Acute Renal Failure

Acute renal failure

50%

increase in baseline serum

creatinine concentration
25% decrease in glomerular filtration
rate (GFR)
Urine output of less than 0.5
mL/kg/hr for at least 6 hours
* No single serum creatinine valuee is
a threshold for ARF

RIFLE Classification

Epidemiology
Between

5% and 25% of all

hospitalized patients may develop
this dissease

 Afferent

and efferent arteriolar

vasoconstriction/vasodilation effects
on GFR and RBF

Afferent

and efferent
vasoconstriction = Angiotensin II

Afferent

E2

vasodilation = Prostaglandin

 Decrease

GFR & RBF = sympathetic

nerves, angiotensin II, endothelin

Increase

GFR & RBF = PGE2, NO,

bradykinin

Why ACEI is contraindicated

in renal artery stenosis?
Pressure

proximal to the renal artery

stenosis is increased while pressure
distal to it is normal or reduced

Lowering

the BP, lowers the pressure

distal to the stenosis lowering RBF &
GFR

Categories
Prerenal-10-25%
Intrinsic Postrenal

50%
10%

of cases

Prerenal ARF
Reduced

blood delivery to the kidney

Due

to intravascular volume
depletion, reduced cardiac output
and hypotension

No

structural damage to the kidney

has occurred

Prerenal ARF
Mild

to moderate decrease in RBF,

intraglomerular pressure is
maintained by dilation of the afferent
artierioles, constriction of efferent
arterioles and redistribution of RBF
to the oxygen sensitive renal
medulla

Functional ARF
Caused

by drugs
NSAIDs impairs prostaglandin-mediated
dilation of the afferent arterioles
ACEI and ARBs inhibit angiotensin IImediated efferent arteriole vasoconcstriction
High dose cyclosporine and tacrolimus are
potent renal vasoconstrictors
Decrease intraglomerular pressure
decrease GFR

Prerenal ARF
Caused

by renal artery stenosis

Intrinsic ARF
Also

known as intrarenal ARF

Damaged is within the kidneys
Acute tubular necrosis (ATN)
Results from toxic (amphotericin B,
aminoglycosides, contrast agents)
and ischemic insult to the kidney

ATN
Necrosis

in proximal tubule
epithelium and BM, decreased
glomerular capillary permeability
and backleak of glomerular filtrate
into the venous circulation
Mediated by intrarenal
vasoconstriction

Intrinsic ARF
Glomerulonephritis,

SLE, interstitial

nephritis, vasculitis
CAN

be a result of prerenal ARF if the

condition is not corrected

Postrenal ARF
Due

to obstruction of urinary outflow

Benign prostatic hypertrophy (BPH),
pelvic tumors and renal calculi
structural damage to the kidneys

Assessment of Renal
Function

Glomerular filtration
rate
Volume

of plasma filtered across the

glomerulus per unit time
Correlates with the filtration,
secretion, absorption, endocrine and
metabolic funciotn of the kidney
Used to compute for the proper
dosing of drugs that undergo renal
elimination (e.g. Vancomycin)

Glomerular filtration
rate
90-120

mL/min
Creatinine clearance (CrCl) is used to
estimate GFR
Urine

volume, urine creatinine concentration

and serum creatinine concentration

CrCl

may underestimate or overestimate

renal function depending on the stage of the
disease

Estimating creatinine
clearance (Cockroft & Gault)
CLcr

for males = (140-age in yrs)

(IBW in kg)
(mL/min)
(72)(Scr in mg/dL)

CLcr

for females = (0.85)(CLcr)

Serum

creatinine is at steady state

and age, wt., and gender reflects
normal muscle mass

Estimating creatinine
clearance (Cockroft & Gault)
CLcr

for = F x (140-age in yrs)(wt.

in kg)
(mL/min)
(Scr in umol/L)

F= 1.04 in females or 1.23 in males

Estimating creatinine
clearance
IBW

in males (kg) = 50 + (2.3 x Ht.

in inches > 60)

IBW

in females (kg) = 45 + (2.3 x Ht.

in inches > 60)

Clinically

obese: (TBW/IBW) X 100 >

120
Adjusted BW = IBW + 0.4(TBW-IBW)

Estimating creatinine
clearance
BSA

in m2 = (Weight in kg/70 kg)0.7

(1.73 m2)

Compute for estimated

CrCl
54

year-old male, Wt. 92 kg, SCr 6.1

mg/dL

32

year-old female, Wt. 88 kg, SCr

3.5 mg/dL

Estimating creatinine
clearance
CL

cr for children = (K)(Ht. In cm)

