RENAL FAILURE
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ACUTE RENAL FAILURE
Acute renal failure (ARF)
Community-acquired Acute renal failure
Hospital-acquired Acute renal failure
ICU-acquired Acute renal failure
Multifocal insult to kidney
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Acute renal failure (ARF)
Polycystic kidney disease
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Acute renal failure (ARF)
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ARF or AKI is an acute decrease in kidney
function (GFR) over hours associated with an
accumulation of nitrogen waste products and
(usually) volume.
2007 American college of clinical pharmacy (ACCP)
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Dec. of ≥ 25% in GFR
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Inc. in SCr ≥ 0.5 mg/dl (in patient with normal renal
function )
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Inc. in SCr ≥ 1 mg/dl (in patient with chronic kidney disease)
Urine output less than 0.5 mL/kg/hour for more than 6 hours.
*Fluid overload
* Acid-base abnormalities
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Inc. in BUN out of proportion to increases in the SCr.
ACUTE RENAL FAILURE
Urine output Classification:
*Anuric < 50/24 hr
*Oliguric 50-500 mL / 24hrs
*Nonliguric > 500 mL / 24 hr
-better outcomes
-easier to manage
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ACUTE RENAL FAILURE
Community-acquired Acute renal failure
Hospital-acquired Acute renal failure
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ACUTE RENAL FAILURE
2- Community-acquired Acute renal failure
• Low incidence (<1%) and high survival rate
of 70%-95%.
• Single insult to the kidney
• Reversible
3- hospital-acquired Acute renal failure
• Moderate incidence(2%-5%)
• Moderate survival rate 30%-50%.
• Single or multifocal insults to the kidney.
• Reversible.
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
ICU-acquired Acute renal failure
Multifocal insult to kidney
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
4- ICU-acquired Acute renal failure
• High incidence (6%-23%)
• Low survival (10%-30%)
5-Multifocal insult to kidney
Poorly reversible
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Estimating glomerular filtration rate
Formula for the Cockcroft-Gault equation:
Estimated creatinine clearance, or GFR =
[(140-Age) * Mass (in kg)] / [72 * Serum creatinine (in mg/dL)] x 0.85 if female
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Cockcroft-Gault equation
Difficult because commonly used equations
(Cockcroft-Gault and MDRD) are not
appropriate
Use in stable SCr
Brater and Jeliffe are probably more accurate
than the Cockcroft-Gault in ARF
ACUTE RENAL FAILURE
Estimating glomerular filtration rate in ARF-cont’d
GFR Calculator for Children
Schwartz Formula
GFR (mL/min/1.73 m2) = k (Height) / Serum Creatinine
k = Constant
o k = 0.33 in Preemie Infants
o k = 0.45 in Term infants to 1 year old
o k = 0.55 in Children to 13 years
o k = 0.65 in Adolescent males (Not females because of the
presumed increase in male muscle mass. The constant remains .55
for females.)
Height in cm
Serum Creatinine in mg/dl
LOINC® Technical Brief
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ACUTE RENAL FAILURE
Estimating glomerular filtration rate in ARF-cont’d
Brater and Jeliffe equations more accurate than
Cockroft-Gault equations but have not been
vigorously validated in the literature. MDRD is not
appropriate in ARF.
2007 American college of clinical pharmacy (ACCP)
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Ess (males) = IBW x (29.3 -[0.203 x (age)])
Ess (females) = IBW x (25.1 -[0.175 x (age)])
Esscorr = Ess x [1.035 - 0.0377(Scr)]
Scr = If serum creatinine values are RISING, enter the most
RECENT SCR. If SCR values are declining enter the
AVERAGE VALUE between the two SCR values.
E = Esscorr - [4 x IBW x (Scr2-Scr1)] / (Time difference in days)
Scr2= latest serum creatinine. Scr1= earlier serum creatinine.
CrCl (ml/min/1.73 M2) = E / (14.4 x Scr)
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CrCl =[293-2.03(age)] x [1.35-0.01685(SCr1+SCr2)] + 49(SCr1+SCr2) * 0.86 if F
(SCr1+SCr2)
(SCr1+SCr2) ∆t day
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Preexisting CKD (eGFR less than 60
mL/minute/1 .73m2)
Volume depletion—Vomiting, diarrhea, poor
fluid intake, fever, diuretic use
Effective volume depletion – CHF, liver disease
with ascites
Obstruction of the urinary tract
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Use of nephrotoxic medications
Intravenous radiographic contrast
Aminoglycosides, amphotericin
NSAIDs and COX-2 inhibitors
ACEIs and ARBs
Cyclosporine and tacrolimus
ACUTE RENAL FAILURE
NONMODIFIABLE
GENETICS
DIABETES
HYPERTENSION
AGE
INFECTION /SEPSIS
CANCER
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ACUTE RENAL FAILURE
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ACUTE RENAL FAILURE
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Pre-renal (functional)
Renal (structural)
Post-renal (obstruction)
2007 American college of clinical pharmacy (ACCP)
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Prerenal AKI
Initially, the kidney is undamaged
Characterized by hypoperfusion to the kidney
Systemic hypoperfusion: Hemorrhage, volume
depletion, drugs, CHF
Isolated kidney hypoperfusion: Renal artery
stenosis, emboli
Urinalysis will initially be normal (no sediment)
but concentrated.
Physical examination: Hypotension, volume
depletion
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Kidney is damaged. Damage can be linked to
structure involved: Small blood vessels, glomeruli,
renal tubules, and interstitium
Most common cause is ATN and others AIN,
vasculitis, and acute glomerulonephritis
Urinalysis will reflect damage
Urine generally not concentrated
Physical examination: Normotensive, euvolemic, or
hypervolemic; check for signs of allergic reactions or
embolic phenomenon
History: Identifiable insult, drug use, infections
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Kidney is initially undamaged
Bladder outlet obstruction is the most common
Lower urinary tract obstruction may be caused by
calculi
Ureteric obstructions cause by clots or intraluminal
obstructions
Extrarenal compression cause postrenal disease
Increased intraluminal pressure upstream of the
obstruction will result in damage if obstruction is not
relieved
PE: Distended bladder, enlarged prostate
History: Trauma, benign prostatic hypertrophy,
cancers
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Avoid nephrotoxic drugs when possible.
Ensure adequate hydration.
Patient education
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Correct primary hemodynamics
Normal saline if volume depleted
Pressure management if needed
Blood products if needed
