1. Dr. Osama El-Shahat
Consultant Nephrologist
Head of Nephrology d ( epartment-NMGH (Egypt

2. OObbjjeeccttiivveess
Diagnosis
Incidence
Mortality
Biomarkers
Treatment
 Non- dialytic support
Dialytic support
Definatino
n
ARF
AKI

3. ARF AKI
1802: Ischuria Renalis (William Heberden)
1909: Acute Bright’s Disease (William Osler)
W.W.I: War Nephritis
W.W.II: Acute Kidney Insufficiency (Bywaters & Beall)
1951: Acute Renal Failure (Homer W. Smith)
2006 : Acute Kidney Injury (AKI Network)

4. WWhhaatt ddoo wwee mmeeaann bbyy AAKKII??
 By AKI we actually mean “loss of small
solute clearance” (urea/creatinine
increase in blood)
 This implies loss of GFR
 So…clinically we actually mean
“acute decrease in GFR”

5. Lameire N, Van BW, Vanholder R. Nat Clin Pract Nephrol 2006; 2:
.364–377
?Can we do staging for AKI

6. AKIN Classification

7. RRIIFFLLEE VVeerrssuuss AAKKIINN
The use of the RIFLE system resulted in a higher detection
rate of AKI during the first 48 hours of ICU stay.
Nephrology Self-Assessment Program - Vol 10, No 3, May 2011

8. What is ? the advantages of RIFLE Criteria
Applying the RIFLE criteria revealed new
insights.
Firstly,the RIFLE classification is feasible
and fairly straightforward.
Secondly, the patients categorized as
RIFLE-F had a far higher mortality than
RIFLE-I and -R patients.
Max Bell et al; Nephrol Dial Transplant 2005 20:354 –
360

9. Number ooff AARRFF HHoossppiittaalliizzaattiioonnss:: 11997799 ttoo 22000022
RRaatteess ppeerr 11,,000000 ppeerrssoonnss
2.5
2.0
1.5
1.0
0.5
0.0
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002
Source: National Center for Health Statistics, National Hospital Discharge Survey

10. Mortality in Sepsis and RIFLE
Critical Care 2007; 11:411

11. CCaauusseess ooff AAKKII
Pre renal Intrinsic renal Post renal
Decrease in
effective
.blood volume
Arterial
occlusion
Or
.stenosis
Homodynamic
.Form
Vascular
.Vasculitis
Malignant
hypertension
Acute
Glomerulo
nephritis
Acute
Interstitial
nephritis
Acute
Tubular
necrosis
.Ischemic .Nephrotoxic
Obstruction
Of
Collecting
System
Or
Extra renal
drainage
Exogenous
Antibiotic
Radio contrast
cisplatin
Endogenous
Intra tubular pigment
.Intra tubular protein
.Intra tubular crystal

12. CAUSES OF AKI
Post-OP, sepsis,
shock,multi-organ
failure 70%
Glomerulonephritis 5%
Nephrotoxic agents 10% reduced blood flow
Obstructive
uropathy 15%
ischemia
acute tubular necrosis

13. Findings that suggest prerenal causes:
Volume depletion
Congestive heart failure
Severe liver disease or other edematous states
Findings that suggest postrenal causes:
Palpable bladder or hydronephrotic kidneys
Enlarged prostate
Abnormal pelvic examination
Large residual bladder urine volume
History of renal calculi,
Findings that suggest intrinsic renal disease:
Exposure to nephrotoxic drugs or hypotensive
Recent radiographic procedures with contrast

14. Examine the urine sediment:
•If no abnormalities: suspect prerenal or postrenal
azotemia
•If eosinophils: suspect acute interstitial nephritis
•If red blood cell casts: suspect glomerulonephritis
or vasculitis
•If renal tubular epithelial cells and muddy brown
casts: suspect acute tubular necrosis

