1. Overview of Acute Kidney Injury (AKI)
Dr. Osama El-Shahat
Consultant Nephrologist
Head of Nephrology department-
NMGH (Egypt)
ISN Educational Ambassador

2. Objectives Definition Diagnosis Treatment Incidence Mortality
Biomarkers
Treatment
Non- dialytic support
Dialytic support

3. What do we mean by AKI? “acute decrease in GFR”
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” 3

4. Can we do staging for AKI?
the Acute Dialysis Quality Initiative, a group of experts in acute kidney dysfunction, consisting of nephrologists and intensivists, proposed the RIFLE criteria for acute kidney dysfunction
Lameire N, Van BW, Vanholder R. Nat Clin Pract Nephrol 2006; 2: 364–377.

5. 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 :354 –360

6. Number of ARF Hospitalizations: 1979 to 2002 Rates per 1,000 persons
The increase in hospitalized cases of ARF is not due to large changes in population. The rate per 1,000 persons in 1979 was 0.16 and in 2002 was 2.was 2.34.
Source: National Center for Health Statistics, National Hospital Discharge Survey

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

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

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

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

11. 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

12. 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
RIFLE- R ( ≥ 50 % increase ): 1.5 ± 0.6 days earlier
RIFLE- I ( ≥ 100 % increase): 1.2 ± 0.9 days earlier
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
≥ 200 % increase
Herget-Rosenthal et al, Kidney Int 2004, 66:

13. 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)

14. Low Dose Dopamine in AKI
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.
Chertow GM; Sayegh MH; Allgren RL Lazarus JMAm J Med, 101(1): Jul
3.5.1: We recommend not using low-dose dopamine to prevent or treat AKI. (1A)

15. 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)

16. Contrast Induced AKI
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)
4.4.1: We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion, in patients at increased risk for CI-AKI. (1A)
4.4.3: We suggest using oral NAC, together with i.v. isotonic crystalloids, in patients at increased risk of CI-AKI. (2D)
4.5.1: We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI. (2C)

17. 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.

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

19. 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

20. Dialysis Interventions for Treatment 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)
KDIGO® AKI Guideline March 2012

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

22. What Modality ? Peritoneal dialysis (PD)
Intermittent Hemodialysis (IHD)
Slow Low-Efficiency Daily Dialysis (SLED)
Continuous Renal Replacement Therapy (CRRT)
Slow Continuous Ultrafiltration (SCUF)
Continuous Venovenous Hemofiltration (CVVH)
Continuous Venovenous Hemodialysis (CVVHD)
Continuous Venovenous Diafiltration (CVVHDF) 22

23. 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

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

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

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

27. Dialysis Interventions for Treatment 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 )
KDIGO® AKI Guideline March 2012

28. Recovery from ARF in IHD vs CRRT
Study
Modality
% recovering renal function
SUPPORT
IHD*
67%**
Morgera et al.
CRRT
90%
Ronco et al.
Mehta et al.
IHD
59%
92%
BEST Kidney†
65%
89% 28

29. Is their an alternative to CRRT ?
Slow Low-Efficiency Daily Dialysis (SLED)
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

30. 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

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

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

33. Vascular access
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.
KDIGO® AKI Guideline March 2012

34. Anticoagulation 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 34

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

36. 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 36

37. 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

38. Thank you