Drug induced nephrotoxicity
Naser Hadavand
19/06/1436
Classification of Drug Induced Disordres
Definitions
 Type
 Onset
 Severity

Definition and Classifications of Adverse Reaction Terms
Adverse Event:
Adverse Drug Reaction:
Side Effect:
Comparison Type A and Type B
A
B
Pharmacologically
predictable
Yes
No
Dose-dependent
Yes
No
Incidence and morbidity High
Low
Mortality
Low
High
Treatment
Adjust
dose
Stop
Adverse Drug Reactions
Unwanted effects of drugs are separated into those represent:
1.
2.
3.
4.
5.
6.
Augmented pharmacological effects of a substance but
qualitatively normal (Type A)
Qualitatively bizarre pharmacological effects (Type B)
Long term effects (Type C)
Delayed effects (Type D)
End of use (Type E)
Failure (Type F)
* Most long term effects are Type A reactions.
Drug induced nephrotoxicity
Introduction

Occurs frequently in patients treated with diagnostic and
therapeutic agents

Manifestation
reversible)

Is seen in which patients?
Decrease in renal function(often
‫‪Incidence‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪ %5‬بیماران بستری در بیمارستان دچار نارسایی حاد کلیوی می شوند‪.‬‬
‫‪ %25‬موارد نارسایی حاد کلیوی حاصل از مصرف دارو می باشد‪ .‬که در ‪ %8‬موارد منجر به‬
‫مرگ می شود‪.‬‬
‫نارسایی کلیوی حاصل از دارو ‪ %7‬کل مسمومیت های دارویی را شامل می شود‪.‬‬
Risk factors:

Idiosyncratic

Direct cumulative toxicity

No generalizable risk factors are applicable to all
drug classes and patient situation ,Exception:
ARF due to NSAIDs & ACEIs

The risk factors are: Preexisting renal insufficiency &
decrease effective renal blood flow from volume
depletion and HF, liver dx.
Recognition and assessment of renal toxicity:

Hospitalized patients:
1-recognized quickly
2-by lab test: BUN,Cr
3-decrease in urine out put(ACEIs,NSAIDs,
Radiographic contrast)

Out patients
dysfunction

Signs
recognized by advanced renal
Classification of drug induced renal disease:



Based on mechanism of toxicity
Presenting of renal manifestations:
CRF,ARF,Pyuria,Hematuria, Proteinuria
Therapeutic use and the various types of nephropathies
they may produced Renal structural and functional
alterations(produced by drugs)
Definitions:










Pseudo Renal Failure
Interstitial Nephritis
Acute interstitial nephritis
Chronic interstitial nephritis
Acute Glomerulonephritis
Acute Tubular Necrosis
Crystal nephropathy
Rhabdomyolysis
Nephrotic Syndrome
minimal-change nephropathy
Pseudo Renal Failure (Normal GFR)

↑ BUN due to protein catabolism , Normal Cr
􀂄 Steroids, tetracyclines

↑ SCr due to competitive inhibition of creatinine secretion, Normal BUN
􀂄 Trimethoprim, Cimetidine, Triamterene
- 15-35% rise SCr fully expressed after 3 days
- More sig in pts with pre-existing renal dysfunction
- Can occur with normal doses
- Completely reversible when drug is discontinued
(J Int Med 1999l246:247-52; TDM 1987;9:161-5)
Definitions:

Interstitial Nephritis
Interstitial nephritis (or Tubulo-interstitial nephritis)
is a form of nephritis affecting the interstitium of the
kidneys surrounding the tubules. This disease can be
either acute, meaning it occurs suddenly, or chronic,
meaning it is ongoing and eventually ends in kidney
failure.
Definitions:





Interstitial Nephritis
When caused by an allergic reaction, the symptoms of acute
tubulointerstitial nephritis are:
- fever (27% of patients)
- rash (15% of patients)
- enlarged kidneys.
Other: Dysuria, and lower back pain.
In chronic tubulointerstitial nephritis: nausea, vomiting, fatigue, and
weight loss. hyperkalemia, metabolic acidosis, and kidney failure.
Blood tests: Eosinophilia, ↑ Cr & BUN
Urinary findings: Eosinophiluria, Isosthenuria, hematuria, Sterile
pyuria: white blood cells and no bacteria
Definitions:

Acute Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis,
abbreviated GN, is a renal disease (usually of both kidneys)
characterized by inflammation of the glomeruli, or small blood
vessels in the kidneys.
It may present with isolated hematuria and/or proteinuria (blood or
protein in the urine); or as a nephrotic syndrome, a nephritic
syndrome, acute renal failure, or chronic renal failure.
Primary causes are intrinsic to the kidney. Secondary causes are
associated with certain infections (bacterial, viral or parasitic
pathogens), drugs, systemic disorders (SLE, vasculitis), or
diabetes.
Definitions:

Acute Tubular Necrosis
Acute tubular necrosis (ATN) is a medical condition
involving the death of tubular cells that form the tubule
that transports urine to the ureters while reabsorbing
99% of the water (and highly concentrating the salts
and metabolic byproducts). Tubular cells continually
replace themselves and if the cause of ATN is removed
then recovery is likely. ATN presents with acute kidney
injury (AKI) and is one of the most common causes of
AKI. The presence of "muddy brown casts" of epithelial
cells found in the urine during urinalysis is
pathognomonic for ATN.
Definitions:

Crystal nephropathy
Several medications that are insoluble in human urine are known
to precipitate within the renal tubules. Intratubular precipitation of
either exogenously administered medications or endogenous
crystals (induced by certain drugs) can promote chronic and acute
kidney injury, termed crystal nephropathy. Clinical settings that
enhance the risk of drug or endogenous crystal precipitation within
the kidney tubules include:
- true or effective intravascular volume depletion
- underlying kidney disease
- and certain metabolic disturbances that promote changes in
urinary pH favoring crystal precipitation.
Definitions:

Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue , breaks down
rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some
of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney
failure. The severity of the symptoms, which may include muscle pains, vomiting and confusion,
depends on the extent of muscle damage and whether kidney failure develops.
The muscle damage may be caused by physical factors (e.g. crush injury, strenuous exercise),
medications, drug abuse, and infections. Some people have a hereditary muscle condition that
increases the risk of rhabdomyolysis.
The diagnosis is usually made with blood tests and urinalysis. The mainstay of treatment is
generous quantities of intravenous fluids, but may include dialysis or hemofiltration in more
severe cases.
Rhabdomyolysis and its complications are significant problems for those injured in disasters
such as earthquakes and bombings. Relief efforts in areas struck by earthquakes often include
medical teams with the skills and equipment to treat survivors with rhabdomyolysis. The
disease was first described in the 20th century, and important discoveries as to its mechanism
were made during the Blitz of London in 1941. Horses may also suffer from rhabdomyolysis
from a variety of causes.
Definitions:

Nephrotic Syndrome
Nephrotic syndrome is a nonspecific kidney disorder characterised by a number
of diseases: proteinuria, hypoalbuminemia and edema.
It is characterized by an increase in permeability of the capillary walls of the
glomerulus leading to the presence of:
- high levels of protein passing from the blood into the urine (proteinuria at least 3.5
grams per day per 1.73m2 body surface area);
- low levels of protein in the blood (hypoproteinemia or hypoalbuminemia),
- Ascites and edema
- High cholesterol (hyperlipidaemia or hyperlipemia)
- Predisposition for coagulation.
Kidneys affected by nephrotic syndrome have small pores in the podocytes, large
enough to permit proteinuria (and subsequently hypoalbuminemia,<25g/L, because
some of the protein albumin has gone from the blood to the urine) but not large
enough to allow cells through (hence no haematuria). By contrast, in nephritic
syndrome red blood cells pass through the pores, causing haematuria.
Nephrotic Syndrom
Diagnosis:




Pro ++++
Proteinuria: >3.5g/d
Hypoalbuminemia: SAlb <30g/L
Edema;
Hyperlipidemia.
Edema
Definitions:

minimal-change nephropathy
Minimal Change Disease (also known as Nil Lesions or Nil Disease
(lipoid nephrosis)) is a disease of the kidney that causes nephrotic
syndrome and usually affects children (peak incidence at 2–3 years of
age).
People with one or more autoimmune disorders are at increased risk of
developing minimal change disease. Having minimal change disease also
increases the chances of developing other autoimmune disorders.
Most cases of MCD are idiopathic, however there have been causes of
secondary MCD identified, including medications, immunizations,
neoplasm, and infection.
Case reports and literature reviews have shown an association between
MCD and malignancies, particularly hematologic malignancies, such as
Hodgkin’s disease, non-Hodgkin lymphomas, or leukemias. Colorectal
cancer-associated MCD is uncommon and has been reported in only a
few cases to date.
CLASSIFICATIONS

Anuric: < 50ml/day urine output

Oliguric: 50-400ml/day urine output

Non-oliguric: >400ml/day urine output
Urine Analysis
Urinalysis (complete) (urine)
Appearance: clear, yellow.
Specific gravity: 1.001 - 1.035
pH: 4.6 - 8.0
Protein: negative
Glucose: negative
Ketones: negative
Bilirubin: negative
Occult blood: negative
WBC esterase: negative
Nitrite: negative
WBC: </= 5 high-power field
RBC: </= 3 high-power field
Renal epithelial cells: </= 3
/high-power field
Squamous epithelial cells:
None or few/high-power field
Casts: none
Bacteria: none
Yeast: none
Kidney Function Tests
Urea Nitrogen blood (BUN)
(serum)
Creatinine (Serum)
7 - 30 mg/dL
Alternative source: 8-25 mg/dL
2.5 - 10.7 mmol urea /L
Alternative source:
2.9-8.9 mmol/L
0.7 - 1.4 mg/dl (<1.2)
</= 106 µmol/L
Male: 0.8 - 2.4 g/day
Female: 0.6 - 1.8 g/day
Male: 7.1 - 21.2 mmol/day
Female: 5.3 - 15.9 mmol/day
Male:
<12 yr: 50-90 mL/minute,
>12 yr: 97-137 mL/minute
Female:
< 12 yr: 50-90 mL/minute,
> 12 yr: 88-128 mL/minute
Creatinine (Urine)
Creatinine Clearance (CrCL)
Note: Creatinine clearance
reference intervals are
based on a body surface
area of 1.73 square meters.
‫ نارسایی کلیوی‬

