Farmakoterapi II

RENAL DISEASE

FISIOLOGI RENAL
oleh: Tunggul Adi P., M.Sc., Apt.
Laboratorium Farmasi Klinik FKIK UNSOED
TUJUAN PEMBELAJARAN
Mahasiswa mampu:
- Menjelaskan fungsi fisiologis ginjal
- Menjelaskan struktur ginjal
- Menjelaskan proses filtrasi, reabsorpsi, dan
sekresi

FUNGSI UTAMA GINJAL
Pengaturan volume dan osmolalitas cairan tubuh
Pengaturan keseimbangan elektrolit
Pengaturan keseimbangan asam basa
Ekskresi (metabolic product, foreign substance,
excess substance)
Produksi dan sekresi hormon (erythropoitin, 1,25-
dihydroxy vitamin D
3
(vitamin D activation), renin)

Renal system important points
Kidneys have excellent blood
supply: 0.5% total body
weight but ~20% of CO
(cardiac output).
Kidneys process plasma
portion of blood by removing
substances from it, and in a
few cases, by adding
substances to it.
Works with cardiovascular
system (and others!) in
integrated manner




A. Renal Vein
B. Renal Artery
C. Ureter
D. Medulla
E. Renal Pelvis
F. Cortex
1. Ascending loop of
Henle
2. Descending loop of
Henle
3. Peritubular capillaries
4. Proximal tubule
5. Glomerulus
6. Distal tubule
GINJAL DAN NEFRON
The functional unit of the kidney: the nephron
Total of about 2.5 million in
the 2 kidneys.
Each nephron consists of 2
functional components:
The tubular component
(contains what will
eventually become urine)
The vascular component
(blood supply)
The mechanisms by which
kidneys perform their
functions depends upon the
relationship between these
two components.
Responsible for urine
formation:
Filtration
Secretion
Reabsorption

Characteristics of the
renal blood flow:
1, high blood flow. 1200
ml/min, or 21 percent of
the cardiac output. 94%
to the cortex
2, Two capillary beds
High hydrostatic pressure
in glomerular capillary
(about 60 mmHg) and
low hydrostatic pressure
in peritubular capillaries
(about 13 mmHg)
Vesa Recta
From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html
Overview of nephron function
Functions of the Nephron
Filtration
Reabsorption
Secretion
Excretion
HUMAN RENAL PHYSIOLOGY
Four Main Processes:

Filtration

Reabsorbtion

Secretion

Excretion
HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Filtration:
First step in urine formation
Bulk transport of fluid from blood to
kidney tubule
Isosmotic filtrate
Blood cells and proteins dont filter
Result of hydraulic pressure
GFR = 180 L/day
HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Reabsorbtion:
Process of returning filtered material to
bloodstream
99% of what is filtered
May involve transport protein(s)
Normally glucose is totally reabsorbed
HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Secretion:
Material added to lumen of kidney from
blood
Active transport (usually) of toxins and
foreign substances
Saccharine
Penicillin
HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Excretion:
Loss of fluid from body in form of urine:
Amount of solute excreted=
amount filtered + amount secreted amount
reabsorbed

Filtration
THE GLOMERULUS
Components of plasma cross the three layers of the glomerular barrier during filtration
Capillary endothelium
Basement membrane (net negative charge)
Epithelium of Bowmans Capsule (Podocytes filtration slits allow size <60kD)
The ability of a molecule to cross the membrane depends on size, charge, and shape
Glomerular filtrate therefore contains all molecules not contained by the glomerular
barrier - it is NOT URINE YET!
Plasma is filtered through the
glomerular barrier
Glomerular filtration
GFR controlled by diameters
of afferent and efferent
arterioles
Sympathetic vasoconstrictor
nerves
ADH and RAAS also have an
effect on GFR.
Autoregulation maintains
blood supply and so
maintains GFR. Also prevents
high pressure surges
damaging kidneys.
Unique system of upstream
and downstream arterioles.

