This document discusses acute kidney injury (AKI), formerly known as acute renal failure (ARF). It begins with definitions of AKI and classifications systems like RIFLE and AKIN. It then covers the epidemiology, etiology, and pathophysiology of prerenal, intrinsic, and postrenal AKI. The clinical presentation, diagnosis, and laboratory findings are outlined. Prevention and treatment strategies aim to identify and address the underlying cause, maintain fluid and electrolyte balance, and monitor for complications.

1. Acute kidney Injury
(AKI)
1
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2. Contents
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 Introduction
 Definition
 Epidemiology
 Etiology
 Pathophysiology
 Clinical Presentation and diagnosis
 Prevention of AKI
 Treatment
 Diuretic resistance
 Evaluation of therapeutic outcomes

3. Objectives
3
 Upon completion of the chapter, the students
will be able to:
 Assess a patient’s kidney function based on
clinical presentation, laboratory results, and
urinary indices.
 Identify pharmacotherapeutic outcomes and
endpoints of therapy in a patient with acute
kidney injury (AKI).
 Apply knowledge of the pathophysiology of AKI
to the development of a treatment plan.

4. Objectives
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 Design a diuretic regimen to treat volume
overload in AKI.
 Develop strategies to minimize the occurrence
of drug and radiocontrast-induced AKI.
 Monitor and evaluate the safety and efficacy
of the therapeutic plan.

5. Brain storming question
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 What is the function of KIDNEY?

6. Introduction
 Functions of kidney
 Excretory Function
 Filtration, secretion, and reabsorption processes
 Regulate volume of blood, electrolyte content and
acid base balance
 Endocrine function
 secretion of renin, erythropoietin
 production and metabolism of prostaglandins and
kinins
 Metabolic function
 the activation of vitamin D3
 metabolism of insulin, steroids, and xenobiotics
6

7. 7
Fig one: Structures of the nephron

8. Definition
 Acute kidney Injury(AKI) is characterized
clinically by an abrupt decrease in renal function
over a period of hours to days resulting in:
 the accumulation of nitrogenous waste products
(azotemia)
 the inability to maintain and regulate fluid,
electrolyte, and acid–base balance
8
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9. Table one: RIFLE Classification
Schemes for Acute Kidney Failure
(AKF)
9
RIFLE by Acute Dialysis Quality Initiation (ADQI)

10. Table two: AKIN* Classification
Schemes for Acute Kidney Injury
(AKI)
10
* AKIN – Acute Kidney Injury Network

11. KDIGO* – AKI Definition
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 AKI is defined as any of the following:
 Increase in SCr by ≥ 0.3 mg/dl (≥ 26.5 μmol/l)
within 48 hours; or
 Increase in SCr to ≥ 1.5 times baseline, which
is known or presumed to have occurred within
the prior 7 days; or
 Urine volume <0.5 ml/kg/h for 6 hours
 *KDIGO - Kidney Disease Improving Global
Outcomes

12. Table three: AKI is staged for severity
according to the following criteria
(KIDGO)
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13. Epidemiology
 Approximately 5% to 7% of all hospitalized
patients develop AKI
 AKI is 5 to 10 times more prevalent in the hospital
setting than in the community setting
 About 5% to 20% of critically ill patients develop
AKI
 30% to 40% of survivors progress to chronic
kidney disease (CKD)
 Mortality generally exceeds 5% for patients in
general wards to 50% for ICU patients
13

14. Table four: Incidence and
Outcomes of Acute Kidney Injury
14

15. Etiology
 (a) prerenal AKI: results from decreased renal
perfusion in the setting of undamaged
parenchymal tissue
 (b) intrinsic AKI: the result of structural damage
to the kidney, most commonly the tubule from
an ischemic or toxic insult,
 (c) postrenal AKI: caused by obstruction of
urine flow downstream from the kidney
15
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16. Fig two: Physiologic classification of AKI
16

17. Pathophysiology- Prerenal AKI
 Prerenal AKI is characterized by reduced blood
delivery to the kidney
 Cause:
 intravascular volume depletion (hemorrhage,
dehydration, extensive burns or GI fluid losses)
 reduced effective circulating blood volume
(reduced cardiac output, sepsis)
 Hypotensive events (e.g., shock or medication-
related hypotension)
 renovascular obstruction or vasoconstriction
(renal artery stenosis, hepatorenal syndrome)
17

