Acute Renal Failure

1
Acute Renal Failure

• Diagnosis
• Staging with RIFLE Criteria
• Lab evaluation
• Clinical features
• Pathophysiology

2
Acute Renal Failure

• Definition may depend on whom you ask
• Surgeon - - low urine output
• Intensivist-- severe acidemia
• Nephrologist-- rising serum creatinine
• Frequency - depends on clinical setting
• 1 of all admissions to hospital
• 2-5 of all individuals during a hospitalization
• 4-15 during cardiopulmonary bypass
• 10-30 of all admissions to ICU

3
Definition

• a sudden and severe decrease in the glomerular
  filtration rate (GFR) sufficient to cause
  increases in BUN and Scr (azotemia), Na/H2O
  retention (edema), and development of acidemia
  and hyperkalemia
• review of 27 studies showed no 2 used the same
  definition chronic renal confusion

4
Whats in a name?

• lack of a universally recognized definition of
  ARF
• 2004 consensus conference
• proposed the term acute kidney injury (AKI) to
  reflect the entire spectrum of ARF recognizing
  that an acute decline in kidney function is often
  secondary to an injury that causes functional or
  structural changes in the kidneys

5
Newest DefinitionMehta CritCare 2007

• An abrupt (within 48 h) reduction in kidney
  function currently defined as
• an absolute increase in serum creatinine of
  either gt 0.3 mg/dl,
• or a percentage increase of gt 50 or a
  reduction in UOP (documented oliguria of lt 0.5
  ml/kg per h for gt 6)

6
The differential for any lab abnormality is

• Lab error
• Lab error
• Lab error
• Iatrogenic
• Polypharmacy
• Real disease
• IN THIS ORDER!

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Acute renal failure (ARF)

• Differential for Lab abnormality Causes
• A rise in the BUN level can occur without renal
  injury, such as in GI or mucosal bleeding,
  steroid use, or protein loading (such as IV
  nutrition)
• A rise in the creatinine level can result from
  medications (eg, cimetidine, trimethoprim) that
  inhibit the kidneys tubular secretion, or an
  increase in creatinine production such as seen in
  Rhabdomyolysis. (muscle breakdown)
• True Anuria is most commonly the result of an
  obstructed foley catheter, or an error in
  recording output. The worst cause of anuria is
  cortical necrosis.

8
Acute renal failure (ARF)

• An abrupt or rapid decline in renal function
• Marked by a rise in BUN (azotemia) or serum
  creatinine concentration
• Immediately after a kidney injury, BUN or
  creatinine levels may be normal
• The only sign of a kidney injury may be decreased
  urine production
• Use RIFLE Criteria to evaluate Risk.

9
Acute Dialysis Quality Initiative

• RIFLE Criteria Helps risk stratify patients with
  renal failure.
• Increased mortality seen with increases in
  creatinine of 0.3 to 0.5 mg/dl (70 increase
  for all pts, 300 increase in cardiac surgery
  pts

10
RIFLE criteria

• Risk low uop for 6 hours, creat up 1.5 to 2 times
  baseline
• Injury creat up 2 to 3 times baseline, low uop
  for 12 hours
• Failure Creat up gt 3 times baseline or over 4,
  anuria
• Loss of Function Dialysis requiring for gt 4 weeks
• ESRD Dialysis requiring for gt 3 months

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(RIFLE Criteria for Acute Renal Failure)Bellomo R
- Crit Care Clin -APR-2005 21(2) 223-37
12
RIFLE estimate of Mortality

• Two studies Uchino Hoste
• No renal failure 4.4 5.5
• Risk 15 8.8
• Injury 29 11.4
• Failure 53.9 26
• Loss of Function
• ESRD

Crit Care Med 2006 341913-7, Hoste CCM 2006
10R73
13
RIFLE criteria

• When markers of severity of illness are looked at
  excluding renal data, no difference in groups is
  seen.