15. Findings that suggest prerenal azotemia :
Urinary sodium concentration <20 mEq/L
Urine : plasma creatinine ratio >30
Renal failure index <1
RReennaall ffaaiilluurree iinnddeexx = (urinary sodium concentration × plasma
creatinine concentration)/urinary creatinine concentration
Urine osmolality >500 mOsm/kg
Findings that suggest acute tubular necrosis or postrenal azotemia:
Urinary sodium concentration >40 mEq/L
Urine:plasma creatinine ratio <20
Renal failure index >1
Urine osmolality <400 mOsm/kg

20. TTiimmiinngg nneepphhrroollooggyy ccoonnssuullttaattiioonn
((Mehta, Am J Med 2002
In-hospital mortality
EEaarrllyy
consult
DDeellaayyeedd
consult
P
40% 67% <0,001
Early nephrologist involvement in patients with AKI
may reduce the risk of a further decrease in kidney
function.
Am J Kidney Dis. 2011;57(2):228-234

21. New urinary biomarkers for the early
detection of acute kidney disease
Neutrophil gelatinase associated lipocalin
Han, Bonventre,Current Opin Crit Care 2004, 10:476–482

22. Early detection of AKI by Cystatin C
•Changes in cystatin C were able to detect the onset of AKI
one to two days earlier than comparable changes in serum creatinine
1. RIFLE- R ( ≥ 50 % increase ): 1.5 ± 0.6 days earlier
2. RIFLE- I ( ≥ 100 % increase): 1.2 ± 0.9 days earlier
3. RIFLE- F ( ≥ 200 % increase): 1.0 ± 0.6 days earlier
Definition of AF
Area under the ROC
Day - 2 Day - 1 Day 0
≥ 50 % increase 0.82 0.97 0.99
≥ 100 % increase 0.92 0.98 0.98
≥ 200 % increase 0.97 0.99 0.99
Herget-Rosenthal et al, Kidney Int 2004, 66: 1115- 1122

23. Loop diuretics in AKI
Diuretics, particularly high doses of loop diuretics, are
frequently administered to patients with acute renal failure.
This is done in part in an attempt to convert oliguric to
nonoliguric acute renal failure.
However, a retrospective observational report found that
the use of diuretics in this setting may increase the risk of
death and no recovery of renal function.
33..44..11: We recommend not using diuretics to prevent AKI. (11BB)
33..44..22: We suggest not using diuretics to treat AKI, except in the
management of volume overload. (22CC)

24. LLooww DDoossee DDooppaammiinnee iinn AAKKII
TThheerree iiss iinnssuuffffiicciieenntt eevviiddeennccee tthhaatt tthhee llooww--ddoossee
ddooppaammiinnee iimmpprroovveess ssuurrvviivvaall oorr oobbvviiaatteess tthhee nneeeedd ffoorr
ddiiaallyyssiiss iinn ppeerrssoonnss wwiitthh aaccuuttee rreennaall ffaaiilluurree.. TThhee rroouuttiinnee
uussee ooff llooww--ddoossee ddooppaammiinnee sshhoouulldd bbee ddiissccoouurraaggeedd uunnttiill
aa pprroossppeeccttiivvee,, rraannddoommiizzeedd,, ppllaacceebboo--ccoonnttrroolllleedd ttrriiaall
eessttaabblliisshheess iittss ssaaffeettyy aanndd eeffffiiccaaccyy..
Is the administration of dopamine associated
with adverse or favorable outcomes in acute
renal failure? Auriculin Anaritide Acute Renal
Failure Study Group.
33..55..11: We recommend not using low-dose dopamine to prevent
or treat AKI. (1A)

25. IV Fluids in AKI
33..11..11: In the absence of hemorrhagic shock, we
suggest using isotonic crystalloids rather than
colloids (albumin or starches) as initial
management for expansion of intravascular volume
in patients at risk for AKI or with AKI. (22BB)

26. Contrast Induced AKI
44..33..22: We recommend using either iso-osmolar or low-osmolar
iodinated contrast media, rather than high-osmolar iodinated contrast
media in patients at increased risk of CI-AKI. (11BB)
We recommend i.v. volume expansion with either isotonic : 44..44..11
sodium chloride or sodium bicarbonate solutions, rather than no i.v.
)volume expansion, in patients at increased risk for CI-AKI. (11AA
We suggest using oral NAC, together with i.v. isotonic : 44..44..33
)crystalloids, in patients at increased risk of CI-AKI. (22DD
We suggest not using prophylactic intermittent hemodialysis : 44..55..11
(IHD) or hemofiltration (HF) for contrast-media removal in patients at
)increased risk for CI-AKI. (22CC

27. Contrast Induced AKI
Bicarbonate or Saline
Among the large
randomized trials there was
no evidence of benefit for
hydration with sodium
bicarbonate compared with
sodium chloride for the
prevention of CI-AKI.

