ACUTE RENAL FAILURE IN ICU

1. DR.ZIKRULLAH

2.  Acute kidney injury (AKI), previously known
as acute renal failure, is characterized by the
sudden impairment of kidney function
resulting in the retention of nitrogenous and
other waste products normally cleared by the
kidneys .
 Sudden decrease in GFR over a period of hours
to days resulting in the failure of the kidney to
maintain fluid and electrolyte homeostasis.

3. Acute kidney injury (AKI), is not a single disease but
a heterogeneous group of conditions that share
common diagnostic features: specifically,
 an increase in the blood urea nitrogen (BUN)
concentration and/or
 an increase in the plasma or serum creatinine (SCr)
concentration
 associated with a reduction in urine volume.

4.  Anuria – no urine output or less than 100ml/24
hours
 Oliguria - <400ml urine output/24 hours or
<16ml/hour
 Polyuria - >2.5L urine output/24 hours

5. Prerenal
Renal hypoperfusion - no structural damage to the
kidneys, Creatinine normalizes in 24-72 hours with
correction of hypoperfused state.
Post-renal
Obstruction to the urine flow, either
unilateral/bilateral- intra-ureteral or extra-ureteral
or obstruction to bladder neck or renal-pelvis .
Intrinsic-renal
Damage or inflammation within the kidney, may be
of primary renal origin or part of systemic disease.

6. The prerenal sources of oliguria are located proximal to
the kidneys and are characterized by a decrease in
renovascular flow.
The disorders in this category include
 low cardiac output from
 hypovolemia,
 mechanical ventilation,
 aortic stenosis, and
 end-stage cardiomyopathy,
 as well as drugs that impair renal autoregulation
(e.g.angiotensin-converting enzyme inhibitors).

7.  Prerenal disorders are responsible for about 30
to 40% of cases of oliguria in the ICU.
 The oliguria in these conditions can usually be
corrected by correcting the underlying
disorder, but prolonged or severe prerenal
conditions can lead to renal injury and oliguric
renal failure.

8. Decreased
Extra cellular
Volume
Hemorrhage
Volume losses
either renal, GI
or other (skin)
Hyperthermia etc.,
Third space loss
Peritonitis, pancreatitis,
SIRS, hypoalbuminemia
etc.,

9. Increased ECV with
Arterial underfilling
Reduced Cardiac
Output
Cardiogenic shock, MI, PE
Tamponade, constrictive
Pericarditis ,
Peripheral Vasoldilatation
Sepsis, anaphylaxis,
anaesthesia,
Cirrhosis, other liver
diseases.

11. These medications cause ARF by inhibiting
angiotensin particularly in certain cases where
angiotensin is playing a major crucial
protective role in maintaining GFR by
constricting the glomerular efferent arteriole.
 Volume Depletion
 B/L Renal artery stenosis
 Congestive Heart Failure
 Diuretic use
 Cirrhosis .

12.  Exacerbated in the presence of conditions with
increased renal vasoconstrictor activity like
 Congestive heart failure (CHF)
 Cirrhosis
 Nephrotic Syndrome,
 Sepsis, Volume depletion, HTN, CKD.
 NSAIDS induced ARF is not seen in Euvolemic
conditions with normal kidney, liver and cardiac
functions.

13. Intra-luminal
•Stone,
•Blood clots,
•Papillary
necrosis
•Pelvic
malignancies
•Prolapsed
uterus
•Retroperitoneal
fibrosis
Intrinsic
Intra-mural
•Urethral stricture,
•BPH,
•Carcinoma
prostate,
• Bladder tumour,
• Radiation
fibrosis
Extrinsic
Post-renal Urinary outflow tract obstruction
Obstruction distal to the renal parenchyma is responsible
for only about 10% of cases of oliguria in the ICU

15.  Vascular
 Glomerular
 Interstitial
 Tubular

16. Large and Medium size vessels
 Renal artery thrombosis or emboli
 Renal vein thrombosis
 Polyarterial nodosa
Small vessel disease
 Atheroembolic phenomenon
 Microangiopathies like TTP, HUS, HELLP and
malignant HTN.

17. Nephritis
 Hematuria
 Proteinuria (1-2gm/d)
 ARF
 May present as Rapidly
progressive
Glomerulonephritis
 Renal Biopsy to
diagnose
Nephrosis
 Massive
proteinuria(>3gm/d)
 Minimal hematuria
 May present as ARF
 Renal Biopsy needed to
diagnose.