Remember: high hydrostatic pressure (P
GC
) at glomerular
capillaries is due to short, wide afferent arteriole (low R to
flow) and the long, narrow efferent arteriole (high R).
GFR depends on diameters of afferent and
efferent arterioles
GFR GFR
Glomerulus
Afferent arteriole Efferent arteriole
Glomerular filtrate
Aff. Art. dilatation
Eff. Art. dilatation Eff. Art.
constriction
Aff. Art.
constriction
Prostaglandins,
Kinins, Dopamine
(low dose), ANP,
NO
Angiotensin II (low
dose)
Angiotensin II
blockade
Ang II (high dose),
Noradrenaline (Symp
nerves), Endothelin, ADH,
Prost. Blockade)
Glomerular Filtration Rate (GFR)
Measure of functional capacity of the
kidney
Dependent on difference in pressures
between capillaries and Bowmans space
Normal = 120 ml/min =7.2 L/h=180 L/day!!
(99% of fluid filtered is reabs.)

Oncotic pressure
Oncotic pressure is the component of
total osmotic pressure due to colloid
particles.

Water molecules cross the membrane to
equalize the concentration of colloid
particles on each side.
Glomerular filtration rate (GFR)
Depends on the difference in hydrostatic and oncotic
pressure on either side of the glomerular basement
membrane






GFR
=
K
f
(P
GC
- P
BS
- COP
GC
)
P = hydrostatic pressure
COP = colloid osmotic pressure
K
f
determined by surface area
and permeability of H
2
O
P
GC P
BS
COP
GC
COP
BS
Glomerular
Capillary (GC)
Bowmans
space (BS)
Reabsorption and secretion
Peritubular reabsorption
Peritubular capillaries provide
nutrients for tubules and retrieve
the fluid the tubules reabsorb.
Oncotic P is greater than
hydrostatic P in these capillaries,
so therefore get reabsorption
NOT filtration.
Must occur since we filter
180l/day, but only excrete 1-
2l/day of urine.
Reabsorb 99% H
2
O, 100%
glucose, 99.5% Na
+
and 50% urea.
Most of this occurs at proximal
convoluted tubule.
Reabsorption
Active Transport requires ATP
Na+, K+ ATP pumps
Passive Transport-
Na+ symporters (glucose, a.a., etc)
Na+ antiporters (H+)
Ion channels
Osmosis

Renal transport systems
Lots of transporter proteins for
different molecules/ions so
they can be reabsorbed.
They all have maximum
transport (T
M
) capacities
where transport saturates i.e.
10mmol/l for glucose.
Over this value, you excrete
the excess in urine, so can be
useful sign of disease either in
kidneys or other systems.
Amino acids also have a high
T
M
value because you try and
preserve as much of these
useful nutrients as possible.

Factors influencing Reabsorption
Saturation: Transporters can get saturated by
high concentrations of a substance - failure to
resorb all of it results in its loss in the urine (eg,
renal threshold for glucose is about 180mg/dl).
Rate of flow of the filtrate: affects the time
available for the transporters to reabsorb
molecules.
What is Reabsorbed Where?
Proximal tubule - reabsorbs 65 % of filtered Na+ as well as Cl
-
,
Ca
2+
, PO
4
, HCO
3
-
. 75-90% of H
2
0. Glucose, carbohydrates,
amino acids, and small proteins are also reabsorbed here.
Loop of Henle - reabsorbs 25% of filtered Na+.
Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs HCO
3
-.
Collecting duct - reabsorbs the remaining 2% of Na+ only if the
hormone aldosterone is present. H
2
0 depending on hormone
ADH.