28. Stage-based management
General Principles
(Stage 1 (RRiisskk
Risk for more severe AKI
Monitor (prevent
(progression
(Stage 2 (IInnjjuurryy
Risk of AKI-related
mortality/morbidity
high
(Conservative therapy
(Stage 3 (FFaaiilluurree
Highest risk of death
Consider RRT
AKI Stage
1 2 3
Discontinue all nephrotoxic agents when possible
Ensure volume status and perfusion pressure
Consider functional hemodynamic monitoring
Monitoring Serum creatinine and urine output
Avoid hyperglycemia
Consider alternatives to radiocontrast procedures
Non-invasive diagnostic workup
Consider invasive diagnostic workup
Check for changes in drug dosing
Consider Renal Replacement Therapy
Consider ICU admission
Avoid subclavian catheters if possible
Risk
Injury
Failure
High Risk

29. Indications for RRT in critically ill AKI patients
Renal Indications
Life-threatening indications
Hyperkalemia
Metabolic Acidosis
Pulmonary edema
Uremic omplications
Gibney et al, Clin J Am Soc Nephrol 2008

30. DDiiaallyyssiiss IInntteerrvveennttiioonnss ffoorr TTrreeaattmmeenntt ooff AKI
55..11..11: IInniittiiaattee RRRRTT eemmeerrggeennttllyy when life-threatening
changes in fluid, electrolyte, and
acid-base balance exist.(Not Graded)
55..11..22: Consider the bbrrooaaddeerr cclliinniiccaall ccoonntteexxtt, the
presence of conditions that can be modified with
RRT, and ttrreennddss ooff llaabboorraattoorryy tests—rather
than single BUN and creatinine thresholds alone
—when making the decision to start RRT. (Not
Graded)
KDIGO® AKI Guideline March 2012

31. ??WWhheenn ttoo ssttaarrtt RRRRTT
Crit Care Med 2008, Vol. 36, No 4 (suppl.(
EEaarrllyy RRRRTT sseeeemmss bbeetttteerr

32. WWhhaatt MMooddaalliittyy ??
1. Peritoneal dialysis (PD)
2. Intermittent Hemodialysis (IHD)
3. Slow Low-Efficiency Daily Dialysis (SLED)
4. Continuous Renal Replacement Therapy
(CRRT)
• Slow Continuous Ultrafiltration (SSCCUUFF)
• Continuous Venovenous Hemofiltration (CCVVVVHH)
• Continuous Venovenous Hemodialysis (CCVVVVHHDD)
• Continuous Venovenous Diafiltration (CCVVVVHHDDFF)

33. Peritoneal Dialysis (PD( In AkI
Advantages
Hemodynamic stability
Slow correction
Easy access placement
No Anticoagulation
Tolerated in children
Disadvantages
Risk of infections
Difficulty to use with abdominals
surgery
Logestics

34. Potential Advantages of CCRRRRTT
Homodynamic stability
Recovery of renal function
Brain edema
Biocompatibility
Removal of cytokines
Nutritional support
Correction of metabolic acidosis

35. CCVVVVHH Avoids Hypertensive Episodes
RRoonnccoo CC eett aall KKiiddnneeyy IInntt 5566 (( ssuuppppll 7722 (( ss--88--ss--1144 ,, 11999999

36. Dialysis Interventions for Treatment of AKI
55..66..22:: We suggest using CRRT, rather than
standard intermittent RRT, for hemodynamically
unstable patients. (2B)
55..66..11: Use continuous and intermittent RRT as
complementary therapies in AKI patients. (Not
Graded
KDIGO® AKI Guideline March 2012