18. Focal/diffuse edema and infiltration of the renal
interstitium with inflammatory cells.
Acute
Interstitial
Nephritis
Drugs
Antibiotics, NSAIDs,
Phenytoin,
allopurinol,
diuretics etc.,
Systemic
Diseases
SLE etc.,
Infections
Staph, Strepto, CMV,
EBV, TB etc.,

19. Ischemia induced
 Shock
 Hemorrhage
 Sepsis
 Trauma
 Pancreatitis
Nephrotoxin induced
 Drugs like IV contrast,
Aminoglycosides,
Ampho B, pentamidine,
Acyclovir, Ethylene
Glycol etc.,
 Endogenous Toxins in
the case of
Rhabdomyolysis,
Hemolysis, uric acid
nephropathy

20. Ischemia-associated AKI is a serious complication in
the postoperative period, especially after major
operations involving significant blood loss and
intraoperative hypotension.
The procedures most commonly associated with AKI
are
 Cardiac surgery with cardiopulmonary bypass
(particularly for combined valve and bypass
procedures),
 vascular procedures with aortic cross clamping, and
 intraperitoneal procedures.

21.  Severe AKI requiring dialysis occurs in
approximately 1% of cardiac and vascular
surgery procedures.
 Longer duration of cardiopulmonary bypass is
a risk factor for AKI.

22.  Community acquired ARF seen in 1% of all
hospitalized patients on admission - 50% of
those patients have underlying CKD.
 Development of ARF in hospitalized patients is
common and carries independent mortality
risk.
 In patients with normal renal function, the
incidence of ARF is about 5%.
 In patients with underlying CKD, the incidence
is about 16%.

23.  ICU associated ARF along with respiratory
failure requiring hemodialysis, the mortality is
>90%.
 ICU associated ARF with out respiratory
failure or hemodialysis, it is 72%
 Non-ICU renal failure associated mortality is
around 32%.

24.  Retention of nitrogenous waste products
 Nausea, vomiting, diarrhea, hiccups, foul taste, dry
crusted mouth, itching,
 Drowsiness, clouding of consciousness, neuropathy,
pericarditis, GI bleeding,
 Coma
 Retention of salt and water
 Pulmonary edema, peripheral edema, ascites, pleural
effusion

25.  Retention of potassium
 Weakness, lassitude, paralysis, EKG changes with
tenting T waves, widening of QRS complex,
increased PR interval, sine wave pattern, cardiac
arrest, VT
 Retention of acid
 Kussmaul respiration, hyperreflexia, hypotension

26.  METABOLIC:
hyperkalemia, hyponatremia,
hypocalcemia, hyperphosphatemia,
hyperuricemia, metabolic acidosis
 CARDIOVASCULAR :
pericarditis/effusion , hypertension ,MI,
arrhythmias, pulmonary edema
 GASTROINTESTINAL:
vomiting, malnutrition ,GI hemorrhage
 CENTRAL NERVOUS SYSTEM:
asterixis ,mental changes ,seizures
 INFECTIONS:
pneumonia ,sepsis

27. Differentiate acute or chronic renal failure
 Distinguishing between acute and chronic renal
failure is important, as the approach to these
patients differs greatly.

28.  Factors that suggest chronicity :
 Long duration of symptoms,
 Absence of acute illness, anaemia,
hyperphosphatemia, and hypocalcaemia,
 Previous Serum creatinine measurements
 Small kidneys on ultrasound (except for in -
Diabetes, PCKD, Urinary Tract Obstruction)

29.  Careful History and tabulation of data
including urinary output, weight, vitals,
medications etc.
 Physical Examination findings including signs
of volume depletion ,
 Urinalysis
 Urinary indices(Urine sodium, creatinine,
FeNa, FeUrea )

30. Prerenal
 High SpGr
 No
proteinuria/hematuria
 U.Na <20
 U.Cr/P.Cr >40
 U.Osm >500
 FeNa <1%
 FeUrea <35%
Intrinsic
 Sp Gr 1.010
 Variable proteinuria
 U.Na >40
 U.Cr/P.Cr <20
 U.Osm <350
 FeNa >1%
 FeUrea >50%

31.  Easiest and least expensive diagnostic procedure.
 The presence of tubular epithelial cells abundant
with epithelial cell casts is virtually pathognomonic
of ATN.
 The presence of white cell casts identifies an
interstitial nephritis, and the presence of pigmented
casts identifies myoglobinuria.

32.  UA positive for heme and proteinuria seen in
Glomerular and Interstitial renal failure.
 Urine eosinophils are seen in AIN,
Atheroembolic disease .
 Urine sediment positive for red cell casts seen
in Glomerulonephritis.

