This document provides an overview of acute kidney injury (AKI). It discusses the definition, epidemiology, etiology, pathophysiology, diagnosis and treatment of AKI. Some key points: - AKI accounts for 5-7% of acute care hospital admissions and 30% of ICU admissions, with mortality rates as high as 50%. It can worsen chronic kidney disease and increase the risk of end-stage renal disease. - Causes include pre-renal issues like hypovolemia, renal issues like acute tubular necrosis, and post-renal issues like obstruction. Diagnosis involves history, physical exam, lab tests of kidney function and imaging. - Treatment focuses on optimizing

1. ACUTE KIDNEY INJURY
 ‘
BY
DR SUMAN ROY
MD PGT
MMCH

2. ACUTE KIDNEY INJURY
 CLAUDE BERNERD (1878)
Milieu exterieur
Milieu interieur
 WALTER B. CANON
Recognises that the constancy of internal state
( homeostatic state) ...To maintain minimum
variability
THE KIDNEY

3. •5-7% of acute care hospital admissions
•30% of ICU admissions with mortality rates –
50%
•AKI worsens CKD
•Severe AKI requiring dialysis increases risk of
developing dialysis-requiring-ESRD.
•Community-acquired AKI: Volume depletion,
ADRs & obstruction of the urinary tract.
•Hospital-acquired AKI: Sepsis, major surgical
procedures, heart or liver failure, IV iodinated
contrast and nephrotoxic drugs
Epidemiology

4. •Diarrhoeal diseases
•Envenomations from snakes, spiders,
caterpillars, and bees
•Malaria
•Leptospirosis
•Crush injuries from earthquakes and
resultant rhabdomyolysis
AKI in Tropics

5. Definition of AKI

6. KDIGO criteria (ungraded)
 Increase in SCr by ≥0.3 mg/dl (≥26.5 umol/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.

7. KDIGO- Staging of AKI

8. R isk
I njury
F ailure
L oss of function
E nd-Stage Renal
disease
RIFLE Criteria

9. In 2002, the Acute Dialysis Quality Initiative (ADQI) was
created with the primary goal of developing consensus and
evidence-based guidelines for the treatment and
prevention of acute kidney injury (AKI). The first order of
business was to create a uniform, accepted definition of
AKI; hence, the RIFLE criteria were born. RIFLE is an
acronym of Risk, Injury, and Failure; and Loss; and End-
stage kidney disease
RIFLE Criteria

11. Risk
Increase in Cr of 1.5-2.0 X baseline or
urine output < 0.5 mL/kg/hr for more
than 6 hours

12. I njury
increase in Cr 2-3 X baseline (loss
of 50% of GFR) or
urine output < 0.5 mL/kg/hr for
more than 12 hours

13. Failure
increase in Cr rises > 3X baseline
Cr (loss of 75% of GFR) or
an increase in serum creatinine
greater than 4 mg/dL, or
urine output < 0.3 mL/kg/hr for
more than 24 hours or anuria for
more than 12 hours.

14. Loss of function
persistent renal failure (i.e. need
for dialysis) for more than 4
weeks.
End-Stage Renal disease
persistent renal failure (i.e. need
for dialysis) for more than 3
months

15. Etiologic Classification of AKI
Acute kidney injury
Pre-renal Intrinsic Post-renal
Glomerular Interstitial VascularTubular

18. Pre-renal AKI

20. Etiology and Pathophysiology
I. Hypovolemia
• Hemorrhage, burns, dehydration
• Gastrointestinal fluid loss: vomiting,
surgical
drainage, diarrhea

21. Renal fluid loss: diuretics, osmotic diuresis
(e.g., diabetes mellitus), hypoadrenalism
Sequestration in extravascular space:
pancreatitis, peritonitis, trauma, burns,
Severe hypoalbuminemia

22. II. Low cardiac output
• Diseases of - myocardium, valves, and
pericardium; arrhythmias; tamponade
• Other: pulmonary hypertension,
massive pulmonary embolus

23. III. Altered renal systemic vascular resistance
ratio
• Systemic vasodilatation: sepsis, anaphylaxis
IV.
Renal hypoperfusion with impairment of renal
autoregulatory responses

24. Pathophysiology:
 Hypovolemia leads to glomerular hypoperfusion,
but filtration rate are preserved during mild
hypoperfusion through several compensatory
mechanisms.
 During states of more severe hypoperfusion,
these compensatory responses are
overwhelmed and GFR falls, leading to prerenal
AKI.

25. IV. NSAIDS- they reduce affarent renal
vasodilation
V. ACEIs and ARBs- limit renal efferent vasoconstriction

26. • Prerenal AKI can complicate any disease that
induces :
 hypovolemia,
low cardiac output,
systemic vasodilatation, or
 selective renal vasoconstriction.

