ACUTE KIDNEY INJURY

DR. GRACE KANSIIME

29TH JULY 2021
Outline

• Patient presentation • Clinical features /classification

• Investigations
• Definition
• Complications
• Epidemiology
• Management /Prevention
• Pathophysiology
• NG , 29 yr old male from Kabale who presented with abdominal
pain X 3/7 admitted on 15/02/2017
• The pain was more marked in the epigastric region,constant,
relieved by non-specified drugs bought from a clinic.
• Pain was assoc with haematemesis and melena stools
• He reported yellow eye discoloration but no body itching.
• Use of herbal medicines for PUD,duration- unspecified
• HBSag,HC,HIV- Negative
• Normal micturition habits and no body swelling .
HPC

• No h/o body swelling

• He reported history of low grade intermittent fever but no

convulsion

• There was hlo LOC for unspecified period of time with gradual
gain in the LOC.
• ROS- Unremarkable
History of Presenting complaints

• He was admitted on ward, and managed for Malaria, UGI

bleeding and DILI for 5/7-Received Iv fluids, blood, Artesunate,
Tramadol, Metronidazole and Ciprofloxacin. Scheduled for
Endoscopy but was not done .
• He was then transferred to ICU because of deteriorating LOC for
Organ support. He received Meropenem, Fetanyl and Rx for
Hyper K+.
Family/Social history

• Only child from his parents.

• All parents died; father (TB),mother (unknown)
• No family h/o DM, HTN, Ca
• Separated with wife, has two chn, all at school.
• Drink alcohol (cage 0/4)
I.C.E
• He thinks he was poisoned, he wants to be relieved of pain and
get better.
Systemic Examinations

• Febrile (Ax.T 38.2 C),severe pallor, deep jaundice, dehydrated,

white nail, urinary catheter insitu. No- oedema, palpable L/N
• P/A; -Normal fullness,soft,mild to moderate generalized
tenderness,
No palpable organ, no shifting dullness, no ascites.
• R/S;-R/R 22bpm,SPO2 98%(RA),Resonant percussion note ,bil.
vesicular B/S,no added B/S.
• CVS; -P/R 128bpm,full vol,regular.BP 100/70 mmHg,H/S 1,2
heard &N.
• CNS; -Fully conscious,but lethargic, oriented(TPP),Normal
speech, No craniopathy,motor (flapping tr)and sensory
modalities intact.
Differential diagnosis
• Upper GI bleeding
-rupture PUD
-bleeding esophageal varices
• Acute hepatitis-?herbal medicine induced
• AKI-drug induced.
• Sepsis
Investigations
CBC Results
WBC 5.65x10^3
Neut 3.87x10^3
Lymp 0.81x10^3
Rbc 1.59x10^6
Hb 4.4g/dl
PLT 495x10^9/µl
MCV 83.6 fL
• BS- MPS +
• INR 4.49
Investigations cont
Biochemistry Test results
Albumin 28.7g/l
Alp 767 U/L
Alt/GPT 44.8 U/L
AST/GOT 88.9 U/L
TOT BIL 673.0 µmol/l
D.BIL 414 µmol/l

SCr 652 µmol/l

Urea 76 mmol/l
Uric acid 1000.2 µmol/l
Poatssium 6.1 mmol/l
Sodium 144.5mmol/l
Chloride 76.2 mmol/l
Diagnosis
• AKI
• Drug induced hepatitis
• Upper GI bleeding
-bleeding PUD
-bleeding esophageal varices
• Malaria.
Management
• IV fluids
• BT
• IV artesunate
• IV abx-meropenem,metronidazole,
• Omeprazole,syrup lactulose
• Heamodialysis (5 sessions)
• Discharged after 2 weeks on Renal ward
Acute Kidney injury– Definitions
• AKI = a sudden reduction of GFR expressed clinically as an abrupt and
sustained rise in BUN and creatinine occurring within 3 months (usu-days-
wks)

• Azotemia - the accumulation of nitrogenous wastes accompanied with

elevation in BUN and creatinine.