Pre Renal:
↑ BUN/ ↑ Cr
>20

Post Renal:
↑ BUN/ ↑ Cr
10 – 20

Renal:
↑ BUN/ ↑ Cr
< 10
Kidney Function Tests
PaCO2:
Normal: 35 - 45 mmHg (4.6 - 6 kPa)
Respiratory acidosis: > 45 mmHg (> 6
kPa)
Respiratory alkalosis: <35 mmHg (<
4.6 kPa)
BE (Base Excess):
-------------------------Normal: -2 to +2 mmol/L
Metabolic acidosis: < -2
mmol/L
Mild
Moderate
Marked
Severe
HCO3-------------------------Normal: 22 - 26 mEq/L
Metabolic acidosis: <22 mEq/L
Metabolic alkalosis: > 26 mEq/L
Severe
Marked
Moderate
[Standard Bicarbonate: Calculated value.
Similar to the base excess. It is defined as
the calculated bicarbonate concentration
of the sample corrected to a PCO2 of
5.3kPa (40mmHg).
Mild
-4 to -6
-6 to -9
-9 to -13
to < -13
Metabolic alkalosis: > +2 mmol/L
> +13
9 to 13
6 to 9
4 to 6
[Base excess (BE) is the mmol/L of base
that needs to be removed to bring the
pH back to normal when PCO2 is
corrected to 5.3 kPa or 40 mmHg.
During the calculation any change in pH
due to the PCO2 of the sample is
eliminated, therefore, the base excess
reflects only the metabolic component
of any disturbance of acid base
balance.]
Anion gap = Na+ - [CL- + HCO3-]
Difference between calculated serum anions and cations.
Based on the principle of electrical neutrality, the serum concentration of cations (positive
ions) should equal the serum concentration of anions (negative ions).
However, serum Na+ ion concentration is higher than the sum of serum Cl- and HCO3concentration.
Na+ = CL- + HCO3- + unmeasured anions (gap).
Normal anion gap: 12 mmol/L (10 - 14 mmol/L)
ESTIMATION OF RENAL FUNCTION

Cockcroft and Gault Equation:
CLCr(ml/min) = (140-Age)×(Wt.)
72(Scr)
= × 0.85 (female)

Estimates renal function when creatinine levels are at
steady-state
 not usually the case in acute renal failure
Serum Creatinine

Creatinine 1.0 mg/dL
Normal GFR

Creatinine 2.0 mg/dL
50% reduction in GFR

Creatinine 4.0 mg/dL
70–85% reduction in GFR

Creatinine 8.0 mg/dL
90–95% reduction in GFR

Estimate Creatinine Clearance: (ml/min)
Cockcroft and Gault equation:
CrCl: (140 - age) x IBW / (Scr x 72) (x 0.85 for females)
Note: if the ABW (actual body weight) is less than the IBW
use the
actual body weight for calculating the CRCL. If the patient
is >65yo and
creatinine<1, use 1 to calculate the creatinine clearance.
Estimate Ideal body weight in (kg)

Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.

Adjusted body weight (ABW):
ABW = IBW + 0.4(Total body weight - IBW)
Normal Blood Gases
Arterial
7.35 - 7.45
pH
Venous
7.32 - 7.42
Not a gas, but a measurement of acidity or alkalinity, based on the hydrogen (H+) ions present. The pH of a solution is equal to
the negative log of the hydrogen ion concentration in that solution: pH = - log [H+].
PaO2
80 to 100 mm Hg.
28 - 48 mm Hg
The partial pressure of oxygen that is dissolved in arterial blood.
New Born – Acceptable range 40-70 mm Hg. Elderly: Subtract 1 mm Hg from the minimal 80 mm Hg level for every year over
60 years of age: 80 - (age- 60) (Note: up to age 90)
HCO3
22 to 26 mEq/liter
(21–28 mEq/L)
19 to 25 mEq/liter
The calculated value of the amount of bicarbonate in the bloodstream. Not a blood gas but the anion of carbonic acid.
PaCO2
35-45 mm Hg
38-52 mm Hg
The amount of carbon dioxide dissolved in arterial blood. Measured. Partial pressure of arterial CO2. (Note: Large A= alveolor
CO2). CO2 is called a “volatile acid” because it can combine reversibly with H2O to yield a strongly acidic H+ ion and a weak
basic bicarbonate ion (HCO3 -) according to the following equation: CO2 + H2O <--- --> H+ + HCO3
–2 to +2 mEq/liter
B.E.
Other sources: normal reference range is
between -5 to +3.
The base excess indicates the amount of excess or insufficient level of bicarbonate in the system. (A negative base excess
indicates a base deficit in the blood.) A negative base excess is equivalent to an acid excess. A value outside of the normal
range (-2 to +2 mEq) suggests a metabolic cause for the abnormality. Calculated value. The base excess is defined as the
amount of H+ ions that would be required to return the pH of the blood to 7.35 if the pCO2 were adjusted to normal.
It can be estimated by the equation:
Base excess = 0.93 (HCO3 - 24.4 + 14.8(pH - 7.4))
Alternatively: Base excess = 0.93×HCO3 + 13.77×pH - 124.58
A base excess > +3 = metabolic alkalosis a base excess < -3 = metabolic acidosis
SaO2
95% to 100%
The arterial oxygen saturation.
50 - 70%
‫داروها بیشتر باعث بروز نارسایی حاد کلیوی می شوند یا‬
‫نارسایی مزمن کلیوی؟‬
‫‪Definitions‬‬
‫‪ Type‬‬
‫‪ Onset‬‬
‫‪ Severity‬‬
‫‪‬‬
‫آیا احتمال دارد بیمار دچار نارسایی کلیوی حاصل از‬
‫داروها شود بدون اینکه برون ده اداری او تغییر کند؟‬
‫آیا مرگ و میر حاصل از نارسایی حاد کلیوی ایجاد شده‬
‫توسط داروها بیشتر از سایر علل آن می باشد؟‬
‫کدامیک از عوارض کلیوی حاصل از داروها وابسته به‬
‫دوز دارو نیست؟‬

Acute interstitial nephritis

Acute Tubular Necrosis

Obstructive
Aminoglycosides

Is once daily dosing less nephrotoxic
compared to traditional dosing?
‫آیا فرموالسیون دارو می تواند در بروز عارضه کلیوی نقش‬
‫داشته باشد؟‬
Amphotericin B

Are Liposomal formulations affect nephrotoxicity
‫تشخیص زودهنگام نارسایی کلیوی حاصل از دارو در کدام‬
‫بیماران رایج تر‪ /‬محتمل تر است؟‬
‫‪ ‬بستری‬
‫‪ ‬سر پایی‬
‫در تمامی بیماران مصرف کننده ‪ ACEI‬افزایش کراتینین‬
‫رخ می دهد؟‬
‫‪ ‬درست‬
‫‪ ‬نادرست‬
‫در تمامی بیماران مصرف کننده ‪ ACEI‬افزایش کراتینین‬
‫رخ می دهد؟‬
‫‪ ‬درست‬
‫‪ ‬نادرست‬
‫آیا با افزایش کراتینین در بیماران مصرف کننده ‪ACEI‬‬
‫دارو باید قطع گردد؟‬
‫‪ ‬بلی‬
‫‪ ‬خیر‬
‫‪ ‬بستگی دارد‬
‫عوارض کلیوی با کدامیک از داروهای زیر بیشتر رخ می‬
‫دهد؟‬
- NSAIDs
- Cyclosporine
- Amphotericin-B
- Radiocontrast Media
- Vasopressors
‫برای جلوگیری از تشکیل کریستال و رسوب داروها در‬
‫توبول ها بهتر است ‪ pH‬ادرار اسیدی باشد یا بازی؟‬
‫‪ ‬اسیدی‬
‫‪ ‬بازی‬
‫‪ ‬بستگی دارد‬
‫کدام گزینه در مورد مکانیسم ایجاد عارضه کلیوی دارویی نادرست است؟‬
A. Tubular cell toxicity — ACE inhibitors
B. Altered intraglomerular hemodynamics — ARBs
C. Crystal nephropathy — Antivirals
D. Rhabdomyolysis — Statins
‫در کدامیک از موارد زیر دارو باید قطع گردد؟‬

Relative Serum Creatinine increase 50% over baseline

Absolute Serum Creatinine increase
 Serum
Creatinine baseline <2 mg/dl: Creatinine increase 0.5
mg/dl over baseline
 Serum Creatinine baseline >2 mg/dl: Creatinine increase 1.0
mg/dl over baseline
60
Drug-Induced Acute Renal Dysfunction


Pseudo Renal Failure
Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
- Intrinsic – ATN vs AIN
ATN – Aminoglycosides, Amphotericin B, Radiocontrast Media
- Obstructive
Methotrexate, Acyclovir, Indinavir, Rhabdomyolysis (Statins)
DRUG-INDUCED RENAL FAILURE
Mechanism
Drug(s)
Reduction of renal
perfusion
NSAIDs, ACEinhibitors,cyclosporine,
tacrolimus, amphotericin B
Direct tubular toxicity Aminoglycosides,
radiocontrast agents,
cyclosporine, tacrolimus,
amphotericin B, pentamidine,
cisplatin
Allergic interstitial
nephritis
Penicillins, cephalosporins,
sulfonamides, NSAIDs
Intratubular
obstruction by
precipitation
Acyclovir, sulfonamides,
chemotherapeutics
ETIOLOGY: pre-renal

Decreased cardiac output: CHF,MI,PE, Beta-blockers

Peripheral vasodilation: bacterial sepsis, vasodilators
(nitrates, hydralazine,etc.)

