prof.Said

1. Dr. SAID KHAMIS
MD (MSc. Nephrology, KUL Belgium)
Professor of Medicine & Nephrology
Faculty of Medicine, Menofyia University, Egypt

2. Case Scenario
You are asked to see a 50-year-old male with diabetes & known CKD;
baseline Scr, 2.0 mg/dL who is admitted with urosepsis. Admission Scr.
Conc. was 2.3 mg/dL & increased to 2.6 mg/dL the following day.
Question 1: Which statement regarding his kidney function is correct?
a) Using the MDRD (Modification of Diet in Renal Disease) Study
equation, his estimated GFR (eGFR) is 34 mL/min/ 1.73 m2
b) Use of the CKD-EPI (CKD Epidemiology Collaboration) equation is
more appropriate for this patient, and his eGFR is 32 mL/min/1.73 m2
c) Using the Cockcroft-Gault formula, his creatinine clearance is 20 to
32 mL/min
d) His eGFR cannot be calculated because his Scr. Conc. is not stable.

3. Case, continued: Review of the patient’s chart shows that he has received
4 L of 0.9% saline solution intravenously in the past 24 hours, and urine
output has increased from 10 to 20 mL/h. On physical examination, vital
signs include blood pressure of 95/65 mm Hg, heart rate of 72 beats/min,
and oxygen saturation of 96% on 2 L/min by nasal cannula. His lungs are
clear. He has peripheral edema (2+).
Question 2: What would you recommend?
a) Continue with volume expansion because his urine output has
increased significantly
b) Add norepinephrine to increase his SBP to >105 mm Hg
c) Continue with volume expansion and add norepinephrine as well
d) Start a trial of intravenous furosemide, which could help manage his
fluid overload

4. Case, continued: Two days later, the patient remains oliguric despite a
trial of furosemide, and his Scr concentration has increased to 5.5
mg/dL. Blood pressure is 105/75 mm Hg. He has peripheral edema (3+),
and oxygen saturation is 91% on 5 L/min by nasal cannula. You plan to
initiate RRT.
Question 3: Which of the following is the best statement with respect to
this set of circumstances?
a) Given the role of sepsis in development of his AKI, continuous RRT
(CRRT) is preferable to intermittent hemodialysis (IHD) for this patient
b) If CRRT is selected, the prescribed dose should be 35 to 40 mL/kg/h
c) CRRT and IHD have similar clinical outcomes
d) RRT can be postponed until the patient develops clear signs of uremia

5. Case, continued: Two weeks later, the patient begins to recover kidney
function. He is discharged from the hospital with a Scr conc. that is
stable at 2.5 mg/dL. He asks you about the long-term impact of the AKI
on his health.
Question 4: What is the best way to respond to his stated concern?
a) Because this was an acute event due to urosepsis, which is now fully
treated, the AKI has no meaningful impact on the course of his
underlying CKD
b) His risk for future dialysis dependency has increased significantly
after this episode of AKI
c) There is no association between his recent AKI & risk for future CVD
d) He should expect further recovery of his kidney function and return to
his baseline over the next few months

6. Answer to Question 1: (d) Because his Scr concentration is increasing, none of the
standard formulas should be used to estimate his kidney function.
Answer to Question 2: He is fluid overloaded, as shown by his markedly positive fluid
balance and the presence of edema. At this point, additional fluid should be
administered with caution because it will likely only exacerbate fluid overload. MAP
is 75 mm Hg and therefore the addition of a vasopressor is not justified. Use of
furosemide may increase urine output and decrease fluid overload; however, it
probably would not change the overall clinical outcome. Thus, (d) is the best answer.
Answer to Question 3: (c) There is no evidence that CRRT has a special role in
patients with sepsis-associated AKI. With regard to CRRT dose, 20 to 25 mL/kg/h has
similar outcomes to higher doses of therapy. The major indication for RRT is the lack
of renal recovery in association with significant fluid overload and progressive
hypoxemia.
Answer to Question 4: (b) AKI is a risk factor for CKD progression and end-stage
kidney disease, as well as cardiovascular events. It is unknown whether he will have
further improvement in kidney function over time, but it seems unlikely because his
Scr concentration is now stable.