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Relieve obstruction. Early diagnosis is
important. Consult urology and/or radiology
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No specific therapy universally effective
Eliminate the causative hemodynamic
abnormality or toxin.
Avoid additional insults.
Fluid and electrolyte management. Prevent
volume depletion or overload and electrolyte
imbalance
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Fenoldopam and Atrial natriuretic peptide : May
reduce need for renal replacement therapy (RRT)
and in-hospital mortality
Loop diuretics: Consider loop diuretics for patients
who are
Oliguric , euvolemic or hypervolemic.
Diuretic does not reduce mortality or improve
renal recovery but may assist in fluid/ electrolyte
management.
Given intravenously at relatively high doses
Low-dose dopamine. Ineffective. Avoid
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Renal replacement therapy—Indications
BUN greater than 100
Volume overload unresponsive to diuretics
Uremia or encephalopathy
Life-threatening electrolyte imbalance e.
Refractory acidosis
ACUTE RENAL FAILURE
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Avoid nephrotoxic drugs.
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Hydration : 0.9% NACL.
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Pt. education
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*Tight glycemic control 80-110 mg/dl using insulin
(reduce ARF by 41%) Also reduce infection, days on
mechanical
ventilation and ICU length of stay.
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
A-Fluid management
- Maintain renal perfusion & production of urine
- Diuretic therapy:
(consider of Pt. who are oliguric and euvolemic, or
hypervolemic)
B. Loop diuretic: bumetanide-furosemide-torsemide –
ethacrynic acid
Parenteral therapy
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Furosemide intermittent therapy:40-80 mg IV q 6-8 hrs
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Furosemide continous inf.: 40-80 mg IV bolus, then 10- 20
mg /hr
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Other diuretics: Thiazide - Metolazone - Mannitol
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Acidosis
1) Restrict dietary protein (< 0.5 g/kg/day of high
quality protein
2) Sodium bicarbonate to maintain bicarbonate
(HCO3 ) > 15 meq /L and arterial P 7.2
3) Dialysis
Electrolyte and nutrition abnormalities
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
2007 American college of clinical pharmacy (ACCP)
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Drugs are responsible for kidney damage
through many mechanisms
Evaluate potential drug-induced nephropathy
based on the period of ingestion, patient risk
factors, and the propensity of the suspected
agent to cause kidney damage
ACUTE RENAL FAILURE
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Idiosyncratic reaction: not predictable
Predictable reactions : High dose
Risk factors
Epidemiology
Kidney at risk
Pseudo drug – induced nephropathy
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Cont’d
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Predictable reactions – based PK and Pt. risk
factors
-Hypoperfusion/ischemia
-Inflammation
-Direct cellular damage
Risk factors
-Prior history of CKD
-Increased age
2007 American college of clinical pharmacy (ACCP)
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7% of all drug toxicities
18%–27% of AKI in hospitals
1%–5% of NSAID users in community
Most implicated medications:
Aminoglycosides
NSAIDs, ACEIs
Contrast dye
Amphotericin
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High exposure to toxin: Kidney receives 20%–
25% cardiac output
High intrarenal drug metabolism
Tubular transport processes
Concentration of solutes (i.e., toxins) in tubules
High-energy requirements of tubule epithelial
cells
Urine acidification
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Drugs that inhibit Cr tubular secretion:
Triamterene; cimetidine
Drugs that increase BUN: Corticosteroids;
tetracycline
Drugs that interfere with Cr assay: Cefoxitin
and other cephalosporins
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Most common drug-induced kidney disease in
the inpatient setting
ACUTE RENAL FAILURE
1-Aminoglycoside nephrotoxicity (1.7 % - 58 % )
Pathogenesis -Proximal tubule damage (obstruction of the
lumen)
-Cationic charge of drug bind to tubular
epithelial cells and uptake into those cells
-Accumulation of phospholipids & toxicity
Presentation
-↑ CRs & ↓ GFR after 6-10 days of therapy
- Non-oliguric RF
- Wasting of K+ and Mg 2+
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
1-Aminoglycoside nephrotoxicity
Risk factors •Relating to dosing (accumulation, prolonged therapy, high
conc.>2mg/L
•Concurrent use of other nephrotoxins
•Pt. pre-existing renal insufficiency (age-poor nutritionshock- gram negative bact )
•Liver disease-↓Albumin, obstructive jaundice, dehydration
•↓K+ - ↓Mg 2+
Prevention -Avoid in high risk Pt.
-Adequate hydration
-↓ the total cumulative aminoglycoside dose
-Avoid other nephrotoxins
-Use of extended interval (once daily) dosing.
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
2. Radiographic contrast media nephrotoxicity (IV contrast)
3rd leading cause of inpatient ARF
• 2 % - 50 % (incidence)
• * Hospital mortality rate 34 %
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Radiographic contrast media nephrotoxicity
Consists of
•Iso-osmolar (300 mOsm/kg)
•low-osmolar (780–800 mOsm/kg)
•high-osmolar (more than 1000 mOsm/kg) agents
• Also categorized as ionic versus nonionic
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
2. Radiographic contrast media nephrotoxicity (IV contrast)
Pathogenesis •Direct tubule toxicity due to reactive oxygen
species
•Renal ischemia
•Hyperosmolar contrast >900 mOsmo/Kg→
osmotic diuresis → dehydration )
•Hypotension
•Renal vasoconstriction
Presentation
-Transient osmotic diuresis followed by tubular
proteinuria
-↑SCr & peak after 2-5 days
-50 % of Pt. Oliguria & some will require dialysis
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ACUTE RENAL FAILURE
Risk factors
•Diabetes mellitus, Pre existing kidney disease
•Volume depletion
•Age older than 75 years
•Anemia
•Conditions with decreased blood flow to the
kidney (e.g., CHF)
•Hypotension
•Other nephrotoxins
•Large doses of contrast (more than 140 mL)
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ACUTE RENAL FAILURE
Prevention
•Hydration: IV NS
•Begin 6–12 hours before procedure.
•Maintain urine output greater than 150
mL/hour
•Discontinue nephrotoxic agents. Avoid
diuretics.
•Use low-osmolar or iso-osmolar contrast
agents in patients at risk
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ACUTE RENAL FAILURE