27. B. Intrinsic Renal AKI:

29. - accounts for nearly 40% of
all AKI
I.Renovascular obstruction
bilateral or unilateral in the
setting of one functioning
kidney
II.Disease of glomeruli or
renal microvasculature
 Acute kidney injury
Intrinsic
Glomerular
Interstitial Tubular
Vascular
Intrinsic Renal AKI

31. III. Acute tubular necrosis(ATN)
 Ischemia: as for prerenal AKI (hypovolemia, low cardiac
output, renal vasoconstriction, systemic vasodilatation)

33. Toxins
 Exogenous: radio contrast, cyclosporine, antibiotics
(e.g. aminoglycosides), chemotherapy (e.g. cisplatin),
organic solvents (e.g. ethylene glycol), acetaminophen,
illegal abortifacients
 Endogenous: Mb, Hb, uric acid, oxalate, plasma cell
dyscrasia (e.g. myeloma)
Postoperative AKI

34. C. Post renal AKI (OBSTRUCTION):

37. Pathophysiology of postrenal AKI
 It 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.

38. POST RENAL
Reduced GFR is due to underperfusion
of glomeruli and, possibly, changes in
the glomerular ultrafiltration
coefficient

40. Diagnostic Evaluation
 History and Physical examination:
 Pre-renal:
 History: vomiting, diarrhoea, glycosuria
causing polyuria, and several medications
including diuretics, NSAIDs, ACE inhibitors,
and ARBs.
 Examination: Physical signs of orthostatic
hypotension, tachycardia, reduced jugular
venous pressure, decreased skin turgor, and
dry mucous membranes are often present in
prerenal azotemia

41. Diagnostic Evaluation
INTRINSIC RENAL:
 Review all medications
 Cause of AKI .
 Dose Adjustment.
 Systemic vasculitis with Glomerulonephritis:
 Palpable purpura
 Pulmonary hemorrhage,
 Sinusitis.
 Atheroembolic
 Livedo reticularis and other signs of emboli to the legs.

 Rhabdomyolysis.
 Signs of limb ischemia

42. Diagnostic Evaluation
 Post- Renal:
Colicky flank pain radiating to the groin
suggests acute ureteric obstruction.
 Nocturia and urinary frequency or hesitancy
can be seen in prostatic disease.
Abdominal fullness and suprapubic pain can
accompany massive bladder enlargement.
Definitive diagnosis of obstruction requires
radiologic investigations.

43. Blood Tests
 CBC
 BUN/creatinine
 Electrolytes
 Uric acid
 PT/aPTT

44. Urine Analysis
Volume
Osmolality
Proteinuria
Urinary Indices: FeNa
& Urinary Sodium
Sediments

46. Imaging
 Renal ultrasound (useful for obstructive
forms)
 Doppler (to assess renal blood flow)
 CT Scan
 Pyelography
 Nuclear Medicine Scans :
DMSA: anatomy.
DTPA and MAG3: renal function,
urinary excretion and upper tract outflow.

48. Cystatin-C
Superior to serum creatinine, as a
surrogate marker of early and subtle
changes of kidney function.
Identifies kidney injury while
creatinine levels remain normal
Allows detection of AKI, 24-48 hours
earlier than serum creatinine

49. Kidney Injury Molecule-1 (KIM-1)
 Type 1 trans-membrane glycoprotein
 Served as a marker of severity of AKI
 Can be used to predict adverse outcomes in
hospitalized patients better than
conventionally used severity markers.

50. Neutrophil gelatinase-
associated lipocalin(NGAL)
 Highly upregulated after inflammation and
kidney injury
 Can be detected in the plasma & urine
within 2 hours of cardiopulmonary bypass–
associated AKI.
 Considered equivalent to troponin in acute
coronary syndrome.

51. Complications of AKI

53. Complications of AKI
 Intravascular overload: may be recognized by weight
gain , hypertension ,elevated central venous pressure (
raise JVP) , Pulmonary edema
Electrolyte disturbance
 Hyperkalemia: (serum K+ >5.5 mEq/L): decreased renal
excretion combined with tissue necrosis or hemolysis.
 Hyponatremia : ( serum Na+ concentration < 135 mEq/L
): excessive water intake in the face of excretory failure

54.  Hyperphosphatemia : ( serum Phosphate
concentration of > 5.5 mg /dl ) failure of excretion
or tissue necrosis
 Hypocalcemia : ( serum Ca++ < 8.5 mg/dl ) results
from decreased Active Vit-D , hyperposhphatemia ,
or hypoalbuminemia
 Hypercalcemia: (serum Ca++ > 10.5 mg /dl) may
occur during the recovery phase following
rhabdomyolysis induced acute renal failure.

55.  Metabolic acidosis :( arterial blood PH < 7.35 ) is
associated with sepsis or severe heart failure
 Hyperuricemia: due to decreased uric acid excretion
 Bleeding tendency : may occur due to platelet
dysfunction and coagulopathy associated with sepsis
 Seizure: may occur related to uremia

56. Treatment of AKI

57. 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

58. Pre-Renal AKI
Prevention and treatment of prerenal
azotemia requires optimization of
renal perfusion.
Severe acute blood loss should be
treated with PRBC transfusion.

59. FLUIDS
 KDIGO advocates use of isotonic crystalloids
rather than colloids (albumin or starches) .
 Colloids may be chosen to avoid excessive fluid
administration requiring large volume
resuscitation, or in specific patient subsets
(e.g., a cirrhotic patient with spontaneous
peritonitis, or in burns).
 Colloids- Albumin is renoprotective and
Hyperoncotic starch shows nephro-
toxicity.