33.  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.

34. 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
ARF

35. Cystatin C –protein:
 Produced by nucleated cells
 Filtered and completely reabsorbed
 Changes in serum levels occur sooner in this
protein.
Other Newer biomarkers are IL-8, NGAL-
neutrophil gelatinase associated lipocalin

36.  Peripheral eosinophilia is seen in AIN,
Atheroembolic disease.
 Hypocomplementemia seen in SLE, MPGN,
Atheroembolic disease .
 Elevated ESR seen in Atheroembolic disease.
 Serologies like ANA, ANCA, Anti GBM, HIV may
be positive in glomerular diseases.
 Elevated LDH seen in Renal Vein Thrombosis
(RVT).

37.  Thrombocytopenia with microangiopathic
hemolysis seen in Thrombotic thrombocytopenic
purpura(TTP),Haemolytic uremic syndrome( HUS).
 Low Haptoglobin, High reticulocyte count seen in
microangiopathic states.
 CPK and uric acid levels, to evaluate for
rhabdomyolysis, uric acid nephropathy.
 Evidence of hepatic insufficiency is useful in
diagnosing hepatorenal syndrome.

38. Ultrasound
 Useful in Post renal ARF.
 Early obstruction may not show significant
hydronephrosis.
 External obstruction encasing the whole
urinary system may not show hydronephrosis,
for e.g., retroperitoneal fibrosis.
 U/S doppler is useful in diagnosing Renal
vein thrombosis.

39. CT scan
 Useful for detecting stones, location of the
obstruction, Tumours .
Isotope renography
 To evaluate the function significance of
obstruction.
 Done with lasix and Mag3 isotope for
evaluating obstruction.

40. Cystoscopy and Retrograde
Pyelography
 To evaluate patients with high clinical
suspicion of obstruction especially in unique
cases of calculi, pyogenic debris, blood clots,
bladder cancer .
Renal Angiography
 In emergent cases of anuria with suspicion of
renal embolization.

41.  Done only in patients with no clear etiology.
 In patients with active urinary sediment (RBCs,
red cell casts ).
 RPGN (rapidly progressive
glomerulonephritis).
 Refractory ATN with out recovery despite no
further renal insults.
 Acute Interstitial nephritis.

44.  Fluid resuscitation and the use of vasopressor
therapy- are universally emphasized in the
prevention and treatment of ARF.
 The controversy regarding crystalloid versus
colloid still contiues.
 The prompt and adequate correction of
hypovolemia and hypotension is much more
important than the type of fluid used.

45.  Volume repletion with isotonic fluids to
improve renal perfusion pressures should be
done in prerenal failure-CVP/ PAWP
monitoring.
 Colloidal substances like blood products in
hemorrhagic shock.
 Management of heart failure by improving
cardiac output.
 Supportive measures for sepsis with
vasopressors .

46. Use of vasopressors in ARF
Concern has been expressed in usage of
vasopressors because renal vasoconstriction
may be increased and the situation exacerbated.
 Overall effect of using norepinephrine in septic
patients is to increase the GFR and urinary
output.
 Lower mortality rates were observed in a
prospective observational trial of almost 100
septic patients who were treated with
norepinephrine .

47.  The use of dopamine to either treat or prevent ARF
is not supported by the literature now.
 Despite several years of use as a renal vasodilator,
low-dose dopamine (2μg/kg/min) has shown no
evidence of benefit in patients with acute oliguric
renal failure

48.  Convertion of oliguric to nonoliguric ARF with
the use of diuretics is not advised and
mortality rates and dialysis requirements are
not changed by this practice.
 Furosemide – loop diuretic used in oliguric
renal failure.
 If furosemide is used in an attempt to promote
urine flow,it is preferred to be given by
continuous infusion

49.  Drugs need to be dosed according to the renal
clearance.
 Electrolyte and acid base correction.
 Foley catheterization –in case of bladder neck
obstruction/prostatic obstruction
 Diuretics- used in overt fluid overload states.

50.  Use of Mannitol has been shown to be associated
with improved renal outcome
 Forced alkaline diuresis together with mannitol is
generally accepted as preventing acute tubular
necrosis in severe crush injury
 N-acetylcysteine- a reactive oxygen metabolite
scavenger, has been advocated as a renal protection
agent specifically in contrast-mediated
nephropathy.