(mL/min/1.73m2)
S crss
Age

Preterm infants up to 1
year

0.33

Full-term infants up to 1
year

0.45

1-12 years

0.55

13-21 years female

0.55

13-21 years male

0.70

Estimating creatinine
clearance
CLcr

for children = (CLcr in

mL/min/1.73 m2)
(mL/min)
(BSA/1.73m2)

CLcr

for children = (CLcr in

mL/min/1.73 m2)
(mL/min)
x (Wt. In kg/70kg)0.7

Estimating renal clearance (Modification of

Diet in renal disease study or MDRD)
eGFR

(mL/min/1.73 m2) = 170 x (Scr)0.999

x (age)-0.176 x (0.762 if female) x
(1.18 if black) x (BUN)-0.17 x (Alb)+0.318

Where

SCr is in mg/dL, BUN is in

mg/dL & Albumin in g/dL
Used to estimate renal function with
GFR < 60 mL/min

Assessment of renal
function
Symptomatology

(signs of uremia,
pruritus, edema, fatigue, weight
gain)

Laboratory

results (blood creatinine,

urinalysis)
Urine

output

Assessment of renal
function
Oliguria

urine output less than 400

mL/ 24 hours

Anuria

urine output less than 50

mL/ 24 hours

Prerenal Renal
FeNa (%)
Urine Na
(mEq/L)
Urine/serum
BUN (umol/L)
Urine/serum
Crea (umol/L)
Urine osm
(mOsm/kg)

<1

>2

< 20

> 40

>8

<3

> 40

< 20

> 500

<400

Course of ATN
Oliguric

phase (7-14 days, 6 weeks)

prerenal AKI
Diuretic phase (1 week)
recommencement of tubular function
Recovery phase tubular cells
regenerate slowly over months , GFR
does not return to initial levels
(elderly recover more slowly & less
completely

Course of ATN
Uremia

& hyperkalemia
Septicemia and acute vascular
events (MI & stroke) are common
cause of deaths associated with AKI
Uremia results in debility

ACEI & ARBs in ARF

Monitor

BP because of hypotension
leading to prerenal ARF
Contraindicated in renal artery
stenosis
Blocks the action of angiotensin II
(increasing efferent arteriolar tone)
resulting in decreased GFR

Goals of treatment
Control

any identifiable underlying

cause of ARF (hypovolemia,
nephrotoxic drugs, ureter
obstruction)
Correct and maintain proper fluid &
electrolyte balance
Treat hyperkalemia and metabolic
acidosis when present
Improve urine output
Treat systemic manifestations of ARF

 There

is no evidence that drug

therapy hastens patient recovery,
shorten length of hospital stay or
improves survival

Prerenal

and postrenal ARF can be

reversed if promptly treated
Intrinsic ARF is more supportive in
nature

Treatment objectives
Correct

reversible causes of ARF

Preventing or minimizing further
renal damage or complications
Discontinue nephrotoxic drugs
Treat underlying infection
Remove any urinary tract infections

Treatment objectives
Correct

and maintain proper fluid &

electrolyte balance
Treat body chemistry alterations
especially hyperkalemia and
metabolic acidosis
Improve urine output
Treat systemic manifestations of ARF

 Conservative

management may
suffice in uncomplicated ARF

Monitor
Fluid

balance (how?), signs of

congestion
Co-morbities/drugs that may
aggravate AKI
Ions (K, Ca, phosphate, bicarbonate)
Acid-base balance
WBC count/differential count
(infection)

Fluid management
Fluid

intake should match fluid losses

Sensible

losses and insensible losses

of 500-1L/day should be included in
fluid balance calculations

Volume

overload should be avoided

to minimize risk of HTN & CHF

Optimize renal perfusion

Central

line may be used

0.9% NaCl is ideal

Establishing adequate
diuresis
Loop

diuretics may be given for fluid

overload & hyperkalemia
Loop diuretics decrease renal tubular
cell metabolic demands and increase
renal blood flow by release of
prostaglandin (renal vasodilator)
Transient deafness may occur at high
infusion rates

Establishing adequate
diuresis
Dopamine

at low doses is a renal

vasodilator in normal kidneys but in
renal failure it is a renal
vasoconstrictor
No clinical benefit
Mannitol is also not beneficial

Problems in AKI or ARF

Uremia
Intravascular fluid
Hyperkalemia
Acidosis
Hypocalcemia

overload

Hyperphosphatemia
Infection

Treatment of uremia
Accumulation

of toxic products of
protein metabolism including urea
Nausea, vomiting, anorexia
Control in the diet