2-Radiographic contrast media nephrotoxicity (IV contrast)
Prevention contrast-induced nephropathy
Non
Emergency
(elective)
(A) NS or ( NaHCo3 in 5% Dex. )
*Before Procedure 1-3 mL/kg/hr for 6-12 hrs
*After Procedure 1 mL/kg/hr
(B) Acetylcysteine
*Before Procedure 600 mg orally 2 time/day for
2dosese
*After Procedure 600 mg orally 2 time/day for
2dosese
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ACUTE RENAL FAILURE
2-Radiographic contrast media nephrotoxicity (IV contrast)
Prevention contrast-induced nephropathy
Emergency
procedures
NaHCO3 in 5% Dex. ) 145mEq/L
(unless alkalosis; then give NS)
IV 3 mL/kg/hr 1hr before to procedure
Continue fluids 1mL/kg/hr for 6 hr (NaHCO3)
Continue fluids 1mL/kg/hr for 12 hr (NS)
Ascorbic acid
*Before procedure 3 g
*After procedure 2 g 2 times/day for 2 doses
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ACUTE RENAL FAILURE
3-Cisplatin and Carboplatin nephrotoxicity
•6 % - 13 % with appropriate dosing and administration
Pathogenesis
Presentation
•Tubule cellular damage
•Eventual loss of GFR &impaired distal tubular
function
•SCr peaks 10-12 days after starting therapy
•↓ Renal magnesium (sever with CNS symptoms)
•Hypokalemia and hypocalcemia
•Irreversible kidney damage
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ACUTE RENAL FAILURE
3-Cisplatin and Carboplatin nephrotoxicity
6 % - 13 % with appropriate dosing and administration
Risk factors
Prevention
*Multiple courses of cisplatin
* Pt. age
*Dehydration
*Concurrent nephrotoxins
*Renal irradiation
*Alcohol abuse
•Avoid concurrent nephrotoxins
•Low dose and dec. frequency of administration
•Aggressive IV hydration 1-4 liters within 24 hrs
of high dose of cisplatin or carboplatin
•Amifostine (cisplatin chelating agent)
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ACUTE RENAL FAILURE
4-Amphotericin B nephrotoxicity
(80%
with cumulative doses of ≥ 4 g)
Pathogenesis
* Direct proximal & distal tubular toxicity→
↑ tubular permeability and necrosis with arterial
vasoconstriction and ischemic injury
*↑Tubular permeability →↑ cellular energy
vasoconstriction leads to ↓ oxygen delivery
Direct proximal and distal tubular toxicity
Arterial vasoconstriction
Presentation
•loss of tubular function lead to electrolyte
wasting(K , Na and Mg)
•↑SCr & ↓GFR (↓ renal blood flow from
vasoconstriction)
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ACUTE RENAL FAILURE
4-Amphotericin B nephrotoxicity
Risk factors
Prevention
(80% with cumulative doses of ≥ 4 g)
•Existing renal dysfunction
•High dose
•Diuretic use
•Volume depletion
•Concomitant nephrotoxins
•Rapid infusion
•Avoid other nephrotoxins (cyclosporine)
•Limit total cumulative dose
•IV hydration (1 L/day) 0.9% NaCL prior to each
dose
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Results from a decrease in intraglomerular pressure
through the vasoconstriction of afferent arterioles
or the vasodilation of efferent arterioles
ACUTEcollege
RENAL
2007 American
of FAILURE
clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
Decrease in intraglomerular pressure:
A. From vasoconstriction of afferent arterioles
B. From vasodilatation of efferent arterioles
ACEI
ARBS
NSAID
CYCLOSPORIN
TACROLIMUS
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Pathogenesis
Hemodynamically –mediated renal failure – Cont’d
*Angiotensin II’s effects of vasoconstriction
of the efferent arteriole are reduced with
ACE inhibitor or ARB therapy *leads to a
decrease in glomerular hydrostatic pressure
and cause decrease in GFR
Reduction in GFR
Presentation SCr rise by up to 30 %
(A)Usually occurs within 2-5 days
(B)Usually stabilize in 2-3 weeks
(C)Increases > 30% may be detrimental
(D)Usually reversible upon drug
discontinuation
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ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
•RF for toxicity:
Risk factors •Pt. with bilateral (unilateral with a solitary
kidney) renal artery stenosis
•Decreased effective renal blood flow (CHF,
cirrhosis)
•Pre-existing kidney disease and volume
depletion
Prevention
*Initial therapy with low doses of short-acting
drugs and gradually titrate upward
*Switch to long-acting drug once tolerance is
established
*Monitor renal function and SCr level
frequently(daily for inpatient) Weekly for
outpatient
*Avoid use of concomitant diuretics if possible
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during initiation of therapy.
ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
Pathogenesis *Vasodilatory prostaglandins help maintain
glomerular hydrostatic pressure via afferent
arteriolar dilation, especially in time of ↓ renal
blood flow
*Administration of an NSAID in the setting of
decreased renal perfusion reduces this
compensatory mechanism by ↓ the production
of prostaglandins
Presentation
*Can occur with days of starting therapy
*Pt. generally have low urine volume and
sodium and an increase in BUN, SCr, K,
edema, and weight.
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ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
Risk factors •*Pre-existing renal disease, system lupus
erythematosus (SLE)
•Pt. with high plasma renin activity (e.g. CHF,
hepatic disease), diuretic therapy,
artherosclerotic disease, and the elderly
Prevention
*Use therapies other than NSAIDs when
appropriate
*Sulindac is a potent NSAID that may affect
renal prostaglandin synthesis to a lesser extent
than other NSAIDs.
*Question the utility of COX-2 specific
inhibitors; have not been found to prevent
renal dysfunction and increase cardiovascular
complications.
*If NSAID-induced ARF is suspected,
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discontinue drug and give supportive care.
ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
•The 5-year risk of developing CKD after
transplantation of a non-renal organ ranges
from 7% to 21%.
•The occurrence of kidney failure in the
transplant patient population has a 4-fold
increased risk of death.
2007 American college of clinical pharmacy (ACCP)
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ACUTE RENAL FAILURE
Pathogenesis
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i
Presentation
Hemodynamically –mediated renal failure – Cont’d
*Results from a dose-related hemodynamic
mechanism
*Causes vasoconstriction of afferent arterioles
through possible ↑↑↑activity of various
vasoconstrictors (thromboxane A2, endothelin,
sympathetic nerveous system) or ↓activity of
vasodilators (nitric oxide, prostacyclin)
*↑vasoconstriction from angiotension II may also
contribute
*Effects usually resolve with dose reduction.
*Can occur within days of starting therapy
*SCr rises and GFR ↓↓
*Pt. often have HTN ↑K and ↓ Mg
*Biopsy is often needed for renal transplant pt.
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ACUTE RENAL FAILURE
Hemodynamically –mediated renal failure – Cont’d
