA NA
Mean
age(yrs) 41.3 40.0 NA 28.3

Gender ratio. 1.2:1 NA 1:1.5 NA

Aetiology.(%)
Pre-renal 15.9 NA NA NA
Sepsis 22.7 17.3 38.0 38.0
Nephro-toxin 11.4 37.5 8.5 15.6
Obstr. 4.5 12.5 25.7 10.0
Acute 20.5
glomerulone
phritis

Out comes
RRT 51.2 NA NA 90.6
Deaths(% 43.5 25.0 39.4 47.6
 EPIDEMIOLOGY
HICs
• Predominantly hospital-
acquired
• Community-acquired AKI
accounts for < 50% of cases.
• Patients tend to be older,
have
 multiple comorbidities, and
have access to dialysis and
intensive care if needed.
• Post-surgical or diagnostic
interventions, or iatrogenic
factors are the main causes.
LMICs
• Predominantly community-
acquired
• Approx 80% of AKI is
communityacquired.
• Occurs mostly as a
complication of a single
disease, patients tend to be
younger and access to care
is limited.
• Sepsis, volume depletion,
toxins (bites,
remedies) and pregnancy-
related complications are
the main causes.
 EPIDEMIOLOGY-RISK FACTORS
 Socioeconomic/Environmental
 Access to portable drinking water
 Waste disposal practices
 Control of infectious disease
1. Access to quality healthcare
• Healthcare-Related
• 1. Admission to ICU
• 2.Diagnostic procedures
• 3.Exposure to nephrotoxic drugs
• 4.Major surgeries (esp. cardiac)
5.Cancer chemotherapy
EPIDEMIOLOGY-RISK FACTORS
• Patient related
➢Modifiable:
Volume depletion
1. Use of nephrotoxic agents
2. Urinary tract obstruction
3. Anaemia
➢Non-modifiable:
Older age
CKD(Strongest risk factor)
Diabetes
4. Organ failures (liver, heart)
AETIOLOGY: Classification of
the major causes of AKI
AETIOLOGY
AETIOLOGY
PATHOPHYSIOLOGY
Mechanisms of Kidney
injury:
1. Pre-renal Azotemia
2. Intrinsic renal AKI
• Vascular
• Glomerular
• Tubulo-interstitial
3. Post renal AKI
• PRERENAL AZOTEMIA:
• The most common form of AKI is
prerenal AKI, which occurs in the setting
of renal hypoperfusion.
• Prerenal AKI is generally reversible when
renal perfusion pressure is restored. By
definition, renal parenchymal tissue is not
damaged.
• More severe or prolonged hypoperfusion
may lead to ischemic injury, often termed
acute tubular necrosis, or ATN.
• Thus, prerenal AKI and ischemic ATN fall
along a spectrum of manifes tations of
 PATHOPHYSIOLOGY-
PRERENAL AZOTEMIA
• Hypovolemia leads to a fall in mean systemic arterial
pressure, which is detected as reduced stretch by
arterial (e.g., carotid sinus) and cardiac
baroreceptors.
• In turn, this triggers a coordinated series of
neurohormonal responses that aim to restore blood
volume and arterial pressure.
• These include activation of the sympathetic nervous
system and renin-angiotensin-aldosterone system,
as well as release of arginine vasopressin.
• In addition, salt loss through sweat glands is
inhibited, and thirst and salt appetite are
stimulated. Renal salt and water retention also
PATHOPHYSIOLOGY
 Pre-renal AKI.

Body fluid loss(external or internal)

 Reduced circulating blood volume

 Reduced renal plasma/blood flow

 Hypoxaemia of Renal tissues

 Apoptotic cell injury/death

 Impaired renal function

 Reduced GFR

 Oliguria/ Salt and fluid retention etc.

 PATHOPHYSIOLOGY:

 Pathology;
 Renal biopsy usually not indicated.
 May be normal or evidence of mild
ischemic tubular injury.
 If renal blood flow restored in time:
 Full recovery possible.
 Progression to ATN if persistent
ischaemia.
 PATHOPHYSIOLOGY

OF INTRINSIC AKI
 PATHOPHYSIOLOGY OF ATN

 Acute tubular necrosis(ATN).

 The Ischaemia/Reperfusion theory/model of ATN.

