2. DEFINITION
AKI is a sudden and usually reversible decrease
in the glomerular filtration rate (GFR) occurring
over a period of hours to days.
The term “Acute Kidney Injury” now replaces
the term ARF; the term Acute Renal Failure
should now be restricted to patients who have
AKI and “need renal replacement therapy”.
3. ‘ACUTE KIDNEY INJURY’
Abrupt reduction [<48 hrs] in kidney
function, defined as an absolute increase in S
creatinine of ≥0.3 mg/dL
A percentage increase in S creatinine of ≥ 50%
[1.5 fold from baseline] or
a reduction in urine output-- documented
oliguria of < 0.5 ml/kg/hr, for more than six
hours.
4.
5.
6. Hilton, R. BMJ 2006;333:786-790
CAUSES OF ACUTE KIDNEY INJURY
AKI
14. Pre-renal AKI
• History
-- blood or volume loss
-- cardiac failure, arrhythmia,
(cardiogenic shock)
-- sepsis
• Physical exam – focus on volume status
– Vital signs – current and preceding the
development of AKI
– Neck veins, lungs, heart, mucous membranes and
edema
15. Pre-renal AKI
• There is no intrinsic kidney damage in
pre-renal AKI; rising BUN and creat occur
because the kidneys are inadequately
perfused.
• Therefore, normal renal physiologic
responses occur, manifested in urine
electrolytes that reflect intact renal
tubular function.
16. Pre-renal AKI
• Intact renal tubular function in the
setting of impaired renal perfusion
results in avid tubular reabsorption of
sodium.
• Therefore, low urine Na (<20 mEq/L)
and low fractional excretion of Na
(<1%) and of urea (<35%) in pre-renal
ARF.
17.
18. Pre-renal AKI
• Laboratory studies
– BUN:creatinine ratio – elevated in pre-renal; >20:1
– Urine sediment: hyaline and fine granular casts
– Urine Specific gravity: high
– Urine dipstick: negative (no blood or protein)
– Urinary to plasma creatinine ratio: high
– Urinary Na: low
– FENa: low
19. • Sustained prerenal azotemia is the main factor
that predisposes patients to ischemia- induced
acute tubular necrosis (ATN)
• Prerenal azotemia and ischemic tubular necrosis
represent a continuum. Azotemia progresses to
necrosis when blood flow is sufficiently
compromised to result in the death of tubular
cells.
• Most cases of ischemic AKI are reversible if the
underlying cause is corrected.
20. Renal or Intrinsic AKI
• In all types of intrinsic AKI, BUN:creat
ratio preserved (10-20:1)
• The history, P/E, and especially urine
analysis will help to differentiate
21. Renal or Intrinsic ARF
– Vascular Type
• Large vessels – must be bilateral
– Renal vein thrombosis
– Renal artery stenosis
• Small vessels
– Vasculitis
– Atheroembolic
– Malignant hypertension
– Thrombotic microangiopathies (HUS/TTP)
22. Renal or Intrinsic AKI
– Glomerular
• History – systemic or primary kidney
• P/E – BP (usually hypertensive)
-- edema
• BUN:creatinine ratio: preserved
• Urine analysis : + protein, blood
RBCs,+
• Often require kidney biopsy
RBC Casts
23. Renal or Intrinsic AKI
– Interstitial
• History – exposure to medications usually 7-
14 days earlier
-- penicillins, cephalosporins, dilantin
• P/E – maculopapular erythematous skin rash
-- 1/3 have fever, arthralgias
• BUN:creatinine ratio: 10-20:1
• Urine analysis: + protein, blood
WBCs, WBC casts, eosinophils
24. Renal or Intrinsic
ATN – Acute Tubular Necrosis
• The most common type of hospital-acquired
ARF
• May be
1) ischemic or
2) nephrotoxic in etiology
• Most common ATN is ischemic, most often due
to a prolonged pre-renal state (prolonged
reduced renal perfusion)
25.