• Uremia – clinical manifestation (symptomatic renal failure)

• Oliguria – UOP < 400-500 mL/24 hours

• Anuria – UOP < 100 mL/24 hours
KDIGO Definition of AKI ( 2012 )
Defined by any of the following:

• Increase in SCr by ≥0.3 mg/dL within 48 hours

• Increase in Scr by ≥1.5 times baseline, which is known

or presumed to have occurred within the prior seven
days

• Urine volume <0.5 mL/kg/h for six hours

• Renal failure results in reduced excretion of nitrogenous waste
products of which urea is the most commonly measured.
• A raised serum urea concentration (uraemia) is classified as: (i)
prerenal, (ii) renal or (iii) postrenal.
• More than one category may be present in an individual patient.
• Other causes of altered serum urea and creatinine concentration are
shown in the table below
 Causes of altered serum urea and creatinine
concentration other than altered renal function
  Decreased concentration Increased concentration
Urea Low protein intake Corticosteroid treatment

  Liver failure Tetracycline treatment

  Sodium valproate treatment Gastrointestinal bleeding

Creatinine Low muscle mass High muscle mass

    Red meat ingestion

    Muscle damage (rhabdomyolysis)

    Decreased tubular secretion (e.g. cimetidine,

trimethoprim therapy)
 Epidemiology
• ≈ 5-10% in hospitalized pts
• ≈ 70% in critically ill pts
• 5-6% ICU pts require RRT
• Once AKI occurred, the treatment is
supportive, at an annual cost $10 billion in
the US.
Epidemiology
• AKI superimposed on CRF- 50%.

• Uncomplicated AKI-mortality rates less than 5-10%.

• AKI complicating non-renal organ system failure- mortality rates

of 50-70%.

• Sepsis-related AKI has a significantly worse prognosis

 Etiology of AKI

80
ATN is the cause
70 in more than 90%.
Sepsis is the leading
60
cause of ATN
50

40 O u tp a tie n t
In p a tie n t
30

20

10

0
P reren al In tr a r e n a l O b s tr u c t Id io p a th
Classification of AKI

Prerenal
Intrinsic/renal
 Interstitial nephritis (10% of cases)
 Tubular necrosis
• Ischemia (50% of cases)
• Toxins (35% of cases)
 Acute glomerulonephritis (5% of cases)
Postrenal
Recognised risk factors for AKI
• Age >75 years
•Hypotension (MAP <65 mmHg,
• Pre-existing CKD (eGFR
systolic pressure <90 mmHg)
<60 mL/kg/1.73 m2)
• Previous episode of AKI •Hypovolaemia
• Debility and dementia •Nephrotoxins, eg gentamicin,
• Heart failure NSAIDs, iodinated contrast
• Liver disease •Antihypertensives in setting of
• Diabetes mellitus hypotension, e.g ACEIs,
• Sepsis diuretics
DRUGS ASSOCIATED WITH AKI
Stages of AKI
• RIFLE-2004
• AKIN-2007
• KDIGO-2012
RIARF: RIFLE
classificationFLE
classification for AKI

26
Definition of AKI based on AKIN
“Acute Kidney Injury Network” ( 2007 )

Stage Increase in Serum Urine Output

Creatinine
1 1.5-2 times baseline <0.5 ml/kg/h for >6 h
OR
0.3 mg/dl increase from
baseline
2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline OR <0.3 ml/kg/h for >24 h

0.5 mg/dl increase if OR
baseline>4mg/dl Anuria for >12 h
OR
Any RRT given
KDIGO Classification of AKI ( 2012 )

Stage Serum creatinine Urine output

1 1.5-1.9× baseline <0.5 ml/kg/hr for 6-12 hrs

OR
>0.3 mg/dL
<0.5 ml/kg/hr > 12 hrs
2 2-2.9× baseline

3 3 times baseline <0.3 ml/kg/hr > 24 hrs

OR OR
increase in Cr to ≥4.0 mg/dL Anuria > 12 hrs
OR
Initiation of RRT

KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012

Category SCr/ GFR Urine output
RIFLE ↑ 1.5,2,3 / ↓ > 25%,50%,75% < 0.5ml/kg/hr for 6 hrs
< 0.5ml/kg/hr for 12 hrs
Loss- AKI > 4 weeks < 0.3ml/kg/hr for 24 hrs OR
ESRD > 3 mo ANURIA for 12 hours