Risk factors *Increased age, high initial cyclosporine dose,
renal graft rejection, hypotension, infection,
and concomitant nephrotoxins
*Monitor serum cyclosporine and tacrolimus
Prevention levels closely
*Use lower doses in combination with other
non-nephrotoxic immunosuppressant
*Calcium channel blockers may help
antagonize the vasoconstrictor effects of
cyclosporine by dilating afferent arterioles.
2007 American college of clinical pharmacy (ACCP)
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Involve the renal tubules and surrounding interstitial
area.
Can be acute or chronic in onset :
Acute onset generally involves interstitial
inflammatory cell infiltrates, rapid loss of renal
function, and systemic symptoms (i. e. fever, rash) .
b . Chronic onset shows interstitial fibrosis, show
decline in renal function, and no systemic symptoms.
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Cause for up to 3 % of all cases of ARF
Results from an allergic hypersensitivity
reaction that affects the interstitium of the
kidney .
Idiosyncratic reaction, so no risk factors are
necessary
Various drugs can cause this type of renal
failure .
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Penicillins :
Classic presentation of AIN
Signs/ sysmptoms occur about 1-2 weeks after
initiation of therapy and include fever,
maculopapular rash, eosinophilia, pyuria,
hematuria and proteinuria. Eosinophiluria may
to also be present .
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NSAIDs:
Onset is much more delayed typically occurring
around 6 months into therapy
Usually occurs in elderly patients on chronic
NSAID therapy
Patients usually do not have systemic symptoms
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Renal biopsy may be needed to confirm
diagnosis
Treatment includes stopping the offending
drug and possibly initiating steroid therapy
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Often progressive and irreversible
Lithium .
i . Toxicity results from a dose-related decrease in
response to antidiuretic hormone
ii . ARF from lithium usually occurs during acute
lithium intoxication
Patients become dehydrated secondary to
nephrogenic diabetes insipidus.
There is also direct damage to the proximal and
distal tubules
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Risks include elevated serum levels and
repeated episodes of ARF from lithium toxicity
Prevention is accomplished by maintaining
lowest serum lithium levels possible, avoiding
dehydration and monitoring renal function
closely
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Cyclosporine :
Presents later into therapy (about 6- 12 months)
than hemodynamically mediated toxicity
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Form of chronic interstitial nephritis affecting the
renal papillae, causing necrosis of the collecting
ducts.
Results from the long-term use of analgesics .
"Classic" example was with products that contained
phenacetin.
Evolves slowly over years
Affects women more than men .
Difficult to diagnose and much controversy still
remains regarding risk, prevention, and cause.
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Results from obstruction of the flow of urine after
glomerular filtratioin.
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Caused by intratubular precipitation of tissue
degradation products or precipitation drugs or their
metabolites .
Tissue degradation products:
Uric acid intratubular precipitation after tumor lysis
following chemotherapy
Drug-induced rhabdemolysis to intratubular
precipitation of myoglobin
Results in rapid decline in renal function with
resultant oliguric or anuric renal failure
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Drug precipitation :
Sulfonamides, methotrexate, acyclovir, ascorbic acid
Can be diagnosed by observing needle-like crystals
in leukocytes found on urinalysis .
Prevention includes pretreatment hydration,
maintaining high urinary volume, and alkalinization
of the urine
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BPH can be worsened by anticholinergic drugs
Bladder outlet or ureteral obstruction from
fibrosis following cyclophophamide for
hemorrhagic cystitis
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Usually does not affect GFR, so does not have
classis signs/symptoms of nephrotoxicity
Few drugs contribute to the formation of
kidney stones: triamterene, sulfadiazine,
indinaver, and ephedrine derivatives
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Proteinuria is the hallmark sign of glomerular
injury and may occur with or without a decrease
in GFR.
A few distinct drugs can cause glomerular
injury .
Heroin : Can be caused by direct toxicity or
toxicity from additives or infection from
injection.
Parenteral gold: results from immune complex
formation along glomerular capillary loops .
Tubular epithelial cell damage
Acute tubular necrosis
 Aminoglycoside antibiotics
 Radiographic contrast media
 Cisplatin/ carboplatin
 Amphotericin B
Osmotic nephrosis
 Mannitol
 Dextrin
 Intravenous immunoglobulin
Hemodynamic ally-mediated
renal failure
 Angiotensin-converting
enzyme inhibitors
 Angiotensin II receptor
antagonists
 Nonsteroidal anti-inflammatory drugs
Tubulointerstitial disease :
Acute allergic interstitial nephritis
 Penicillins
 Ciprofloxacin
 Nonstreroidal ani-inflammatory drugs
 Omeprazole
 Furosemide
Chronic interstitial nephritis
 Cyclosporine
 Lithium
 Aristolochic acid
Papillary necrosis
 Combined phenacetin, aspirin,
and caffeine analgesics
Obstructive nephropathy
Renal vasculitis, thrombosis, and
Intratubular obstruction
Cholesterol embolic
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Acyclovir
Vasculitis and thrombosis
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Sulfadiazine
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Hydralazine
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Indinavir
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Propylthiouracil
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Foscarnet
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Allopurinol
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Methotrexate
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penicillamine
Extrarenal obstruction
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Gemcitabine
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Tricyclic antidepressant
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Mitomycin C
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Indinavir
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Methamphetamines
Nephrolithiasis
Cholesterol emboli
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Triamterene
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Warfarin