26. Renal or Intrinsic
ATN – Acute Tubular Necrosis
• History – prolonged pre-renal state
-- exposure to nephrotoxin
aminoglycoside antibiotics
ethylene glycol
pigments (myoglobin, hemoglobin)
• P/E – assess volume status (to exclude pre-
renal AKI)
27. Renal or Intrinsic
ATN – Acute Tubular Necrosis
• BUN:creatinine ratio: preserved (10-20:1)
• Urine analysis : negative protein, blood
-- granular casts (dirty brown casts)
-- renal tubular epithelial cells
• Urine chemistries – Urinary Na: high (>40 meq/L)
FENa: high (>2%)
Urinary to plasma creatinine ratio: low
28. Contrast-Induced AKI
Prevalence
• Less than 1% in patients with normal renal
function
• Increases significantly with renal insufficiency
Risk factors
• Renal insufficiency
• Diabetes mellitus
• Multiple myeloma
• High osmolar (ionic) contrast media
• Contrast medium volume
29. Contrast-induced AKI
Clinical Characteristics
• Onset - 24 to 48 hrs after exposure
• Duration - 5 to 7 days
• Non-oliguric (majority)
• Dialysis - rarely needed
• Urinary sediment - variable
• FENa: Low
31. Post-Renal AKI
• Elevated pressure in urinary conduits results in
renal parenchymal destruction if unrelieved
• important to rule out quickly:
– potential for recovery of renal function is
often inversely related to the duration of the
obstruction
32. Post-Renal AKI
• History – symptoms (frequency, hesitancy, etc)
-- carcinoma, DM, stones, medications
• P/E – distended bladder, prostatic enlargement, pelvic
masses , lymph nodes
• Laboratory studies-- elevated BUN:creat ratio
-- unremarkable urine sediment
-- variable urine chemistries
• Renal ultrasound – hydronephrosis
• Treatment is to relieve the obstruction
– Bladder catheterization
– Nephrostomy tubes
35. Serum Creatinine as a marker
for AKI and GFR
Normal S.Creatinine is 0.6-1.2mg/dl and is the
most commonly used parameter to assess renal
function.
Unfortunately the correlation between
S.Creatinine concentration and GFR may be
confounded by several factors.
36. There is abrupt drop in GFR but the S.Cr. does not start going up for
24 or 36 hours after the acute insult .
40
80
0
GFR
(mL/min)
0 7 14 21 28
4
Days
2
0
6
Serum
Creatinine
(mg/dL)
Relationship between GFR and serum creatinine in
AKI
37. Creatinine is not an ideal marker
1.Creatinine excretion is dependent on renal factors
independent of function:
– Certain medications such as cimetidine and
trimethoprim interfere with proximal tubular
creatinine secretion and may cause rise in S.
creatinine without fall in GFR.
38. 2. S.Creatinine is dependent on nonrenal factors
independent of renal function
S.Creatinine is dependent on muscle mass,
infection, volume of distribution, age, gender, race,
body habitus, diet, presence of amputations.
Eg. S. Creatinine of 1.2mg/dl in a 40kg elderly
signifies severe reduction of GFR while the same
value in a 100kg represents a normal renal function
3. Creatinine production and excretion must be in a
steady state before creatinine may be used in any
formula for the estimation of GFR.
