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1. Dr. Farmer
Prevention and
Treatment of Acute
Kidney Injury in the
ICU

2. Prevention and Treatment of Acute Kidney
Injury in the ICU
J. Christopher Farmer

3. Learning Objectives
To discuss…
– Pathophysiology, risk factors, and etiologies of
AKI
– Current and emerging methods of early diagnosis
– Prevention of AKI
– Treatment of AKI

4. Epidemiology and Pathophysiology

5. Increasing Incidence of AKI
Nash, et al: Am J Kidney Dis; 2002, 39:390

7. Arterial Vasodilatation and Renal
Vasoconstriction in Patients with Sepsis

8. Diagnosis and Classification of AKI

9. Diagnostic Criteria for AKI
An abrupt (within 48 hours) reduction in
kidney function currently defined as:
1.An absolute increase in serum creatinine of more than
or equal to 0.3 mg/dl, or
2.A percentage increase in serum creatinine of more
than or equal to 50% (1.5 fold from baseline), or
3.A reduction in urine output (documented oliguria of
less than 0.5 ml/kg per hour for more than 6 hours)
Mehta et al: Critical Care; 2007, 11:R31-R39

10. “RIFLE” Criteria for AKI
Bellomo & the ADQI workgroup: Critical Care; 2004, 8:R204-R212

11. Classification of AKI Severity
Mehta et al: Critical Care; 2007, 11:R31-R39

12. Mortality Associated with Rising Serum
Creatinine
Unadjusted
Adjusted for age & sex
Multivariable analyses
Chertow, et al: J Am Soc Nephrol; 2005, 16:3365-3370

13. FENa = (UNa/PNa) / (UCr/PCr) X 100
 Calculating the FENa is useful in AKI only in the presence of
oliguria
 In patients with prerenal azotemia, the FENa is usually less
than 1%
 In ATN, the FENa is greater than 1%.
 Exceptions to this rule are ATN caused by radiocontrast
nephropathy, severe burns, acute glomerulonephritis, and
rhabdomyolysis
 In the presence of liver disease, FENa can be less than 1% in
the presence of ATN
 Because administration of diuretics may cause the FENa to be
greater than 1%, these findings cannot be used as the sole

14. FEUrea = (Uurea/Purea) / (UCr/PCr) X 100
 Fractional excretion of urea (FEUrea) can be
obtained since urea transport is not affected by
diuretics
 FEUrea of less than 35% is suggestive of a prerenal
state

15. Early Detection of AKI is Difficult
Jo, et al: Clin J Am Soc Nephrol; 2007, 2:356-365

16. “Earlier” Detection of AKI

17. Induction of NGAL protein after unilateral or
bilateral ischemia
Mishra, et al: J Am Soc Nephrol; 2003, 14:2534-2543

18. Urinary IL-18 as an Early Marker of AKI
IL-18 as a marker for the
diagnosis of ATN and
delayed graft function:
•ROC - discriminatory power
of IL-18 for the diagnosis of
ATN
•The area under the ROC
curve was 0.95
Parikh et al: AJKD; 2004, 43:405-14

19. Future “Cardiac Biomarkers” of AKI?
Parikh et al: KI; 2006, 70:199 -203

20. Biomarker Sample Source Assay Commercial Development
NGAL plasma Western blot In development (Biosite)
NGAL urine Western blot In development (Abbott)
IL-18 urine ELISA NONE
KIM-1 urine ELISA NONE
Cystatin-C plasma Immunonephelometry In development (Dade-
Behring)
Coming soon?

21. Prevention of AKI

22. Prevention of AKI
Venkataraman, et al: Crit Care
Med; 2008, 36:S166-S171

?
X

23. Maintaining Renal Perfusion Pressure
 No absolute number is considered adequate with regard to mean
arterial pressure, and target mean arterial pressure should be
individualized based on the patient's baseline physiology
 Vasopressors should be used to improve perfusion pressure only after
adequate volume repletion is accomplished
 No reliable evidence that norepinephrine is associated with increased
risk of AKI when used to treat arterial hypotension
 Intra-abdominal hypertension is associated decreased renal perfusion
and may result in AKI
 Prompt recognition, monitoring, and early surgical treatment offer the
best potential for recovery

24. Role of Loop Diuretics in AKI
 maintaining a greater urine flow to flush out the tubules with loop
diuretics has been advocated to prevent AKI
 Two meta-analyses have pooled studies evaluating the role of loop
diuretics in the prevention of AKI
– The first systematic review compared fluids alone with diuretics in people
at risk for AKI from various causes and found no benefit from diuretics with
regard to its incidence, need for dialysis, or mortality
– In the second recent meta-analysis (RCTs, n = 849 patients), no difference
among patients treated with loop diuretics was found in hospital mortality,
need for renal replacement therapy, or number of dialysis sessions needed

25. Treatment of AKI

26. John et al: Chest 2007;132:1379-1388
Principles of Solute Transport in
Hemodialysis and Hemofiltration

27. Hemofiltration versus Hemodiafiltration

28. Definitions of RRT Modalities
Pannu et al: JAMA; 2008, 299: 793-805

29. Renal Replacement Therapy in Patients with
Acute Renal Failure
Pannu et al: JAMA; 2008, 299: 793-805

30. Standard IHD versus Slow Low Efficiency
Dialysis (SLED)

31. Initiation of RRT
John, S. et al. Chest 2007;132:1379-1388

32. Potential Complications with CRRT

33. Conclusions
 Prevention of AKI is better than treatment of
AKI
– Prognosis and mortality
– Maintain renal perfusion status, treat sepsis
promptly, avoid nephrotoxins
 Be familiar with the various modalities of
renal replacement therapies