18. Pathophysiology- Prerenal AKI
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 With a mild to moderate decrease in renal blood
flow, intraglomerular pressure is maintained by:
 Stimulation of the sympathetic nervous and
the RAAS and release antidiuretic hormone
 dilation of afferent arterioles & constriction of
efferent arterioles
 redistribution of renal blood flow to the
oxygen-sensitive renal medulla

19. Pathophysiology- Prerenal AKI
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 If, however, the decreased renal perfusion is
severe or prolonged,
 these compensatory mechanisms may be
overwhelmed, and prerenal AKI will be
clinically evident.
 Sustained prerenal conditions can result,
however, in glomerular ischemia causing acute
tubular necrosis (ATN)
 Drugs may cause a functional AKI when they
interfere with these autoregulatory mechanisms

20. 20
Fig three: Drugs that alter renal hemodynamics by causing
afferent arteriole vasoconstriction or efferent arteriole

21. Pathophysiology- Intrinsic AKI
 Intrinsic AKI results from direct damage to the
kidney
 Categorized on the basis of the injured
structures within the kidney:
 Tubules
 The renal vasculature
 Glomeruli
 Interstitium
21
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22. Pathophysiology- Intrinsic AKI
 Tubular Damage
 Approximately 85% caused by ATN
50% are a result of renal ischemia, often arising
from an extended prerenal state (hypotension,
vasoconstriction)
35% are the result of exposure to direct tubule
toxins,
endogenous (myoglobin, hemoglobin, or uric
acid)
exogenous (contrast agents, aminoglycoside
antibiotics, penicillins, sulfonamides etc)
22

23. Pathophysiology- Intrinsic AKI
 The clinical evolution of ATN is characterized by
three distinct phases:
 Initiation
 Maintenance
 recovery
 The hallmarks of the initiation phase are:
 Ischemic injury
 GFR reduction
23
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24. Pathophysiology- Intrinsic AKI
 Ischemic injury causes tubular epithelial cell
necrosis or apoptosis an extension phase
(continued hypoxia and an inflammatory response -
involving the nearby interstitium)
 The loss of epithelial cells between the filtrate and
the interstitium results in:
 denudation of basement membrane
 inability of the basement membrane to
appropriately regulate fluid and electrolyte
transfer
24

25. Pathophysiology- Intrinsic AKI
 As a result,
 the glomerular filtrate starts leaking back into
the interstitium and is reabsorbed into the
systemic circulation.
 urine flow is obstructed by accumulation of
sloughed epithelial cells, cellular debris, and
formation of casts
 The onset of ATN can occur over hours to days
25
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26. Pathophysiology- Intrinsic AKI
26
 Regardless of the etiology; tubular injury, back
leakage, and obstruction
 lead to a loss in the ability to concentrate urine,
decreased urine output, and, ultimately, GFR
 Continued kidney hypoxia or toxin exposure after
the original insult
 kill more cells and propagates the inflammatory
response
 extend the injury and delay the recovery process
 damage and kill the tubular epithelial cells in the
corticomedullary junction

27. Pathophysiology- Intrinsic AKI
 When the toxin or ischemia is removed,
 a maintenance phase ensues and may last
anywhere from a few weeks to several months
 The maintenance phase is eventually followed by
a recovery phase,
 during which new tubule cells are regenerated
 The recovery phase is associated with a notable
diuresis,
 which requires prompt attention to maintain fluid
balance, or a secondary prerenal injury may
occur.
27

28. Pathophysiology- Intrinsic
AKI
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 Renal Vasculature Damage
 Occlusion of the larger renal vessels resulting
in AKI is not common but can occur
if large atheroemboli or thromboemboli
occlude renal arteries
 Smaller vessels can also be obstructed by
atheroemboli or thromboemboli,
the damage is limited to the vessels
involved,
the development of significant AKI is
unlikely

29. Pathophysiology- Intrinsic
AKI
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These vessels are susceptible to
inflammatory processes that lead to:
microvascular damage
vessel dysfunction when the renal capillaries
are affected
 Neutrophils invade the vessel wall, causing
damage that can include:
 thrombus formation, tissue infarction, and
collagen deposition within the vessel
structure

30. Pathophysiology- Intrinsic
AKI
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 Diffuse renal vasculitis can be mild or severe,
with severe forms promoting concomitant
ischemic ATN.
 The Scr is usually elevated when the lesions
are diffuse; thus, the area of damage is large.

