Acute kidney injury (AKI) is a potentially life-threatening syndrome that occurs primarily in hospitalized patients and frequently complicates the course of critically ill patient. Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output

1. ACUTE KIDNEY INJURY
(AKI)
Abdulsalam Halboup
M.Pharma (Clinical)

2. ACUTE KIDNEY INJURY
 Acute kidney injury (AKI) is abrupt reduction in kidney
functions as evidence by changed in laboratory values; serum
creatinine, blood urea nitrogen(BUN)and urine output.
 Acute kidney injury (AKI) is diagnosed if one of the
following criteria is met :
 increase in serum creatinine (SCr) of at least 0.3 mg/dL
within 48 hours,
 a 50% increase in baseline SCr within 7 days, or
 a urine output of less than 0.5 mL/kg/hour for at least 6
hours.

3. EPIDEMIOLOGY AND ETIOLOGY
 Between 5% and 7% of all hospitalized patients develop
AKI.
 A greater prevalence of AKI is found in critically ill
patients ( ICU-Acquired AKI).
 Despite improvements in the medical care of individuals
with AKI, mortality generally exceeds 50%.

4. EPIDEMIOLOGY

5. CLASSIFICATION OF AKI
 Criteria used for AKI classification
RIFLE: Risk, Injury, Failure, Loss of Kidney
Function and End Stage Renal Disease).
AKIN: Acute Kidney Injury Network
KDIGO: Kidney Disease Improving Global
Outcome

6. AKI CLASSIFICATION SYSTEMS

7. PATHOPHYSIOLOGY
There are typically three categories of AKI:
 1-prerenal AKI
 2- intrinsic AKI
 3- Postrenal AKI

9. PRERENAL AKI
 Prerenal AKI: is characterized by reduced blood
delivery to the kidney.
 A common causes are:
 Volume depletion
 hemorrhage
 dehydration
 GI fluid losses.
 Decrease effective circulatory blood volume
 Decrease cardiac output (CHF, MI, hypotension
 Pulmonary hypertension
 Liver failure
 Sepsis
 Functional
 ACEIs, NSAIDs, ARBs, Cyclosporine and tacrolimus
 Prompt correction of volume depletion can restore kidney
function to normal because no structural damage to the
kidney has occurred.

10. INTRINSIC AKI
Damage is within the kidney (structure of the nephron,);
 Vascular damage (renal thrombosis)
 Glomerular damage (nephrotic/nephritic
glomerulonephritis
 Acute tubular necrosis(ATN)(it accounts for 50% of all cases of AKI)
 Ischemia (hypotension, sepsis
 Endogenous toxins(uric acid ,hemoglobin
 Exogenous toxin
 Aminoglycosides
 contrast induced nephropathy (CIN)
 amphotericin B
 Acute interstitial nephritis
 NSAIDs
 infections
 Prerenal AKI can progress to intrinsic AKI if the underlying
condition is not promptly corrected

11. POSTRENAL AKI
 Postrenal AKI is due to obstruction of urinary
outflow
 Bladder outlet obstruction
 Benign prostatic hypertrophy
 Prostate cancer
 Anticholinergic drug
 Ureteral obstruction
Malignancy
 Pelvic / renal obstruction
 Postrenal AKI accounts for less than 10% of cases of
AKI
 Rapid resolution of Postrenal AKI without structural
damage restore kidney function

13.  By monitoring Scr on a routine basis, it can be
estimated whether kidney function is improving or
worsening.
 Kidney function can also be evaluated based on urine
output. Oliguria and anuria
 Oliguria is defined as urine outputs of less than 400 ml
over 24 hours
 anuria is defined as urine output of less than 50 mL over
24 hours.

14. CLINICAL PRESENTATION AND DIAGNOSIS OF AKI
 Peripheral edema
 Weight gain
 Nausea/vomiting/diarrhea/anorexia
 Mental status changes
 Fatigue
 Shortness of breath
 Pruritus

15. LABORATORY TESTS
 Elevated Scr (normal range approximately 0.6-1.2
mg/dL [53 to 106 μmol/L])
 Elevated BUN concentration (normal range
approximately 8 to 25 mg/dL [2.9-8.9 mmol/L])
 Decreased CrCl (normal 90–120 mL/min)
 BUN: creatinine ratio
 greater than 20:1 in Prerenal AKI
 Less than 20:1 in intrinsic or Postrenal AKI
 Hyperkalemia
 Metabolic acidosis

16. PREVENTION APPROACHES
 Non-pharmacology for prevention
 Hydration to prevent contrast induced nephrotoxicity
 KDIGO guideline recommend using normal saline or
sodium bicarbonate infusion
Normal saline regimen: 1ml/kg/h for 12hours before
and after procedure.
Sodium bicarbonate regimen: 3ml/kg/hours for one
hour before procedure and 1ml/kg/hours for 6 hours
postcontrast.