AKIN ↑ 1.5-2 OR 0.3mg/dl ↑ BL Same as above

↑ 2-3 from BL
↑3 from BL OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given

KDIGO ↑1.5-1.9 X BL OR > 0.3mg/dl ↑ Same as above

↑2-2.9 X BL
↑ 3X BL OR increase in Cr to ≥4.0
mg/dL
OR
Initiation of RRT
Pathophysiology
• Decreased renal blood flow stimulates salt and water retention
to restore vol. and pressure.
• When Volume or Pressure is decreased, the baroreceptors
receptors reflexes located in Aortic arch and Carotid sinus are
activated→symphat nn activation →renal afferent arteriolar
vasoconstriction & renin secretion thru ℬ1receptor.
Pathophysiology cont
• Constriction of the afferent arterioles causes a decrease in
intraglomerular pressure which ↧GFR.
• Renin converts Angiotensin 1 to 11,which stimulates Aldosterone
release→salt and water absorption in the distal collecting tubules.
• A decrease in vol. or pressure is a non osmotic stimulus for Hypothalamic
prodn of ADH →H2O reabsorption
Pathophysiology cont
Pathophysiology cont
• Thru unknown mechanism, activation of SNS→enhanced prox.
tubular reabsorption of salt & water as well as BUN,Cr,Uric acid,
HCO3

• The net effect of these mechanism is decreased output and

decreased urinary excretion of Sodium.
Initial investigation of AKI
• Urea and electrolytes, and creatinine
• Bicarbonate
• Full blood count – if platelets low, request
blood film/
lactate dehydrogenase (to diagnose
haemolytic uraemic syndrome/ thrombotic
thrombocytopenic purpura)
• Liver function tests (to diagnose hepatorenal
syndrome)
Initial investigation of AKI
• Ca2+/PO4 3– (to d i
agn ose m y e l
om a)
• Creatine kinase (to diagnose myeloma)
• Blood cultures (if sepsis suspected)
• Urinalysis – if blood, protein, leucocytes or nitrites, send
midstream urine
• Ultrasound scan of renal tract and bladder
 Acute tubular necrosis
• ATN is the most common cause of acute renal failure AKI
• Results from nephrotoxic or ischemic injury that damages
the kidney tubular epithelium.
• Damage to the kidney cells prevents normal functioning.

• Ischemic acute tubular necrosis:

-Occurs as a result of vasodilation associated with sepsis and when
hypotension is prolonged.

• Toxic acute tubular necrosis:

-Results from injury by drugs (gentamicin, amikacin, vancomycin) and
chemicals (radiopaque dye administered in radiologic diagnostic
studies).

37
Pathogenesis of ATN

Adapted from Google images

Some causes of acute tubular necrosis
• Haemorrhage • Haemoglobinaemia (due to
• Burns haemolysis, e.g. in falciparum
• Diarrhoea and vomiting, fluid loss from malaria, 'blackwater fever')
fistulae
• Hepato-renal syndrome
• Pancreatitis
• Diuretics • Radiological contrast agents
• Myocardial infarction
Drugs, e.g. aminoglycosides,
NSAIDs, ACE inhibitors, platinum
• Congestive cardiac failure
derivatives
• Endotoxic shock
• Snake bite
• Abruptio placentae
• Myoglobinaemia • Pre-eclampsia and eclampsia
Phases of ATN

Initiation

Oliguric or anuric phase

Diuretic phase

Recovery phase
 Phases of ATN
Initiation phase:
-Period from the initial insult until cell injury occurs.

-Characterized by acute decrease in GFR (90 - 120 mL/

min/1.73 m2) to very low levels, with a sudden increase in SCr
and BUN concentrations.

