defintion of AKI and staging. various aspects of AKI including management

1. Approach to a
patient with Acute
Kidney Injury
Dr. Sayan Chakraborty
JR-3, Dept. of Tropical Medicine,
School of Tropical Medicine, Kolkata
Email: dr.sayan@gmail.com

2. Epidemiology
• 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

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

4. Definition of AKI

5. 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.

6. KDIGO- Staging of AKI

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

8. RIFLE Criteria
Risk
 Increase in Cr of 1.5-2.0 X baseline or
 urine output < 0.5 mL/kg/hr for more than 6 hours.
Injury
Failure
Loss of function
End-Stage Renal disease

9. RIFLE Criteria
Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for more than 6 hrs
Injury
• 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.
Failure
Loss of function
End-Stage Renal disease

10. RIFLE Criteria
Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
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.
Loss of function
End-Stage Renal disease

11. RIFLE Criteria
Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24
hrs or anuria for more than 12 hours
Loss of function
 persistent renal failure (i.e. need for dialysis) for
more than 4 weeks.
End-Stage Renal disease

12. RIFLE Criteria
Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24
hrs or anuria for more than 12 hours
Loss of function: 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.

14. Etiopathogenesis
of
AKI

15. Classification of AKI
Acute Kidney Injury
Pre-renal Intrinsic Post-renal
Glomerular Interstitial VascularTubular
55% 40% 5%
85%10%<5% <5%

17. Pre-renal AKI

23. Non- oliguric AKI
• Non- Oliguric: In hospital set-up, secondary
Nephrotoxic agents like:
Aminoglycosides (10-30%), even in therapeutic
ranges, manifestation after 5-7 days of therapy
Amphotericin B: Dose & duration dependent;
polyuria, hypomagnesemia, hypocalcemia,
&nongap metabolic acidosis
• Non-oliguric has better prognosis than oliguric
one.

24. ICU vs Non-ICU AKI
• Non-ICU AKI, kidney usually being the only
failed organ, mortality rates of up to 10%.
• ICU AKI often associated with sepsis and
with non-renal multi-organ system failure,
mortality rates of over 50%

25. 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

26. 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

27. 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.

28. Blood Tests
• CBC
• BUN/creatinine
• Electrolytes
• Uric acid
• PT/aPTT

29. Urine Analysis
•Volume
•Osmolality
•Proteinuria
•Urinary Indices: FeNa
& Urinary Sodium
•Sediments

31. 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.

33. Important biomarkers
•Cystatin C
•Neutrophil gelatinase-associated lipocalin (NGAL)
•Interleukin-18
•Kidney injury molecule-1
•N-acetyl-D-glucosaminidase

35. 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

36. 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.

37. 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.

38. Complications of
AKI

40. Major causes of AKI
in Specific
Clinical settings

44. Treatment of AKI

45. 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

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

47. 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.

48. 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.

49. 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)

50. 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

51. 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.

52. Treatment of
Intrinsic AKI

53. 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,
hyperkalemia, and hypercalcemia.

54. 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.

55. 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.

56. 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.

57. 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

58. 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.

59. 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

60. 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

61. 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.

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

63. Modes Of Dialysis
• Hemodynamically stable- IHD
• Hemodynamically unstable
1. CRRT
2. PD
3. SLED

64. 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.

65. Recent Publications

66. Recent Publications

67. • 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

68. References
• Brenner and Rector's The Kidney 9th ed. - M. Taal (Saunders,
2012)
• Harrison's Principles of Internal Medicine, 19th edition (2015)
• Paul Marino The ICU Book(3rd Ed)
• The Washington manual of Critical care 2nd edition
• Kidney Disease: Improving Global Outcomes (KDIGO) Acute
Kidney Injury Work Group. KDIGO Clinical Practice Guideline
for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138
• Rahman et al Acute kidney injury: A guide to diagnosis and
management; American Family Physician, Volume 86, Number
7 October 1, 2012
• Ronco C Acute Kidney Injury: from clinical to molecular
diagnosis; Ronco Critical Care (2016) 20:201