60. Vasopressors
 Appropriate use of vasoactive agents
improve kidney perfusion in volume-
resuscitated patients with vasomotor
shock.
 Dopamine associated with a greater
number of adverse events than Nor-
epinephrine.

61. Low Dose Dopamine
• Its use has been abandoned by most
subsequent to negative results of
various studies .
• KDIGO recommends not using low-
dose dopamine to prevent or treat AKI.
(1A)

62. Cirrhosis and Hepatorenal
Syndrome
 Albumin may prevent AKI in those treated
with antibiotics for SBP
 Bridge therapies [in combination with IV
Inf albumin (25–50 mg/d)] include:
 terlipressin (a vasopressin analog),
 combination therapy with octreotide (a
somatostatin analog) and midodrine (an α
1-adrenergic agonist), and norepinephrine

63. Cardio-Renal Syndrome
 Optimization of cardiac function .
 May require use of
inotropic agents
preload- and afterload-reducing agents,
antiarrhythmic drugs,
mechanical aids such as an intra-aortic
balloon pump.

64. Treatment of Intrinsic
AKI

65. Diuretic
• Renoprotective : Potentially lessening ischemic
injury
•Can also be harmful, by worsening established AKI.
• No evidence of incidence reduction.
• KDIGO recommend not using diuretics to prevent
AKI
• KDIGO suggest not using diuretics to treat AKI,
except in the management of volume overload
• Indicated only for management of fluid balance,

66. FENOLDOPAM Fenoldopam mesylate: pure dopamine
type-1 receptor agonist
 Without systemic adrenergic stimulation.
 No conclusive studies available.
 For critically ill patients with impaired
renal function, a continuous infusion of
fenoldopam 0.1mg/kg/min improves renal
function when compared to low dose
dopamine.

67. Erythropoietin
• Potential clinical benefit of erythropoietin in
AKI in animal studies.
• Renoprotective action of erythropoietin related
to pleomorphic properties including anti-apoptotic
& anti-oxidative effects, stimulation of cell
proliferation, and stem-cell mobilization.
• Although one recent RCT in the prevention of
human AKI was negative, the usefulness of
erythropoietin in human AKI should be further
tested in RCTs.

68. Growth factor intervention
• IGF-1 is a peptide with renal vasodilatory,
mitogenic and anabolic properties.
• KDIGO Work Group recommends against
its use in patients with AKI.

69. Rhabdomyolysis
• Aggressive volume repletion (may require 10 L of
fluid/day)
• Alkaline fluids beneficial
• Diuretics may be used if fluid repletion is adequate
& no urine output
• Dialysis
• Focus on calcium and phosphate status because of
precipitation in damaged tissue

70. Glomerulonephritis
or Vasculitis
• May respond to immunosuppressive agents and/or
plasmapheresis
• Allergic interstitial nephritis due to medications
requires discontinuation of the offending agent.
• Glucocorticoids have been used, but not tested in
randomized trials.
• AKI due to scleroderma (scleroderma renal crisis)
should be treated with ACE inhibitors.

71. Aminoglycoside Induced AKI
• KDIGO suggest not using aminoglycosides for the t/t of
infections unless no suitable, less nephrotoxic, therapeutic
alternatives are available
• Avoid in high risk patients of age > 65 years, DM, septic
shock
• Single dose daily rather than multiple-dose daily t/t
regimens
• Topical or local applications of aminoglycosides (e.g.,
respiratory aerosols, instilled antibiotic beads), rather than
I.V. application, when feasible

72. AMPHOTERICIN B
NEPHROTOXICITY
• KDIGO suggest using lipid formulations of
amphotericin B rather than conventional
formulations
• Use azole antifungal agents and/or the
echinocandins rather than conventional
amphotericin B, if equal therapeutic efficacy can be
assumed.
• Some studies indicate that the liposomal form of
amphotericin B is less nephrotoxic than lipid
complex or colloidal dispersion forms

73. Post-renal
 Prompt relief of urinary tract obstruction.
 Relief of obstruction is usually followed by
an appropriate diuresis and may require
continued administration of IVF &
electrolytes for a period of time.

74. Indications for Dialysis
 A – Acidosis
 E – Electrolyte disturb, usually
hyperkalemia
 I – Intoxications (lithium, ethylene
glycol, etc)
 O – Overload (volume overload)
 U – Uremia (symptoms, signs )

75. Modes Of Dialysis
 Hemodynamically stable- IHD
 Hemodynamically unstable
1. CRRT
2. PD
3. SLED

76. Prognosis
 Pre-renal and Post- renal better prognosis.
 Kidneys may recover even after dialysis
requiring AKI.
 10% of cases requiring dialysis develop
CKD.
 Die early even after kidney function recovers
completely.

77.  Diagnose early – Biomarkers have great
potential
 Look for etiology
 Prevent rather than treat
 No role of low dose dopamine, diuretics in
prevention and treatment
 Initiate RRT when indicated