Secretion
Proximal tubule uric acid, bile salts,
metabolites, some drugs, some creatinine
Distal tubule Most active secretion takes
place here including organic acids, K+, H+,
drugs
Countercurrent exchange
The structure and transport
properties of the loop of Henle
in the nephron create the
Countercurrent multiplier
effect.
A substance to be exchanged
moves across a permeable
barrier in the direction from
greater to lesser concentration.
Image from http://en.wikipedia.org/wiki/Countercurrent_exchange
Loop of Henle
Goal= make isotonic filtrate into
hypertonic urine (dont waste
H
2
0!!)
Counter-current multiplier:
Descending loop is permeable to
Na+, Cl-, H
2
0
Ascending loop is impermeable to
H
2
0- active NaCl transport
Creates concentration gradient in
interstitium
Urine actually leaves hypotonic but
CD takes adv in making hypertonic
Na
+
absorption
Na
+
absorbed by active transport
mechanisms, NOT by T
M
mechanism.
Basolateral ATPases establish a
gradient across the tubule wall.
Proximal tubule is very permeable to
Na
+
, so ions flow down gradient,
across membranes.
Microvilli create large surface area for
absorption.
Electrical gradient created also draws
Cl
-
across.
H
2
O follows Na
+
due to osmotic force.
Means fluid left in tubule is
concentrated.
Glucose handling
Glucose absorption
also relies upon the
Na
+
gradient.
Most reabsorbed in
proximal tubule.
At apical membrane,
needs Na
+
/glucose
cotransporter (SGLT)
Crosses basolateral
membrane via glucose
transporters (GLUTs),
which do not rely
upon Na
+
.
Amino acid handling
Preserve as much of these essential nutrients as possible.
Can be absorbed by GI tract, products of protein catabolism, or de novo
synthesis of nonessential amino acids.
T
M
values lower than that of glucose, so can excrete excess in urine.
Amino acid transporters rely upon Na
+
gradient at apical membrane, but a
couple of exceptions dont.
Exit across basolateral membrane via diffusion , but again, some exceptions rely
on Na
+
.

K
+
handling
K
+
is major cation in cells and balance
is essential for life.
Small change from 4 to 5.5 mmoles/l
= hyperkalaemia = ventric. fibrillation
= death.
To 3.5 mmoles/l = hyperpolarise =
arrhythmias and paralysis = death.
Reabsorb K
+
at proximal tubule.
Changes in K
+
excretion due to
changes in K
+
secretion in distal tubule
Medullary trapping of K
+
helps to
maximise K
+
excretion when K
+
intake
is high.
K
+
handling
K
+
reabsorption along the
proximal tubule is largely
passive and follows the
movement of Na
+
and fluid (in
collecting tubules, may also rely
active transport).
K
+
secretion occurs in cortical
collecting tubule (principal
cells), and relies upon active
transport of K
+
across
basolateral membrane and
passive exit across apical
membrane into tubular fluid.
Hormones Produced by the Kidney
Renin:
Released from juxtaglomerular apparatus when low blood flow or low
Na+. Renin leads to production of angiotensin II, which in turn
ultimately leads to retention of salt and water.
Erythropoietin:
Stimulates red blood cell development in bone marrow. Will increase
when blood oxygen low and anemia (low hemoglobin).
Vitamin D3:
Enzyme converts Vit D to active form 1,25(OH)
2
VitD. Involved in
calcium homeostasis.
Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance
Renin/AII and Regulation of GFR







GFR = K
f
(P
GC
- P
BS
- COP
GC
)
flight or fright
sympathetic tone
afferent arteriolar constriction
(divert cardiac output to other
organs)
P
GC

GFR and renal blood flow

Renin/AII and Regulation of GFR







GFR = K
f
(P
GC
- P
BS
- COP
GC
)
Low BP sensed in afferent
arteriole or low Na in distal tubule
renin released
renin converts angiotensinogen to
Angiotensin I
ACE converts AI to AII
efferent > afferent arteriolar
constriction
P
GC
GFR (this is
AUTOREGULATION of GFR)
P
GC

constricts
Aldosterone
Secreted by the adrenal glands in
response to angiotensin II or high
potassium
Acts in distal nephron to increase
resorption of Na+ and Cl- and the
secretion of K+ and H+
NaCl resorption causes passive
retention of H
2
O
Anti-Diuretic Hormone (ADH)
Osmoreceptors in the brain (hypothalamus) sense
Na+ concentration of blood.
High Na+ (blood is highly concentrated) stimulates
posterior pituitary to secrete ADH.
ADH upregulates water channels on the collecting
ducts of the nephrons in the kidneys.
This leads to increased water resorption and
decrease in Na concentration by dilution
ACUTE RENAL FAILURE/
GAGAL GINJAL AKUT
Tunggul Adi P., M.Sc., Apt.
Lab Farmasi Klinik, Farmasi, FKIK,
UNSOED
Tujuan pembelajaran
Mahasiswa mampu menjelaskan definisi,
epidemiologi, prognosis, etiologi, patofisiologi
ARF atau GGA
Mahasiswa mampu menjelaskan gejala/tanda
dan pemeriksaan ARF
Mahasiswa mampu menjelaskan manajemen
terapi ARF