31. Pathophysiology- Intrinsic
AKI
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 Glomerular Damage
 Account 5%
 Similar damage observed in the renal
vasculature by the same mechanisms can
occur
in addition to severe inflammatory processes
specific to the glomerulus

32. Pathophysiology- Intrinsic AKI
 Interstitial Damage
 If the renal interstitium becomes severely inflamed
and edematous,
 it can lead to development of acute interstitial
nephritis (AIN).
 AIN may be caused by drugs, infections, and,
rarely, autoimmune idiopathic diseases.
32
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33. Pathophysiology- Intrinsic AKI
33
 Acute interstitial injury is characterized by:
 lesions comprised of monocytes, eosinophils,
macrophages, B cells, or T cells,
clearly identifying an immunologic response as
the injurious process affecting the interstitium.
 If symptoms of AIN remain unrecognized, and the
exposure to the causative agent continues,
 persistent renal dysfunction associated with
interstitial fibrosis and tubular atrophy may
develop

34. Pathophysiology - Postrenal AKI
 Postrenal AKI
 accounts for less than 5% of all cases of AKI
 occurs as the result of obstruction at any level
within the urinary collection system from the
renal tubule to the urethra
 Cause:
Bladder outlet obstruction
Prostatic hypertrophy, infection, cancer
Improperly placed bladder catheter
Anticholinergic medication
34

35. Pathophysiology - Postrenal AKI
 Ureteral
 Cancer with abdominal mass
 Retroperitoneal fibrosis
 Nephrolithiasis
35

36. Pathophysiology - Postrenal
AKI
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 Renal pelvis or tubules
 Nephrolithiasis
Oxalate
Indinavir
Sulfonamides
Acyclovir
Uric acid
 Extremely elevated uric acid concentrations
from chemotherapy-induced tumor lysis
syndrome

37. Pathophysiology - Postrenal AKI
 At the location of the obstruction, urine will
accumulate in the renal structures above the
obstruction and cause increased pressure
upstream.
 The ureters, renal pelvis, and calyces all
expand, and the net result is a decline in GFR.
 If renal vasoconstriction ensues, a further
decrement in GFR will be observed.
37
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38. ARF
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Fig four: Classification of acute kidney injury (AKI) based on

39. Clinical course (1)
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 The oliguric phase
 occurs over 1 to 2 days
 is characterized by a progressive decrease in
urine production
 last from days to several weeks
Urine production of
<500 mL/day is termed oliguria
<50 mL/day Is termed anuria
>500 mL/day of urine output- Nonoliguric
renal failure

40. Clinical course (2)
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 Diuretic phase
 a period of increased urine production occurs
over several days
 Result from
in part, a return to normal GFR before
tubular reabsorptive capacity has fully
recovered
the elevated osmotic load from uremic toxins
the increased fluid volume retained during
the oliguric phase

41. Clinical course (3)
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 The recovery phase
 occurs over several weeks to months, depending
on the severity of the patient’s ARF
 signals
the return to the patient’s baseline kidney
function,
normalization of urine production
the return of the diluting and concentrating
abilities of the kidneys.

42. Clinical Presentation and
diagnosis
 Symptom & sign
 Change in urinary habits (e.g., decreased
urine output or urine discoloration)
 Sudden weight gain
 Severe abdominal or flank pain
 Severe headache
 Nausea, vomiting, diarrhea,
 Edema
 Fever
 Colored or foamy urine
 In volume-depleted patients, orthostatic
hypotension
42

43. Clinical Presentation and
diagnosis
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 Physical Examination Findings
 Increased blood pressure
 Jugular venous distention (JVD)
 Pulmonary edema
 Rales
 Hypotension or orthostatic hypotension (prerenal
AKI)
 Rash (intrinsic AKI due to acute interstitial
nephritis)
 Bladder distention (postrenal bladder outlet
obstruction)