39. Fractional Excretion of Na
• Since urinary indices depend on urine sodium
concentration, they should be interpreted cautiously if the
patient has received diuretic
Spot urine Na may be affected (raised) by diuretic use and
baseline impaired kidney function (CKD where maximum
urine Na reabsorption is impaired)
Fractional excretion of Na accounts for this by including
creatinine:
FxExNa = urine [Na] ÷ plasma [Na] X 100
urine creatinine ÷ plasma creatinine
40. RENAL INDICES
• Renal Failure Index (RFI)
RFI = urine [Na]
urine creatinine /serum creatinine
41. URINE AND SERUM
LABORATORY VALUES
Prenal Renal
BUN/Cr >20 <20
FeNa <1% >1%
RFI <1% >1%
UNa (mEq/L) <20 > 40
Specific gravity high low
Pre-renal
42. URINE ANALYSIS
• Dipstick for blood, protein – Suggests a
renal inflammatory process
• Microscopy may show cells, casts, crystals
43. RBCs in Urine
Present in
glomerulonephritis ,
vasculitis ,
HUS TTP
scleroderma crisis
47. Pigmented Granular Casts
• Pigmented
granular (“muddy
brown”) casts are
characteristic of
acute tubular
necrosis
48. Crystals
• Urate crystals – acute urate nephropathy
• Oxalate crystals –ethylene glycol ingestion
/acyclovir/ indinavir
• Eosinophiluria > 5 % of WBC s
AIN ,atherothrombotic
disease
49. Haematology
• Full blood count, blood film:
– Eosinophilia may be present in acute interstitial
nephritis,
cholesterol embolization, or vasculitis (CSS)
– Thrombocytopenia and red cell fragments suggest
thrombotic microangiopathy –TTP, HUS
• Coagulation studies
– Disseminated intravascular coagulation associated
with sepsis
50. Immunology
Antinuclear antibody (ANA) , Anti-double stranded
(ds) antibody -
ANA positive in SLE and other autoimmune
disorders;DNA antibodies anti-ds DNA antibodies
more specific for SLE
C3 & C4 complement concentrations-
Low in SLE, acute post infectious
glomerulonephritis, Cryoglobulinemia
ASO and anti-DNAse B titres
High after streptococcal infection
51. Immunology...
• ANCA
• p-ANCA - Anti PR3 antibodies
• c-ANCA - Anti MPO antibodies
– Associated with systemic vasculitis - Wegener’s
granulomatosis; Microscopic polyangiitis.
• AntiGBM antibodies
– Present in Goodpasture’s disease
60. AKI: PREVENTION
Recognize patients at risk (postoperative
states, cardiac surgery, septic shock)
Prevent progression from prerenal to renal
Preserve renal perfusion(isovolemia, cardiac
output, normal blood pressure)
Avoid nephrotoxins (aminoglycosides,
NSAIDS, amphotericin)
61. GENERAL PROTOCOL FOR
MANAGEMENT OF AKI
• Treat the underlying disease
• Strictly monitor intake and output (weight,
urine output, insensible losses, IVF)
• Monitor serum electrolytes
• Adjust medication dosages according to GFR
• Avoid highly nephrotoxic drugs
• Attempt to convert oliguric to non-oliguric
renal failure (furosemide)
62. FLUID THERAPY
If patient is fluid overloaded
• fluid restriction (insensible losses)
• attempt furosemide 1-2 mg/kg
• Renal replacement therapy
If patient is dehydrated:
• restore intravascular volume first
• then treat as euvolemic
If patient is euvolemic:
• restrict to insensible losses (30-35 ml/100kcal/24 hours) +
other losses (urine, chest tubes, etc)
63. SODIUM
• Most patients have dilutional hyponatremia
which should be treated with fluid restriction
• Severe hyponatremia (Na< 125 mEq/L) : dialysis
or hemofiltration
64. POTASSIUM
• Oliguric renal failure is often complicated by
hyperkalemia, increasing the risk of cardiac
arrhythmias
• Treatment of hyperkalemia:
– sodium bicarbonate (1-2 mEq/kg)
– insulin + hypertonic dextrose
– sodium polystyrene : 1 gm/kg .
(Hypernatremia and hypertension are
potential complications)
– dialysis
65. MANAGEMENT OF AKI
Metabolic acidosis – soda bicarb ., if < 15 meq
Hyperphosphatemia – PO4 binders –sevalamer
Hypocalcemia –calcium carbonate
Nutrition –restriction of dietary protein < 0.8 g/kg /d
calories – 25-30 kcal /kg/d
enteral nutrition preferred
66. Criteria for Initiation of RRT
Anuria
Oliguria
Pulmonary edema
Hyperkalemia >6.5mmol/L
Severe acidemia <7.2
Uremic encephalopathy
Uremic pericarditis