Primary references
Di Piro
Koda-Kimble
Chapter of Acute Renal Failure
KEY CONCEPTS
Acute renal failure (ARF) is a common complication in the
hospitalized patient and is associated with a high mortality
rate.
ARF is predominantly categorized based on the anatomic
area of injury or malfunction: (a) prerenaldecreased
renal blood flow, (b) intrinsica structure within the kidney
is damaged, and (c) postrenalan obstruction is present
within the urine collection system.
Risk factors for ARF include advanced age, acute infection,
pre-existing chronic respiratory or cardiovascular disease,
dehydration, and chronic kidney disease
KEY CONCEPTS
ARF lacks a specific and sensitive sign to herald
its onset. Hence, a thorough patient history,
including medications, recent procedures and
illnesses, physical examination, and laboratory
assessment of serum and urine are necessary
components of an ARF evaluation after an
elevated serum creatinine (Scr ) is noted.
Prevention is key; there are very few therapeutic
options for the therapeutic management of
established ARF.
KEY CONCEPTS
Supportive management remains the primary
approach to prevent or reduce the complications
associated with ARF. Supportive therapies
include: renal replacement therapies (RRTs),
nutritional support, avoidance of nephrotoxins,
and blood pressure and fluid management.
For those patients with prolonged or severe ARF,
RRTs are the cornerstone of support and facilitate
an aggressive approach to fluid, electrolyte and
waste management.
DEFINISI
ARF is broadly defined as a decrease in glomerular filtration rate
(GFR), generally occurring over hours to days, sometimes over
weeks, that is associated with an accumulation of waste products,
including urea and creatinine.
This relatively abrupt decline in renal function is in contrast to
CKD, which is defined by the presence of proteinuria/albuminuria
for at least 3 months, in combination with a GFR of <90
mL/min/1.73 m2. A decrease in urine output is often observed,
but is not required for ARF to be present.
Compared to a normal urine output of 1,200 mL/day, patients
with ARF are often categorized as being anuric (urine output < 50
mL/day), oliguric (urine output < 500 mL/day), or nonoliguric
(urine output > 500 mL/day).
Epidemiologi dan prognosis
ETIOLOGI
The etiology of ARF can be divided into broad categories
based on the anatomic location of the injury associated
with the precipitating factor(s). The management of
patients presenting with this disorder is largely predicated
on identification of the specific etiology responsible for the
patients current acute kidney injury.
Traditionally, the causes of ARF have been categorized as
(a) prerenal, which results from decreased renal perfusion
in the setting of undamaged parenchymal tissue, (b)
intrinsic, the result of structural damage to the kidney,
most commonly the tubule from a ischemic or toxic insult,
and (c) postrenal, caused by obstruction of urine flow
downstream from the kidney
ETIOLOGI
The most common cause of hospital-acquired
ARF is prerenal ischemia as the result of reduced
renal perfusion secondary to sepsis, reduced
cardiac output, and/or surgery.
Drug-induced ARF may account for 18% to 33%
of in-hospital occurrences.
Other risk factors for developing ARF while
hospitalized include advanced age (>60 years of
age), male gender, acute infection, and
preexisting chronic diseases of the respiratory or
cardiovascular systems.
ETIOLOGI

PATOFISIOLOGI
Fungsional ARF
In functional ARF, a decline in GFR secondary to a reduced
glomerular hydrostatic pressure, which is the driving force
for the formation of ultrafiltrate, can occur without damage
to the kidney itself. The decline in glomerular hydrostatic
pressure may be a direct consequence of changes in
glomerular afferent (vasoconstriction) and efferent
(vasodilation) arteriolar circumference.
These clinical conditions are most commonly seen in
individuals who have reduced effective blood volume (e.g.,
heart failure, cirrhosis, severe pulmonary disease, or
hypoalbuminemia) or renovascular disease (e.g., renal
artery stenosis) and who cannot compensate for changes
in afferent or efferent arteriolar tone.