37. Study Modality recovering renal function%
SUPPORT *IHD **67%
.Morgera et al CRRT 90%
.Ronco et al CRRT 90%
.Mehta et al
IHD
CRRT
59%
92%
†BEST Kidney
IHD
CRRT
65%
89%

38. Is their an aalltteerrnnaattiivvee ttoo CCRRRRTT ??
Slow Low-Efficiency Daily Dialysis (SSLLEEDD(
 Typically performed over 6-12 hours
Can be performed with a conventional
dialysis machine
– A little less labor intensive
– Requires less training/startup
Fliser D and Kielstei JT Nat Clin Pract Nephrol, 2006

39. Slow Low-Efficiency ( Daily Dialysis (SSLLEEDD
 Major advantages: flexibility, reduced costs,
low or absent anticoagulation
 Similar adequacy and hemodynamics
One small study (16 pts) showed slightly higher
acidosis and lower BP (Baldwin 2007)
VA trial (Palevsky NEJM 2008) suggests similar
outcomes as CRRT and IRRT.
Vanholder et al. Critical Care 2011, 15:204

40. Mode of
therapy
Principle method of
solute clearance
CVVH Convection
CVVHD Diffusion
CVVHDF Convection & Diffusion
SCUF (Ultrafiltration (fluids

41. ? HHooww wwee ccaann ddoo iitt
Processes of care, more pertinent to
Nephrologists:-
Vascular Access
Membrane characteristics
Solution
 Anticoagulation
Dose

42. Vascular access
55..44..11: We suggest initiating RRT in patients with AKI via an
uncuffed nontunneled dialysis catheter, rather than a
tunneled catheter. (2D)
55..44..22: When choosing a vein for insertion of a dialysis
catheter in patients with AKI, consider these preferences (Not
Graded):
 First choice: right jugular vein;
 Second choice: femoral vein;
 Third choice: left jugular vein;
 Last choice: subclavian vein with preference for the dominant side.
KDIGO® AKI Guideline March 2012

43. SSoolluuttiioonnss ffoorr CCRRRRTT
Bicarbonate­versus
lactate­based
fluid replacement in CVVH
Prospective, randomized study
Results :
 Serum lactate concentration was
significantly higher and the
bicarbonate was lower in patients
treated with lactate­based
solutions
 Increased incidence of CVS
events in pts ttt with lactate
solution
 Hypotension
 Increased dose of inotropic
support
barenborck and colleague
Barenbrock M et al; Kidney Int (2000

44. Dialysis Interventions for Treatment of AKI
55..77..33: We suggest using bicarbonate, rather than
lactate, as a buffer in dialysate and replacement
fluid for RRT in patients with AKI and liver
failure and/or lactic acidemia. (2B)
KDIGO® AKI Guideline March 2012

45. TThhee MMeemmbbrraannee
High Flux membrane , synthetic , biocompatable ,
acting by providing both methods of detoxications:
a)Diffusion : for low molecular weight toxins.
b)Convection : for large molecules.
55..55..11: We suggest to use dialyzers with a biocompatible
membrane for IHD and CRRT in patients with AKI. (2C)
KDIGO® AKI Guideline March 2012

46. Modality Advantages Disadvantages
Heparin Good anticoagulation Thrombocytopenia bleeding
LMWH Less thrombocytopenia bleeding
Citrate Lowest risk of bleeding Metabolic alkalosis,
hypocalcemia special dialysate
Regional Heparin Reduced bleeding Complex management
Saline flushes No bleeding risk Poor efficacy
Prostacycline Reduced bleeding risk Hypotension poor efficacy

47. DDoossee
55..88..11: The dose of RRT to be delivered should be
prescribed before starting each session of RRT. (Not
Graded)
We recommend frequent assessment of the actual
delivered dose in order to adjust the prescription.
(1B)
55..88..22: Provide RRT to achieve the goals of electrolyte,
acid-base, solute, and fluid balance that will
meet the patient’s needs. (Not Graded)

48. CCCCoooonnnncccclllluuuussssiiiioooonnnnssss
Early detection and treatment of AKI may improve
outcomes.
Even a minor acute reduction in kidney function has an
adverse prognosis.
Hunting AKI in ICU….use a RIFLE .
Continuous renal replacement therapy is a standard of
care and has improved outcomes from AKI in critically
ill patients.
Early start of CRRT is associated with better recovery of
AKI than IHD but no difference on mortality.
There is a dialysis dose effect on out come.

