Epidemiology of Acute Kidney Injury (AKI) By Dr. Usama Ragab Lecturer of Internal Medicine I have discussed the epidemiology, etiology of acute kidney injury

1. AKI Epidemiology
Dr. Usama Ragab Youssif, MD
Lecturer of Medicine
Zagazig University

2. History
• William Heberden described ARF, then known as ischuria renalis, for the first time in 1802.
• ARF, then known as Acute Bright's disease, was described in William Osler's Textbook for
Medicine (1909) as occurring "as a result of toxic agents, pregnancy, burns, trauma, or kidney
operations.“
• During WWI, the syndrome was known as war nephritis and was reported in several publications.
• Crush syndrome was largely forgotten until the WWII, when Bywaters and Beall published their
seminal paper on the subject. Because of histological evidence of patchy necrosis of renal tubules
at autopsy, this clinical entity was labelled as acute tubular necrosis (ATN).
• Homer W. Smith who is credited for the introduction of the term acute renal failure, in a chapter
on Acute renal failure related to traumatic injuries in his 1951 textbook The kidney-structure and
Function in Health and Disease.

3. Definition
Acute kidney injury (AKI) is a clinical syndrome defined by either an abrupt increase in
serum creatinine concentration by ≥0.3 mg/dL within 48 hours, a ≥1.5-fold increase in
serum creatinine over the prior 7 days, or urine output <0.5 mL/kg/h for 6 hours.
Endorsed by KDIGO: only one criterion needs to be present to fulfill the definition.
It highlights the increased mortality resulting from even small increases in creatinine.

4. AKI not ARF
The term ‘acute kidney injury’ (AKI) replaces the term
‘acute renal failure’
Even seemingly minor changes in serum creatinine levels
are associated with a significant increase in mortality
AKI should be regarded as a spectrum of injury that may
progress to organ failure

5. Oliguria is usually, but
not invariably, a feature

6. Urine output?
50 kg i.e., 25mls/ hr. 120 kg i.e., 60mls/ hr.
0.5 ml/kg/hour looks different for different individuals

7. Why is it
important to
identify?
• AKI is associated with increased
risks of adverse outcomes such
as progression to chronic kidney
disease (CKD), end-stage renal
disease (ESRD), and mortality.
• Therefore, early diagnosis,
treatment, and proper follow-up
are essential.

8. ARF or AKI
J Am Soc Nephrol 18: 1987–1994, 2007

9. Risk Factors: Adults
Chronic kidney disease
(or history of)
Diabetes Heart failure Sepsis, Hypovolaemia
Age 65 years or over
Use of drugs with
nephrotoxic potential
(for example, NSAIDs,
ACE inhibitors)
Use of iodinated
contrast agents within
past week
Oliguria
Liver disease
Limited access to
fluids, e.g. via
neurological
impairment
Deteriorating early
warning scores
Symptoms or history
of urological
obstruction

10. Risk
factors:
children
and young
people
As for
adults,
with the
following
additional
risks:
Abnormal or deteriorating paediatric early
warning score
Young age, disability or cognitive impairment
with dependency on carers for access to fluids
Severe diarrhoea, especially bloody diarrhoea
Signs or symptoms of nephritis (for example,
oedema or haematuria)
Haematological malignancy
Hypotension

11. Assessing
Risk of AKI
Acute illness:
in adults
in children and young
people
Adults having
iodinated contrast
agents
Adults having surgery
In patients with no
obvious acute illness,
with risk factors

12. Epidemiology
KDIGO estimate a worldwide AKI prevalence
of 72,100 per million population, the majority
of which are community-acquired.
The burden of AKI may be highest in
developing countries.
Individuals with CKD are at increased risk of
AKI (and AKI is a risk factor for progression of
CKD)

13. Epidemiology
(cont.)
Incidence of dialysis-dependent AKI: 7200 per
million population annually.
5 – 10% of general hospital admissions.
20 – 25% of patients with sepsis and ≈ 50% with
septic shock.
50% of all ITU admissions (where it acts as an
independent risk factor for mortality of 20 –
60%, depending on AKI stage).