Hypovolemia: blood loss,Severe dehydration, diarrhea,
burns, third-spacing, diuresis(diuretics)

Vascular Obstruction: NSAIDS, ACE-I, Vasopressors,
renal artery occlusion
‫درد‬
‫‪‬‬
‫‪‬‬
‫مسکن های غیر اوپیوئیدی‬
‫‪ ‬داروهای ضد التهاب غیر استروئیدی(‪)NSAIDs‬‬
‫‪ ‬استامینوفن‬
‫مسکن های اوپیوئیدی‬
‫‪ ‬اوپیوئیدهای قوی‬
‫‪ ‬اوپیوئید های ضعیف‬
History
1

The first reference to aspirin was by a 5th century BC Greek physician who rote of a bitter
powder that came from the bark of the willow tree, and it eased pains and reduced fever.

The medicinal part of the plant is the inner bark of the tree. The active extract of the bark is
called salicin after the Latin name for the white willow tree. It was isolated in crystalline
form in 1828 by Henri Leroux, a French pharmacist. Raffaele Piria, an Italian chemist was
able to convert it to salicylic acid. Salicylic acid was isolated from the herb called
meadowsweet by German researchers in 1839. While it was somewhat effective, it also
caused digestive problems when consumed in high doses.

A French chemist, Charles Frederic Gerhardt, first prepared acetylsalicylic acid in 1853
(named aspirin in 1899). This preparation of aspirin was one of many reactions Gerhardt
conducted for his paper on anhydrides and he did nothing further with it. Six years later in
1859, von Gilm created the substance again. In 1897, a chemist at Friedrich Bayer and Co.
began investigating acetylsalicylic acid as a less-irritating replacement for the commonly
used salicylate medicines. By 1899 Bayer was marketing it world wide. obtained
acetylsalicylic acid and claimed to discover aspirin. Regardless of that, aspirin was finally
manufactured and put on the market to help those in pain or with fever.
History
2

Sodium salicylate, discovered in 1763, was the first NSAID. Gastrointestinal
toxicity (particularly dyspepsia) associated with the use of acetylsalicylic acid
(ASA) led to the introduction of phenylbutazone, an indoleacetic acid derivative,
in the early 1950s; this was the first non-salicylate NSAID developed for use in
patients with inflammatory conditions.

Phenylbutazone is a weak prostaglandin synthetase inhibitor that also induces
uricosuria. It was shown to be a useful agent in patients with ankylosing
spondylitis and gout. Concerns related to bone marrow toxicity, particularly in
women over the age of 60, have essentially eliminated the use of this drug.

Indomethacin was developed in the 1960s as a substitute for phenylbutazone. The
following years witnessed the development of more and more NSAIDs in an
effort to enhance patient compliance (by decreasing the absolute number of pills
and frequency with which they are taken each day), reduce toxicity, and increase
the antiinflammatory effect.
‫ليست داروهای موجود‬
Aspirin
Celecoxib
Diclofenac
Indomethacin
Ibuprofen
Ketorolac
Mefenamic acid
Naproxen
Sulindac
Salicylic acid
Piroxicam
Tolmetin
Sodium salicylate
Indomethacin
Naproxen
Classical NSAID’s
+
GCS
Endothelium, brain, spinal cord
N.B.: COX-2 also in •• Kidney
(Macula densa), ovaries, uterus
Pharmacokinetics:
- Most NSAIDs are absorbed completely
- Have negligible first-pass hepatic metabolism
- Tightly bound to serum proteins
- Have small volumes of distribution
- Half-lives of the NSAIDs vary but in general can be divided into :
"short-acting" (less than six hours, including ibuprofen, diclofenac,
ketoprofen and indomethacin) and
"long-acting" (more than six hours, including naproxen, celecoxib,
meloxicam, nabumetone and piroxicam).
Patients with hypoalbuminemia (due, for example, to cirrhosis or active
rheumatoid arthritis) may have a higher free serum concentration of the drug.
Drug interactions

NSAIDs reduce renal blood flow and thereby
decrease the efficacy of diuretics,
Indications

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are
present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions,
such as cancer and cardiovascular disease.

NSAIDs are generally indicated for the symptomatic relief of the following conditions:

Rheumatoid arthritis
Osteoarthritis
Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis,
Reiter's syndrome)
Acute gout
Dysmenorrhoea (menstrual pain)
Metastatic bone pain
Headache and migraine
Postoperative pain
Mild-to-moderate pain due to inflammation and tissue injury
Muscle stiffness and pain due to Parkinson's disease
Pyrexia (fever)
Ileus
Renal colic
Ductus arteriosus is not closed within 24 hours of birth
Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for
inhibition of platelet aggregation. This is useful in the management of arterial
thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits
platelet aggregation by inhibiting the action of thromboxane A2.









NSAIDs - Common Adverse Effects








Platelet Dysfunction
Gastritis and peptic ulceration with bleeding
(inhibition of PG + other effects)
Acute Renal Failure in susceptible
Sodium+ water retention and edema
Analgesic nephropathy
Prolongation of gestation and inhibition of labor.
Hypersenstivity (not immunologic but due to PG
inhibition)
GIT bleeding and perforation
‫عوارض جانبی‪NSAIDs‬‬
‫‪ ‬عوارض کلیوی‬
‫‪ ‬شیوع ‪%1-10‬‬
‫‪ ‬احتیاط مصرف ‪ NSAIDs‬در بیماران با نارسایی کلیوی و مصرف کنندگان‬
‫داروهای مسدودكننده گیرنده آنژیوتانسین (لوزارتان‪ ،‬والزارتان) و مهار کننده‬
‫های ‪( ACE‬کاپتوپریل‪ ،‬اناالپریل)‬
‫‪ ‬توجه به سطح کراتينین در بیماران مسن و بیماران دچار نارسایی کلیوي‬
‫‪NSAIDs/COXibs‬‬
‫‪‬‬
‫‪ %5‬بیماران مصرف کننده ‪ NSAIDs‬در سال دچار نارسایی حاد کلیوی می شوند‪ .‬که‬
‫باعث بستری در بیمارستان یا افزایش طول مدت بستری می شود‪.‬‬
NSAIDs/COXibs


Use with caution in CKD (grade 3 or greater)
Inhibit renal vasodilatory prostaglandins E2 & I2
􀂄 Produced by COX-2

Reversible reduction in GFR
􀂄 Higher risk if intravascular volume depletion
􀂄 Management: D/C drug, use alternate analgesia

Hypertension
􀂄 Edema, sodium and water retention
􀂄 Mean increase SBP 5 mm Hg

Hyperkalemia Risk
􀂄 blunting of PG-mediated renin release
‫چه مدت پس از قطع مصرف ‪ NSAIDs‬مشکالت کلیوی‬
‫حاصل از آنها بهبود می بابد؟‬
‫‪ ‬یک هفته‬
‫‪ ‬دو هفته‬
‫‪ ‬یک ماه‬
‫‪ ‬سه ماه‬
‫‪ ‬یک سال‬
‫‪ ‬برگشت پذیر نمی باشد‬
‫کدام ‪ NSAIDs‬مشکالت کلیوی کمتری ایجاد می کنند؟‬
‫کدام ‪ NSAIDs‬مشکالت کلیوی کمتری ایجاد می کنند؟‬
‫‪Sulindac‬‬
‫‪‬‬
‫‪Naproxen‬‬
‫‪‬‬
Analgesic nephropathy
Analgesic nephropathy involves damage to one or both kidneys caused by overexposure to
mixtures of medications, especially over-the-counter pain remedies (analgesics).
- Injuries: renal papillary necrosis and chronic interstitial nephritis.
- Result: decreased blood flow to the kidney, rapid consumption of antioxidants, and
subsequent oxidative damage to the kidney. This kidney damage may
lead to progressive chronic renal failure, abnormal urinalysis results,
high blood pressure, and anemia.
Analgesic nephropathy

Causes, incidence, and risk factors
- Analgesic nephropathy involves damage within the internal
structures of the kidney. It is caused by long-term use of analgesics,
especially over-the-counter (OTC) medications that contain phenacetin
or acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)
such as aspirin or ibuprofen.
- About 6 or more pills per day for 3 years increases the risk some for
this problem. This frequently occurs as a result of self-medicating, often
for some type of chronic pain.
- Analgesic nephropathy occurs in about 4 out of 100,000 people,
mostly women over 30. The rate has decreased significantly since
phenacetin is no longer widely available in OTC preparations.
Analgesic nephropathy
Risk factors include:
- Use of OTC analgesics containing more than one active ingredient
- Chronic headaches, painful menstrual periods, backache, or
musculoskeletal pain
- History of dependent behaviors including smoking, alcoholism, and
excessive use of tranquilizers
Analgesic nephropathy
Symptoms
There may be no symptoms. Symptoms of chronic kidney disease are often present over
time and may include:










Weakness, Fatigue
Increased urinary frequency or urgency
Blood in the urine
Flank pain or back pain
Decreased urine output
Decreased alertness : Drowsiness , Confusion, delirium , Lethargy
Decreased sensation, numbness (especially in the legs)
Nausea, vomiting
Easy bruising or bleeding
Swelling, generalized
Analgesic nephropathy
Signs and tests