-Lasts hours to days depending on the cause. Prompt

treatment can alleviate irreversible damage.

41
Oliguric or anuric phase
• This phase lasts 5-8 days in the non-oliguric patient and 10-16
days in the oliguric (< 500 CC of urine/24 hours) one.

• The GFR is greatly reduced resulting in high BUN, elevated SCr

creatinine, hyper k+, and metabolic acidosis (rapid breathing,
confusion, shock or death in severe cases).
Phases of ATN (Continued….)
 Diuretic phase: This phase lasts 7-14 days and is characterised
by an increase in GFR and sometimes by polyuria (urine output
2-4 L/day).

Recovery phase:
-Kidney tubular cells that have survived prior injury contribute to
the healing process through proliferation and migration to the
damaged areas.
-Oliguric or nonoliguric patients may have increased urine output,
and kidney function slowly returns to normal or near normal.

43
 Assessment and Diagnosis
• Acidosis: pH of <7.35 indicates severe acute kidney insult.
• BUN: Increased (normal range 5-25 mg/dL).
• Creatinine: Increased (normal range 0.5-1.5).
• Creatinine clearance: Decreased (normal range 110-120 mL/
min); values <50 mL/min indicates significant kidney
dysfunction.
• BUN: Creatinine ratio. 20:1 (Ischemia); 10:1 (Toxic).

44
 Disease states that increase the risk of ATN

Underlying chronic kidney disease.

Older age, diabetes, and hypertension.

Heart failure.

Respiratory failure.

Sepsis.

Trauma.

Contrast-induced nephrotoxic injury.

45
 Hemodynamic Monitoring and Fluid Balance
(Continued…)
• Daily weight, accurate intake and output monitoring. These
are powerful indicators of fluid gains or losses over 24 hours

• Physical assessment: Signs that suggest extracellular fluid

depletion include thirst and decreased skin turgor.

• Signs that imply intravascular fluid volume overload include

pulmonary congestion, increasing heart failure, and high BP.

46
How do we assess a pt with AKI?
• Is this acute or chronic renal failure?
• Establish baseline Cr and assess Cr trend
• History and examination
• Small kidneys on ultrasound (except for in -
Diabetes, PCKD, Urinary Tract Obstruction)

Hilton et al, BMJ 2006;333;786-790

 AKI: Focused History
• Prenal hx: N/V/D? Oral intake? Diuretics? Hx of heart dz,
liver dz, previous renal dz?
• Post-renal sxs: hesitancy, frequency, urgency, weak stream,
dribbling, feeling of incomplete bladder emptying, flank pain. h/o
kidney stones or BPH? Spinal cord injury? Anticholingergic meds?
• Any recent illnesses? Fever? Rashes?
• Any recent surgery?
• Cardiovascular instability?
• Toxin exposure: new medications (Abx, NSAIDs)? IV contrast?
• Change in urination, any edema/SOB/Wt. gain?
• Look for temporal link of exposure or risk factor to
elevation of Cr or decline in UOP
How to assess volume?
History (intake, fluid loss, meds)
Postural blood pressure and pulse
Daily weights
In’s/Out’s, fluid balance/fluid challenge

Signs of volume depletion:

-Dry mouth, Increased thirst, Lightheadedness, Muscle cramps,
extremities are cool to the touch, palpitations, reduced and dark
urine, syncope
-PE: Listlessness/AMS/LOC, tachycardic, weak rapid pulse,
hypotensive (orthostatic vitals), tachypnic, increased Temp, poor
capillary refill, decreased skin turgor, flattened neck veins, little or
no urination for several hrs
Features of AKI
• Hypertension
• Oedema with weight gain
• Hyperkalemia
• Nausea/Vomiting
• Pulmonary edema
• Ascites
• Asterixis
• Encephalopathy
• Rising creatinine and urea
• Rising potassium
• Decreasing Hb
• Acidosis
• Hyponatraemia
• Hypocalcaemia
 Criteria for distinction between pre-renal
and intrinsic causes of renal dysfunction
  Prerenal Intrinsic
Urine specific gravity > 1.020 < 1.010