44. Clinical Presentation and
diagnosis
 Laboratory Tests
 Elevations in the serum potassium, BUN,
Creatinine, and phosphorous, or a reduction in
calcium and the pH (acidosis), may be present.
 An increased serum white blood cell count may be
present in those with sepsis-associated ARI, and
eosinophilia suggests acute interstitial nephritis.
 Urine microscopy can reveal cells, casts, or
crystals that help distinguish among the possible
etiologies and/or severities of ARI
44

45. Clinical Presentation and
diagnosis
 An elevated urine specific gravity suggests
prerenal ARI, as the tubules are concentrating
the urine.
 Urine chemistry also indicates the presence of
protein, which suggests glomerular injury, and
blood, which can result from damage to virtually
any kidney structure.
45
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46. Clinical Presentation and
diagnosis
 Other Diagnostic Tests
 Urinary catheterization
 Renal ultrasonography or cystoscopy may be
needed to rule out obstruction
 Computed tomography
 Magnetic resonance imaging
 Renal angiography
 Retrograde pyelography
 Renal biopsy is rarely used, and is reserved
for difficult diagnoses.
46

47. Table five: Diagnostic Parameters for
Differentiating Causes of Acute Kidney
Injury
47
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48. Fractional excretion of sodium
(FENa)
 The FE Na+ is a measurement of how actively
the kidney is reabsorbing sodium
 The FE Na+ is calculated as:
 FE Na+ = (UNa × PCr ) /(UCr× PNa) x 100%
 where UNa = urine sodium, PCr= plasma
creatinine, UCr= urine creatinine, and PNa=
plasma sodium.
48
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49. Table six: Urinary Findings as a
guide to the Etiology of AKI
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50. Table six: Urinary Findings as a
guide to the Etiology of AKI
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51. Table seven: Advantages and
Disadvantages of Novel Clinical
Biomarkers of AKI
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52. Prevention of AKI
 Desired outcome
 The goals of AKI prevention are to
 (a) screen and identify patients at risk,
 (b) monitor high-risk patients until the risk has
subsided,
 (c) implement prevention strategies when
appropriate
52
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53. Nonpharmacologic Therapies
 Prevention of Radiocontrast dyes induced
nephrotoxicity
1. Hydration
 Normal saline infusion (1 mL/kg/h for 12 hours before and
12 hours after the procedure).
 MOA: diluting the contrast media, preventing renal
vasoconstriction that contributes to hypoxia and
ischemia, and minimizing tubular obstruction
 Sodium bicarbonate regimen is 154 mEq/L (154 mmol/L)
infused at 3 mL/kg/h for 1 hour before the procedure and
at 1 mL/kg/h for 6 hours after the procedure.
 MOA: reduce the formation of oxygen free radicals by
alkalinizing renal tubular fluid
53

54. Nonpharmacologic Therapies
 2. Renal Replacement Therapy
 Prophylactic administration of RRT (such as
hemodialysis and peritoneal Dialysis) to patients
who are at high risk of AKI
N.B. KDIGO guidelines do not currently
recommend RRT for prevention of CIN
54
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55. Pharmacologic Therapies
 1. Loop Diuretics, theoretical advantages:
 decreased risk of tubular obstruction 20 to an
increased urine flow and flushing out of debris;
 increased urine output that may be beneficial in
itself
 decreased risk of ischemic injury as the result of
inhibition of the sodium/potassium chloride
cotransporter and thus a reduction in oxygen
demand
 enhanced renal blood flow due to increased
availability of renal prostaglandins
55

56. Pharmacologic Therapies
56
 But, they neither reduce the incidence of AKI nor
improve patient outcomes, (mortality, need for RRT,
and renal recovery
2. Vasodilator Therapy
 a. Dopamine
 IV dopamine (1 to 3 mcg/kg/min) increase renal blood
flow, induce natriuresis and diuresis
 controlled studies have found that low-dose
dopamine did not prevent AKI, need for dialysis, or
mortality compared with placebo
 KDIGO guidelines do not support the use of low dose
dopamine