Fungsional ARF
Functional ARF is very common in individuals
with heart failure who receive an ACEI or an ARB
in an attempt to improve their left ventricular
function. Because the decline in efferent
arteriolar resistance resulting from the inhibition
of angiotensin II occurs within days, if the dose is
increased too rapidly, a decline in GFR with a
concomitant rise in the serum creatinine will be
noticeable. If the increase in the serum
creatinine is mild to moderate (an increase of
less than 30% from baseline) the medication can
be continued
PRERENAL ARF
Prerenal ARF results from hypoperfusion of the renal
parenchyma, with or without systemic arterial
hypotension.
Renal hypoperfusion with systemic arterial hypotension
may be caused by a decline in intravascular or effective
blood volume that can occur in those with acute blood loss
(hemorrhage), dehydration, hypoalbuminemia, or diuretic
therapy.
Renal hypoperfusion without systemic hypotension is most
commonly associated with bilateral renal artery occlusion,
or unilateral occlusion in a patient with a single
functioning kidney. Other the most common cause is
atherosclerosis, with severe abrupt occlusion sometimes
occurring as the result of an embolism
INTRINSIC
Acute intrinsic renal failure results from
damage to the kidney itself. Conceptually,
acute intrinsic renal failure can be categorized
on the basis of the structures within the
kidney that are injured: the renal vasculature,
glomeruli, tubules, and the interstitium.
Penyebab terbesar (sekitar 85 %) adalah
tubular damage.
Lihat tabel etiologi
POST RENAL
Postrenal ARF may develop as the result of obstruction at any level
within the urinary collection system from the renal tubule to
urethra
It is often caused by a prostatic process (hypertrophy, cancer or
infection)
It may also be the result of an improperly placed urinary catheter.
Anticholinergic medications may also prevent bladder emptying
and cause ARF.
Lihat tabel etiologi
Wherever 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.
CLINICAL PRESENTATION OF ARF
General
The initiating sign or symptom prompting the
eventual diagnosis of ARF is highly variable,
depending on the etiology. It may be an
elevated Scr , decreased urine output, blood
in the urine, pain during voiding, or severe
abdominal or flank pain.
Determine if the renal complication is acute,
chronic, or the result of an acute change in a
patient with known CKD.




URINE OUTPUT



Acute anuria (< 50 mL/day of urine output) is
typically caused by either complete urinary
obstruction or a catastrophic event (e.g., shock or
acute cortical necrosis).
Oliguria (< 500 mL/day of urine output), which
often develops over several days, suggests
prerenal azotemia.
Nonoliguric (> 500 mL/day of urine output) renal
failure usually results from acute intrinsic renal
failure or incomplete urinary obstruction.
Physical examination finding in ARF
Diagnostic Parameters for
Differentiating Causes of ARF

Urine Analysis Findings as a Guide to
the Etiology of ARFailure

ISSUE of SCr
There is currently no consensus on the degree
and time frame of changes in Scr values that
clearly defines the presence of ARF. The
difficulty of using Scr as a diagnostic
laboratory test for patients with ARF is its lack
of sensitivity to rapid changes in GFR. An
abrupt cessation in glomerular filtration will
not yield an immediate measurable change in
Scr.
ISSUE of SCr
Glomerular filtration rate (GFR;
mL/min) and serum creatinine
(Scr ; g/dL) versus time
following acute renal injury.
Prior to time 0, a GFR of 120
mL/min and a Scr of 1.0 g/dL
exist. At time 0, an abrupt renal
artery thrombus forms,
depriving one kidney of renal
blood flow. Composite GFR
immediately declines by 50% to
approximately 60 mL/min.
However, Scr does not increase
immediately, as it is dependent
on creatinine production and
attainment of steady-state
serum concentrations.
Perhatian dalam membaca hasil lab
Instead of using fixed numbers to determine renal function,
changes in the value, even if it remains within the normal
range, may indicate marked impairment of renal function.
Patients with reduced creatinine production, such as those
with low muscle mass either because of being bedridden
for long periods of time, may have very low baseline Scr
values (<0.6 mg/dL) and thus the presence of a gradual Scr
rise to normal values (0.8 to 1.2 mg/dL) may actually
indicate reduced GFR.
Scr and BUN are extensively removed during acute
hemodialysis treatments, so when assessing any change in
these parameters in the ARF patient, one must pay close
attention to when the lab specimens were collected
relative to the dialysis procedure.
ACUTE RENAL FAILURE
(PREVENTION, TREATMENT, AND
MANAGEMENT)
Tujuan pembelajaran
Mahasiswa mampu menjelaskan manajemen
pencegahan dan terapi ARF