Indinaver

Thrombolytic agents
Glomerular Disease
Pseudo –renal failure

Gold

Corticosteroids

NSAIDs

Trimethoprim

Pamidronate

Cimetidine
CHRONIC KIDNEY DISEASE (CKD)
Background :
 Kidney disease is in underreported and undertreated
in the United States. In 1984, there were fewer than
100.000 persons with end-stage kidney disease
requiring. In 2004, there were about 472.000 patients
with ESRD ( 335.000 on maintenance dialysis).
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The number of persons with earlier stages of kidney
disease has increased
It is estimated that 10.9 % of adults in the United
States have CKD
The National Kidney Foundation Kidney Disease
Outcome Quality Initiative Advisory Board
recommends a definition of CKD and staging
guidelines


Definition :
Kidney damage for > 3 months, as defined by
structural or functional abnormality of the
kidney, with or without decreased GFR,
manifested by either pathologic abnormalities;
or markers of kidney damage, including
abnormalities in the composition of blood or
urine, or abnormalities in imaging tests


Definition :
GFR < 60 mL/minute/1.73 m2 for > 3 months,
with or without kidney damage
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Stages of CKD :
Stage 1 kidney damage with normal or increased
GFR (GFR= 90 mL/ minute/ 1.73 m2).
Stage 2 kidney damage with mild decrease in GFR
(GFR=60- 89 mg/ minute/ 1.73 m2) .
Stage 3 moderate decrease in GFR (GFR 30- 59 mL/
minute/ 1.73 m2).
Stage 4 severe decrease in GFR (GFR 15- 29 Ml/
minute/ 1.73 m2).
Stage 5 kidney failure (GFR< 15 mL/minute/ 1.73
m2 or on dialysis).
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Etiology :
Diabetes (40% of new cased of ESRD in USA)
b . Hypertension (25 % of new cases)
Glomerulonephritis (10 %) .
Others : urinary tract disease, polycystic kidney
disease, lupus, analgesic nephropathy, unknown
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Risk Factors for kidney disease :
Susceptibility :advanced age, reduced kidney
mass and low birth weight, racial/ ethnic
minority, family history, low income or
education, systemic inflammation, dyslipidemia.
Initiation : diabetes, hypertension, autoimmune
disease, polycystic kidney diseases drug toxicity.
Progressing : hyperglycemia, elevated blood
pressure, proteinuria, smoking
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Albuminuria/ proteinuria :
Marker of kidney damage and cardiovascular
(CV) risk factor.
Definitions :
Normal albumin excretion < 30 mg/24 hours
Microalbuminuria 30- 300 mg/ 24 hours
Macroalbuminuria (overt proteinuria) >300
mg/24 hours
Nephrotic range proteinuria > 3 g/24 hours.
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Assessment for Proteinuria :
Spot urine : untimed sample is adequate for adults
and children (screening test)
First morning urine specimen preferred
Urine dipstick
Confirm positive dipstick tests (+ 1 or greater) with
quantitative tests (albumin: creatinine ratio)
Proteinuria is confirmed by 2 or more quantitative
tests (1-2 weeks apart) .
Monitor proteinuria with quantitative tests
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Factors that can interfere with testing for
abluminuria/ proteinuria :
Fluid balance : dehydration (+)
fluild overload (-)
Hematuria (+)
Exercise (+)
Urine proteins other than albumin (-)
Drugs that increase urine PH>6 (+)
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Assessment of Renal Function (GFR) :
Measurement of GFR :
Inulin, iothalamate and others not routinely used
Measurement of CrCl via a urine collection
Reserve for vegetarians, patients with low muscle
mass, amputation, dietary assessment and
documentation of need to start dialysis .
In most cases, equations will overestimate renal
function because cretonne levels will be low in
patients with very low muscle mass. Urine
collection will give a better estimate in these
patients .
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
Assessment of Renal Function (GFR) :
Serum creatinine:
Avoid use as sole assessment of renal function
Dependent no age, sex, weight, muscle mass
Calculated using Cockcroft and Gault (mL/min
CrCl) – overestimates GFR .
(140- age) x ideal body weight (IBW)/ (SCr x 72) x
(0.85 if female)
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Estimated GFR using Modification of Diet in Renal
Disease (MDRD) study data
Estimated GFR (mL/minute/ 1.73 m2) in patients
with known CKD (<90 mL/minute) .
GFR (mL/minute/1.73 m2)= 186 x SCr -1.154 x Age 0.203 (0.742 if female) x (.21 if African – American) .
MDRD formulae are not validated in all population
groups (validated in Caucasian/ AfricanAmerican, men and women). Not studied in
diabetes, pediatrics, elderly, or obese.
Children :
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Schwartz – Estimates creatinine clearance
(mL/minute)
0.55 x body length (in cm) /SCr .
Counahan- Barratt – Estimates GFR (mL/minute/
1.73 m2).
0.43 x body length (in cm) /SCr .
Diabetic Nephropathy
Pathogenesis :
 Hypertension (systemic and intraglomerular)
 Glycosylation of glomerular proteins
 Genetic links
Diagnosis :
 Long history of diabetes mellitus (DM)
 Proteinuria
 Retinopathy (suggests microvascular disease).
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Monitoring :
Type I : Begin annual monitoring for
microalbuminuria 5 years for diagnosis
Type II : Begin annual monitoring immediately
(don’t know long they’ve had DM)
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Management/ Slowing Progression :
Aggressive BP management :
Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure
(JNC) VII goal is < 130/80.
ACE inhibitors and ARBs are preferred, Drugs
should be used with microalbuminuria even if
patient is normo-tensive .
Calcium channel blockers are second line to
ACE/ARBs. Data emerging for combined therapy
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
Intensive Blood Glucose Control :
Glycosylated Hb <7 %
Protein Restriction – not good data in diabetes.
Patients should avoid high-protein diets
Non –diabetic Nephropathy :
 Manage hypertension .
If proteinuric use ACE, ARB
Minimize protein in diet
a . Controversial. May slow progression based on
Modification of Diet in Disease (MDRD) study
but may also impair nutrition .