57. Pharmacologic Therapies
 b. Fenoldopam mesylate
 a selective dopamine A-1 receptor agonist that
increases renal blood flow, natriuresis, and
diueresis
 current KDIGO guidelines do not recommend its use
(Due to a lack of large multicenter trials as well as risk of
hypotension)
 c. Natriuretic Peptides
 atrial natriuretic peptide (ANP) and brain
natriuretic peptide (BNP)
mediate vasodilation, diuresis, and natriuresis
 current KDIGO guidelines do not recommend its use
(Due to the need for further research on appropriate
57

58. Pharmacologic Therapies
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3. Antioxidants
 a. Ascorbic Acid
 alleviate oxidative stress caused by CIN-
associated ischemia reperfusion injury.
 3 g orally before the procedure, then 2 g orally
twice daily for two doses after the procedure
 current KDIGO guidelines do not recommend
its use (clinical studies have reported
inconsistent results)

59. Pharmacologic Therapies
 b. N-Acetylcysteine (NAC)
 antioxidant that has been widely studied in the
prevention of CIN in patients with renal
insufficiency
 600 to 1,200 mg orally every 12 hours for 2 to
3 days, with the first two doses administered
prior to contrast exposure
59
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60. Pharmacologic Therapies
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 4. Insulin
 current KDIGO guidelines suggest using
insulin therapy to target plasma glucose of
110 to 149 mg/dL (6.1 to 8.3 mmol/L)
 5. Adenosine Receptor Antagonists
(theophylline)
 KDIGO guidelines suggest against using
theophylline for prevention of CIN (Due to the
risk of adverse effects as well as a relatively
small benefit)

61. Treatment of AKI
 Desired Outcomes
 Short-term goals include:
minimizing the degree of insult to the kidney,
reducing extrarenal complications
Expediting(facilitating) the patient's recovery
of renal function.
 The ultimate goal is to have the patient's renal
function restored to his or her pre-AKI
baseline.
61
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62. General Approach to
Treatment
 Prerenal sources of AKI should be managed with
hemodynamic support and volume replacement.
 If the cause is immune related, as may be the
case with interstitial nephritis or
glomerulonephritis, appropriate
immunosuppressive therapy must be promptly
initiated
 Postrenal therapy focuses on removing the
cause of the obstruction.
62
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63. General Approach to
Treatment
 Supportive care is the mainstay of AKI
management regardless of etiology
 RRT may be necessary to maintain fluid and
electrolyte balance while removing
accumulating waste products.
63
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64. Nonpharmacologic
 Initial modalities to reverse or minimize prerenal
AKI include
 eliminating medications associated with
diminished renal blood flow
 improving cardiac output
 removing a prerenal obstruction
64
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65. Nonpharmacologic
 For dehydration - appropriate fluid replacement
therapy
 Moderately volume-depleted patients
Oral rehydration fluids
If IV fluid is required, isotonic normal saline is
the replacement fluid of choice
initiated with 250 to 500 mL of normal
saline over 15 to 30 minutes
1 to 2 L is usually adequate
65
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66. Nonpharmacologic
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 Patients with diabetic ketoacidosis or a
hyperosmolar hyperglycemic state often have a
10% to 15% total-body water deficit, and more
aggressive fluid replacement is necessary.

67. Nonpharmacologic
 Up to 10 L may be required in the septic
patient during the first 24 hours, because of
the profound increase in vascular capacitance
and fluid leakage into the extravascular,
interstitial space
 Patients with anuria or oliguria
 Slower rehydration, such as 250 mL boluses
or 100 mL/h infusions of normal saline(reduce
the risk for pulmonary edema)
67
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68. Nonpharmacologic
 Dehydration resulting from severe diarrhea is
often accompanied by metabolic acidosis
caused by bicarbonate losses.
 5% dextrose with 0.45% sodium chloride
(NaCl) plus 50 mEq (50 mmol) of sodium
bicarbonate per liter, administered as bolus
 followed by a brisk continuous infusion (200
mL/h) until rehydration is complete, acidosis
corrected, and diarrhea resolved
68
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69. Nonpharmacologic
 If the prerenal AKI is a result of blood loss or is
complicated by symptomatic anemia
 red blood cell transfusion to a hematocrit no
higher than 30% is the treatment of choice.
 Albumin - limited to individuals with severe
hypoalbuminemia (e.g., liver disease and
nephritic syndrome) who are resistant to
crystalloid therapy.
 Severe hypoalbuminemia-associated third
spacing that complicates fluid management, and
albumin may be useful in this setting.
69
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70. Nonpharmacologic
 The most common interventions of intrinsic or
post obstructive AKI involve fluid and electrolyte
management.
 Supportive care goals for the hospitalized
patient with any type of AKI include:
 maintenance of adequate cardiac output
 blood pressure to allow adequate tissue
perfusion
70
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71. Nonpharmacologic
 Renal Replacement Therapies (RRT)
 Intermittent Hemodialysis(IHD)
 Continuous Renal Replacement Therapies
continuous venovenous hemofiltration
(CVVH)
continuous venovenous hemodialysis
(CVVHD)
Continuous venovenous hemodiafiltration
(CVVHDF)
71
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72. 72
Fig Five: Continuous renal replacement therapy (CRRT)
variants