PREVENTION AND TREATMENT
Desired Outcome
Prevention is critical.
The goals are (a) to prevent ARF, (b) avoid or minimize further renal
insults that would worsen the existing injury or delay recovery, and
(c) provide supportive measures until kidney function returns.
The risk of developing ARF may be predictable (such as decreased
perfusion secondary to abdominal surgery, coronary bypass surgery,
acute blood loss in trauma, and uric acid nephropathy)
When patients with risk factors for developing ARF are scheduled
for surgery, the clinician should be aware that the likelihood of the
patient developing ARF is high and consider preventative measures,
including discontinuation of medications that may enhance the
likelihood of renal damage (e.g., NSAIDs, angiotensin-converting
enzyme inhibitors).
General Approach to Prevention
Optimal daily fluid intake (approximately 2 L/day) to
avoid dehydration,
Fluid balance can be evaluated by measuring acute
changes in weight, as other typical sources for weight
changes in an adult occur over more prolonged
periods, and blood pressure changes.
If the patient has a history of nephrolithiasis, they may
benefit from dietary restrictions, depending on the
type of stones that were present in the past.
If a patient has a Foley catheter in place, proper care
and monitoring needs to be performed to ensure that
postobstructive ARF does not develop.
Nonpharmacologic Therapies
Radiocontrast dye nephrotoxic and hydration
Adequate hydration and sodium loading prior
to radiocontrast dye administration have been
shown to be beneficial therapies. A trial
comparing infusions of 0.9% NaCl or 5%
dextrose with 0.45% NaCl administered prior
to radiocontrast dye infusion conclusively
demonstrated that normal saline was
superior in preventing ARF.
Nonpharmacologic Therapies
Radiocontrast dye nephrotoxic and hydration
The benefits of 0.9% NaCl infusions have been found in
similar studies, suggesting this regimen should be used
in all at-risk patients who can tolerate the sodium and
fluid load. In addition to the correction of dehydration,
saline administration may result in dilution of contrast
media, prevention of renal vasoconstriction leading to
ischemia, and avoidance of tubular obstruction.
Sodium bicarbonate provides more protection than
saline, perhaps by reducing the formation of pH-
dependent oxygen free radicals.
Nonpharmacologic Therapies
Radiocontrast dye induced nephrotoxic (RCIN)
and preventive dialysis
Overall, evidence to date does not support
any consistent significant benefit with the
routine use of extracorporeal blood
purification to prevent RCIN over standard
medical therapy
Nonpharmacologic Therapies
Amphotericin B nephrotoxic
The nephrotoxic potential of amphotericin B
deoxycholate can be reduced significantly simply
by slowing the infusion rate from a standard 4-
hour infusion to a slower 24-hour infusion of the
same dose. In a patient with risk factors for the
development of ARF, liposomal forms of
amphotericin B can be used. These liposomal
formulations are more expensive, but have been
associated with a lower incidence of kidney
damage.
Pharmacologic Therapies
Low-dose dopamine (2 mcg/kg/min) common
practice, but less evidence supported
Forrest plot showing relative risks
(diamonds) and 95% condence
intervals (lines) for
all studies and for sub groups A, B,and C.
Subgroup A included 14 studies
enrolling 661 patients but excluded
studies using radiocontrast dye.
Subgroup B was limited to heart disease
and included four studies enrolling 271
patients. Subgroup C excluded statistical
outliers in terms of either control group
event rate or the effect size for each
outcome as determined by analysis of
variance.
Pharmacologic Therapies
Diuretics
The use of diuretics to prevent nephrotoxicity may actually result in
intravascular volume depletion and thereby increase the risk of ARF.
A trial of forced diuresis, in which mannitol, furosemide, and/or
dopamine were given, and the resultant urinary losses were
replaced with intravenous solutions, found that diuretic use
resulted in little benefit compared to the administration of IV
solutions alone. Interestingly, these investigators noted that
patients who were unable to increase their urine output after
diuretic administration were more likely to develop ARF than were
patients who did respond to diuretics. While this unresponsiveness
to diuretics might simply be an indication of preexisting kidney
damage, similar reports have linked diuretic unresponsiveness to
increased mortality rates in critically ill patients with ARF
Pharmacologic Therapies
Acetylcysteine
The mechanism for N-acetylcysteines ability to reduce
the incidence of contrast dye induced nephrotoxicity is
not clear, but likely is due to its antioxidant effects.
Given the consistent findings of its efficacy and its
relatively low cost, N-acetylcysteine should be given to
all patients at risk for CIN.
The recommended N-acetylcysteine dosing regimen for
prevention of CIN is 600 mg orally every 12 hours for 4
doses with the first dose administered prior to contrast
exposure.
Pharmacologic Therapies
Glycemic control
Strict glycemic control is recognized as an
important goal for outpatient diabetics;
however, intensive insulin therapy may now
also become the standard of care for all
critically ill patients to prevent ARF and
improve mortality.
ESTABLISHED ARF
FOUNDATIONS
Treat any life threatening conditions
Identify any cause of ARF that warrants
specific treatment
Desired outcome
Short-term goals include minimizing the
degree of insult to the kidney, reducing
extrarenal complications, and expediting the
patients recovery of renal function. The
ultimate goal is to have the patients renal
function restored to their pre-ARF baseline.
General Approach to Treatment
Prerenal sources of ARF 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.
It is important to approach the treatment of established ARF with an
understanding of the patients comorbidities and baseline renal function.
Loss of kidney function combined with other clinical conditions, such as
cardiac and liver failure, are associated with higher mortality than that
associated with the development of ARF alone.
At times, the most efficacious remedy for ARF is management of the
comorbid precipitating event. Appreciation of the baseline renal function
is also important at the outset of ARF management, because the presence
of CKD indicates the highest degree of renal function that can be attained
after ARF resolution. Finally, the presence of CKD indicates that the
kidneys have less reserve, and thus there is a greater likelihood that the
individual may not fully recover from the current insult.
General Approach to Treatment
Once acute renal failure is established, the cause is
known, and any specific therapy implemented,
supportive care is the mainstay of ARF management
regardless of etiology. RRT may be necessary to
maintain fluid and electrolyte balance while removing
accumulating waste products. The slow process of
renal recovery cannot begin until there are no further
insults to the kidney. In the case of ATN, the recovery
process typically occurs within 10 to 14 days after
resolution of the last insult. The recovery period will be
prolonged if the kidney is exposed to repeated insults.
Management priorities