A physical examination may show signs of interstitial nephritis or kidney failure.
Blood pressure may be high
abnormal heart or lung sounds
There may be signs of premature skin aging
Lab tests may show blood and pus in the urine, with or without signs of infection
There may be mild or no loss of protein in the urine.
Tests that may be done include:
- CBC
- sedimentation in the urine
- Intravenous pyelogram(IVP)
- Toxicology screen
- Urinalysis
Analgesic nephropathy
Treatment




The primary goals of treatment are to prevent further damage and to treat any existing
kidney failure.
Stop taking all suspect painkillers, particularly OTC medications.
Signs of kidney failure should be treated as appropriate. This may include diet changes, fluid
restriction, dialysis or kidney transplant, or other treatments.
Counseling, behavioral modification, or similar interventions may help you develop
alternative methods of controlling chronic pain.
Expectations (prognosis)

The damage to the kidney may be acute and temporary, or chronic and long term.
Analgesic nephropathy
Complications







Acute renal failure
Chronic renal failure
Interstitial nephritis
Renal papillary necrosis (tissue death)
Urinary tract infections, chronic or recurrent
Hypertension
Transitional cell carcinoma of the kidney or ureter
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Cyclosporine, Tacrolimus


Can cause:
- pre-renal (hemodynamically mediated)
- chronic interstitial nephritis
Pre-renal – dose-related
􀂄 preglomerular arteriolar vasoconstriction or
direct proximal tubule damage
􀂄 ↑ SCr ~ 30%
􀂄 More common in first 6 mos of therapy
􀂄 Hypertension, ↑ K, ↓ Mg may occur
􀂄 Reversible with lowering dose (caution rejection)
􀂄 Monitor blood levels
􀂄 Renal biopsy to distinguish acute CyA
nephrotoxcity from allograft rejection
‫تست تشخیص ی عارضه کلیوی حاصل از سیکلوسپورین از‬
‫رد پیوند چیست؟‬
‫‪BUN/Cr‬‬
‫‪‬‬
‫‪Angiography‬‬
‫‪‬‬
‫‪Biopsy‬‬
‫‪‬‬
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Side Effects
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – In Whom and When?
Indications:


Potentially all patients with heart failure
First-line treatment (along with beta-blockers) in NYHA class I–IV heart failure
Contra-indications:

History of angioneurotic oedema
Cautions/seek specialist advice:


Significant renal dysfunction (creatinine >2.5 mg/dL or 221 µmol/L) or
hyperkalaemia (K+ >5.0 mmol/L)
Symptomatic or severe asymptomatic hypotension (SBP <90 mmHg)
Drug interactions to look out for:



K+ supplements/ K+ sparing diuretics (including spironolactone)
NSAIDs*
*avoid unless essential
AT1-receptor blockers
Afferent Arteriolar vasoconstrictors


Vasodilatory Prostaglandin Inhibitors
- NSAIDs
- COX-2 Inhibitors
Direct Afferent Arteriolar Vasoconstrictors
- Cyclosporine
- Amphotericin-B
- Radiocontrast Media
- Vasopressors
Efferent Arteriolar vasodilators


Renin-Angiotensin-Aldosterone
- ACEIs
- ARBs
Direct Efferent Arteriolar Vasodilators
- CCBs dihydropyridine: Diltiazem, Verapamil
Acute Renal Failure:
PRE-RENAL




ACEI/ARB
NSAIDs
Diuretics
Immunosuppressives (CyA, Tacrolimus)
Acute Renal Failure:
PRE-RENAL

ACEI/ARB
At the start of the treatment a decrease of urine
volume and increase of creatinine by 30% indicates
 Damage is reversible
 Rehydration of patient is advisable
 Initiate treatment with short acting (captopril) and titrate
later with long acting

ACE Inhibitors & ARBs



Uremia, hyper K, dialysis dependence
Cr > 3.5  consult nephrology!
Avoid in bilat renal artery stenosis
- ARB causes less renal failure than ACE Inhibitor






Strategy:
BP, K, Cr
“diuretic holiday” x days before start
start captopril 1st, then long-acting
Ramipril: CrCl < 40, give 25% of normal dose
Losartan: avoid if GFR < 30
Risk Factors for ARF with ACEI/ARB

Decreased intravascular volume
(dehydration, diuretic overuse, poor fluid intake, CHF, vomiting, diarrhea)

Use of afferent vasoconstrictor agents
(NSAIDs, cyclosporine, tacrolimus)

Sepsis

Renal-artery stenosis

Polycystic kidney disease
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving (continued)
Worsening renal function:
•
Some increase in urea (blood urea nitrogen), creatinine and K+ is to be expected after
initiation; if the increase is small and asymptomatic no action is necessary
•
•
An increase in creatinine of up to 50% above baseline, or 3 mg/dL (266 µmol/L),
whichever is the smaller, is acceptable
An increase in K+  6.0 mmol/L is acceptable
•
If urea, creatinine or K+ rise excessively, consider stopping concomitant nephrotoxic
drugs (e.g. NSAIDs), other K+ supplements/ K+ retaining agents (triamterene, amiloride)
and, if no signs of congestion, reducing the dose of diuretic
•
If greater rises in creatinine or K+ than those outlined above persist, despite adjustment of
concomitant medications, halve the dose of ACE inhibitor and recheck blood chemistry; if
there is still an unsatisfactory response, specialist advice should be sought
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving (continued)
Worsening renal function (cont.):
•
•
If K+ rises to >6.0 mmol/L, or creatinine increases by >100% or to above 4 mg/dL (354
µmol/L), the dose of ACE inhibitor should be stopped and specialist advice sought
Blood chemistry should be monitored serially until K+ and creatinine have plateaued
NOTE: it is very rarely necessary to stop an ACE inhibitor and clinical deterioration is
likely if treatment is withdrawn; ideally, specialist advice should be sought before
treatment discontinuation
ACE-Inhibitors
“A limited increase in serum creatinine of as much as
35% above baseline with ACE inhibitors or ARBs
is acceptable and not a reason to withhold treatment
unless hyperkalemia develops.”
“an increase in SCr level, if it occurs, will happen
within the first 2 weeks of therapy initiation.”
JNC-7
‫با توجه به مطالب ارائه شده‪ ACEIs ،‬نفروتوکسیک‬
‫هستند یا نفروپروتکتیو؟‬
Angiotensin Receptor Blocker: Mechanism of Action
Renin
Angiotensinogen
Angiotensin I
ACE
Other Pathways
AT I
Receptor
Blocker
ATI
Angiotensin II
Receptors
AT II
Receptor
Blocker
ATII
Vasoconstriction Proliferative Vasodilation
Action
Antiproliferative
Action
Angiotensin II Receptor Antagonists
Candesartan
Eprosartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan
(Atacand)
(Tevetan)
(Avapro)
(Cozaar)
(Benicar)
(Micardis)
(Diovan)
Angiotensin II Receptor Antagonists
Valsartan
Valsartan
Valsartan
Valsartan
Valsartan
Valsartan
160 mg
160 mg
40 mg
40 mg
80 mg
80 mg
CAPSULE
ORAL
TABLET
ORAL
TABLET
ORAL
CAPSULE
ORAL
CAPSULE
ORAL
TABLET
ORAL
Losartan Potassium 25 mg
Losartan Potassium 50 mg
Losartan
Potassium/Hydrochlorothiazide 50/12.5 mg
Eprosartan 300 mg
Eprosartan 600 mg
TABLET
ORAL
TABLET
ORAL
TABLET
ORAL
Tablet
ORAL
Tablet
ORAL
( Losartan
Potassium
50mg +
Hydrochlorothi
azide 12.5mg)
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
- Intrinsic – ATN vs AIN
ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media
AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine,
NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
Dose of Aminoglycosides





G,T: 3-5mg/kg/d
A: 15-25mg/kg/d
S: 1g/d
P: 0.5-1g QID
N: 1g q4-6h
127
Aminoglycosides
Serum concentration - Sampling
G&T
 Peak: 5-8 mcg/ml
 Trough: less 2 mcg/ml
A
 Peak: 20-30 mcg/ml
 Trough: less 10 mcg/ml
V
 Peak: 15-30 mcg/ml
 Trough: less 5-20 mcg/ml
Infusion time: G & A
mg)
128
30 min, V 60 min(less 1250 mg) , 90 min(more 1250
Antibiotics

Aminoglycosides
 Trough >2mg/L, repeated course in months 
nonoliguric ATN
 Recommendations:
 hi
OD dose (5-7mg/kg/24h x 2-3wks) is less nephrotoxic and
equally effective
 Follow levels, correct K
 CrCl > 60, 1-2.5mg/kg Q8H
 CrCl 40-60, Q12H
 CrCl 20-40, Q24H
 CrCl <20, loading dose then monitor levels
‫سمیت کلیوی‬
Neomycin < Gentamicin,Tobramycin > Netilmicin,Streptomycin
Risk factor for Aminoglycoside Nephrotoxicity
Related to AMG dosing
•Large total cummulative dose
•Prolong therapy
•High peak or trough conc.
•Recet previous AMG therapy
Related to Predisposing
condition in the patient
•Preexisting renal insufficiency
•Increased age
•Poor nutrition
•Shock
Related to synergistic
nephrotoxicity
•Gramnegative bactermia
AMG combination with
•Liver disease
•Cyclosporin
•Hypoalbuminemis
•Amphotericin B
•Obstructive jaundice
•Vancomycin
•K+ or Mg++ deficiency
•Diuretics
Irreversible Damage!
Aminoglycoside Nephrotoxicity
Prevention
• Switching to alternative
antibiotics
• Avoid volume depletion,
concomitant therapy with
other nephrotoxic drugs
• Limit total dose
• Decreasing the frequency
of AMG dosing to at least
daily (as direct by renal
clearance)
Management
• Monitor Scr, concentration,
renal fn and electrolytes
• Discontinue AMG if
changes are seen.
Aminoglycoside

