the presentation highlights on the approach of a patient with AKI: i.e History, physical findings, investigations

1. Hailemariam Bekele
Hayelom Michael
Acute Kidney Injury

2. Objectives
 Define “Acute Kidney Injury” (AKI)
 Understand pathophysiologic mechanisms in AKI
 Review the diagnostic approach to AKI
 Identify the syndromes of AKI
 Identify strategies to prevent AKI
 Review the roles of supportive care and renal
replacement therapy and pearls in the therapy and
management of AKI

3. Out line
 Introduction
 Anatomy of kidney
 Epidemiology
 Diagnosis
clinical features
investigation
 Management
 Complications

4. Introduction: Acute Kidney Injury
 Acute kidney injury (AKI)
has now replaced the term
acute renal failure
 A universal definition and
staging system has been
proposed to allow earlier
detection and management
of AKI

5. Definition: acute kidney injury is a syndrome
characterized by:
• Sudden decline in GFR (hours to days )
• Retention of nitrogenous wastes
• Disturbance in extracellular fluid volume and
• Disturbance in electrolyte and acid base
homeostasis

6.  The loss of kidney function is most easily
detected by measurement of the serum creatinine
 Serum creatinine is used to estimate the
glomerular filtration rate (GFR).
 Serum creatinine does not accurately reflect the
GFR
 Recognizing the need for a uniform definition for
ARF, the ADQI group proposed a consensus
graded definition, called the RIFLE criteria

7. RIFLE Criteria
 The RIFLE criteria consists of three graded levels
of injury (Risk, Injury, and Failure)
 Based upon either the magnitude of elevation in
serum creatinine or urine output,
 Two outcome measures (Loss and End-stage
renal disease
 The RIFLE strata are as follows

8. RIFLE Strata
The 2nd International Consensus Conference of the Acute
Dialysis Quality Initiative (ADQI) Group

9.  Azotemia: an abnormal increase in
concentration of urea and other nitrogenous
substances in the blood plasma
 Uremia: the complex of symptoms due to severe
persisting renal failure that can be relieved by
improving clearance
 Oliguria: UOP <~400 ml/24hrs
 Anuria: UOP < ~200 ml/24hrs

10. Epidemiology
 AKI complicates approximately 5% of hospital
admissions.
 Up to 30% of admissions to intensive care units.
 The epidemiology of AKI differs tremendously
between developed and developing countries
 owing to differences in demographics, economics,
geography, and co morbid disease burden.

11.  While certain features of AKI are common
to both,
 particularly since urban centers of some
developing countries increasingly
resemble those in the developed world
 many etiologies for AKI are region-
specific such as :

12.  Envenomations from snakes, spiders,
caterpillars, and bees;
 Infectious causes such as malaria and
leptospirosis; and
 Crush injuries and resultant rhabdomyolysis
from earthquakes

13.  Most AKI is reversible, the kidney being relatively
unique among major organs
 its ability to recover from almost complete loss
of function.
 Nevertheless, AKI is associated with major in-
hospital morbidity and mortality,
 in large part due to the serious nature of the
illnesses that precipitate the AKI.

14. Etiologic Classification of AKI
Acute kidney injury
Pre-renal Intrinsic Post-renal
Glomerular Interstitial VascularTubular

16. A. Prerenal AKI :
•Pre renal AKI is the most common(55 %) form of AKI
•Represents a physiologic response to mild to
moderate renal hypo perfusion.
• Prerenal AKI is rapidly reversible upon restoration of
renal blood flow and glomerular ultrafiltration
pressure.

17.  More severe hypoperfusion may lead to ischemic
injury of renal parenchyma and intrinsic renal
AKI.
 Thus, prerenal AKI and intrinsic renal AKI due to
ischemia are part of a spectrum of manifestations
of renal hypoperfusion.