51.  Activated protein C and steroid replacement
(in those patients who demonstrate a steroid
deficiency) have been shown to reduce
mortality in patients with severe sepsis.
 Avoid nephrotoxic agents like Contrast dye,
NSAIDs, Aminoglycosides .
 Nutritional support with parenteral or enteral
feeding in ICU

52. Volume overload –salt restriction<1-1.5g/d.
water restriction-<1 litre /d
diuretics
 Hyponatremia –restriction of oral &
intravenous fluids
 Hyperkalemia – K binding resins ,
glucose + insulin
Ca gluconate, Na bicarbonate
 Metabolic acidosis – Na bicarb ., if < 15 meq
 Hyperphosphatemia – PO4 binders .

53. Renal replacement therapy
Modes of dialysis:
 IHD (Intermittent RRT)
Quick removal of solutes over 3-4 hours.
In ICU, hypotensive patients are not the best
candiadtes for this type of HD.
 CRRT (Continuous renal replacement therapy).
Modality of choice in critically ill patients.
 Peritonial dialysis

54.  Peritoneal dialysis uncommonly used for
managing ARF.
 It may be used in locations where IHD or
CRRT are not available.

55.  Dialysis = diffusion =passive
movement of solutes across a
semi-permeable membrane
down concentration gradient
 Good for removal of small
molecules
 Ultrafiltration = convection =
solute + fluid removal across
semi-permeable membrane
down a pressure gradient
(solvent drag)
 Better for removal of fluid and
medium-size molecules

56. •Miller's Anesthesia, 7th ed. 2009
 Hemodialysis -solute passively diffuses down
concentration gradient
 Dialysate flows countercurrent to blood flow.
 Urea, creatinine, K move from blood to dialysate
 Ca and bicarb move from dialysate to blood.
 Hemofiltration: uses hydrostatic pressure gradient
to induce filtration of plasma water + solutes across
membrane.
 Hemodiafiltration: combination of dialysis and
filtration.

57. 1. Oliguria < 200ml/12 hours
2. Anuria < 50 ml/12 hours
3. Hyperkalemia > 6.5 mmol/L
4. Severe acidemia pH < 7.0
5. BUN > 80meq/L
6. Uraemic complications
7. Dysnatraemias > 160 or < 115meq/L
8. Hyper/(hypo)thermia
9. Drug overdose with dialysable drug

58. •Allows control of intra/extravascular
volume
•Corrects acid-base disturbances
•Corrects uraemia & effectively clears
“toxins”
•Promotes renal recovery
•Improves survival
•Is free of complications
•Clears drugs effectively

59.  Intermittent hemodialysis (IHD)
 Continuous renal replacement
therapy (CRRT)
 Peritoneal dialysis
 Hybrid therapies, like Slow Low
efficiency Dialy
diafiltration(SLEDD).

60.  Oldest and most common technique
 Primarily simple diffusive treatment: blood and
dialysate are circulated in countercurrent manner
 Some amount of fluid removal occurs by
ultrafiltration due to pressure driving through circuit
 Best for removal of small molecules.
 A double lumen catheter is placed in the internal
jugular subclavian or femoral vein.
 Typically performed for 4 hours 3 times in a wk .

61.  Introduced in 1980s
 Involves either dialysis (diffusion-based solute
removal) or filtration (convection-based solute
and water removal) treatments in a continuous
mode with slower rate of solute or fluid
removal
 CRRT includes continuous hemofiltration,
hemodialysis and hemodiafiltration, all of
which can be performed using arteriovenous or
venovenous extracorporeal circuits.

62.  Continuous venovenous hemofiltration (CVVH):
Uses blood pump to remove fluids/solutes by
convection ie along a pressure gradient.
 This is the convective flow of water and dissolved
solutes down a pressure gradient caused by
hydrostatic or osmotic forces
 It provides better removal of large MW solutes e.g.
B2-microglobulin, improved clearance of low MW
uraemic toxins and better cardiovascular stability
and Bp control than HD.

63.  Continuous venovenous hemodialysis
(CVVHD): Uses pump + dialysate run at low
flow rate countercurrent to blood flow.
 Continuous venovenous hemodiafiltration
(CVVHDF): combines diffusion for small solute
removal + convection for large solutes.

64.  Arteriovenous versions (CAVH, CAVHD and
CAVHDF) are similar to venovenous except
use AV access and blood pump not required.
 Diadvantages: requires arterial cannulation (+
venous)
 Unreliable flow in patients with ↓ BP or severe PVD
 Requires more anticoagulation
 VV preferred due to lower risk, and faster/more
reliable flow

65.  Used for fluid removal in overloaded CHF
patients
 Blood is driven through a highly permeable
filter in a venovenous mode to primarily
remove water, not solute.
 The ultrafiltrate produced during membrane
transit is not replaced so it corresponds to the
fluid loss.
•Miller's Anesthesia, 7th ed. 2009

66.  Least useful form of CRRT in the ICU
 Blood in capillaries of peritoneal membrane is
exposed to dialysate in abdomen
 Continuous or intermittent
 Inefficient solute/volume clearance can occur if
unstable or poor intestinal blood flow
 Can’t be used if intraabdominal pathology- risk of
peritonitis
 Respiratory burden to patient.