14
Acute renal failure (ARF)

• History and Physical examination
• Nephrotoxic drug ingestion
• History of trauma or unaccustomed exertion
• Blood loss or transfusions
• Congestive heart failure
• Exposure to toxic substances, such as ethyl
  alcohol or ethylene glycol

15
Acute renal failure (ARF)

• History and Physical examination
• Exposure to mercury vapors, lead, cadmium, or
  other heavy metals, which can be encountered in
  welders and miners
• Hypotension
• Volume contraction
• Vomiting/Diarrhea/Sweating/Nursing Home
• Evidence of connective tissue disorders or
  autoimmune diseases

16
Pathophysiology

• ARF may occur in 3 clinical patterns

BUNCr gt 201
BUNCr 10-201
BUNCr gt 201
17
Pathophysiology

• ARF may occur in 3 clinical patterns
• Suggested by labwork

BUNCr gt 201 Pre-Renal or Post-Renal
BUNCr 10-201 Intra-Renal
BUNCr lt 101 Extrinsic Production of
Creatinine or a dialysis patient.
18
Acute renal failure (ARF)

• Patients can have
• Oliguria
• Daily urine volume of less than 400 mL/d and has
  a worse prognosis, except in prerenal failure
• Anuria is urine output of less than 100 mL/d and,
  if abrupt in onset, is suggestive of bilateral
  obstruction or catastrophic injury to both
  kidneys
• Rapid or slow rise in creatinine levels
• Differences in urine solute concentrations and
  cellular content

19
Prerenal ARF

• Prerenal ARF represents the most common form of
  kidney injury and often leads to intrinsic ARF if
  it is not promptly corrected
• From any form of extreme volume loss
• GI, renal (diuretics, polyuria), cutaneous (eg,
  burns), and internal or external hemorrhage can
  result in this syndrome
• Systemic vasodilation or decreased renal
  perfusion
• Anesthetics
• Drug overdose
• Heart failure
• Shock (eg, sepsis, anaphylaxis)

20
Prerenal ARF

• Afferent Arteriolar vasoconstriction leading to
  prerenal ARF
• Hypercalcemic states
• Radiocontrast agents
• NSAIDs
• Amphotericin
• Calcineurin inhibitors
• Norepinephrine
• Other pressor agents
• Hepatorenal syndrome
• Functional renal failure
• develops from diffuse
• vasoconstriction in vessels supplying the kidney.

21
Prerenal ARF

• Efferent arteriolar vasodilation can induce
  prerenal ARF in volume-depleted states in the
  face of
• ACE Inhibitors
• ARBs
• Otherwise safely tolerated and beneficial in most
  patients with chronic kidney disease
• Both cause afferent and efferent dilation, but
  efferent more

22
Intrinsic ARF

• Structural injury in the kidney
• Most common form is acute tubular necrosis (ATN)
• Either ischemic or cytotoxic 
• Loss of brush borders
• Flattening of the epithelium
• Detachment of cells
• Formation of intratubular casts
• Dilatation of the lumen
• Although these changes are observed
  predominantly in proximal tubules, injury to the
  distal nephron can also be demonstrated. The
  distal nephron may also be subjected to
  obstruction by desquamated cells and cellular
  debris. 

23
Intrinsic ARF

• Intrarenal vasoconstriction is the dominant
  mechanism for the reduced glomerular filtration
  rate (GFR) in patients with ATN.
• Tubular injury seems to be an important
  concomitant finding
• Urine backflow and intratubular obstruction (from
  sloughed cells and debris) reduced net
  ultrafiltration.
• Stressed renal microvasculature is more sensitive
  to potentially vasoconstrictive drugs and
  otherwise tolerated changes in systemic blood
  pressure.  
• Injured kidney vasculature has an impaired
  vasodilatory response and loses its
  autoregulatory behavior
• Dialysis may re-injure the kidneys as a result

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Intrinsic ARF

• Tubular
• Cytotoxic
• Crystals
• Tumor lysis syndrome
• Ethylene glycol poisoning
• Megadose vitamin C
• Acyclovir
• Indinavir
• Methotrexate
• Drugs
• Aminoglycosides
• Lithium
• Amphotericin B
• Pentamidine
• Cisplatin
• Ifosfamide
• Radiocontrast agents

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A few words about markers of renal failure
26
Relationship Between GFR and Serum Creatinine in
ARF
120
80
GFR (mL/min)
40
0
6
Serum Creatinine (mg/dL)
4
2
0
0
7
14
21
28
Days
27
Serum Creatinine

• Creatinine is more specific at assessing renal
  function than BUN but it corresponds only loosely
  to GFR 1315.
• For example, a serum creatinine (SCrt)of 1.5
  mg/dL (133 mmol/L), at steady-state, corresponds
  to a GFR of approximately 36 mL/min in an
  80-year-old white woman, but approximately77
  mL/min in a 20-year-old black man.