Drug interactions with other nephrotoxic medications:
 Cephalothin
 Cyclosporin
and other Cephalosporins
A
 Cisplatin
 NSAIDs
 ACE
Inhibitors
 Loop Diuretics
 Amino acids
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
- Intrinsic – ATN vs AIN
ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media
AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine,
NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
Amphotericin B nephrotoxicity

Dose dependant
↓ RBF & GFR
↑ SCr,concentrate urine and K,Na,Mg wasting

Risk factors: Higher average daily doses ,diuretic use,
Volume depletion

Prevention:
Limiting the dose
Volume repletion
Amphotericin+IV saline
Liposomal amphotericin with lipids
CCBs
Discontinuation
‫کدام دسته دارویی بیشترین میزان نارسایی کلیوی را در‬
‫بیماران بستری در بیمارستان ایجاد می کنند؟‬
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
- Intrinsic – ATN vs AIN
ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media
AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine,
NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
IV Contrast



Vasospasm & ARF
Risk factors: DM, myeloma, CRF, dehydration,
diuretics, CHF
Prophylaxis:
 Hold NSAIDs & diuretics, 24h pre & post contrast
 IV NS pre & post contrast
 2 x 600mg PO Acetylcysteine
 Low dose, low-osmolar contrast
 Avoid multiple procedures in 48h
 Monitor renal fxn for 48h
Case:
A 46-year-old morbidly obese man was admitted to
the medical intensive care unit with respiratory failure.
He required pressure-control ventilation and high levels
of sedation with continuous-infusion lorazepam. He
developed Stenotrophomonas maltophilia pneumonia;
treatment included scheduled intravenous trimethoprimsulfamethoxazole. On day 17 of his hospital course,
3 days after starting the trimethoprim-sulfamethoxazole, the
patient developed acute renal failure consistent with acute
tubular necrosis. therefore, all drugs were discontinued,
and laboratory data were collected. A marked osmol gap,
metabolic acidosis, and renal toxicity were attributed .
Propylene glycol is a viscous, colorless liquid solvent used
for many drugs with poor aqueous solubility. For many years,
propylene glycol has been thought of as safe; however, a
review of the literature reveals cases of propylene glycolassociated hyperosmolality, anion gap metabolic acidosis,
hemolysis, hyperosmolality, osmol gap, central nervous
system depression, arrhythmias, and, although less
commonly, renal dysfunction. Several case reports link high
doses of intravenous lorazepam with propylene glycolrelated toxicities. Other commonly prescribed drugs, including
intravenous nitroglycerin, digoxin, phenobarbital, phenytoin,
diazepam, trimethoprim-sulfamethoxazole and etomidate,
contain large amounts of propylene glycol and have also
been associated with toxicity. Laboratory signs of propylene
glycol toxicity include hyperosmolality, hyperlactatemia, and
osmol gap.
Serum Osmolality
2(Na) + BUN/2.8 + Glucose/18
Anion Gap
Na - (CL + HC03)
Osmolar Gap



Calculated Osmoles
= 2(sodium) + urea + glucose= 290-300
osmolar gap
= calculated - measured osmoles = 0-10
Theoretically, unaccounted osmols may signify a toxic
alcohol ingestion.(i.e.. ETOH)
( Mannitol, Alcohols, Dye, DMSO, Glycerol, Acetone, Sorbital )

Not sensitive enough to rule out a toxic alcohol ingestion.
Anion Gap

AG= (sodium) - (bicarbonate + chloride)=12-16

High Anion Gap Metabolic Acidosis
Methanol
Uremia
Diabetic Ketoacidosis
Paraldehyde
INH, iron
Lactate
Ethylene glycol
Salicylates
Cyanide
Alcoholic Ketoacidosis
Toluene
‫عارضه کلیوی کدام یک از استاتین ها بیشتر است؟‬
‫ آتورواستاتین و سیم واستاتین‬‫‪ -‬روزوواستاتین و پراواستاتین‬
ECSTASY
TREATMENT

Hypotension Control:
Normal Saline Infusion: 10-20 ml/kg
Vasopressor amines( Dopamine, norepinepherine)

Cardiac Dysrhythmeia
Amidaron, Lidocaine, Atropine
 Rhabdomyolysios Treatment:
Normal Saline Infusion, Diuretic (Mannitol,
Furosemide)
ETIOLOGY: post renal

Bladder obstruction
infection
tumor
BPH
anticholinergics (diphenydramine, meclizine, benztropine)
ganglionic
blockers (trimethaphan)
Classification of nephrotoxic drugs by their therapeutic use:
Cardiovascular:
ACEIs,CCBs,Mannitol,
Methyldopa
Triamterene,Warfarin
Propranolol,
Neuropsychiatric:
Amoxapine,CBZ,Li,Pb,
Phenytoin,VA
Immunosuppresiv:
Corticosteroid
Cyclosporine
OKT3
Leukocyte A interferon
Antimicrobial:
Acyclovir,AG,
Cephalosporin,Cipro
AmphotericinB,TC
Pentamidine,Vanco,
TMP,Erythro,Penicillin
Gastrointestinal:
Cimetidine,Magnesium
Ranitidine
Phosphate enemas
Drugs to abuse:
Amphetamine
Cocaine
Heroin
Phencyclidine
Rheumatolgic:
Acetaminophen,ASA
Allopurinol,NSAIDs
D-penicillamine,Gold
Cancer chemotherapy:
Carboplatinum,Cisplatin
Methotrexate,
Mithramycin, IL2
Nitrosoureas,
Miscellaneous:
Ascorbic acid
Glyburide,Lovastatin
Radiographic contrast
.
178
2
0

The best option for a patient with severe pulmonary
edema, who remains anuric after trials of 10 and 20
mg/h IV furosemide is:
A) Increase the dose of furosemide to 40 mg/h
B) Change the furosemide to bolus dosing; start with 200 mg IV
C) Add metolazone 5 mg daily
D) Discontinue furosemide and begin metolazone 10 mg twice
daily
E) Change to bumetanide 2 mg/h

The best option for a patient with severe pulmonary
edema, who remains anuric after trials of 10 and 20
mg/h IV furosemide is:
A) Increase the dose of furosemide to 40 mg/h
B) Change the furosemide to bolus dosing; start with 200 mg IV
C) Add metolazone 5 mg daily
D) Discontinue furosemide and begin metolazone 10 mg twice
daily
E) Change to bumetanide 2 mg/h

Which of the following therapies might worsen fluid or electrolyte
disturbances typically present in the patient with ARF?
A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by
Clostridium difficile
B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45
mL daily as needed for bowel movement
C) Diltiazem 10 mg/h for rate control because of atrial fibrillation
D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once
E) All of the above

Which of the following therapies might worsen fluid or electrolyte
disturbances typically present in the patient with ARF?
A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by
Clostridium difficile
B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45
mL daily as needed for bowel movement
C) Diltiazem 10 mg/h for rate control because of atrial fibrillation
D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once
E) All of the above

Prerenal ARF can be exacerbated by the continuation
of all of the following medications, except?
A) Lisinopril
B) Metolazone
C) Indomethacin
D) Prednisone
E) Valsartan

Prerenal ARF can be exacerbated by the
continuation of all of the following medications,
except?
A) Lisinopril
B) Metolazone
C) Indomethacin
D) Prednisone
E) Valsartan

All of the following should be assessed daily in a
patient with ARF, except?
A) Liver aminotransferases
B) Serum creatinine
C) Weight
D) Medication dosages
E) Urine output

All of the following should be assessed daily in a
patient with ARF, except?
A) Liver aminotransferases
B) Serum creatinine
C) Weight
D) Medication dosages
E) Urine output

Which of the following is not an important
consideration when selecting a dosage of a renally
eliminated antibiotic in a patient with ARF?
A) Cardiac output
B) Fluid status
C) Renal replacement therapy
D) Estimated GFR
E) Hemoglobin

Which of the following is not an important
consideration when selecting a dosage of a renally
eliminated antibiotic in a patient with ARF?
A) Cardiac output
B) Fluid status
C) Renal replacement therapy
D) Estimated GFR
E) Hemoglobin

In a patient with ARF and gram-negative sepsis
receiving gentamicin therapy, which of the following
should be considered in developing a treatment
regimen?
A) Gentamicin removal can be faster in ARF compared to CKD
B) Administration of the gentamicin immediately post the
intermittent hemodialysis session
C) Careful assessment of the patient’s actual volume of
distribution of gentamicin
D) Determining the viability of other antimicrobial alternatives
E) All of the above

In a patient with ARF and gram-negative sepsis
receiving gentamicin therapy, which of the following
should be considered in developing a treatment
regimen?
A) Gentamicin removal can be faster in ARF compared to CKD
B) Administration of the gentamicin immediately post the
intermittent hemodialysis session
C) Careful assessment of the patient’s actual volume of
distribution of gentamicin
D) Determining the viability of other antimicrobial alternatives
E) All of the above

Which of the following is false regarding ARF in the
hospitalized patient?
A) Occurs in approximately 7% of hospitalized patients
B) Is associated with increased mortality
C) Can lead to long-term kidney damage and life-long
hemodialysis
D) Should be aggressively treated with high-dose diuretics

Which of the following is false regarding ARF in the
hospitalized patient?
A) Occurs in approximately 7% of hospitalized patients
B) Is associated with increased mortality
C) Can lead to long-term kidney damage and life-long
hemodialysis
D) Should be aggressively treated with high-dose diuretics