18. Causes

19. Etiology and Pathophysiology
I. Hypovolemia
• Hemorrhage, burns, dehydration
• Gastrointestinal fluid loss: vomiting, surgical
drainage, diarrhea

20.  Renal fluid loss: diuretics, osmotic diuresis (e.g.,
diabetes mellitus), hypoadrenalism
 Sequestration in extravascular space:
pancreatitis, peritonitis, trauma, burns,
 Severe hypoalbuminemia

21. II. Low cardiac output
• Diseases of - myocardium, valves, and
pericardium; arrhythmias; tamponade
• Other: pulmonary hypertension, massive
pulmonary embolus

22. III. Altered renal systemic vascular resistance
ratio
• Systemic vasodilatation: sepsis, anaphylaxis IV.
Renal hypoperfusion with impairment of renal
autoregulatory responses

23. Pathophysiology:
 Hypovolemia leads to glomerular hypoperfusion,
but filtration rate are preserved during mild
hypoperfusion through several compensatory
mechanisms.
 During states of more severe hypoperfusion,
these compensatory responses are overwhelmed
and GFR falls, leading to prerenal AKI.

24. IV. NSAIDS- they reduce affarent renal
vasodilation
V. ACEIs and ARBs- limit renal efferent
vasoconstriction

25. • Prerenal AKI can complicate any disease that
induces :
 hypovolemia,
low cardiac output,
systemic vasodilatation, or
 selective renal vasoconstriction.

26. B. Intrinsic Renal AKI:

27. - accounts for nearly 40% of
all AKI
I.Renovascular obstruction
bilateral or unilateral in the
setting of one functioning
kidney
II.Disease of glomeruli
orrenal microvasculature
 Acute kidney injury
Intrinsic
Glomerular
Interstitial Tubular
Vascular

29. III. Acute tubular necrosis(ATN)
 Ischemia: as for prerenal AKI (hypovolemia,
low cardiac output, renal vasoconstriction,
systemic vasodilatation)

31. Toxins
 Exogenous: radio contrast, cyclosporine,
antibiotics (e.g. aminoglycosides), chemotherapy
(e.g. cisplatin), organic solvents (e.g. ethylene
glycol), acetaminophen, illegal abortifacients
 Endogenous: Mb, Hb, uric acid, oxalate, plasma
cell dyscrasia (e.g. myeloma)
Postoperative AKI

32. C. Post renal AKI (OBSTRUCTION):

33. accounts for ~5% of AKI.
I. Ureteric: calculi, blood
clot, sloughed papillae,
cancer, external
compression(e.g.retroperiton
eal fibrosis)
II. Bladder neck
• Neurogenic bladder,
prostatic hypertrophy,
calculi, cancer, blood clot
III. Urethra: stricture,
congenital valve, phimosis

34. Pathophysiology of postrenal AKI
 It involves hemodynamic alterations
triggered by an abrupt increase in
intratubular pressures
 An initial period of hyperemia from
afferent arteriolar dilation is followed
by intrarenal vasoconstriction from the
generation of angiotensin II,
thromboxane A2, and vasopressin,
and a reduction in NO production.

35.  Reduced GFR is due to
underperfusion of glomeruli and,
possibly, changes in the glomerular
ultrafiltration coefficient

36. Approach to a patient with AKI

37. Careful history is essential
 Exposure to nephrotoxins and drugs
 Anuria may indicate post-renal causes
 Skin rashes may indicate allergic nephritis
 Evidences of volume depletion: diarrhea, bleeding
 Pelvic and per-rectal examination: look for evidence
of abortion
 Ischemia or trauma to the legs or arms may indicate
rhabdomyolysis

38.  A history of prostatic disease, nephrolithiasis
 Recent surgical or radiologic procedures
 Past and present use of medications
 Family history of renal diseases

39. Physical examination
 should be focused to rule out possible
differential diagnoses
 Prerenal AKI: is suggested by clinical signs of
intravascular volume depletion (e.g. orthostatic
hypotension , rapid pulse and poor skin turgor)
 Congestive heart failure (e.g. raised JVP , S3 ,
dependent edema , and pulmonary rales )