49. TThhaannkk yyoouu

50. Indications for RRT in critically ill AKI patients
RReennaall RReeppllaacceemmeenntt RReennaall SSuuppppoorrtt
 Life-threatening indications
Hyperkalemia
Acidemia
Pulmonary edema
 Uremic complications
 Solute control
 Fluid removal
 Regulation of acid-base and
electrolyte status
 Nutrition
 Fluid removal in congestive
heart failure
 Cytokine manipulation in
sepsis
 Cancer chemotherapy
 Treatment of respiratory
acidosis of ARDS
 Fluid management in
multiorgan failure

51. Contrast-induced AKI
Use the lowest possible dose of contrast : 4.3.1 
medium in patients at risk for CI-AKI. (Not
(Graded
We recommend using either iso-osmolar : 4.3.2 
or low-osmolar iodinated contrast media, rather
than high-osmolar iodinated contrast media in
(patients at increased risk of CI-AKI. (1B

52. Contrast-induced AKI
We recommend i.v. volume expansion with : 4.4.1 
either isotonic sodium chloride or sodium
bicarbonate solutions, rather than no i.v. volume
expansion, in patients at increased risk for CI-(
AKI. (1A
We recommend not using oral fluids alone : 4.4.2 
(in patients at increased risk of CI-AKI. (1C
We suggest using oral NAC, together with : 4.4.3 
i.v. isotonic crystalloids, in patients at increased
(risk of CI-AKI. (2D

53. Contrast-induced AKI We suggest not using theophylline to prevent : 4.4.4 
(CI-AKI. (2C
We recommend not using fenoldopam to : 4.4.5 
(prevent CI-AKI. (1B
We suggest not using prophylactic : 4.5.1 
intermittent hemodialysis (IHD) or hemofiltration
(HF) for contrast-media removal in patients at
(increased risk for CI-AKI. (2C

54. Medications
We recommend not using diuretics to prevent : 3.4.1 
(AKI. (1B
We suggest not using diuretics to treat AKI, : 3.4.2 
(except in the management of volume overload. (2C
We recommend not using low-dose dopamine : 3.5.1 
(to prevent or treat AKI. (1A
We suggest not using fenoldopam to prevent or : 3.5.2 
(treat AKI. (2C

55. WWhhaatt ddoo wwee mmeeaann bbyy AAKKII??
 By AKI we actually mean “loss of small
solute clearance” (urea/creatinine
increase in blood)
 This implies loss of GFR
 So…clinically we actually mean
“acute decrease in GFR”

56. ?How to define AKI
Serum creatinine or other solute
If serum creatinine, do we choose
• Absolute increase ?
• Percent increase ?
• Over what time ?
• Minimum peak ?

58. CChhaannggee ooff ccaassee mmiixx iinn AAKKII
11997744--11997799 11999955--22000000
8855%% 9922%%
MMoorrttaalliittyy:: 5544%% MMoorrttaalliittyy :: 5533%%
RRiiccccii,, RRoonnccoo CCrriitt CCaarree CClliinn 2211::335577--336666,,22000055

59. Incidence of ARF, need of RRT, and mortality in
187 patients with proven sepsis
((surgical ICU Ghent –16 months
23
50
28
53
69
70
60
50
40
30
20
10
0
Mortality ICU Mortality hosp Need of RRT
- ARF
+ ARF
%
Hoste et al JASN 14:1022-1030,2003

60. Hospital mortality rates in RRT patients and matched
control critically ill patients in Austria
70
60
50
40
30
20
10
0
Controls RRT
80
70
60
50
40
30
20
10
0
Control RRT
< 40-60 > 60
%
Hospital mortality
40 > 40-60 60 <
Metnitz et al Crit Care Med 30:2051-2058, 2002 Age groups

61. ACUTE KIDNEY
INJURY
The most frequent scenario is of AKI
occurring in the setting of circulatory
disturbance caused by severe illness
particularly if sepsis is involved.