 Universally accepted theory of AKI based on exptal

animal studies,biopsy and post mortem findings

 Persisting pre-renal injury:

 Direct toxic injury(toxins,drugs ,inflammation etc)

lead to:
 PATHOPHYSIOLOGY OF ATN

 Severe oxidative stress to renal

tissues(epithelial and vascular endothelium)
 Activation of the renal stress response
xterised by cellular depletion of ATP.
 ATP depletion leads to production of
hypoxanthine and subsequently to free
oxygen radicals that are injurious to tissues.
PATHOPHYSIOLOGY OF ATN
• The pathophysiologic hub of ATN is
ATP-system(ATP,ADP,AMP) depletion.
• The activation of tissue inflammatory
response system with mobilisation of
acute inflammatory mediators
cytokines,(IL-6, TNF-alpha etc)
chemokines and eicosanoids rantes
myeloperoxidase etc.
PATHOPHYSIOLOGY OF ATN
The consequence of the
pathophysiologic process lead to:
1. Glomerullar vascular endothelial cell
damage.
2. Sloughing of glomerular tissues and
blocking of fliteration.
3. Tubular epithelial cell necrosis and
sloughing into the tubular pathways
4. Obstruction of the tubules with
cellular debris leading to obstruction
to urine flow.
5. Intense interstitial inflammation and
infiltration with inflammatory cells
PATHOPHYSIOLOGIC PHASES OF
• Intrinsic AKI (ischemic ATN):-
The course of ischemic ATN is typically
characterized by four phases: initiation,
extension, maintenance, and recovery.
• 1. Initiation phase (lasting hours to days),
GFR declines because
• (1) glomerular ultrafiltration pressure is
reduced as renal blood flow falls
• (2) the flow of filtrate within tubules is
obstructed by casts comprised of shed
epithelial cells and necrotic debris
• (3) there is backleak of glomerular filtrate
through injured tubular epithelium.
 PATHOPHYSIOLOGIC PHASES OF
INTRINSIC AKI (ISCHAEMIC ATN
• 2. Extension phase follows the initiation phase and is
characterized by continued ischemic injury and
inflammation. It has been proposed that endothelial
damage (resulting in vascular congestion) contributes to
both of these processes.
• 3. During the maintenance phase (typically 1– 2 weeks),
GFR stabilizes at its nadir (typically 5–10 mL/min), urine
output is lowest, and uremic complications may arise
• 4. The recovery phase is characterized by tubular
epithelial cell repair and regeneration as well as a gradual
return of GFR toward premorbid levels. The recovery
phase may be complicated by a marked diuretic phase due
to delayed recovery of epithelial cell function (solute and
water reabsorption) relative to glomerular filtration.
PATHOPHYSIOLOGY OF NEPHROTOXINS ASSOCIATED
AKI
1. Drugs causing AKI by Acute tubular necrosis:
Aminoglycosides and Amphotericin B, cisplatin,
carboplatin,
2. Causing AKI by Intratubular obstruction(ITO):
Vancomycin, Acyclovir,
3. Causing AKI by Direct tubular toxicity(DTT):
Foscamet, Pentamidine, Tenofovir, cidofovir
4. Causing AKI by both DTT and ITO: Ethylene
glycol, Herbal remedies, Melamine, warfarin
5. Causing AKI by Acute Interstitial Nephritis
(AIN): Penicillins, Cephalosporin, quinolones,
Sulphonamides, rifampin, Ipilimumab,
Tremelimumab, Nivolumab, Peribrulivumab
6. Causing AKI by Acute Tubulointerstial Nephritis
 PATHOPHYSIOLOGY- POST RENAL AKI
• During the early stages of obstruction (hours to
days), continued glomerular filtration leads to
increased intraluminal pressure upstream to the site
of obstruction.
• The pathophysiology of post renal 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.
• Secondary reductions in glomerular function are
due to underperfusion of glomeruli and, possibly,
changes in the glomerular ultrafiltration coefficient.
CLINICAL PRESENTATION
History
• Aetiology: • Exposure to
1. Fever nephrotoxins
2. Gastroenteritis • Medications
3. Blood loss • Herbal remedies
4. Urinary symptoms • Contrast agents
• Co-morbid conditions 1. Urine output
1. Hypertension • Uraemia
2. DM • Nausea
3. Kidney disease • Vomiting
4. Heart failure 1. Altered sleep
5. CLD pattern
CLINICAL PRESENTATION
Physical Examination
• Signs suggesting Signs of fluid retention
underlying cause: 1. Peri-orbital swelling
1. Fever 2. Pedal oedema
2. Dehydration 3. Ascites
3. Hypotension • Signs indicative of need
4. Ongoing blood loss for dialysis:
5. Evidence of trauma 1. Asterixis
• Signs of comorbid 2. Altered consciousness
conditions 3. Features of pulmonary
1. Elevated BP oedema
2. Raised JVP 4. Epigastric tenderness
3. Pallor 5. Pericardial friction rub
4. Jaundice
 INVESTIGATIONS
Urine: • Imaging:
1. Urinalysis 1. USS
2. Urine microscopy 2. CT
3. Spot urine for Pr/Cr Others:
ratio 1. FBC
4. Urine electrolytes 2. Cultures
and creatinine 3. Serology
• Blood chemistry: 4. ECG/Echo
1. E/U/Cr 5. LFTS
2. ABG 6. Serum
3. Ca, PO4, Albumin lactate
4. Uric Acid 7. Toxicology
 INVESTIGATIONS
Laboratory Parameter Typical Result
Urines: Less than 400ml(oliguria),less THAN
24-Hr volume 100 Mls (anuria) > 500ML(Non-oliguria)
Urinarysediments Present(ATN) scanty/absent(Pre-renal)
FR Na% >1(ATN) <1(Pre-renal)