15. Causes

16. Before we
proceed
Azotemia= accumulation of nitrogenous waste
Uremia= symptomatic AKI e.g., mood changes,
loss of appetite, tremors
Anuria is non passage of urine, in practice is
defined as passage of less than 100 milliliters of
urine in a day.
Oliguria is defined as urinary output less than
400 ml per day

18. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion)
Prerenal AKI is characterized by a decrease in glomerular filtration
rate (GFR) in response to impaired renal perfusion with intact renal
parenchyma.
However, intact tubular function with high urine osmolality and low
urine sodium concentrations should not necessarily be interpreted as
prerenal AKI, as many intrinsic etiologies, such as glomerulonephritis
or AKI due to sepsis, may initially have intact tubular function.

19. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion)
Decreased effective circulatory volume
(Hypovolemia)
Reduced COP
1. Hemorrhage: Traumatic, surgical, postpartum,
gastrointestinal GI).
2. GI fluid loss: Vomiting, diarrhea, surgical
drainage.
3. Kidney loss: Diuretic therapy, osmotic diuresis
in diabetes, and adrenal insufficiency.
4. Vasodilatory loss of the extravascular
compartments: Sepsis syndromes, acute
pancreatitis, peritonitis, severe trauma, burns,
and severe hypoalbuminemia.
1. Diseases of the myocardium, valves, and
pericardium;
2. arrhythmias;
3. massive pulmonary embolism;
4. positive–pressure mechanical ventilation

20. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion)
Vascular abnormalities
Impaired renal autoregulation and
hypoperfusion
1. Vasodilation: Sepsis, hypotension caused by
antihypertensive medications (including drugs
that reduce afterload), and general anesthesia.
2. Vasoconstriction: Hypercalcemia,
norepinephrine, epinephrine, tacrolimus,
cyclosporine (INN cyclosporin), and amphotericin
B.
COX inhibitors (nonsteroidal anti-inflammatory
drugs [NSAIDs]), angiotensin-converting enzyme
inhibitors (ACEIs), angiotensin receptor blockers
(ARBs), and direct renin inhibitors.

21. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion)
Hyperviscosity syndrome Renal vessel occlusion
1. Multiple myeloma
2. Waldenström
macroglobulinemia
3. Polycythemia.
1. Renal artery occlusion:
Atherosclerosis,
thromboembolism, dissecting
aneurysm, and systemic
vasculitis.
2. Renal vein occlusion:
Thromboembolism and
external compression.

22. Pathogenesis of prerenal failure
The kidneys receive about 25%
of the cardiac output at rest.
If cardiac output is reduced or if
there is hypovolemia, regional
vasoconstriction occurs limiting
the blood flow to organs other
than the heart and brain.
Initially the blood flow is
diminished to the skin then GIT
and muscles.
Usually, the kidney can maintain
GFR close to normal despite
wide variations in renal
perfusion (autoregulation
through VC of efferent).
Further decrease of COP or
intravascular volume leads to
further depression of renal
perfusion with drop of
glomerular filtration due to
selective cortical
vasoconstriction → oliguria.

23. II- Intrinsic Renal Causes
Small vessel disease Acute tubular necrosis (ATN)
Thrombotic microangiopathy (TMA) (hemolytic–
uremic syndrome [HUS], thrombotic
thrombocytopenic purpura [TTP]), cholesterol crystal
embolization, disseminated intravascular coagulation
(DIC), preeclampsia or eclampsia, malignant
hypertension, systemic lupus erythematosus (SLE),
and progressive systemic sclerosis (scleroderma renal
crisis).
1. Ischemia: Prolonged prerenal AKI.
2. Exogenous toxins: Radiographic contrast
agents, cyclosporine, antibiotics (eg,
aminoglycosides), chemotherapy (cisplatin),
ethylene glycol, methanol, and NSAIDs.
3. Endogenous toxins: Myoglobin, hemoglobin,
monoclonal proteins (eg, in multiple
myeloma).
4. Crystals: Uric acid, oxalic acid (a metabolite of
ethylene glycol), acyclovir (INN aciclovir)
(particularly IV), methotrexate, sulfonamides,
and indinavir.