Causes of diuretic resistance include the following except:
A) Inappropriate diuretic dose or regimen
B) NSAID-associated decrease in sodium resorption
C) Presence of heart failure
D) Vasodilator-associated reduction in renal blood flow 19

Causes of diuretic resistance include the following except:
A) Inappropriate diuretic dose or regimen
B) NSAID-associated decrease in sodium reasorption
C) Presence of heart failure
D) Vasodilator-associated reduction in renal blood flow 19

The most common manifestation of drug-induced
kidney disease is:
A) Proteinuria
B) Pyuria
C) Hematuria
D) A decline in the glomerular filtration rate (GFR)
E) A reduction in tubular secretion

The most common manifestation of drug-induced
kidney disease is:
A) Proteinuria
B) Pyuria
C) Hematuria
D) A decline in the glomerular filtration rate (GFR)
E) A reduction in tubular secretion

Which of the following drugs would be the most likely
culprit in a patient with newly diagnosed renal
intratubular obstruction?
A) Ibuprofen
B) Losartan
C) Amphotericin B
D) Ciprofloxacin
E) Acyclovir

Which of the following drugs would be the most likely
culprit in a patient with newly diagnosed renal
intratubular obstruction?
A) Ibuprofen
B) Losartan
C) Amphotericin B
D) Ciprofloxacin
E) Acyclovir

Hemodynamically mediated renal failure induced by
angiotensin-converting enzyme inhibitors (ACEI)
involves all of the following except:
A) Enhanced efferent arteriolar constriction
B) Patients with renal artery stenosis at increased risk
C) Decrease in glomerular capillary hydrostatic pressure
D) Reduced glomerular ultrafiltration
E) None of the above

Hemodynamically mediated renal failure induced by
angiotensin-converting enzyme inhibitors (ACEI)
involves all of the following except:
A) Enhanced efferent arteriolar constriction
B) Patients with renal artery stenosis at increased risk
C) Decrease in glomerular capillary hydrostatic pressure
D) Reduced glomerular ultrafiltration
E) None of the above

Which of the following drugs has been associated
with chronic interstitial nephritis?
A) Cyclosporine
B) Ifosfamide
C) Lithium
D) Streptozotocin
E) All of the above

Which of the following drugs has been associated
with chronic interstitial nephritis?
A) Cyclosporine
B) Ifosfamide
C) Lithium
D) Streptozotocin
E) All of the above

The following renal structural-functional alteration is
associated with exposure to radiographic contrast
media:
A) Allergic interstitial nephritis
B) Intratubular obstruction
C) Glomerulosclerosis
D) Acute tubular necrosis
E) Papillary necrosis

The following renal structural-functional alteration is
associated with exposure to radiographic contrast
media:
A) Allergic interstitial nephritis
B) Intratubular obstruction
C) Glomerulosclerosis
D) Acute tubular necrosis
E) Papillary necrosis

The preferred agent for preventing cisplatin-induced
nephrotoxicity is:
A) Fenoldopam
B) Amifostine
C) Dopamine
D) Acetylcysteine
E) Mesna

Each of the following statements regarding
aminoglycoside-induced acute tubular necrosis is true
except:
A) Risk factors include prolonged therapy and increased age
B) It manifests as a gradual increase in serum creatinine 4 to
6 weeks after exposure to the drug
C) Patients typically present with nonoliguria, maintaining
urine volumes greater than 500 mL/day
D) Toxicity of various aminoglycosides is related to cationic
charge of the drug
E) “Once-daily” dosing is one method to maintain
antimicrobial efficacy while reducing nephrotoxicity 12

Each of the following statements regarding
aminoglycoside-induced acute tubular necrosis is true
except:
A) Risk factors include prolonged therapy and increased age
B) It manifests as a gradual increase in serum creatinine 4 to
6 weeks after exposure to the drug
C) Patients typically present with nonoliguria, maintaining
urine volumes greater than 500 mL/day
D) Toxicity of various aminoglycosides is related to cationic
charge of the drug
E) “Once-daily” dosing is one method to maintain
antimicrobial efficacy while reducing nephrotoxicity

The signs and symptoms of penicillin-induced allergic
interstitial nephritis include all of the following except:
A) Rash, eosinophilia, pyuria
B) Fever, eosinophilia, reduced intraglomerular pressure
C) Fever, rash, eosinophilia
D) Elevated serum creatinine, rash, eosinophilia
E) Hematuria, proteinuria, oliguria

The signs and symptoms of penicillin-induced allergic
interstitial nephritis include all of the following except:
A) Rash, eosinophilia, pyuria
B) Fever, eosinophilia, reduced intraglomerular pressure
C) Fever, rash, eosinophilia
D) Elevated serum creatinine, rash, eosinophilia
E) Hematuria, proteinuria, oliguria

A 60-year-old woman with a 5-year history of NSAID
use is prescribed enalapril and develops acute renal
failure. What is the most likely cause of her renal
failure?
A) Acute allergic interstitial nephritis
B) Chronic interstitial nephritis
C) Minimal change glomerular injury
D) Focal segmental glomerulosclerosis
E) Hemodynamically-mediated renal failure

A 60-year-old woman with a 5-year history of NSAID
use is prescribed enalapril and develops acute renal
failure. What is the most likely cause of her renal
failure?
A) Acute allergic interstitial nephritis
B) Chronic interstitial nephritis
C) Minimal change glomerular injury
D) Focal segmental glomerulosclerosis
E) Hemodynamically-mediated renal failure

Potential causes of pseudo-renal failure include all of
the following except:
A) Competitive inhibition of creatinine tubular secretion by
cimetidine
B) Drug induced increase in protein catabolism
C) Direct interference with the enzymatic measurement of
creatinine
D) Increased synthesis and release of creatinine into
serum
E) Competitive inhibition of creatinine tubular secretion by
trimethoprim

Potential causes of pseudo-renal failure include all of
the following except:
A) Competitive inhibition of creatinine tubular secretion by
cimetidine
B) Drug induced increase in protein catabolism
C) Direct interference with the enzymatic measurement of
creatinine
D) Increased synthesis and release of creatinine into
serum
E) Competitive inhibition of creatinine tubular secretion by
trimethoprim
279
‫تنظیم دوز داروها در نارسایی کلیوی‬
Drug Therapy Individualization with Renal Insufficiency
‫همه سئواالت فوق‬

Which of the following is the most common cause
of intrinsic ARF?
A) Tubular damage from aminoglycoside use
B) Glomerular damage from severe inflammation
C) Tubular damage from prolonged ischemia
D) Occlusion of the renal vasculature

The best option for a patient with severe pulmonary
edema, who remains anuric after trials of 10 and 20
mg/h IV furosemide is:
A) Increase the dose of furosemide to 40 mg/h
B) Change the furosemide to bolus dosing; start with 200 mg IV
C) Add metolazone 5 mg daily
D) Discontinue furosemide and begin metolazone 10 mg twice
daily
E) Change to bumetanide 2 mg/h

Which of the following therapies might worsen fluid or electrolyte
disturbances typically present in the patient with ARF?
A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by
Clostridium difficile
B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45
mL daily as needed for bowel movement
C) Diltiazem 10 mg/h for rate control because of atrial fibrillation
D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once
E) All of the above

Prerenal ARF can be exacerbated by the continuation
of all of the following medications, except?
A) Lisinopril
B) Metolazone
C) Indomethacin
D) Prednisone
E) Valsartan

All of the following should be assessed daily in a
patient with ARF, except?
A) Liver aminotransferases
B) Serum creatinine
C) Weight
D) Medication dosages
E) Urine output

Which of the following is not an important
consideration when selecting a dosage of a renally
eliminated antibiotic in a patient with ARF?
A) Cardiac output
B) Fluid status
C) Renal replacement therapy
D) Estimated GFR
E) Hemoglobin

A 58-year-old male with unknown past medical history
has prerenal acute renal failure from acute blood loss
because of a limb amputation in an industrial
accident, and aggressive fluid resuscitation is
initiated. Which of the following set of monitoring
parameters are most appropriate for during the next 8
hours?
A) Urine output, rales, and blood pressure
B) Heart rate, blood pressure, and BUN
C) Bowel sounds, blood pressure, funduscopic findings
D) Blood pressure, serum potassium, and serum sodium
E) Blood pressure, weight, and blood glucose

The use of serum creatinine as a marker of glomerular
filtration rate (GFR) in the setting of ARF is limited by:
A) The test is not readily available in most laboratories
B) Its lack of responsiveness to abrupt changes in GFR
C) Its accuracy increases in the setting of volume
overload
D) The glomerulus increases its filtration of creatinine
during ARF
E) Numerous medications cross-react with the assay,
rendering the results unreliable

Which if the following is true regarding the treatment
of established ARF?
A) Dopamine 2 mcg/kg/min is effective to reverse intrinsic
ARF
B) The liberal use of loop diuretics hasten GFR recovery
C) Mannitol is useful to employ in the anuric patient
D) The mainstays of therapy are primarily supportive in
nature E) Thyroxine is helpful to increase GFR in the
elderly patient with subclinical hypothyroidism

Which if the following is true regarding the treatment
of established ARF?
A) Dopamine 2 mcg/kg/min is effective to reverse intrinsic
ARF
B) The liberal use of loop diuretics hasten GFR recovery
C) Mannitol is useful to employ in the anuric patient
D) The mainstays of therapy are primarily supportive in
nature
E) Thyroxine is helpful to increase GFR in the elderly
patient with subclinical hypothyroidism