40.  Acute allergic interstitial nephritis: is suggested
by signs of allergy (e.g. periorbital edema,
esosinophilia , maculopapular rash , and
wheezing )

41.  Lower Urinary tract obstruction: is suggested by
suprapubic or flank mass or symptoms of bladder
dysfunction (e.g. hesitancy, urgency)
Uremia: - clinical syndrome resulting from
the adverse effect of renal failure on other
organ systems (only very few develop in acute
renal failure)

42. Diagnostic work up
1. Urinalysis: Microscopic evaluation of
urinary sediment.
 Presence of few formed elements or hyaline
casts is suggestive of prerenal or postrenal
azotemia.
 Many RBCs may suggest calculi , trauma ,
infection or tumor
 Eosinophilia : occurs in 95 % of patients with
acute allergic nephritis
 Brownish pigmented cellular casts and many
renal epithelia cells are seen in patients with
acute tubular necrosis (ATN )

43.  Pigmented casts without erythrocytes in the
sediment from urine but with positive dipstick
for occult blood indicates hemoglobinuria or
myoglobinuria

44.  Dipstick test: trace or no proteinuria with pre-
renal and post-renal AKI;
 mild to moderate proteinuria with ATN and
moderate to severe proteinuria with glomerular
diseases.
 RBCs and RBC casts in glomerular diseases
 Crystals, RBCs and WBCs in post-renal ARF.

45. 2. Urine and blood Chemistry:
 Most of these tests help to differentiate prerenal
azotemia, in which tubular reabsorption function
is preserved from acute tubular necrosis where
tubular reabsorption is severely disturbed.
Osmolality or specific gravity: decreased in ATN
and pos-renal AKI (urine is diluted) , while
increased in pre-renal AKI ( urine is concentrated)

46.  BUN/plasma creatinine ratio: the BUN/plasma
creatinine ratio is normal at 10-15:1 in ATN, but
may be greater than 20:1 in prerenal disease due
to the increase in the passive reabsorption of
urea that follows the enhanced proximal
transport of sodium and water. Thus, a high ratio
is highly suggestive of prerenal disease as long
as some other cause is not present. But this
criterion is not highly specific.

47.  Renal failure index: ratio of urine Na+ to urine
to plasma creatinine ratio
 (UNa/Ucr/Pcr) . Values less than 1 % are
consistent with prerenal AKI,where as a
 Value > 1% indicates ATN

48.  Fractional excretion of Na+: is ratio of urine-to-
plasma Na ratio to urine-to-plasma creatinine
expressed as a percentage [ (UNa/PNa)/(Ucr/Pcr
)X 100]. Value below 1% suggest prerenal
failure , and values above 1% suggest ATN
• Serum K+ and other electrolytes

49. 3. Radiography/imaging
 Ultrasonography: helps to see the presence of
two kidneys, for evaluating kidney size and
shape, and for detecting hydronephrosis or
hydroureter.
 It also helps to see renal calculi, and renal vein
thrombosis.
 Retrograde pyelography: is done when
obstructive uropathy is suspected

50. Complications of AKI
 Intravascular overload: may be recognized by
weight gain , hypertension ,elevated central
venous pressure ( raise JVP) , Pulmonary edema
Electrolyte disturbance
 Hyperkalemia: (serum K+ >5.5 mEq/L): decreased
renal excretion combined with tissue necrosis or
hemolysis.
 Hyponatremia : ( serum Na+ concentration < 135
mEq/L ): excessive water intake in the face of
excretory failure

51.  Hyperphosphatemia : ( serum Phosphate
concentration of > 5.5 mg /dl ) failure of excretion
or tissue necrosis
 Hypocalcemia : ( serum Ca++ < 8.5 mg/dl )
results from decreased Active Vit-D ,
hyperposhphatemia , or hypoalbuminemia
 Hypercalcemia: (serum Ca++ > 10.5 mg /dl) may
occur during the recovery phase following
rhabdomyolysis induced acute renal failure.