7. What I Am Going to Talk About
• Definition of AKI
• Historical Backgrounds
• Introduction & Epidemiology
• Etio-pathological Classification of AKI
• Risk assessment of AKI
• Evaluation & general management of patients with
AKI
• Treatment and prevention of AKI
• Summary and Conclusion

8. What I’m Not Going to Talk About
• Vasopressors
• Dopamine agonists
• Natriuretic peptides
• Adenosine agonists
• N-acetylcysteine
• Loop diuretics and osmotic diuretics
• Prophylactic dialysis/HF

9. Definition of AKI
• AKI is defined by an abrupt decrease in
kidney function that includes but not limited
to ARF.
• It is a broad clinical syndrome with various
aetiologies
KDIGO,2012

10. “That’s a new term the nephrologists came up
with, they’re still working on a definition for it”
Definitions…

12. Diagnosis of AKI, CKD and AKD
Functional criteria Structural criteria
AKI Increase in SCr by 50% within 7 days, OR No criteria
Increase in SCr by 0.3 mg/dl (26.5µmol/l)
within 2 days, OR Oliguria
CKD GFR <60 ml/min per 1.73m2 >3 months Kidney damage for
>3 months
AKD AKI, OR Kidney damage for
GFR <60ml/min per 1.73m2 for <3 months, OR <3 months
Decrease in GFR by ≥35% or increase in
SCr by >50% for <3 months
NKD GFR ≥60ml/min per 1.73 m2 Stable SCr No damage

13. Historical Backgrounds
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)

14. Introduction
• AKI is a global problem and occurs in the
community and in the hospital
• It is a predictor of immediate and long term adverse
outcomes.
• World wide incidence of AKI is poorly known

15. Incidence of AKI around the world
• USA - 24 cases /1000 discharge
• Kuwait - 4 per 100,000 cases / year
• Nigeria - 12 per year in children
• North India - 20 cases / 1000 discharge
• Bangladesh -24 cases /1000 discharge
in a tertiary care hospital

16. Why Does It Matter?
• AKI is commoner than
many realise
• Mortality from AKI
remains high
• AKI doubles hospital
length of stay
• AKI predicts
subsequent mortality
and CKD
• AKI is costly

17. 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

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

19. Classification of AKI
• Pre-renal
• Renal
• Post-renal

20. Causes of AKI
Pre renal Intrinsic renal Post renal
Decrease in
effective
blood volume.
Arterial
occlusion
Or
Stenosis..
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.

21. Causes of AKI

22. Risk assessment of AKI

23. Acute Kidney Injury Conceptual Model
Death
Complications
Normal
Increased
risk
Kidney
failure
Damage  GFR
Antecedents
Intermediate Stage
AKI
Outcomes
Markers such as
NGAL, KIM-1 and
IL-18 are
surrogates
Damage
GFR
Mehta et al . Critical Care 2007;11:R31
Stages defined by
creatinine and
UOP are
surrogates

24. What’s Important?
Baseline risks Clinical conditions Drugs
Advanced age Sepsis Contrast media
Diabetes Hypotension/Shock Antibiotics
CKD Volume depletion Chemotherapy
Heart failure Rhabdomyolysis NSAIDs
Liver failure Cardiac/vasc surg ACEI/ARB
Male gender Non-renal solid organ Tx
Race/genetic Mechanical ventilation
Low albumin Abdominal compartment
syndromeArterial disease
ADQI 4th Consensus Conference

25. Evaluation and general management of
patients with AKI
• Patients should evaluate promptly to
determine the cause.
• Monitor the patients with Scr & urine
output .
• Manage according to cause & stage of AKI
• Evaluate patients at 3 months for resolution
or worsening of preexisting CKD.

26. 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

27. Biomarkers for early diagnosis of AKI
Biomarkers Associated Injury
• Cystatin –C Proximal tubular Injury
• KIM-1 Ischaemic and Nephrotoxin
• NGAL Ischaemic and Nephrotoxin
• Cytokine- Toxic and
IL6,8,18 Delayed graft function
• a-GST & n-GST Proximal and distal T injury

31. Treatment and prevention of AKI
• Management of Specific cause
• Management of Hypotension and shock
• Treatment of infection
• Glycaemic control and nutrition support
• Use of diuretic
• Vasodilator therapy
• Growth factor intervention
• Role of Erythropoietin
• RRT