Fluid management
Patient

should be weighed daily to

determine fluid volume status
Control in the intake of fluid and lowsalt

Dietary measures
High-calorie,
Reduce

low-protein diet

renal workload by decreasing

production of end products of protein
catabolism that the kidneys cannot
excrete
Prevent ketoacidosis
Alleviate manifestations of uremia

Dietary measures
Sodium

intake should be restricted if

edema & HTN is present

Potassium

intake must be limited in

most patients
Drugs that increase K
(spironolactone, ACEI, ARBs)

Treatment of
hyperkalemia
Intracellular

K is released (esp. in
sepsis, tissue damage) and excretion
is decreased
Regulate the diet and drugs (K
sparing diuretics)
Emergency

treatment if level > 7.0

mmol/L or ECG changes (tall, peaked
T waves, reduced P waves, increase
QRS complexes)

Treatment of hyperkalemia
Dialysis
Administer

calcium chloride or
gluconate to replace and maintain
body calcium and counteract the
cardiac effects of acute
hyperkalemia

Treatment of
hyperkalemia
IV

calcium is contraindicated in
patients with ventricular fibrillation &
renal calculi

ECG

should be monitored

Calcium

gluconate should not be

mixed with solutions containing
NaHCO3 due to precipitation

Treatment of
hyperkalemia
Adverse

effect of Ca gluconate:
hypotension, tingling sensations &
renal calculus

DI:

may increase digoxin toxicity

Treatment of
hyperkalemia
Sodium

bicarbonate IV can be
given as an emergency measure to
treat hyperkalemia & metabolic
acidosis

Rationale:

Renal tubules cannot

reabsorb form the glomerular filtrate
& increase arterial pH shift K+ into
cells

Treatment of
hyperkalemia
Monitoring:

can lead to sodium and

fluid overload

May
ABG

precipitate calcium salts

and serum electrolytes must be

monitored

Treatment of hyperkalemia
Regular

insulin IV (8-12 u) with 50%

dextrose
Causes intracellular shift of potassium
Deposits potassium with glycogen in the
liver
Monitoring:

fluid overload and serum glucose

Salbutamol

may also be given (temporary

emergency measure), does not permanently
lower K

Treatment of hyperkalemia
Sodium

polystyrene sulfonate (SPS)

Potassium-removing resin
(exchanges sodium for potassium)
Distributed in the intestines and
excreted in the feces
Route

of administration? oral

Treatment of
hyperkalemia
Monitoring

of SPS: sodium,
bicarbonate, chloride, pH and
________________
Potassium between 4-5 mEq/L
Potassium depletion irritability,
confusion, cardiac arrhythmias, ECG
changes and muscle weakness
Monitor

for signs of HTN and CHF

Treatment of
hyperkalemia
SPS

oral should be mixed with water

or sorbitol not with orange juice
As enema with water or sorbitol,
never with mineral oil

Treatment of
hyperkalemia
Adverse

effects: constipation, fecal

impaction, vomiting & diarrhea
Should not be used as a sole agent
Interactions:

Magnesium hydroxide
and nonabsorbable cation-donating
laxatives & antacids may decrease
the effects systemic alkalosis

Treatment of metabolic
acidosis
Inability

of the kidneys to excrete H+

ions, contributes to hyperkalemia
Sodium bicarbonate IV is given in
arterial pH is below 7.35

Treatment of metabolic
acidosis
Increase

intracellular Na+ through

activating Na+/H+ exchanger and
promotes increase Na+/K+ ATPase
increasing intracellular sequestration
of K

Treatment of metabolic
acidosis
Adverse

effect: Fluid overload due to

sodium
Next
Do

treatment alternative is dialysis

not give simultaneously with Ca

gluconate in a single IV line due to
precipitate formation

Treatment of
hyperphosphatemia
Phosphate

is normally excreted by
the kidneys

Treatment of
hyperphosphatemia
IV

calcium is the first line of therapy

Reduces phosphorus conc. by
chelation
Oral calcium binds to dietary P in the
GI tract
Calcium carbonate is used to treat
acute, life-threatening
hyperphosphatemia with acute
hypocalcemia when volume overload
is present

Treatment of
hyperphosphatemia
Aluminum

hydroxide oral can bind

excess phosphate in the intestines
Onset of action: 6-12 hours
Side effects: anorexia
Monitoring: serum phosphate or
calcium
Can cause calcium resorption & bone
demineralization

Treatment of
hypocalcemia
Due

to Ca malabsorption due to
disordered vit D metabolism
Calcium gluconate for low levels
Replaces and maintains body
calcium, raising the serum calcium
level immediately
Mild

hypocalcemia: oral calcium

(carbonate, chloride, gluconate or
lactate) supplementation

Treatment of
hyponatremia
Fluid

restriction for moderate or

asymptomatic hyponatremia
For sodium level below 120 mEq/L,
________________ IV
Replaces and maintains sodium and
chloride increasing extracellular
tonicity