Sodium(mmol/l) Normal or low

Potassium(mmol/l) Hyperkalemia (>5.5
Chloride(mmol/l) Normal or low
Bicarbonate(mmol/l) Low(<10 metabolic acidosis

Urea(mmol/l) High(>20) 2x baseline

Creatinine(umol/l) High(>200) 2x baseline
Uric acid High (>1.5 baseline)
Calcium Normal or low
Phosphorus Normal or high(>1.5 baseline)
INTERPRETATION OF
URINE FINDINGS
URINARY INDICES IN AKI
Urinary Indices Pre renal ATN
Specific gravity >1.020 <1.010

Urinar osm. >500 <300

(mosm/kg water)
Urinary Sodium <20 >40
(meq/L)
U/P Urea Nitrogen >8 <3

U/P Creatinine >40 <20

Fractional excretion <1 >1
of Na(FeNa %)
U/P Na/U cr) x100

Renal failure index(U <1 >1

 RADIOLOGIC EVALUATION IN AKI
• Normal-sized kidneys are expected in AKI.
• Enlarged kidneys in a patient with AKI
suggest the possibility of acute inter-stitial
nephritis or infiltrative diseases.
• Ultrasound or CT scan should be undertaken
to investigate obstruction in individuals with
AKI unless an alternate diagnosis is apparent.
• Findings of obstruction include dilation of the
collecting system and hydroureteronephrosis.
• Obstruction can be present without radiologic
abnormalities in the setting of volume
depletion, retroperitoneal fibrosis,
encasement with tumor, and also early in the
 RENAL BIOPSY
• Renal biopsy is reserved for patients
in whom prerenal and postrenal AKI
have been excluded and the cause of
intrinsic AKI is unclear.
• Renal biopsy is useful when clinical
assessment and laboratory
investigations suggest diagnoses other
than ischemic or nephrotoxic injury
that may respond to disease-specific
therapy. Examples include
glomerulonephritis, vasculitis, and
allergic interstitial nephritis.
NOVEL BIOMARKERS FOR AKI DIAGNOSIS
 MANAGEMENT OF AKI
• Requirements for effective management of AKI patient.

• Serious medical condition with potential for multi organ

dysfunction.
• Effective management requires multi disciplinary
team. (Nephrologists, Renal nurse, Dietician,
Intensivist/nurse, chemical pathologist etc)
• Pre-requisites for effective care include:
1. Dedicated knowledge driven competent staff.
2. Effective and efficient Laboratory service capable of
hourly results.
3. Intensive care unit capable of Cardio respiratory
support
4. ICU with in-situ dialysis system capable of CRRT.
PRINCIPLES OF MANAGEMENT
Principles of management therefore
entails:
1. Maintenance of the internal
metabolic milieu
2. Ensuring Fluid and electrolyte
balance( preventing fluid retention
and acid base disequilibrium)
3. Preventing malnutrition( calorie
balance)
4. Preventing/ treating inter current
infections.
5. Preventing and dealing with any other
complications that may arise.
AKI GENERAL ISSUES
1. Optimization of systemic and renal
hemodynamics through volume
resuscitation and judicious use of
vasopressors.

2. Elimination of nephrotoxic agents

(e.g., ACE inhibitors, ARBs, NSAIDs,
aminoglycosides) if possible.

3. Initiation of renal replacement

therapy when indicated.
MGT OF SPECIFIC ISSUES
1.Nephrotoxin-specific
a. Rhabdomyolysis: aggressive intravenous
fluids; consider forced alkaline diuresis
b. Tumor lysis syndrome: aggressive
intravenous fluids and allopurinol or
rasburicase.
2. Volume overload
c. Salt and water restriction
d. Diuretics
e. Ultrafiltration
MGT OF SPECIFIC ISSUES