NONPHARMACOLOGIC
Initial modalities to reverse or minimize prerenal ARF include removal of medications
associated with diminished renal blood flow or the physical removal of a prerenal
obstruction.
If dehydration is evident, then appropriate fluid replacement therapy, should be initiated.
Moderately volume-depleted patients can be given oral rehydration fluids; however, if
intravenous fluid is required, isotonic normal saline is the replacement fluid of choice, and
large volumes may be necessary to provide adequate fluid resuscitation.
Typically, IV fluid challenges are initiated with 250 to 500 mL of normal saline over 15 to 30
minutes with an assessment after each challenge of the patients volume status. Unless
profound dehydration is present, as may be seen in diabetic ketoacidosis or hyperosmolar
hyperglycemic states, 1 to 2 L is usually adequate.
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.
The patient should be monitored for pulmonary edema, peripheral edema, adequate blood
pressure (diastolic blood pressure >60 mm Hg), normoglycemia and electrolyte balance.
Urine output may not be promptly observed, as the kidney continues to retain sodium and
water until rehydration is achieved. 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.
Special condition
Hyperkalemia
Special condition
Pulmonary oedema
Oxygenation
Opioid or nitrate to treat decompensated heart
Furosemide 250 mg in 50 ml 0.9% saline over one
hour, with an effect seen within 1-2 h for diuresis
If not successfull RRT
Acidosis
Moderate acidosis Sodium bicarbonate
Severe acidosis (blood pH <7.2 and oligoanuric)
RRT
Indications for RRT

Indications for RRT

Diuretic resistance in ARF patients

Monitoring for patients with
establishes ARF