28
Creatinine and the critically ill patient

• Creatinine is formed from nonenzymatic
  dehydration of creatine in the liver 98 of the
  creatine pool is in muscle.
• Critically ill patients may have abnormalities in
  liver function and markedly decreased muscle
  mass.
• Additional factors that influence creatinine
  levels include conditions of increased production
  (eg, trauma, fever, immobilization) or conditions
  of decreased production (eg, liver disease,
  decreased muscle mass, aging).

29
Creatinine and the critically ill patient

• In addition, tubular reabsorption (back-leak)
  may occur in conditions that are associated with
  decreased urine flow rate.
• Finally, the volume of distribution (VD) for
  creatinine (total body water) influences SCrt and
  may be increased dramatically in critically ill
  patients in the short term, its concentration in
  plasma can be altered dramatically by rapid
  plasma volume expansion. The creatinine is
  diluted by extra volume.

30
Urine Output

• commonly measured parameter of renal function in
  the ICU and is more sensitive to changes in renal
  hemodynamics than biochemical markers of solute
  clearance however, it is far less specific
  except when severely reduced or absent
• severe ARF can exist despite normal urine output
  (ie, nonoliguric ARF) but changes in urine output
  often occur long before biochemical changes are
  apparent
• nonoliguric ARF has a lower mortality rate than
  oliguric ARF, thus urine output is used to
  differentiate ARF conditions
• Classically, oliguria is defined (approximately)
  as urine output of less than 5mL/kg/d or 0.5
  mL/kg/h however, no study exists to diagnose
  when oliguria is a true early marker of
  developing renal failure

31
Modification of Diet in Renal Disease (MDRD)
Calculation for GFR
Cockcroft Equation GFR 140 - AGE X Pt WT
X 0.85 Serum Creat 70
for female
The Cockcroft-Gault formula is calculated from
the patient's age, body weight, and serum
creatinine level. The MDRD uses the serum
creatinine level and age alone to estimate GFR,
with adjustments for sex and African American
race. (gt90 normal)
32
New markers for ARF

• Creatinine is not very sensitive
• Cystatin C may identify ARF 1.5 days earlier than
  creatinine
• KI 2004 601115-1122
• KIM-1 Kidney Integrelin Molecule
• NGAL another Integrelin, which leaks into the
  urine after tubular cell death.

33
Acute Kidney Injury Network (AKIN)
34
Clinical Features of Acute Renal Failure

• General Management
• Pre-renal
• Pathophysiology of ATN
• Other Intrinsic Causes of ARF.

35
Reason for Nephrology Consultation
25
15
60
Ref Paller Sem Neph 1998, 18(5), 524.
36
Approach to ARF

• Pre-Renal
• Intra-Renal
• Post- Renal
• Pseudo-ARF
• There are other things which can raise the BUN
  and Creatinine!

37
Approach to ARF

• Pre-Renal
• Most common
• Due to NPO, Diuretics, ACE inhibitors, NSAIDS
• Due to renal artery disease, CHF with poor EF.
• Usually BUN / creat ratio over 20.
• Usually creat lt 2.5

38
Approach to ARF

• Intra-Renal
• Most commonly pre-renal tipping over into true
  renal injury.
• Acute Tubular Necrosis is result (70)
• Tubulo-Interstitial Nephritis (20)
• Acute vasculitis/GN rare (5-10 )

39
Intrinsic Renal Failure

• Prerenal ARF
• Intrinsic ARF
• acute tubular necrosis
• acute interstitial nephritis
• acute glomerulonephritis
• acute vascular syndromes
• intratubular obstruction
• Postrenal ARF

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Instigating Factors for ARF in a Referral Hospital
11
5
30
30
12
12
Ref Paller Sem Neph 1998, 18(5), 524.
41
Approach to ARF

• Post- Renal
• Most commonly due to obstruction at bladder
  outlet
• Prostate problems
• Neurogenic bladder
• Stone
• Urethral stricture (esp after CABG)

42
Initial Treatment of ARF

• Fluid Resuscitation
• Always place Foley Catheter
• Stop offending agents
• NSAIDS, Contrast, ACE/ARB, potassium
• Watch labs
• Consider diuretics/Natrecor

43
Acute Renal Failure

• Definitions
• Azotemia - the accumulation of nitrogenous wastes
• Uremia - symptomatic renal failure
• Oliguria - urine output lt 400-500 mL/24 hours
• Anuria - urine output lt 100 mL/24 hours