For the patient with ARF, goals include:
A) Avoid exposure to additional nephrotoxins
B) Minimize extrarenal complications
C) Expedite recovery of renal function
D) Restore previous degree of renal function
E) All of the above

In a patient with ARF and gram-negative sepsis
receiving gentamicin therapy, which of the following
should be considered in developing a treatment
regimen?
A) Gentamicin removal can be faster in ARF compared to CKD
B) Administration of the gentamicin immediately post the
intermittent hemodialysis session
C) Careful assessment of the patient’s actual volume of
distribution of gentamicin
D) Determining the viability of other antimicrobial alternatives
E) All of the above 17

Which of the following is false regarding ARF in the
hospitalized patient?
A) Occurs in approximately 7% of hospitalized patients
B) Is associated with increased mortality
C) Can lead to long-term kidney damage and life-long
hemodialysis
D) Should be aggressively treated with high-dose diuretics

Causes of diuretic resistance include the following except:
A) Inappropriate diuretic dose or regimen
B) NSAID-associated decrease in sodium resorption
C) Presence of heart failure
D) Vasodilator-associated reduction in renal blood flow 19

A 76-year-old, 60-kg patient with a history of heart
failure is admitted for severe nausea and fever of
several days’ duration, as well as acute onset of chest
pain. There is a single serum creatinine value of 2.4
mg/dL, and tests for several drugs eliminated
primarily by the kidney are ordered. It is 2:00 in the
afternoon. Choose the best consideration for those
agents eliminated primarily by the kidney.
A) The creatinine clearance can be calculated to estimate
a GFR, and then an adjusted dosing regimen should
implemented for the duration of this admission.
B) Send out the initially ordered doses immediately and do
not check if any were administered in the emergency
room.
C) Assess if any drugs were recently administered, and
only recommend one day of new therapies if not already
started; request a second serum creatinine value to
assess if the patient’s renal function is stable; check to see
if the patient is producing any urine as a additional
assessment of renal function.
D) Assess if any drugs were recently administered, and
send out one dose.

In continuous renal replacement therapy (CRRT), the
following is true:
A) Goal of therapy in CRRT is a ultrafiltration rate of 25
mL/h/kg
B) Thrombosis is a concern where anticoagulation can be
necessary
C) Requires specialized staff and equipment
D) Is frequently used in unstable patients where IHD can
increase the risk of a hypotensive episode
E) All the above

The most common manifestation of drug-induced
kidney disease is:
A) Proteinuria
B) Pyuria
C) Hematuria
D) A decline in the glomerular filtration rate (GFR)
E) A reduction in tubular secretion

Regarding drug-induced kidney disease, all of the
following are applicable except:
A) Temporal relationship with potentially toxic agent
B) The offending agent is rarely identified
C) Significant source of morbidity in the hospital setting
D) Abrupt and sustained reduction in GFR
E) The most common presentation in the hospital setting is
acute tubular necrosis

Which of the following drugs would be the most likely
culprit in a patient with newly diagnosed renal
intratubular obstruction?
A) Ibuprofen
B) Losartan
C) Amphotericin B
D) Ciprofloxacin
E) Acyclovir

Hemodynamically mediated renal failure induced by
angiotensin-converting enzyme inhibitors (ACEI)
involves all of the following except:
A) Enhanced efferent arteriolar constriction
B) Patients with renal artery stenosis at increased risk
C) Decrease in glomerular capillary hydrostatic pressure
D) Reduced glomerular ultrafiltration E) None of the above
5

Which of the following drugs has been associated with
chronic interstitial nephritis? A) Cyclosporine B) Ifosfamide
C) Lithium D) Streptozotocin E) All of the above 6

Which of the following drugs has been associated with

Which of the following drugs has been associated
with chronic interstitial nephritis?
A) Cyclosporine
B) Ifosfamide
C) Lithium
D) Streptozotocin
E) All of the above

Which of the following drugs has been associated with
collapsing glomerulosclerosis?
A) Propylthiouracil
B) Aminoglycosides
C) Pamidronate
D) Radiographic contrast media
E) Hydralazine

The following renal structural-functional alteration is
associated with exposure to radiographic contrast
media:
A) Allergic interstitial nephritis
B) Intratubular obstruction
C) Glomerulosclerosis
D) Acute tubular necrosis
E) Papillary necrosis

All of the following strategies can be used to prevent
radiographic contrast media nephrotoxicity except:
A) Amifostine
B) Acetylcysteine
C) Low osmolality agents
D) Hydration
E) Reduced doses of contrast

The preferred agent for preventing cisplatin-induced
nephrotoxicity is:
A) Fenoldopam
B) Amifostine
C) Dopamine
D) Acetylcysteine
E) Mesna

All of the following drugs are linked to the
development of antineutrophil cytoplasmic antibody
(ANCA)-positive vasculitis except:
A) Hydralazine
B) Allopurinol
C) Warfarin
D) Propylthiouracil
E) Penicillamine

Each of the following statements regarding
aminoglycoside-induced acute tubular necrosis is true
except:
A) Risk factors include prolonged therapy and increased age
B) It manifests as a gradual increase in serum creatinine 4 to
6 weeks after exposure to the drug
C) Patients typically present with nonoliguria, maintaining
urine volumes greater than 500 mL/day
D) Toxicity of various aminoglycosides is related to cationic
charge of the drug
E) “Once-daily” dosing is one method to maintain
antimicrobial efficacy while reducing nephrotoxicity 12

The preferred treatment for a patient with druginduced minimal change glomerular injury
accompanied by interstitial nephritis is:
A) Amifostine
B) Cyclophosphamide
C) Pamidronate
D) Prednisone
E) Hydration

The signs and symptoms of penicillin-induced allergic
interstitial nephritis include all of the following except:
A) Rash, eosinophilia, pyuria
B) Fever, eosinophilia, reduced intraglomerular pressure
C) Fever, rash, eosinophilia
D) Elevated serum creatinine, rash, eosinophilia
E) Hematuria, proteinuria, oliguria

A 60-year-old woman with a 5-year history of NSAID
use is prescribed enalapril and develops acute renal
failure. What is the most likely cause of her renal
failure?
A) Acute allergic interstitial nephritis
B) Chronic interstitial nephritis
C) Minimal change glomerular injury
D) Focal segmental glomerulosclerosis
E) Hemodynamically-mediated renal failure

Potential causes of pseudo-renal failure include all of
the following except:
A) Competitive inhibition of creatinine tubular secretion by
cimetidine
B) Drug induced increase in protein catabolism
C) Direct interference with the enzymatic measurement of
creatinine
D) Increased synthesis and release of creatinine into
serum
E) Competitive inhibition of creatinine tubular secretion by
trimethoprim
Glomerulonephritis

In a patient with nephrotic syndrome, which of the
following is not expected to be present?
A) Proteinuria
B) Edema
C) Hyperlipidemia
D) Hypercoagulable state
E) Hematuria

Which of the following is not expected to reduce
proteinuria when used for patients with
glomerulonephritis?
A) Angiotensin-converting enzyme (ACE) inhibitors
B) Angiotensin II receptor blockers
C) Nondihydropyridine calcium channel blockers (e.g.,
diltiazem)
D) Dihydropyridine calcium channel blockers (e.g.,
nifedipine, amlodipine)
E) All of the above are expected to reduce proteinuria

Treatment of which of the following is expected to
reduce the progression of renal failure in patients
with glomerulonephritis?
A) Edema
B) Proteinuria
C) Hyperlipidemia
D) Coagulopathy
E) Hematuria

ACE inhibitors are often used in patients with
glomerulonephritis because of their ability to
reduce:
A) Proteinuria
B) Blood pressure
C) Immunologically induced glomerular damage
D) Both A and B
E) All A, B, and C

Intravascular thrombosis is a common and serious
complication of nephrotic syndrome associated with
which of the following glomerular disease?
A) Minimal-change nephropathy
B) Focal segmental glomerulonephritis
C) Membranous nephropathy
D) Immunoglobulin A nephropathy
E) Membranoproliferative glomerulonephritis

Which of the following glomerulonephritis is more
commonly seen in pediatric patients?
A) Minimal-change nephropathy
B) Focal segmental glomerulonephritis
C) Immunoglobulin A nephropathy
D) Membranous nephropathy
E) Membranoproliferative glomerulonephritis

Which of the following agent is known to be most
effective in inducing remission in patients with recently
diagnosed minimal-change nephropathy?
A) Steroid
B) Cyclosporine
C) Azathioprine
D) Cyclophosphamide
E) Levamisole

Which of the following is not correct regarding the use of
cyclosporine for the treatment of minimal-change
nephropathy?
A) Cyclosporine may reduce lymphokine production by
activated T lymphocytes
B) Cyclosporine may improve the permselectivity of
GBM
C) Cyclosporine is often effective in preventing relapse
D) Cyclosporine is often effective in inducing remission
during relapse
E) Cyclosporine is useful for patients who are steroid
dependent

Compared with minimal-change nephropathy, patients
with focal segmental glomerulonephritis are:
A) More likely to be adults
B) Less responsive to steroid treatment
C) More likely to develop progressive renal failure
D) Only A and B above are correct
E) All A, B, and C above are correct

In patients with mild focal segmental glomerulonephritis,
which of the following is (are) commonly used?
A) ACE inhibitors
B) Angiotensin II receptor blockers
C) Immunosuppressive agents
D) Both A and/or B can be used
E) All A, B, and C are necessary to induce remission

Fish oil may be beneficial in certain patients with which
of the following types of glomerulonephritis?
A) Minimal-change nephropathy
B) Focal segmental glomerulonephritis
C) Immunoglobulin A nephropathy
D) Membranous nephropathy
E) Membranoproliferative glomerulonephritis