34. Management of Hypotenison and
shock in AKI
Careful titration of fluid:
• ORS for children and infant
• IV isotonic Saline for adults
• 4% albumin Vs saline for ICU
• Hydroxyethyl Starch Vs Albumin for ICU
Bouchard J,MehtaRL,2010;Finfer et al, N Engl J Med,2004

35. • Colloids
– Albumin
– Gelatins
– Starches
Or
• Crystalloids
– 0.9% saline
– Dextrose
– Balanced solutions

36. Fluid Prescribing: Lessons Not Learned
• NCEPOD Extremes of Age (1999)
– Fluid management in the elderly is often poor; it should be
accorded the same status as drug prescription
• Scottish Audit of Surgical Mortality (2009)
– Fluid balance in the surgical patient remains problematic,
often managed by relatively junior staff and continuing
education and use of appropriate guidance is to be
encouraged
• NICE IV fluid therapy in adults in hospital (2013)
– Errors in prescribing, leading to insufficient or excessive
provision of IV fluids or electrolytes, are common and have
adverse effects on patient morbidity and mortality

37. Vasoactive medication:
• Nor-epinephrine, dopamine or vasopressin only
after dehydration is corrected to maintain BP
-Useful in septic shock, burns, liver failure
-Not suitable for Cardiogenic shock
Marik,Intensive Care Med,2002;KellumJA,Decker J,2001
Management of Hypotension and shock in
AKI

38. Glycaemic control and nutritional support in
AKI
Tight glycaemic control :
• Pl. glucose -80-110 mg/dl
• Total calorie intake -20-30 kcal/kg
• Protein intake -0.8-1.0 g/ kg/day-
Non-catabolic state
-1.0-1.5 g/kg/day-
Catabolic state
Van den Berghe et al,N Engl J Med,2001

39. Role of Diuretics in AKI
• No evidence to reduce incidence or severity of AKI
• Indicate only if patients are volume over loaded
• Diuretic only Convert oliguric to non oliguric
• It promote earlier diuresis but no effect on survival
Ho and Power; Anaesthesia,2010;
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)

40. “No BP – No Pee Pee”
M. C. Smith

42. Role of Vasodilator therapy in AKI
• Low dose dopamine – no benifit
• Fenoldopen – not useful
• Atrial natruretic peptide - not useful
Friedrich et al, Ann. Intern med,2005

43. Growth factor intervention in AKI
• Recombinant human IGF-1- Not useful
Hirscberg et al,Kid Int,1999

44. Role of EPO in the prevention of AKI
• Use of Erythropoetin in the Prevention of
AKI in ICU –Not Useful
Endre et al,, Kid Int, 2010

46. Role of RRT in AKI
• Indicated only if Acute and severe renal failure,
volume over load, hyperkalema, acidosis &
symptoms of uraemia
• Intermittent HD and CRRT- found equally effective
• SLED – combines both IHD and CRRT
Rabindranath et al,Syst. Review,2007;
Bagshaw et al,Crit Care Med,2008.

47. Role of PD Vs HD in AKI
• Optimum Treatment of AKI remain uncertain
• Studies looking at various therapeutic approach
give different results
• Optimum dose of PD is uncertain
• Considered reasonable ttt option in Developing
Countries & during environmental disasters.
Karen Yeates,PDI,2012

48. AKI : 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

49. Summary and Conclusion
• AKI is a heterogeneous disorder that is common in hospitalized
patients and associated with short- & long-term morbidity and
mortality.
• When AKI is present, prompt workup of the underlying cause should
be pursued, with specific attention to reversible causes.
• Measures to prevent AKI include optimization of volume status and
avoidance of nephrotoxic medications.
• Crystalloids are preferred over colloids for most patients, and
hydroxyethyl starches should be avoided..

50. Summary and Conclusion
• Volume overload in the setting of AKI is associated with adverse
outcomes, so attention should be paid to overall fluid balance.
• Currently there are no targeted pharmacotherapies approved for the
treatment of AKI.
• The optimal timing of renal replacement therapy in critically ill
patients with AKI is unclear, but is an area of active investigation.
• Recent studies suggest that AKI is not a “self-limited” process, but
is strongly linked to increased risk for chronic kidney disease,
subsequent AKI, and future mortality

54. Thank you for your attention
Phramongkutklao Hospital and
College of Medicine