Treatment of
hyponatremia
Hypertonic

sodium chloride should

be administered very slowly to avoid
pulmonary edema, central pontine
demyelination and circulatory
overload

Management of systemic
manifestations
Treatment
Mannitol

of fluid overload & edema

or loop diuretic may be

used
Thiazide

diuretics are avoided

Management of systemic
manifestations
Loop

(high-ceiling) diuretics
More potent and rapid acting than
thiazide diuretics

Management of systemic
manifestations
cause overdiuresis orthostatic
hypotension, fluid and electrolyte
abnormalities (______calcemia,
____kalemia, ____chloremia,
_____natremia, _____magnesemia)
and transient ototoxicity with rapid
IV injection
Vital signs should be monitored
Monitor ____________ in diabetics
May

Management of systemic
manifestations
Sensitive

to sulfonamides may be
sensitive to bumetanide &
furosemide

Furosemide

and ethacrynic acid may

produce agranulocytosis

Management of systemic
manifestations
Interactions:

aminoglycosides
NSAIDs & probenecid
Ethacrynic acid may potentiate the
anticoagulant effect of warfarin

Management of systemic
manifestations
Mannitol

(route?)
Osmotic diuretic
MOA: increases the osmotic pressure
of the glomerular filtrate
Fluid from interstitial spaces is drawn
into blood vessels, expanding
plasma volume and maintaining or
increasing urine flow

Management of systemic
manifestations
May

be given to prevent ARF in highrisk patients (undergoing surgery,

severe trauma) or oliguric ARF
Contraindicated in anuria, severe
dehydration, pulmonary
edema/congestion & intracranial
hemorrhage
May

worsen pulmonary edema &

circulation overload

Management of systemic
manifestations
Adverse

effects: fluid & electrolyte

abnormalities, water intoxication,
headache, confusion, blurred vision,
thirst, nausea & vomiting

Monitoring:

vital signs, urine output,

daily weight, cardiopulmonary
status, serum & urine Na & K

Treatment of infections
Due

to bladder catheters, central

catheters, peripheral IV lines should
be used with care
Serum culture & sensitivity
Broad spectrum antibiotic can be
used while awaiting results

Dialysis
If

all strategies fail

For ARF with acute fluid overload,
anuria, severe hyperkalemia,
metabolic acidosis, BUN level above
100 mg/dL

Why dialysis?
Remove

uremic toxins rapidly when

severe symptoms are present (e.g.
altered sensorium)
Resistant to diuretics
Correct electrolyte and acid-base
imbalances (contraindication to
sodium bicarbonate)

Hemodialysis
For

patients with reduced peritoneal

membrane, hypercatabolism or
acute hyperkalemia
Involves shunting of blood through a
dialysis membrane containing unit
for diffusion, osmosis & ultrafiltration
Vascular access via arteriovenous
fistula or external shunt

Hemodialysis
Receives

heparin to prevent clotting

Clotting of the hemofilter,
hemorrhage, hepatitis, anemia,
septicemia, cardiovascular problems,
air embolism, rapid shifts in fluid &
electrolyte balance, itching,
headache, seizures, nausea,
vomiting, aluminum osteodystrophy

Hemodialysis

Hemodialysis

Hemofiltration

Peritoneal dialysis
Preferred

for patients with bleeding

disorders and cardiovascular disease
Peritoneum is used as a
semipermeable membrane
Plastic catheter is inserted into the
peritoneum provides access for the
dialysate, which draws fluids, wastes
and electrolytes across the
peritoneal membrane by osmosis
and diffusion

Peritoneal dialysis

Peritoneal dialysis
Intermittent

PD - automatic cycling
mode lasting 8-10 hours, 3x a week,
for working patients
Continuous ambulatory PD 24
hours with 4 exchanges daily,
patient can remain active during
treatment

Peritoneal dialysis
Continuous

cyclic PD dialysis takes

place at night, last exchange is
retained in the peritoneal cavity
during the day, then drained that
evening

Advantages:

lack of serious
complications, retention of normal
fluid & electrolyte balance, reduced
cost, simplicity, reduced or no need

Peritoneal dialysis
Complications:

hyperglycemia,
constipuation, & infection of the
catheter site, high risk of peritonitis

Ideal drug for use in a patient

with renal failure
No

active metabolites
Disposition unaffected by fluid
balance changes
Disposition unaffected by protein
binding changes
Response unaffected by altered
tissue sensitivity
Wide therapeutic margin
Not nephrotoxic