44
Acute Renal failure Cause

• Acute renal failure is an abrupt renal
  impairment, presenting in a fall of GFR within
  hours or days.
• The result is a severe imbalance of fluid and
  electrolyte homeostasis accompanied by
  accumulation of nitrogenous waste.
• Occurs in response to a variety of insults
• Hemodynamic
• Immunological
• Toxic
• obstructive

45
Acute Renal failure
Causes of acute renal failure
Differentiation between Pre-renal, renal and
post-renal causes
Prerenal Intrinsic Renal Postrenal
Hypovolemia Decreased active blood volume Decreased cardiac output Renovascular obstruction Acute tubular necrosis Interstinal nephritis Glomerular disease (acute glomerulonephritis) Small vessel diease Intrarenal vasoconstriction (in sepsis) Tubular obstruction Bilateral ureteric obstruction Unilateral ureteric obstruction Bladder outflow obstruction
46
Acute Renal failure
Complications of acute renal failure
Hyperkalemia (? ECG abnormalities) Decreased
bicarbonate (acidosis) Elevated urea Elevated
creatinine Elevated uric acid Hypocalcemia Hype
rphosphatemia
47
In many cases kidney can recover from acute renal
failure The function may have to be temporarily
replaced by dialysis for 2 days to 2
weeks disturbed fluid or electrolyte
homeostasis must be balanced primary causes
like necrosis, drug toxicity or obstruction must
be treated
48
Manifestations of ARF

• Azotemia progressing to uremia
• Hyperkalemia
• Metabolic acidosis
• Volume overload
• Hyperphosphatemia
• Accumulation and toxicity of medications excreted
  by the kidney

49
Pathogenesis of Prerenal Azotemia
Renal Vasoconstriction
50
Prerenal Acute Renal Failure

• BUNCreatinine ratio
• gt 201
• Urine indices
• Oliguria
• usually lt 500 mL/24 hours but may be
  non-oliguric
• Elevated urine concentration
• UOsm gt 700 mmol/L
• specific gravity gt 1.020
• Evidence of high renal sodium avidity
• UNa lt 20 mmol/L
• FENa lt 0.01
• Inactive urine sediment

51
Classification of the Etiologies of Acute Renal
Failure
Acute Renal Failure
52
Intrinsic Acute Renal Failure

• Acute tubular necrosis (ATN)
• Acute interstitial nephritis (AIN)
• Acute glomerulonephritis (AGN)
• Acute vascular syndromes
• Intratubular obstruction

53
Acute Tubular Necrosis
54
Acute Tubular Necrosis

• Ischemic
• prolonged prerenal azotemia
• hypotension
• hypovolemic shock
• cardiopulmonary arrest
• cardiopulmonary bypass
• Sepsis

• Nephrotoxic
• drug-induced
• radiocontrast agents
• aminoglycosides
• amphotericin B
• cisplatinum
• acetaminophen
• pigment nephropathy
• hemoglobin
• myoglobin

55
Pathophysiology of ATNTubular Epithelial Cell
Injury and Repair
Ischemia/ Reperfusion
Necrosis
Apoptosis
Loss of polarity
Normal Epithelium
Cell death
Differentiation Reestablishment of polarity
Sloughing of viable and dead cells with luminal
obstruction
Proliferation
Adhesion molecules
Na/K-ATPase
Migration , Dedifferentiation of Viable Cells
56
Pathophysiology of ATN
57
Pathophysiology of Acute Tubular Necrosis

• Mechanisms of decreased renal function
• Vasoconstriction
• Tubular obstruction by sloughed debris
• Backleak of glomerular filtrate across denuded
  tubular basement membrane

58
Acute Tubular NecrosisUrinary Findings
59
Acute Tubular Necrosis

• Urine indices
• Urine volume
• may be oliguric or non-oliguric
• Isosthenuric urine concentration
• UOsm ? 300 mmol/L
• specific gravity ? 1.010
• Evidence of renal sodium wasting
• UNa gt 40 mmol/L
• FENa gt 0.02
• Urine sediment
• tubular epithelial cells
• granular casts
• BUN Creatinine ratio 101
• Evidence of toxin exposure

60
Phases of Ischemic ATN
Prerenal
Initiation
GFR
Extension
Recovery
Maintenance
Time 2 days to 2 weeks typical
61
Prognosis ofAcute Tubular Necrosis

• Mortality dependent upon comorbid conditions
• overall mortality 50
• Recovery of renal function seen in 90 of
  patients who survive - although not necessarily
  back to prior baseline renal function

62
Time for a break