52.  Metabolic acidosis :( arterial blood PH < 7.35 ) is
associated with sepsis or severe heart failure
 Hyperuricemia: due to decreased uric acid
excretion
 Bleeding tendency : may occur due to platelet
dysfunction and coagulopathy associated with
sepsis
 Seizure: may occur related to uremia

53. Management of AKI
1. Prevention:
• Because there are no specific therapies for
ischemic or nephrotoxic AKI,
Many cases of ischemic AKI can be avoided by
close attention to cardiovascular function and
intravascular volume in high-risk patients, such
as the elderly and those with preexisting renal
insufficiency.

54. • Indeed, aggressive restoration of intravascular
volume has been shown to reduce the incidence of
ischemic AKI dramatically after major surgery or
trauma, burns, or cholera prevention is of
paramount importance.

55.  The incidence of nephrotoxic ARF can be
reduced by tailoring the dosage of potential
nephrotoxins to body size and GFR; for
example, reducing the dose or frequency of
administration of drugs in patients with
preexisting renal impairment

56.  Preliminary measures
• Exclusion of reversible causes: Obstruction
should be relived , infection should be treated
• Correction of prerenal factors: intravascular
volume and cardiac performance should be
optimized

57.  Maintenance of urine output: Loop diuretics
may be usefully to convert the oliguric form of
ATN to the nonoliguric form.
 High doses of loop diuretics such as Furosemide
(up to 200 to 400 mg intravenously) may
promote diuresis in patients who fail to respond
to conventional doses

58.  Specific Therapies:
• To date, there are no specific therapies for
established intrinsic renal ARF due to ischemia or
nephrotoxicity.
• Management of these disorders should focus on
elimination of the causative hemodynamic
abnormality or toxin, avoidance of additional
insults, and prevention and treatment of
complications.
• Specific treatment of other causes of intrinsic
renal ARF depends on the underlying pathology.

59. Prerenal ARF:
• The composition of replacement fluids for
treatment of prerenal ARF due to hypovolemia
must be tailored according to the composition of
the lost fluid.
• Severe hypovolemia due to hemorrhage should
be corrected with packed red blood cells, whereas
isotonic saline is usually appropriate replacement
for mild to moderate hemorrhage or plasma loss
(e.g., burns, pancreatitis).

60.  Urinary and gastrointestinal fluids can vary
greatly in composition but are usually
hypotonic. Hypotonic solutions (e.g., 0.45%
saline) are usually recommended as initial
replacement in patients with prerenal ARF due
to increased urinary or gastrointestinal fluid
losses, although isotonic saline may be more
appropriate in severe cases

61.  Subsequent therapy should be based on
measurements of the volume and ionic content
of excreted or drained fluids. Serum potassium
and acid-base status should be monitored
carefully.

62. Postrenal ARF:
 Management of postrenal ARF requires close
collaboration between nephrologist, urologist,
and radiologist.
• Obstruction of the urethra or bladder neck is
usually managed initially by transurethral or
suprapubic placement of a bladder catheter, which
provides temporary relief while the obstructing
lesion, is identified and treated definitively.
Similarly, ureteric obstruction may be treated
initially by percutaneous
catheterization of the dilated renal pelvis or ureter.

63. 4. Supportive Measures: (Conservative therapy
)
• Dietary management:
 Generally, sufficient calorie reflects a diet that
provides 40-60 gm of protein and 35-50 kcal/kg
lean body weight.
 In some patients, severe catabolism occurs and
protein supplementation to achieve 1.25 gm of
protein /kg body weight is required to maintain
nitrogen balance.
 Restricting dietary protein to approximately 0.6
g/kg per day of protein of high biologic value
(i.e., rich in essential amino acids) may be
recommended in sever azotemia.

64. Fluid and electrolyte management :
 Following correction of hypovolemia, total oral
and intravenous fluid administration should be
equal to daily sensible losses (via urine, stool,
and NG tune o surgical drainage ) plus estimated
insensible ( i.e. , respiratory and derma ) losses
which usually equals 400 – 500 ml/day. Strict
input output monitoring is important.