3. Hyponatremia.
a. Restriction of enteral free water intake,
minimization of hypotonic intravenous
solutions including those containing dextrose.
b. Hypertonic saline is rarely necessary in
AKI. Vasopressin antagonists are generally
not needed.
4. Hyperkalemia
a. Restriction of dietary potassium intake
b. Discontinuation of potassium-sparing
diuretics, ACE inhibitors, ARBs, NSAIDs.
c. Loop diuretics to promote urinary
potassium loss
d. Potassium binding ion-exchange resin
(sodium polystyrene sulfonate).
e. Insulin (10 units regular) and glucose (50
mL of 50% dextrose) to promote entry of
potassium intracellularly.
f. Inhaled beta-agonist therapy to promote
entry of potassium intracellularly.
g. Calcium gluconate or calcium chloride (1 g)
MGT OF SPECIFIC ISSUES
5. Metabolic acidosis
a. Sodium bicarbonate (if pH <7.2 to keep
serum bicarbonate >15 mmol/L).
b. Administration of other bases, e.g., THAM.
c. Renal replacement therapy
6. Hyperphosphatemia
d. Restriction of dietary phosphate intake.
e. Phosphate binding agents (calcium acetate,
sevelamer hydrochloride, aluminum
hydroxide—taken with meals)
 MGT OF SPECIFIC ISSUES
7. Hypocalcemia
a. Calcium carbonate or calcium gluconate if
symptomatic
8. Hypermagnesemia
a. Discontinue Mg2+ containing antacids
9. Hyperuricemia
b. Acute treatment is usually not required except
in the setting of tumor lysis syndrome (see
above)
10. Nutrition
c. Sufficient protein and calorie intake (20–30
kcal/kg per day) to avoid negative nitrogen
balance.
d. Nutrition should be provided via the enteral
route if possible.
INDICATIONS FOR
DIALYSIS IN AKI
Clinical:
1. Persistent oligo-anuria.
2. Resistant gross oedema.
3. Uraemic encephalopathy.
4. Uraemic pericarditis/effusion.
5. Acute Pulmonary oedema.
Metabolic:
6. Severe hyperkalaemia(K+ >6.5
mmol/L).
7. Severe Metabolic Acidosis(Hco3
<10mmo/L
DIALYSIS OPTIONS IN
AKI
Intermittent haemodialysis:
1. Traditional intermittent HD
2. Hybrid therapies
➢SLED
➢EDD
• Peritoneal dialysis.
• Continuous renal replacement therapies:
1. HF
2. HDF
• No evidence that any one modality is
superior to the others
LONG TERM
COMPLICATIONS OF AKI
OUTCOMES OF AKI
• Full clinical metabolic and renal
recovery.
• Good clinical recovery, but
residual renal impairment.
• Dialysis dependent.
• Progression to ESRD.(aki as
risk factor to ESRD)
• Death in hospital.(20-80% in
most series)
DETERMINANTS OF GOOD
OUTCOME
1. Type of AKI(Pre-renal better than
ATN)
2. Early detection and early intervention.
3. Early referral to nephrology service.
4. Management in intensive care setting.
5. Good Laboratory support.
6. Knowledgeable and dedicated staff.
7. Early dialysis in those indicated.
PREVENTION OFAKI
Community level.
1. Community awareness
2. Campaigns against drug
abuse and use of native
herbs and potions.
3. Campaign against improper
drug marketing.
4. Education on early warning
symptoms and signs.
5. Early presentation to
hospital.
 PREVENTION OF AKI
Hospital/clinic level
1. High index of suspicion among workers in
acute care units.
2. Adequate hydration of patients and
correction of fluid electrolyte imbalance.
3. Meticulous attention by
surgeons/Obstetricians to prevent
urologic injuries.
4. Proper peri-operative care.
5. Early clinical detection.
6. Prompt medical intervention.
7. Early nephrologist involvement in the
care.
 CONCLUSION
• AKI is commonly encountered in clinical
settings. It is associated with high morbidity
and mortality.
• Both the aetiology and mechanisms of kidney
injury can be grouped anatomically into pre-
renal, intrinsic renal and post-renal.
• Diagnosis and staging is currently according
the KDIGO criteria.
• Treatment of AKI is primarily non-dialytic
with dialysis reserved for situations where
there are life-threatening complications.
• AKI is associated with long-term
consequences, including an increased risk of
 REFERENCES
1. Harrison Principles of Internal Medicine, 21st edition,
Volume 1&2, page 2296-2308, 2022.
2. Pedro Chimezie Emem-Chioma et al:Clinical outcomes of
dialysis-treated acute kidney injury patients at the
university of port harcourt teaching hospital,
Nigeria,ISRN Nephrol. 2012.
3. Bonventre JV, Yang L: Cellular pathophysiology of ischemic
acute kidney injury.J Clin Invest 121:4210, 2011.
4. Hoste EAJ et al: Global epidemiology and outcomes of
acute kidney injury. Nature Rev Nephrol 14:607, 2018.
5. Kidney Disease: Improving Global Outcomes (KDIGO)
Acute Kidney Injury Work Group: KDIGO Clinical Practice
Guidelines for Acute Kidney Injury. Kidney Int Supp 2:1,
2012.
Thank You For
Listening!