24. II- Intrinsic Renal Causes
Acute interstitial nephritis (AIN) Glomerulonephritis (GN)
1. Allergic: Beta–lactam antibiotics, sulfonamides,
trimethoprim, rifampin (INN rifampicin),
NSAIDs, diuretics, captopril, and proton pump
inhibitors.
2. Infectious: Bacterial (legionella, leptospirosis),
viral (cytomegalovirus, BK virus), and fungal
(candidiasis).
3. Infiltrative: Malignant (lymphoma, leukemia),
granulomatous (sarcoidosis), and idiopathic.
4. Autoimmune: Sjögren syndrome,
tubulointerstitial nephritis with uveitis (TINU)
syndrome, IgG4-related kidney disease (IgG4-
RKD), SLE.
1. Anti–glomerular basement membrane
(GBM) disease (sometimes referred to as
Goodpasture syndrome or disease).
2. Antineutrophil cytoplasmic antibody
(ANCA)-associated GN (granulomatosis with
polyangiitis [formerly Wegener
granulomatosis]), Churg-Strauss syndrome,
microscopic polyangiitis).
3. Immune complex–mediated GN (SLE,
postinfectious, cryoglobulinemia, and primary
membranoproliferative GN).

25. II- Intrinsic Renal Causes
Other causes
1. Acute graft rejection following renal transplantation.
2. Acute renal cortical necrosis
3. Chinese herb nephropathy
4. Acute phosphate nephropathy
5. Warfarin-related nephropathy
6. Loss of the solitary functioning kidney.

26. III- Post-renal causes
Intrinsic Extrinsic
1. Intra-luminal: e.g. stone, blood clot,
papillarynecrosis
2. Intra-mural: e.g. urethral stricture,
prostatic hypertrophy or malignancy,
bladder tumour, radiation fibrosis
1. Pelvic malignancy
2. Retroperitoneal fibrosis

27. Prerenal acute kidney injury and
acute tubular necrosis account for
approximately 65% to 75% of acute
kidney injury cases in hospitalized
patients.

28. Another classification
A. Pharmacological
B. Non-Pharmacological

29. Pharmacological causes
Pre-renal
Volume depletion SGLT2 inhibitors, diuretics
Intrarenal/afferent arteriolar
vasoconstriction
NSAIDs (including COX-2 inhibitors); amphotericin
B; calcineurin inhibitors; iodinated radiocontrast
agents
Efferent arteriolar vasodilation Renin inhibitors; ACE inhibitors; ARBs

30. Pharmacological causes (cont.)
Intrinsic
Acute tubular necrosis Aminoglycosides; vancomycin, particularly in combination with piperacillin-tazobactam; polymyxins; lithium;
amphotericin B; pentamidine; cisplatin; foscarnet; tenofovir; cidofovir; carboplatin; ifosfamide; zoledronate;
contrast agents. sucrose; immune globulins; mannitol; hydroxyethyl starch; dextran; synthetic cannabinoids;
amphetamines
Acute interstitial nephritis Etiologies of acute interstitial nephritis are like those for chronic tubulointerstitial nephritis. Acute interstitial
nephritis may lead to chronic tubulointerstitial nephritis with protracted exposure
Acute glomerulonephritis ANCA-associated drugs, such as minocycline and levamisole (veterinary antihelminthic used in some cocaine
preparations)
Acute vascular syndromes Drug-induced TMA: quinine; cancer therapies (gemcitabine, mitomycin, bortezomib, sunitinib); calcineurin
inhibitors (cyclosporine, tacrolimus); drugs of abuse (cocaine, ecstasy, intravenous extended-release
oxymorphone); clopidogrel; anti-angiogenesis drugs; interferon; mTOR inhibitors
Intratubular obstruction Crystals: sulfonamides; triamterene; ciprofloxacin; ethylene glycol; acyclovir; indinavir; atazanavir; methotrexate;
orlistat; large doses of vitamin C; sodium phosphate purgatives

31. Natural history
The clinical presentation of AKI varies depending on the cause, severity, and
associated diseases related to renal injury.
Most patients with mild to moderate AKI are asymptomatic and identified by
laboratory testing.
Patients with severe AKI may have symptoms of uremia including fatigue, loss of
appetite, weight loss, pruritus, nausea, vomiting, muscle cramps, and changes in
mental status.