65.  Hypervolemia: can usually be managed by
restriction of salt and water intake and diuretics.
 Metabolic acidosis: is not treated unless serum
bicarbonate concentration falls below 15
mmol/L or arterial pH falls below 7.2.
 More severe acidosis is corrected by oral or
intravenous sodium bicarbonate.

66.  Initial rates of replacement are guided by estimates of
bicarbonate deficit and adjusted thereafter according
to serum levels.
 Patients are monitored for complications of
bicarbonate administration such as hypervolemia,
metabolic alkalosis, hypocalcemia, and hypokalemia.
 From a practical point of view, most patients
requiring sodium bicarbonate need emergency
dialysis within days.

67.  Hyperkalemia: cardiac and neurologic complications
may occur if serum K+ level is > 6.5 mEq/L
o Restrict dietary K+ intake
o Give calcium gluconate 10 ml of 10% solution over 5
minutes
o Glucose solution 50 ml of 50 % glucose plus Insulin
10 units IV
o Give potassium –binding ion exchange resin
o Dialysis: it medial therapy fails or the patient is very
toxic

68.  Hyperphosphatemia is usually controlled by
restriction of dietary phosphate and by oral
aluminum hydroxide or calcium carbonate,
which reduce gastrointestinal absorption of
phosphate.
 Hypocalcemia does not usually require
treatment.

69. • Anemia: may necessitate blood transfusion if
severe or if recovery is delayed.
• GI bleeding: Regular doses of antacids appear to
reduce the incidence of gastrointestinal
hemorrhage significantly and may be more
effective in this regard
than H2 antagonists, or proton pump inhibitors.
• Meticulous care of intravenous cannulae, bladder
catheters, and other invasive devices is mandatory
to avoid infections

70. Dialysis
 Indications and Modalities of Dialysis: -
Dialysis replaces renal function until
regeneration and repair restore renal function.
Hemodialysis and peritoneal dialysis appear
equally effective for management of ARF.
Absolute indications for dialysis include:
 􀂾 Symptoms or signs of the uremic syndrome
 􀂾 Refractory hypervolemia
 􀂾 Sever hyperkalemia
 􀂾 Metabolic acidosis.

71. Clinical course and prognosis
 Stages: acute renal failure due to ATN typically
occurs in three stages: Azotemic , Diuretic , and
recovery phases. The initial azotemic stage can
be either oliguric or non oliguric type.
• Morbidity and mortality: are affected by the
presence of oliguria o GI bleeding, septicemia,
metabolic acidosis and neurologic abnormalities
are more common in oliguric patients than in
nonoliguric patients.

72.  The mortality rate for oliguric patients is
50 % where as that of nonoliguric patients
is only 26 %

73. Prognosis:
 The mortality rate among patients with ARF
approximates 50. It should be stressed, however, that
patients usually die from sequelae of the primary
illness that induced ARF and not from ARF itself
 Mortality is affected by both severity of the
underlying diseases and the clinical setting in which
acute renal failure occurs. E.g. the mortality of ATN
is 60 % when it results from surgery or trauma, 30 %
when it occurs as a complication of medical illnesses,
and 10-15 % when pregnancy is involved.

74. • Ischemia associated ATN has 2X the mortality
risk of nephrotoxic ATN.
• In agreement with this interpretation, mortality
rates vary greatly depending on the cause of ARF:
~15% in obstetric patients, ~30% in toxin-related
ARF, and ~60% following trauma or major
surgery.

75.  Oliguria (<400 mL/d) at time of presentation and a
rise in serum creatinine of >3 mg/dl are associated
with a poor prognosis and probably reflect the
severity of renal injury and of the primary illness.
• Mortality rates are higher in older debilitated patients
and in those with multiple organ failure

76. • Patients with no complicating factors who
survive an
episode of acute renal failure have a 90 % chance
of
complete recovery of kidney function.