17. PHARMACOLOGICAL THERAPY
 For prevention of CIN
 Ascorbic acid:3g orally pre and 2mg orally for two
doses postprocedure and N-acetylcysteine(600-1200mg
orally every 12 hours for 2-3 days, the first two doses
precontrast
 Current KDIGO guideline suggest moderate control of
blood glucose to level of 110-149 mg/dl with insulin
prevent ICU-Acquired AKI

18. TREATMENT OF ACUTE KIDNEY INJURY

19.  Goal of treatment:
 Minimize the degree of kidney insult
 Reduce extrarenal complication
 Restoration of renal function to pre AKI is the
ultimate goal

20. TREATMENT APPROACHES
 Currently, there is no definitive therapy for
AKI, supportive care is the mainstay of
management regardless of etiology.

21. SUPPORTIVE CARE IN AKI
 Supportive care includes :
 Adequate nutrition,
 correction of electrolyte and acid-base abnormalities
(particularly hyperkalemia and metabolic acidosis)
 Fluid management,
 Correction of any hematologic abnormalities
 Medical management of infections, cardiovascular and
GI conditions, and respiratory failure
 all drugs should be reviewed, and dosage adjustments
made based on an estimate of the patient’s GFR.

22. NON-PHARMACOLOGICAL THERAPY
 Maintenance of adequate cardiac output and blood
pressure to optimize tissue perfusion
 Discontinue medication associated with diminished renal
blood flow
 Initiate appropriate fluid and electrolyte
 Renal replacement therapy RRT in sever AKI
 Hemodialysis
 Peritoneal dialysis
Absolute indications for dialysis usually include:
 BUN greater than 100 mg/dL (35.7 mmol/L)
 Potassium greater than 6 mEq/L (6 mmol/L)
 Magnesium greater than 9.7 mg/dL (4.0 mmol/L)
 Metabolic acidosis with a pH less than 7.15
 Diuretic-resistant fluid overload.

23. RENAL REPLACEMENT THERAPY

24. PHARMACOLOGIC THERAPY
 Loop diuretics : are effective to reduce fluid
overload.
 it can worsen AKI.
 Thiazide diuretics, when used as single agents, are
generally not effective for fluid removal.
 Mannitol is also not recommended for treating volume
overload associated with AK.
 Potassium sparing diuretics are not recommended.
 low dose dopamine LDD is not indicated in treating the
AKI.

25.  Equipotent dose of loop diuretics (Furosemide,
bumetanide, torsemide and ethacrinic acid ) all have
similar efficacy
 Ethacrynic acid is reserved for sulfa-allergic patient
 Continues infusion of loop diuretic overcome
 diuretic resistance
 associated with less adverse effect than intermittent bolus
 Dose:
 Initial iv loading dose equivalent to (40-60mg
furosemide )
 Continuous infusion equivalent to 10-20mg/h

26. STRATEGY TO OVERCOME DIURETIC
RESISTANCE
 Administration of agents from different
pharmacological classes, they act synergistically
 Thiazide (works on: distal convoluted tubule)
 loop diuretics (works on: ascending loop of Henle)

28. ELECTROLYTE MANAGEMENT
 Serum electrolyte should be monitored
daily.
 Hyperkalemia is the most common and serious
electrolyte abnormality in AKI
 Hypernatremia and fluid retention commonly
occur …require daily calculation of sodium intake
 Phosphorus and magnesium should be
monitored

29. PREVENTION OF ACUTE RENAL
FAILURE
 Avoidance
 The best preventive measure for AKI, especially in individuals at
high risk, is to avoid medications that are known to precipitate AKI.
Nephrotoxicity is a significant side effect of
 aminoglycosides,
 ACE inhibitors, angiotensin receptor
antagonists(ARBs),(what are the risk factors?)
 Amphotericin B
 NSAIDs
 Cyclosporine, tacrolimus,
 Radiographic contrast agents GFR less than 60 mL/min
, diabetes, dehydration, age more than 65 years,
 How to reduce CI-AK?