62. CCCCoooonnnncccclllluuuussssiiiioooonnnnssss
Data from high quality RCTs are lacking
The current trend is to provide RRT earlier
There may be a recovery advantage to using CRRT
vs. HD for initial management of AKI but no
difference on mrtalitaty
 Dose: No benefit to “intensive” therapy
DDiiaallyyttiicc SSuuppppoorrtt ooff AAKKII ==
IInnddiivviidduuaalliizzaattiioonn

63. Urine NGAL excretion post cardiac surgery in children
Neutrophil gelatinase associated lipocalin
Mishra J, et al, Lancent 2005; 365:1231-1238

64. Management priorities in AKI
((I
Detect as early as possible even minimal AKI
Exclude other renal causes of AKI
Search for and correct prerenal and postrenal
factors
Review medications and stop nephrotoxins
Optimize cardiac output and renal blood flow
Restore and/or increase urine flow
Monitor fluid intake and output, daily weight

65. Management priorities in AKI
((II
Search for and treat acute complications
(hyperkalemia, hyponatremia, acidosis
hyperphosphatemia , pulmonary edema)
Provide early nutritional support
Search for and aggressively treat infections
Initiate dialysis before uremic complications
emerge
Dose drugs appropriate for their clearance
Stop and repair ongoing intracellular injury

66. DDoossee
Optimal intensity of RRT is controversial
RCT of 1124 critically ill pts with AKI and sepsis or at
least one organ failure to intensive or less intensive
renal-replacement therapy
Hemodynamically unstable pts received CRRT or
SLEDD, stable pts IRRT
Intensive RRT= IRRT or SLEDD 6x/wk or CRRT at 35
ml/kg/hr
Less intensive RRT= IRRT or SLED 3x/wk or CRRT at 20
ml/kg/hr
VA/NIH Acute Renal Failure Trial Network. (NEJM 2008;359:7(:

67. No difference in mortality
VA/NIH Acute Renal Failure Trial Network. (NEJM 2008;359:7(:

68. The RENAL Replacement Therapy Study
1508 Critically ill patients with ARF on CVVHF were
randomized to:-
 llooww (25 mL/kg/hr – 747 patients)
 hhiigghh intensity (40 mL/kg/hr – 761 patients) effluent rates.
There was no
difference in 90 day
mortality rate
(44.7%) or the need
for RRT at 90 day
between the two
treatment groups.
N Engl J Med. 2009 Oct 22;361(17(:1627-38

69. 55..33..22..11: For anticoagulation in intermittent RRT, we
recommend using either unfractionated or
low-molecular weight heparin, rather than
other anticoagulants. (1C)
55..33..22..22: For anticoagulation in CRRT, we suggest using
regional citrate anticoagulation rather than
heparin in patients who do not have
contraindications for citrate. (2B)
KDIGO® AKI Guideline March 2012

70. 55..88..11: The dose of RRT to be delivered should be prescribed
before starting each session of RRT. (Not Graded)
We recommend frequent assessment of the actual delivered
dose in order to adjust the prescription. (1B)
55..88..22: Provide RRT to achieve the goals of electrolyte,
acid-base, solute, and fluid balance that will meet
the patient’s needs. (Not Graded)
KDIGO® AKI Guideline March 2012
DDoossee

71. More than 200
different definitions
of ARF +++
 58 creatinine
levels (1.5
to 10 mg/dl)
 33 UO thresholds
(0 à 950
ml/24h)

72. Community acquired Hospital-acquired ICU-acquired
Incidence Low Moderate (5%( High (10-20%(
Cause Single Multiple MOF
pre>post>renal pre>ATN>post MOF + ATN
Outcome good less good poor
70-90% survival 30-50% survival 10-30%survival
Schrier & Gottschalk, . Diseases of the Kidney, 1996