32. Natural history (cont.)
Oliguria or anuria occurs in ~50% of patients and is frequently
seen with prerenal AKI, acute renal cortical necrosis,
thromboembolism, and thrombotic microangiopathy.
Normal or even increased urine output can be seen in
intrinsic etiologies of AKI.

33. There are 4 phases that can be distinguished in the
natural history of AKI
1. Initiation phase: This phase presents with normal urine output as
it commences from the initial impact of the insult (cause) until the
point of actual kidney damage. The duration of this phase is usually
several hours and varies depending on the causative factor.
2. Oliguria (urine output 100-400 mL/d) or anuria (urine output
<100 mL/d): This phase occurs when urine output is typically
between 50 and 400 mL/d. It develops in ~50% of patients and
lasts an average of 10 to 14 days but can vary from 1 day to 8
weeks.

34. There are 4 phases that can be distinguished in the
natural history of AKI (cont.)
3. Polyuria: This phase begins with rapidly increasing urine output over several
days after a period of oliguria or anuria. It occurs due to tubular dysfunction
and is manifested by sodium wasting and polyuria. Serum creatinine and urea
levels may not decrease for several days. The duration of polyuria is
proportional to the duration of oliguria/anuria and may last up to several
weeks. This phase of AKI is associated with considerable risk of dehydration and
severe loss of electrolytes, particularly potassium and calcium.
4. Recovery phase: During this phase urine output gradually returns to normal
and serum creatinine and urea begin to normalize. It may take up to several
months for complete recovery or for a new baseline function to be established.

35. Presentation
• Malaise
• Anorexia, Nausea and Vomiting
• Pruritis
• Dehydration
• Confusion, convulsions
Symptoms
• Hypertension
• Fluid overload: peripheral oedema, SOB/ bibasal crackles/raised JVP
• Dehydration: postural hypotension, poor urine output (palpable bladder)
Signs

36. Classification
Systems

37. The RIFLE criteria for AKI (2002)
• The distinction between acute and chronic renal failure, or even acute-on-chronic
renal failure, cannot be readily apparent in a patient presenting with uraemia.
• In view of these difficulties, the Acute Dialysis Quality Initiative group proposed
the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria utilizing
either increases in serum creatinine or decreases in urine output.
• It characterizes three levels of renal dysfunction (R, I, F) and two outcome
measures (L, E).
• These criteria indicate an increasing degree of renal damage and have a predictive
value for mortality.

38. Acute Kidney Injury Network (AKIN) classification
(2004)
• More recently, AKIN (an international network of AKI experts) modified
RIFLE to incorporate small changes in SCr occurring within a 48h period
and to remove changes in GFR as diagnostic criteria.

40. KDIGO AKI definition (2012)
• AKI, classified by either of the earlier listed criteria, may identify slightly
different patients: RIFLE may not detect ≈10% of AKIN-identified cases, and
AKIN may miss ≈25% RIFLE cases.
• KDIGO have recently produced a definition that incorporates the key
elements of both, and it is likely that this definition will become the
accepted standard.