Urine osmolality (mOsm/kg) > 500 < 350

Urine sodium (mmol/L) < 20 > 40

< 1% > 1%
FeNa = UNa ÷ Ucr
PNa Pcr

FE, fractional excretion; P, plasma; U, urine; Cr, creatinine;

Na, sodium
Further work-up
U/A, Urine protein/Cr, Urine Eosinophilla
FeNa, FeUrea
CPK, uric acid
Urine microscopy:
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN

Post-void residual (>100-150 ml c/w voiding dysfunction)

bladder catheterization
renal ultrasound
 Management of AKI: general
principles
• No therapy to date have shown efficacy in
treating AKI.
• Identify the etiology and treat the
underlying cause
• Optimization of hemodynamics to increase
renal perfusion
• Lack of benefit – low dose dopamine, loop
diuretics only if markedly fluid overload
• Identify and aggressively treat infection
(early removal of foley catheters, and
minimize indwelling lines)
Management of AKI:
treat complications
• Correct fluid imbalances: strict I/O’s, daily wts.
determine fluid balance goals daily, fluid
selection or diuresis, readjust for UOP
recovery, post diuresis or dialysis
• Electrolyte imbalances (low K/phos diet,
binder)
• Metabolic acidosis (Bicarb deficit, mode and
rate of replacement)
Management of AKI:
treat complications
• Nutrition: adjust TPN/protein intake
• Drug dosing: adjustment for eGFR to avoid under or over dosing,
timing for dialysis, reassess dosing for renal recovery or dialysis
modality)
• Procedural considerations (prefer non-contrast CT, appropriate
to delay contrast exposure, prophylaxis)
 Nephrotoxic Drug Exposure
• Minimizing nephrotoxin
• Avoid Aminoglycosides, Amphotericin,
Bactrim, Vancomycin, NSAIDs, IV contrast,
Fleet’s enemas

• Renal dose medications – especially

antibiotics and monitor level

• Cautious use (metformin, long acting oral

hypoglycemic agents, insulin, gemfibrozil and
statins, neurotin, colchicine/allopurinol,
morphine/codeine, lmwh)
Complications of AKI
• Hyperkalemia
• Acidemia
• Pulmonary edema
• Uremia –
encephalopathy,
pericarditis
Complications of AKI- remember
 Ancient Chinese Medical Text
The inferior doctor treats actual illness.
The mediocre doctor attends to impending illness.
The superior doctor prevents illness.

2600 BC - Huang Dee Nai-Chang

Best cure is to prevent !
Be aware of pts who are at risk for AKI
Volume depletion or Hypotension
Sepsis
Pre-existing renal, hepatic, or cardiac dz
Diabetes mellitus
Elderly
Exposure to nephrotoxins
Aminoglycosides, amphotericin, immunosuppressive
agents, chemo., NSAIDs,, RAAS blockers, intravenous
contrast media
Post cardiac or vascular Surgery pts or ICU pts with
multiorgan failure
 Take Home Messages: AKI
• AKI is increasingly common.
• It involves high cost of management, has high
morbidity and mortality risks.
• The most common cause of in-hospital AKI is
ATN that results from multiple acute insults
(sepsis, ischemia, or nephrotoxins).
• No drug treatment has been shown to limit the
progression of, or speed up recovery from AKI.
• Review medications and adjust doses
• Recognize risk factors
• The Best Treatment is PREVENTION and avoid
further renal damage!!!
THANK YOU!
References
• Kumar and Clark text book of medicine
• KDIGO guidelines 2012
• Articles
Educational resources
• An app developed by the Royal College of
Physicians of Edinburgh that is free to download
www.rcpe.ac.uk/policy-standards/acute-kidney-injury-app
• An AKI core competency framework for
healthcare professionals, endorsed by the
Academy of Medical Royal Colleges
www.aomrc.org.uk/doc_details/9503-acute-kidney-injury-
a-competency-framework
• The RRAPID app and e-book, which contain an
AKI risk calculator and a NEWS calculator
http://rrapid.leeds.ac.uk