This document discusses acute kidney injury (AKI), including its definition, classification systems, causes, biomarkers, treatment, and management. It provides a brief history of terms used to describe AKI and summarizes current classification systems. It also outlines causes of AKI, the advantages of various biomarkers for early detection, and general principles and indications for renal replacement therapy (RRT). Modalities of RRT including peritoneal dialysis, intermittent hemodialysis, slow low-efficiency dialysis, and continuous renal replacement therapy are compared.

1. Dr. Osama El-Shahat
Consultant Nephrologist
Head of Nephrology Department
New Mansoura General Hospital (international)
ISN Educational Ambassador

5. Objectives
Treatment
 Non- dialytic support
Dialytic support
Diagnosis
Incidence
Mortality
Biomarkers
Definatinon
ARF AKI

6. 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)

7.  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”
What do we mean by AKI?

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

9. AKIN Classification

10. 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

11. Number of ARF Hospitalizations: 1979 to 2002
Rates per 1,000 persons
0.0
0.5
1.0
1.5
2.0
2.5
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002
Source: National Center for Health Statistics, National Hospital Discharge Survey

12. Kidney International advance online publication , 1
May 2013
Mortality in AKI

13. Causes of AKI
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.

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

15. Timing nephrology consultation
(Mehta,Am J Med 2002)
In-hospital mortality
Early
consult
Delayed
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

16. Kidney International (2013) 83, 901–908
Early Referral

17. Biomarkers are foot prints of actual
organ damage
 Creatinine Not A Biomarker
 The creatinine level is influenced by multiple non-
renal factors, such as age, gender, muscle mass, muscle
metabolism, diet, medications, and hydration status
 In AKI, the serum creatinine level can take several
hours or days to reach a new steady state and thus does
not reflect the actual decrease in GFR in the acute
setting
 Because of renal reserve, the serum creatinine level
may not rise until more than half of the kidney
function has been lost

18. Creatinine is late, or is it too late?

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

20. Early detection of AKI by Cystatin C
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
•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
Herget-Rosenthal et al, Kidney Int 2004, 66: 1115- 1122

21. Indications of Renal Biopsy
1
Urine
No cast
FENa<1%
Muddy
brown cast
FENa>1%
Red cell
cast
White cell
cast
eosinophil
Pre-renal
ATN Glomerular Interstitial
Biopsy
2. Unknown cause
3. Prolonged ATN

22. 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.
3.4.1: We recommend not using diuretics to prevent AKI. (1B )
3.4.2: We suggest not using diuretics to treat AKI, except in the
management of volume overload. (2C )

23. There is insufficient evidence that the low-dose dopamine
improves survival or obviates the need for dialysis in persons with
acute renal failure. The routine use of low-dose dopamine should be
discouraged until a prospective, randomized, placebo-controlled trial
establishes its safety and efficacy.
Is the administration of dopamine associated with adverse or
favorable outcomes in acute renal failure? Auriculin Anaritide
Acute Renal Failure Study Group.
Low Dose Dopamine in AKI
3.5.1: We recommend not using low-dose dopamine to prevent or
treat AKI. (1A)

24. IV Fluids in AKI
3.1.1: 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.
(2B)

25. Contrast Induced AKI
isotonic sodiumwith eitherexpansionvolume.i.v:We recommend4.4.1
. volume expansion,i.v, rather than nochloride or sodium bicarbonate solutions
)A1AKI. (-in patients at increased risk for CI
or)IHD(hemodialysisnot using prophylactic intermittent:We suggest4.5.1
hemofiltration (HF) for contrast-media removal in patients at increased risk for
)C2AKI. (-CI
, incrystalloidsisotonic.i.vwithtogether,NACoral:We suggest using4.4.3
)D2AKI. (-patients at increased risk of CI
4.3.2: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. (1B)

26. 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.
Contrast Induced AKI

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

28. Indications for RRT in critically ill AKI patients
Renal Indications
Life-threatening indications
Hyperkalemia
Metabolic Acidosis
Pulmonary edema
Uremic omplications

29. Dialysis Interventions forTreatment of AKI
 5.1.1: Initiate RRT emergently when life-threatening
changes in fluid, electrolyte, and acid-base balance
exist.(Not Graded)
 5.1.2: Consider the broader clinical context, the presence
of conditions that can be modified with RRT, and trends
of laboratory tests—rather than single BUN and
creatinine thresholds alone—when making the decision
to start RRT. (Not Graded)

30. Conclusions
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 .
Early referral will improve outcome

32. When to start RRT ?
Crit Care Med 2008, Vol. 36, No 4 (suppl.)
Early RRT seems better

33. What Modality?

34. Renal ReplacementTherapy in AKI
1. Peritoneal dialysis (PD)
2. Intermittent Hemodialysis (IHD)
3. Slow Low-Efficiency Dialysis (SLED)
4. Continuous Renal Replacement Therapy (CRRT)
• Slow Continuous Ultrafiltration (SCUF)
• Continuous Venovenous Hemofiltration (CVVH)
• Continuous Venovenous Hemodialysis (CVVHD)
• Continuous Venovenous Diafiltration (CVVHDF)

35. 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

36. PD … the modality first used for the treatment of KI

37. Blood Purif 2013;36:226–230 DOI: 10.1159/000356627

39. What are the modalities of CRRT ?
Mode of
therapy
Principle method of
solute clearance
CVVH Convection
CVVHD Diffusion
CVVHDF Convection & Diffusion
SCUF Ultrafiltration (fluids)

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

41. CVVH Avoids Hypertensive Episodes
Ronco C et al Kidney Int 56 ( suppl 72 ) s-8-s-14 , 1999

42. Dialysis Interventions forTreatment of AKI
5.6.2: We suggest using CRRT, rather than standard
intermittent RRT, for hemodynamically unstable
patients. (2B)
5.6.1: Use continuous and intermittent RRT as
complementary therapies in AKI patients. (Not Graded

43. Recovery from ARF in IHD vs CRRT
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%

44. Is their an alternative to CRRT ?
 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 KielsteiJT Nat Clin Pract Nephrol, 2006
Slow Low-Efficiency Daily Dialysis (SLED)

45. Slow Low-Efficiency Daily Dialysis (SLED)
 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

46. How we can do it ?
Processes of care, more pertinent to
Nephrologists:-
 Vascular Access
 Membrane characteristics
 Solution
 Anticoagulation
 Dose

47.  5.4.1: We suggest initiating RRT in patients with AKI via an
uncuffed nontunneled dialysis catheter, rather than a
tunneled catheter. (2D)
 5.4.2: 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.
Vascular access
KDIGO® AKI Guideline March 2012

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

49. 5.3.2.1: For anticoagulation in intermittent RRT, we
recommend using either unfractionated or
low-molecular weight heparin, rather than
other anticoagulants. (1C)
5.3.2.2: 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

50. Conclusions
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 .
Early referral will improve outcome

51. Conclusions
 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
mortality
 Dose: No benefit to “intensive” therapy
Dialytic Support of AKI = Individualization