73. Table Eight: Common Indications
for
Renal Replacement Therapy
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73

74. Pharmacologic
 Once the kidney has been damaged by an
acute insult initial therapies should be directed:
 to prevent further insults to the kidney, thereby
minimizing extension of the injury.
 The time to recovery from AKI is determined
from the most recent insult to the kidney, not the
first insult.
74
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75. Pharmacologic
 If sepsis is present, antibiotic therapy regimens
should be adjusted:
 for decreased renal elimination
 the potential for increased elimination if the
agent is removed by hemodialysis
 the ability to treat the infection to prevent
further damage to the kidney.
75
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76. Pharmacologic
 To date, no pharmacologic approach to reverse the
decline or accelerate the recovery of renal function
has been proven to be clinically useful.
 Frusemide
reserved for fluid-overloaded patients who make
adequate urine in response to diuretics to merit
their use
lower cost, availability in oral and parenteral
forms, and reasonable safety and efficacy
profiles
initial furosemide doses, which should not
76

77. 77
Fig six : Algorithm for treatment of extracellular fluid

78. 78
Fig Six : Algorithm for treatment of extracellular fluid

79. Pharmacologic
 Mannitol,
 an osmotic diuretic
 can only be given parenterally
 A typical starting dose is mannitol (20%) 12.5 to 25 g
infused intravenously over 3 to 5 minutes.
 It has little nonrenal clearance
 so when given to anuric or oliguric patients,
mannitol will remain in the patient, potentially
causing a hyperosmolar state.
 Additionally, mannitol may cause AKI itself,
 so monitor carefully by measuring urine output and
serum electrolytes and osmolality.
79

80. Diuretic resistance
 The inability to respond to administered diuretics
is common in AKI
 Diuretic resistance may occur simply
because of
 excessive sodium intake overrides the ability
of the diuretics to eliminate sodium.
 Reduced number of functioning nephrons on
which the diuretic may exert its action.
 Glomerulonephritis, are associated with heavy
proteinuria.
80
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81. Diuretic resistance
 Intraluminal loop diuretics cannot exert their
effect in the loop of Henle because they are
extensively bound to proteins present in the
urine.
 Reduced bioavailability of oral furosemide
because of intestinal edema, often associated
with high preload states, which further reduces
oral furosemide absorption.
81

82. Diuretic resistance
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82
 An effective technique to overcome diuretic
resistance is:
to administer loop diuretics via continuous
infusions instead of intermittent boluses
Increase frequency of administration
Combine with other diuretics

83. Table Nine: Common Causes of Diuretic
Resistance in Patients with AKI
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83

84. Table Nine: Common Causes of
Diuretic Resistance in Patients with
AKI
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84

85. Diuretic resistance
 Metolazone, unlike other thiazides, produces
effective diuresis at a GFR <20 mL/min (0.33 mL/s).
 This combination of metolazone and a loop
diuretic has been used successfully in the
management of fluid overload in patients with
heart failure, cirrhosis, and nephrotic syndrome.
 Despite a lack of supporting evidence, oral
metolazone at a dose of 5 mg is commonly
administered 30 minutes prior to an IV loop diuretic
to allow time for absorption.
85

86. 86
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Table Ten :Key Monitoring Parameters for Patients
with Established Acute Renal Injury