67.  Also known as Extended daily dialysis (EDD)
or slow continuous dialysis (SCD)
 Hybrid therapy: IRRT at lower blood and
dialysate flows for prolonged times (Usually ≥
5 hrs)
 Uses conventional dialysis machines
 Flexibility of duration and intensity
 Major advantages: reduced costs, low or
absent anticoagulation

68.  CRRT requires continuous anticoagulation to
prevent clotting in the CRRT circuit
 ICU patients often at increased risk of bleeding
and hypercoagulable states.
 Many options:
 Systemic anticoagulation with heparin (mst
common), LMWH, heparinoids, thrombin
antagonists
 Regional citrate anticoagulation (preferred)
 Other regional anticoagulation ie heparin/protamine

69. Advantages of early RRT:
 Theoretical benefits: may attenuate organ injury
from acidemia, uremia, fluid overload, and
systemic inflammation
 Several non-randomized studies have reported
improved outcomes associated with early RRT .
 One RCT has compared early and late initiation of
RRT and conclusion was survival at 28 days and
recovery of renal function was equivalent in both
the groups.

70.  Earlier initiation of RRT in critically ill patients
with AKI may have a beneficial impact on
survival .
 Many studies recommend initiation of RRT
prior to the development of advanced uremic
symptoms, or when the BUN reaches 80 - 100
mg/dL
 No known threshold of fluid overload for
initiating RRT

71.  Until “evidence of recovery of kidney function”
 Improved UOP in oliguria
 Decreasing creatinine
 Creatinine clearance minimum 20 mL/min.

72.  Theoretical benefits to both.
 At least 7 RCTs and 3 meta-analyses have not
demonstrated difference in outcome.
 A metaanalysis of 9 randomized trials: No effect on
mortality or recovery based on type of RRT used.
 Suggestion was that continuous RRT had fewer
episodes of hemodynamic instability and better
control of fluid balance .

73.  Specific patient populations who may benefit
from CRRT
 Hemodynamic instability
 Combined acute renal and hepatic failure
 Improved CV instability and intracranial
pressure
 Acute brain injury
Vanholder et al. Critical Care 2011, 15:204

74.  Practicality and flexibility
 Uses same machines as chronic HD
 Multiple patients per day
 Less expensive than CRRT (by about ½)
 Fewer bleeding complications
 CRRT requires continuous anticoagulation
 Superior solute clearance, more rapid removal
of toxins (due to higher flows)
Vanholder et al. Critical Care 2011, 15:204

75.  Specific patient populations benefitting from
IRRT:
 High bleeding risk
 Ie. after recent surgery
 Acute treatment of hyperkalemia, rhabdomyolysis,
poisoning, tumor lysis syndrome
Vanholder et al. Critical Care 2011, 15:204

76.  RRT has been proposed as a “Extracorporeal
blood purification therapy (EBPT)” as
adjuvant therapy for SEPSIS/MODS for
removal of harmful inflammatory mediators or
endotoxemia
 Very less support from animal models and
small clinical studies
•Miller's Anesthesia, 7th ed. 2009

77.  AKI in the ICU is common and associated with
high mortality.
 The best time to initiate and stop RRT is
controversial
 No good data that CRRT is better than IRRT in
the ICU, except for a few specific situations
 Consider CRRT if severely unstable pts, severe
volume overload, combined renal/hepatic failure
 IRRT best if there is bleeding risk or acute
hyperkalemia or cases of poisoning.

78.  No drugs are Currently available to enhance or
hasten renal recovery once ARF occurs.
 There is now clear evidence that ARF is
associated with excess mortality, irrespective of
whether the patient requires renal replacement
therapy.
 Hence prevention is the only powerful tool to
improve outcome of AKI
78

79. 79
Identification of patients at high risk to develop
AKI-Elderly, DM, HT. Sepsis
Non Pharmacological Pharmacological
 Ensuring adequate
hydration (reversing
dehydration).
 Maintenance of
adequate mean
arterial
pressure>65mmHg
 Minimizing exposure
to nephrotoxins.
 Loop diuretics,
 Mannitol,
 Vasopressors if
necessory.

80. THANK YOU