Other guidelines to slow progression:




Manage hyperlipidemia. follow NCEP
guidelines
Goal LDL <100
Statins are first line
Stop smoking
Indications for Renal Replacement Therapy :
 A – acidosis (not responsive to bicarbonate) .
 E – electrolyte abnormality (hyperkalemia;
hyperphosphatemia) .
 I – intoxication (boric acid; ethylene glycol; lithium;
methanol; Phenobarbital; salicylate; theophylline) .
 O – fluid overload (symptomatic(pulmonary
edema)).
 U – uremia (pericarditis and weight loss) .
Two Primary modes of dialysis .
 Hemodialysis – most common modality.
 Peritoneal Dialysis.
Hemodialysis (Intermittent for ESRD) .
Access :
a . Atreriovenous fistula
 Natural, formed by anastomosis of artery and vein .
 Lowest incidence of infection and thrombosis, lowest
cost, longest survival .
 Takes weeks/ months to “mature”.
Hemodialysis (Intermittent for ESRD) .
Arteriovenous graft :
 Synthetic (polytetrafluoroethylene, or PFTE)
 Often used in patients with vascular disease
Catheters :
 Commonly used if permanent access is not available
 Problems include high infection and thrombosis
rates. Low blood flows lead to inadequate dialysis
Hemodialysis
Dialysis Membranes :
High flux and High Efficiency :
 Large pores. Can remove some drugs that were
impermeable to standard membranes (vancomycin).
 Large amounts of fluid removal (utrafiltrate).
Hemodialysis
Adequacy :
a . Kt/ v – unities parameter. K = clearance, t=time on
dialysis, and V is volume of distribution of urea.
Kidney Disease Outcomes Quality Initiative
(KDOQI) set goal of > 1.2 .
b . URR: urea reduction ration. URR=BUN post/BUN
pre x 100% Goal 65 % .
Common complications of hemodialysis :
Intradialytic :
 Hypotension – Primarily related to fluid removal.
Common in elderly and diabetics .
Treatment: Limit fluid gains between sessions,
give normal or hypertonic saline, midodrine.
 Less well studied agents includes include
fludrocortisones, selective serotonin reuptake
inhibitors (SSRIs) .
Common complications of hemodialysis :
Intradialytic :
 Cramps – Vitamin E or Quinine (controversial due
to adverse effect profile)
 Nausea/ vomiting
 Headache/ chest pain/ back pain
Common complications of hemodialysis :
Intradialytic :
Vascular access complications : Most common –
with catheters .
 Infection : Staphylococcus aureus. Need to treat
aggressively. May need pull catheter.
 Thrombosis: Suspected with low blood flows. Oral
antiplatelets for prevention not used due to lack of
efficacy.
 Can treat with alteplase I mg per lumen
Factors That Affect Efficiency of Hemodialysis:
 Type of dialyzer used (changes in membrane
surface area and pore size)
 Length of therapy
 Dialysis flow rate
 Blood flow rate
 Development of polarized protein layer on the
filter surface
Continuous Hemodialysis for Acute Renal Failure:
 CAVH/CVVH. Removes fluid and solutes by
dialysis. CAVH differs from CVVH in that the “VV’
access requires an in-line pump. Used primarily
when fluid removal is most important .
 CVVHD/CAVDH. dialysate which flows in
countercurrent to blood flow. Fluid and solute
removal greater with this procedures. Used when
there is a need for fluid removal and better solute
clearance.
Peritoneal Dialysis :
Dialysis fluid may be instilled onto peritoneum (fill), allowed
to dwell for specified amount of time, and then drained .
 Solutes and fluids diffuse across peritoneal membrane.
 PD is usually not used to treat acute renal failure in adults.
Peritonitis:
 Infection of peritoneal cavity, diabetic and elderly patients
have a higher infection rate, a major cause of PD failure.
 Treatment
 Most common Gram +ve organisms include S.aureus,
S.epidermis, Streptococci . most common Gram –ve organisms
include E.coli and P.aeruginosa.
Empiric treatment should cover both Gram +ve & -ve bacteria.
Adjust as needed.

Types of peritoneal dialysis:
 CAPD. Classic, requires mechanical process,
can be interruptive to daytime routine.
 Automated PD (APD). Many variants but
continuous cycling PD (CCPD) most common.
Patients undergo multiple exchanged during
sleep via a cycling machine. Minimize potential
contamination. Lowest incidence of peritonitis.
Anemia
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In CKD , anemia is generally treated with Hgb<11 g/dl. Several factors are
responsible for; decreased erythropoietin production (most important), shorter
lifespan of RBCs, blood loss during dialysis, iron deficiency, anemia of chronic
disease, renal osteodystrophy.
Prevalence :
a . 67% of persons beginning dialysis have had a reported hematocrit <30 % .
Signs and symptoms .
a . Symptoms of anemia of CKD are similar to anemia associated with causes .
Anemia work –up :

i . Hb/Hct .

ii . MCV (mean corpuscular volume) .

iii . Reticulocyte count .

iv . Iron Studies .

Transferrin saturation (total iron/ total iron binding capacity) – assesses iron .

Ferretin – measures stored iron .

v . Stool guaiac .
Treatment :
Erythropoietin receptor agonists

Goal is to achieve target Hb 11 mg/dl . Most recent KDOQI
guidelines warn against intentional increasing HgB< 13 g/dL.
Epotein – a :

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Binds to and activates erythropoietin receptor .
May be administered SQ (subcutaneously), IV, or IP
(intraperitoneal).
Initial dose 80- 120 units/kg/ week SQ divided into 2-3
doses/ week .
Initial dose 120- 180 units/ kg/ week IV divided into 2-3
doses/ week .
Higher doses are required for once a week dosing than for 2-3
doses/ week/ dosing .
Darbepoetin-a
 Bind to and activates erythropoietin receptor .
 May be administered SQ or IV .
 Initial dose 0.45 mcg/ kg weekly; typically 40 mcg .
 Dose adjustment is based on Hgb response.
 Adjustment parameters are the same for epotein-a
or darbepoetin-a .
 Dosage adjustments upward should not be made
more frequently than every 4 weeks .
Monitoring for effect :
 Both epoetin-a and darbepoeitn-a require similar
monitoring parameters.
 Monitor Hb initially every 1-2 weeks then 2-4
weeks when stable.
 Monitor BP as it may rise (treat as necessary) .
 Iron stores .
 Ferretin : HD target is 200- 500, PD/CKD target
is 100- 500 .
 TSAT target is > 20 % (upper limit of 50%
removed from recent guidelines .
Common causes of inadequate response to erythropoietin therapy.
 Iron deficiency is the most common cause of EPO resistance.
Increased use of intravenous iron products has reduced the
problem, however .
Other causes in patients with adequate stores (First three most
common) :
 Infection/ inflammation.
 Chronic blood loss.
 osteitis fibrosa.
 Aluminum toxicity .
 Hemoglobinopathies.
 Foliate or vitamin B12 Deficiency.
 Multiple myeloma.
 Malnutrition.
 Hemolysis.
 Vitamin C deficiency.
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Iron therapy :
Most patients with CKD and receiving
erythropoietin therapy require parenteral iron
therapy to meet needs (increased requirements,
decreased oral absorption) .
Most adults require 1 g or more of elemental iron stores.
Iron stores usually replete several weeks .
For adult dialysis patients, an empiric 100 mg dose
is usually given and equations are rarely used.
Monitor transferrin saturation and Ferretin as
noted during erythropoietin therapy ) .
Iron Therapy
Replacement therapy
%TSAT< 20% and ferritin
< 100- 200 mg/dL
Maintenance therapy
(iron stores in goal)
Iron overload % TSAT >
50% and/ or ferritin> 500
Initial test dose
Iron Dextran
Ferric Gluconate