41. KDIGO Classification
KDIGO stage Serum creatinine criteria Urine output criteria
1
1.5 – 1.9 times baseline
OR ≥0.3mg/dL (>26.4μmol/L) in ≤48h
<0.5mL/kg/h for
6 – 12h
2
2 – 2.9 times baseline <0.5mL/kg/h for ≥12h
3
≥3 times baseline
OR increase in SCr to ≥4.0mg/dL (354μmol/L)
OR initiation of RRT
<0.3mL/kg/h for ≥24h OR
anuria for ≥12h

42. AKI → AKD
Strict adherence to definitions of both acute (AKI) and chronic (CKD)
renal disease may miss individuals with functional or structural
abnormalities present for <3 months but who may benefit from active
intervention to restore kidney function (thus avoiding permanent
damage and adverse outcomes).
For this reason, KDIGO have proposed the term AKD to include not only
those with AKI, but also those with GFR <60mL/min/1.73 m2 for <3
months or a decrease in GFR by ≥35% or an increase in SCr by >50% for
<3 months.

43. Risk Assessment (KDIGO Guided)
• 2.2.1: We recommend that patients be stratified for risk of AKI according to their
susceptibilities and exposures. (1B)
• 2.2.2: Manage patients according to their susceptibilities and exposures to reduce
the risk of AKI (see relevant guideline sections). (Not Graded)
• 2.2.3: Test patients at increased risk for AKI with measurements of SCr and urine
output to detect AKI. (Not Graded) Individualize frequency and duration of
monitoring based on patient risk and clinical course. (Not Graded)

44. Evaluation
2.3.1: Evaluate patients with AKI promptly to determine the cause, with special
attention to reversible causes. (Not Graded)
2.3.2: Monitor patients with AKI with measurements of SCr and urine output to
stage the severity, according to Recommendation 2.1.2. (Not Graded)

45. Evaluation
2.3.3: Manage patients with AKI according to the stage (see Figure 4) and
cause. (Not Graded)
2.3.4: Evaluate patients 3 months after AKI for resolution, new onset, or
worsening of pre-existing CKD (Not Graded)
• If patients have CKD, manage these patients as detailed in the KDOQI CKD
Guideline (Guidelines 7–15). (Not Graded)
• If patients do not have CKD, consider them to be at increased risk for CKD
and care for them as detailed in the KDOQI CKD Guideline 3 for patients at
increased risk for CKD. (Not Graded)

46. AKI Stage Centered Approach
Avoid subclavian catheters if possible
High Risk
Discontinue all nephrotoxic agents when possible
Consider invasive diagnostic workup
Consider Renal Replacement Therapy
1 2 3
Non-invasive diagnostic workup
Ensure volume status and perfusion pressure
Check for changes in drug dosing
Consider functional hemodynamic monitoring
Monitor Serum creatinine and urine output
Consider ICU admission
Avoid hyperglycemia
Consider alternatives to radiocontrast procedures

47. Referral to
nephrologist
Complications associated with AKI
Stage 3 AKI
eGFR is less than < 30 ml/min/1.73 m2 after
AKI episode
Patients with renal transplant and AKI
CKD stage 4 or 5

48. Consider
RRT if
Hyperkalaemia
Metabolic acidosis
Symptoms or complications of uraemia
such as pericarditis or encephalopathy
Fluid overload +/- pulmonary oedema

49. Prognosis
• The overall mortality in patients with AKI is high, and AKI is
considered an independent risk factor for mortality.
• Mortality rates are population-dependent, ranging between 10%
and 80%.
• Patients with uncomplicated AKI have mortality rates of ~10%.
• Patients presenting with AKI and multiorgan failure have
mortality rates >50%.

50. Prognosis
• In patients requiring RRT mortality rises to >80%.
• Death is usually a result of the severity of the underlying
disease-causing AKI rather than the renal injury itself.
• It has been shown that from 20% to 50% of patients with AKI
progress to CKD and 3% to 15% develop ESRD, even those
who initially recover sufficient kidney function to discontinue
dialysis.

51. Mortality
Prompt improvement (<24h) in renal, cardiovascular, or
respiratory function is associated with a better chance
of survival.
Despite improvements in many aspects of clinical care
(particularly nutrition and renal replacement therapy),
overall mortality in AKI requiring RRT remains >50%
(reflecting a high incidence in the elderly and those
with multi-organ failure).
The underlying cause will play a role, e.g. lower for
nephrotoxin-driven AKI (<30%) vs higher for sepsis- and
trauma-related AKI (≈60%).

52. Thanks