IVP: 100 m IV 3
times/ week during
HD for 10 doses (1
gram).
 IVPB: 500- 1000 mg
in 250 mL NSS
infused over at least I
hour (option for non
hemodialysis
patients)
25- 100 mg/week IV X 10
Week
Hold therapy

Yes. 25 mg one-time test
dose
No
Iron Sucrose
125 mg IV 3 times/

week during HD for 8
doses (1 gram)

100 mg IV 3 times/
during HD for 10
doses (1 gram)
For non-dialysis CKD
200 mg IV X 5 doses
31.25- 125 mg/ week IV X 25- 100 mg/week IV x 10
10 weeks
weeks
Hold therapy
Hold therapy
No
Oral iron products Available in the United States :
Strength
Ferrous
Sulfate
Ferrous
Gluconate
Ferrous
Fumarate
Polysaccharide
Iron complex
300- 325 mg
325 mg
325 mg
150 mg
38 mg
106 mg
150 mg
Elemental iron/ 65 mg
tablet
Usual dose
1 tablet PO TID 2 tablet PO TID 1 tablet PO BID 2 tablets/ day
PO
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Pathophysiology: Calcium and phosphorous homeostasis is
complex; it involves the interplay of hormones affecting the
bone, gastrointestinal tract, the kidneys and parathyroid
hormone (PTH).
Process may begin as early as GFR 60 mL/minute. Most
important force behind the process is hyperphosphatemia!
Nephron loss : decreased production of 1,25
dihydroxyvitamin D3 and phosphate retention .
Increased Phosphorous levels :
Inhibition of activation of vitamin D, reducing absorption of
calcium in the gut .
Decrease levels of ionized (free calcium) .
Direct stimulation of PTH secretion .
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
Elevated PTH Levels :
Decreased reabsorption of phosphorus and
increased reabsorptin of calcium in proximal
tube – this renal adaptive mechanism is lost as
GFR falls below 30 mL/minute .
Important : calcium in not well absorbed
through the gut at this point, and calcium
levels are maintained by increased bone
reabsorption via elevated PTH .
Unabated calcium loss from the bone results in
renal osteodystrophy.
Prevalence :
 Major cause of morbidity and mortality in patients
undergoing dialysis.
 Is now aggressively treated with dietary
phosphate restriction, phosphate binders, and
vitamin D analogs .
Signs and symptoms :
 Insidious onset : patients may complain of fatigue,
musculoskeletal and gastrointestinal complaints;
calcification may be visible on x-ray; bone pain and
fractures can occur if progression is left untreated .
Laboratory abnormalities :
 Phosphorus .
 Corrected calcium .
 Intact parathyroid hormone .
Treatment :
 Goals of therapy
KDOQI Guidelines for Calcium, Phosphorus, Ca x PO 4 product, and Parathyroid
Hormone in CKD Stages 3-5
*
CKD Stage 3
CKD Stage 4
CKD Stage 5
Calcium (mg/Dl)*
Normal
Normal
8.4- 9.5
Phosphorus (mg/dL)
2.7- 4.6
2.7- 4.6
3.5- 5.5
Ca x PO4 product
< 55
< 55
< 55
Parathyroid
Hormone (pg/ Ml)
35- 70
70- 110
150- 300
Use Corrected calcium = serum Ca+ (0.8 x (normal albumin – patient albumin)).
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Treatment :
Nondrug therapy :
Dietary phosphorus restriction 800- 120 mg/day.
Dialysis removes various amounts of
phosphorus depending on treatment modalities .
CAPD can remove – 300 mg/day .
Conventional HD can remove 500- 700 mg/day .
High-flux HD can remove – 900 mg/day .
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Drug therapy :
1- Phosphate binders : take with meals to bind
phosphorus in the gut; products from different groups
are used together for additive effect .
a- Calcium – containing phosphate binders (calcium
carbonate, calcium acetate) .
Considered initial binder of choice; relatively
inexpensive.
Also treat hypocalcaemia, which sometimes occurs in
patients with CKD .
Calcium carbonate can also decrease metabolic acidosis .
Use may be limited by development of hypocalcaemia .
Total elemental calcium per day = 2000 mg/day( 1500mg binder; 500 – mg diet) .
b- Aluminum- containing phosphate binders (aluminum
hydroxide, aluminum carbonate, sucralfate) .
 Effectively lower phosphorus levels .
 Avoid. Not used as frequently due to aluminum toxicity
(adynamic bone disease, encephalopathy, and
erythropoietin resistance) .
 Deferoxamine chelation therapy may be required for
aluminum toxicity .
c-Sevelamer : a nonabsorbable phosphate binder :
 Effectively binds phosphorus .
 Consider if calcium – phosphorus factor > 55 mg2/ dL2.
 Decreases LDL cholesterol and increases HDL cholesterol .
 Hypocalcaemia may occur if sevelamer is sole phosphate
binder.
d- Lanthanum carbonate :
 As effective as aluminum in phosphate binding
capability.
 Tasteless, chewable wafer .
 Consider if calcium x phosphorus product >55
mg2/ dL2.
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2-Vitamin D analogs: suppress PTH synthesis and
reduce PTH concentrations ; therapy is limited by
resultant hypocalcaemia, hyperphosphatemia and
elevated calcium- phosphorus product; pulse therapy is
preferred over daily therapy .
products include: calcitriol , Paricalcitol , Doxercalciferol
a-Calcitriol is the pharmacologically active from of 1,2
hydroxyvitamin D3, FDA label- approved for the
management of hypocalcemia, and the prevention and
treatment of secondary hyperparathyroidism .
Oral and parenteral formulations .
Does not require hepatic or renal activation .
Low-dose daily oral therapy reduces hypocalcemia, but
does not reduce PTH levels significantly .
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b- Paricalcitol : vitamin D analog; FDA label-approved for the
treatment and prevention of secondary hyperparathyroidism .
Parenteral and oral formulation .
Does not require hepatic or renal activation .
Less incidence of hypocalcaemia (decreased mobilization of calcium
from the bone and decreased absorption as frequent as every 2
weeks .
Dose adjustment as frequent as every 2 weeks .
c-Doxercalciferol: vitamin D analog; FDA label-approved for the
treatment and prevention of secondary hyperparathyroidism .
Parenteral and oral formulation .
Pro-drug, requires hepatic activation; may have more physiologic
levels .
Less incidence of hypocalcaemia (decreased mobilization of calcium
from bone and decreased absorption of calcium from gut.
Dose adjustments at 4-8 week intervals .
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3- Cinacalcet HCL : attaches to calcium receptor on
parathyroid gland, resulting in negative feedback suppression
of PTH secretion .
Initial dose is 30 mg irrespective of patient PTH level .
Monitor serum calcium every 1-2 weeks (risk of
hypocalcaemia ≈ 5%); do not start therapy if serum Ca < 8.4
mg/dL .
Can be used in patients irrespective of phosphate binder
(important) or vitamin D analog use .
Caution in patients with seizure disorder (hypocalcaemia may
exacerbate).
Adverse effects are nausea (30 %) and diarrhea (20 %) .
CYP 2D6 metabolism: dose reductions in drugs with narrow
therapeutic indexes may be required (flecainide, tricyclic
antidepressants, thioridazine) .
Ketoconazole increases cinacalcet concentrations up to 2-fold.
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Dosages of many drugs will require adjustment to
prevent toxicity in patients with CKD; adjustment
strategies will vary depending on whether patient is
receiving renal replacement therapy or not, and the
type of renal replacement therapy
Pharmacokinetic Principles Can Guide Therapy
Adjustments :
Absorption :
a . Oral absorption can be decreased .
Nausea and vomiting .
Increased gastric PH (uremia) .
Edema .
Physical binding of drugs to phosphate binders .
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Distribution :
Changes in concentrations of highly protein bound and highly
water soluble drugs change as extracellular fluid status changes.
Acidic and neutral protein bound drugs are displaced by toxin
build-up. Other mechanisms include conformational changes of
plasma protein site .
Phenytoin is a classic example .
Hypoalbuminemia correction .
Conc. adjusted= Conc. measured / {(0.2 x measured albumin)+ 0.1)}
Renal failure adjustment .
Conc .adjusted = Conc. measured / (0.1 x measured albumin)+ 0.1).
Patients will have lower total concentrations despite having
adequate free concentrations .
Dosage adjustment of phenytoin not needed, just a different
approach to evaluating to evaluating level
Metabolism :
 Variable changes can occur with uremia .
 Metabolites can accumulate .
 Excretion :
 Decreased .
Pharmacodynamic Changes Can Also Occur .
 Patients with CKD can be more sensitive to
benzodiazepines.

General Recommendations :
Approach :
 Patient history and clinical data .
 Estimate CrCl (Joliffe or Brater in ARF;
Cockroft-Gault in stable renal function ) .
 Identify medications that require modification

Dose Adjustments in Decreased Renal Function
Agent
Dose Adjustment
Antibiotics
Almost all antibiotics will require dosage dosage adjustment
(exceptions: cloxacillin, clindamycin, linezolid, metronidazole,
macrolides )
Cardiac medications
Atenolol,ACEIs, digoxin, nadolol, sotalol; avoid potassiumsparing diuretics if CrCl < 30 ml / min
Lipid-lowering therapy
Clofibrate, fenofibrate, statins
Narcotics
Codeine, avoid meperidine; other drugs may also accumulate .
Antipsychotic/ antiepileptic agents
Chloral hydrate, gabapentin,
lithium,paroxetine,primidone,topiramate,trazodone,vigabatrin
Hypoglycemic agents
Acarbose, chloropropamide, glyburide, glipizide insulins,
metformin.
Antiretrovirals
Individualize therapy: monitor CD4 counts, viral load and
adverse effects (agents requiring dose adjustment:
lamivudine, adefovir, didanosine, stavudine, tenofovir,
zalcitabine, zidovudine).
Miscellaneous
Allopurinol, colchicines, H2-receptor antagonists, ketorlac,
terbutaline
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
Calculate drug individualized for patient .
Published data .
Rowland – Tozer estimate .
Q = 1 ( fe (1- KF) ) .
Q = kinetic parameter or drug adjustment factor .
Fe = fraction of drug renally excreted unchanged .
Kf= ratio of patients CrCl to normal (120 mL/minutes) .
Monitor patient (e.g., renal function; clinical parameters)
and drug concentration (if applicable) .
Revise regimen as appropriate .
Drug Dosing in Hemodialysis :
Dosing changes in hemodialysis patients may be necessary
of accumulation due o kidney failure and/or because the
procedure may remove drug from the circulation .

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
Drug-related factors affecting drug removal during
dialysis :
Molecular weight- with high flux membranes larger
molecules (like vancomycin) can be removed .
Water soluble – non soluble drugs not likely
removed .
Protein binding – Because albumin cannot pass
through membrane, neither can protein-bound
drugs.
Volume of distribution – Drugs with small volume of
distribution (Vd) (<1L/Kg) are available in central
circulation for removal. Large Vd's can't be removed
(digoxins, tricyclic antidepressants) .

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


Procedure-related factors affecting drug
removal :
Type of dialyzer- High flux widely used now .
Blood flow rate; increased rate will increase
deliver and maintain gradient across
membrane .
Duration of dialysis session .
Dilaysate flow rate; high rate of flow will
increase removal by maintaining gradient
across membrane .