Which of the following is correct with respect to
treatment for membranous nephropathy?
A) Spontaneous remission is common, and steroid treatment alone
is commonly used to reduce proteinuria and progression of disease
B) Spontaneous remission is common, and steroid treatment alone
is not effective in reducing proteinuria and progression of disease
C) Spontaneous remission is unlikely, and steroid treatment is
needed to reduce proteinuria and progression of disease
D) Spontaneous remission is unlikely, and steroid treatment alone is
not effective in reducing proteinuria and progression of disease
E) Steroid and cytotoxic agents are commonly needed to induce
remission

A patient with IgA nephropathy who has normal renal
function, isolated micro-hematuria, and proteinuria less
than 1 g/day should be:
A) Observed closely without specific treatment
B) Given fish oil
C) Given steroid treatment
D) Given cytotoxic agents
E) Given cyclosporine

Which of the following is not normally considered when
selecting the optimal treatment for patients with lupus
nephritis?
A) Type of underlying lesion
B) Disease activity according to pathologic findings
C) Severity of symptoms
D) Duration of symptoms
E) All of the above are commonly considered

Which of the following is frequently used for chronic
maintenance treatment of lupus nephritis?
A) Steroid
B) Cytotoxic agent
C) Cyclosporine
D) Mycophenolate mofetil
E) Fish oil

Monoclonal antibodies has been evaluated for the
treatment of which of the following glomerular disease?
A) Minimal-change nephropathy
B) Focal segmental glomerulonephritis
C) IgA nephropathy
D) Lupus nephritis
E) Poststreptococcal glomerulonephritis

The presence of crescents in glomeruli of patients with
rapidly progressive glomerulonephritis (RPGN)
indicates:
A) Severe disease requiring early aggressive therapy
B) Type I RPGN
C) Type II RPGN
D) Type III RPGN
E) The need for close observation but no specific
treatment

Which of the following is (are) known to cause
glomerulonephritis?
A) Group A streptococci
B) Hepatitis C virus
C) HIV
D) Parasites
E) All of the above

Antibiotic treatment after poststreptococcal
glomerulonephritis may:
A) Prevent subsequent poststreptococcal
glomerulonephritis
B) Reduce severity of disease
C) Prevent the spread of infection to family members
D) Both B and C
E) Both A and C
‫تنظیم دوز داروها در نارسایی کلیوی‬
Drug Therapy Individualization with Renal Insufficiency

Which of the following is the predominant mechanism
by which the bioavailability of some drugs is
increased in patients with severe stage 5 chronic
kidney disease?
A) Decreased renal clearance
B) Decreased first-pass metabolism
C) Increased volume of distribution
D) Increased plasma protein binding

Which of the following drugs will most likely have an
increased fraction unbound in patients with end-stage
renal disease (ESRD)?
A) Clonidine
B) Disopyramide
C) Phenytoin
D) Propafenone

Unbound drug concentrations for drugs that are
highly protein bound should not be used to monitor
therapy and make dose modifications in patients with
chronic kidney disease.
A) True
B) False

The metabolism of many drugs is altered in patients
with renal insufficiency. Select which of the following
statements is true regarding this phenomenon:
A) The onset of the effect on metabolism is rapid, thus there is no
difference between patients with acute and chronic kidney disease
B) The observed reductions in nonrenal clearance in CKD patients are
not proportional to the reductions in glomerular filtration rate (GFR)
C) The effect on metabolism is greater in patients with ARF than in
patients with ESRD
D) Data suggest a differential effect on the individual CYP450
enzymes with the activity of some enzymes being reduced, although
the activity of other enzymes is not affected
E) The degree of increase in drug metabolism is highly variable

Which of the following statements regarding renal
drug excretion is true?
A) The P-glycoprotein transport system in the kidney is also
involved in the tubular secretion of anionic drugs
B) The decrease in renal drug clearance for drugs that are
primarily secreted will be proportional to the reduction in
glomerular filtration rate
C) The renal clearance (CLr) of a drug that undergoes
secretion (CLr >300 mL/min) is likely to be reduced more in a
patient with glomerulonephritis than in one with tubulointerstitial
renal disease
D) A patient with acute tubular necrosis will have lower ßlactam renal clearance than a patient with chronic
glomerulonephritis (assuming comparable CLcr)

An HIV-infected patient who has a creatinine clearance
(CLcr) of 34 mL/min is to receive tenofovir for the
treatment of human immunodeficiency virus (HIV) infection
(in combination with other antiretroviral agents). After
intravenous administration of tenofovir, approximately 75%
of the dose is recovered in the urine as unchanged drug.
Based on this information, calculate the most appropriate
dosing interval for this patient with impaired renal function.
Assume the normal dosing interval (TN) is every 24 hours.
A) 12 hours
B) 24 hours
C) 36 hours
D) 48 hours
E) 72 hours

A 72-year-old, 65-kg man is to receive ciprofloxacin.
The usual dose of ciprofloxacin is 500 mg twice daily
for patients with normal renal function. Calculate a
new dose to be given every 12 hours. The patient’s
measured CLcr is 48 mL/min, and the relationship
between ciprofloxacin oral clearance (CL/F) and renal
function is CL/F (mL/min) = 2.83 (CLcr) + 363.
A) 125 mg every12 hours
B) 250 mg every 12 hours
C) 375 mg every 12 hours
D) 500 mg every 12 hours

A.C. is to receive amoxicillin for a suspected urinary
tract infection. His measured CLcr is 45 mL/min, and
the clearance and fraction of drug eliminated renally
unchanged of amoxicillin in a patient with normal
renal function (CLcr = 120 mL/min) are 221 mL/min
and 86%, respectively. What do you project his
clearance of amoxicillin will be?
A) 150 mL/min
B) 119 mL/min
C) 102 mL/min
D) 83 mL/min
E) 19 mL/min

Which of the following statements concerning the
relative efficiency of drug removal by dialysis is false?
A) Peritoneal dialysis is less effective than hemodialysis at
removing drug substances
B) High-flux hemodialysis drug clearances are greater in
ARF patients than in CVVHD
C) The clearance (mL/min) values of all drugs with
continuous renal replacement therapies are smaller than
the values reported with conventional hemodialysis
D) CVVH clearance of a given drug always will be less
than CVVHDF clearance
E) Conventional hemodialysis produces greater removal of
most drugs when compared with high-flux hemodialysis

Which of the following drugs is least likely to be
removed by conventional hemodialysis (i.e.,
hemodialysis using a cellulose membrane)?
A) Foscarnet (MW = 94; Vd = 0.7 1/kg; Fraction bound = 0.17)
B) Cefazolin (MW = 454; Vd = 0.2 1/kg; Fraction bound = 0.50)
C) Ceftriaxone (MW = 450; Vd = 0.2 1/kg; Fraction bound =
0.90)
D) Inulin (MW = 5,200; Vd = 0.05 1/kg; Fraction bound = 0.00)

Which of the following is the optimal approach to
determine the effect of hemodialysis on the
pharmacokinetics of a new drug?
A) Determine the half-life of the drug during dialysis and compare with
the value observed in those with normal renal function
B) Calculate the recovery clearance, CL = amount in dialysate/AUC0-t
in serum during dialysis
C) Collect the dialysate and calculate the ratio of the concentration of
the drug in dialysate to concentration of drug in blood
D) Measure the blood clearance, CLblood = Qb[(CLarterial –
CLvenous)/CLarterial]
E) Determine the total-body clearance of the drug when administered
on a nondialysis day relative to the total-body clearance observed
when the drug is given during dialysis

T.D. is a 34-year-old, 60-kg man with a residual CLcr of
8 mL/min who has been receiving hemodialysis for 3
months. He was just started on gabapentin 300 mg
orally every 8 hours by his neurologist. What dosage
regimen would you recommend given that the volume
of distribution is 0.7 L/kg, the fraction eliminated in the
urine unchanged is 90%, and protein binding is 3%?
A) 300 mg every 8 hours
B) 150 mg every 8 hours
C) 50 mg every 8 hours
D) 300 mg every 24 hours
E) 300 mg every 48 hours

S.M. is a 58-year-old, 75-kg man with a residual CLcr of 9
mL/min who has been receiving hemodialysis for 9
months. His nephrologist wants to start him on gentamicin
(initial dose 150 mg IV over 0.5 hours) to treat an infected
foot. What do you project his serum concentration will be
in 40 hours, just prior to his next dialysis session, given
that the volume of distribution is 0.3 L/kg, the
CLgentamicin = CLcr × 0.983, and protein binding is 3%?
A) 8.3 mg/L
B) 6.6 mg/L
C) 4.8 mg/L
D) 2.5 mg/L
E) 1.8 mg/L

If the serum gentamicin concentration was determined to
be 3.6 mg/L, what do you project S.M.’s gentamicin serum
concentration will be after 4 hours of dialysis with a highflux dialyzer for which the reported gentamicin clearance is
116 mL/min?
A) 0.7 mg/L
B) 1.1 mg/L
C) 1.6 mg/L
D) 2.0 mg/L
E) 2.5 mg/L 15

The serum gentamicin concentration after the end of
dialysis is determined to be 1.8 mg/L. What is the
supplemental dose that should be given to achieve a
target peak concentration of 8 mg/L? Calculate the dose
using the simplified approach.
A) 75 mg
B) 90 mg
C) 110 mg
D) 220 mg
Prevention

Identify at risk patients


Optimise renal perfusion


IV fluids, inotropes, central line
Maintain adequate diuresis


pre-existing CRF, diabetes, jaundice, myeloma, elderly
Mannitol, frusemide, NOT dopamine
Avoid nephrotoxic agents

ACE inhibitors, NSAIDS, radiological contrast,
aminoglycosides
Interventions to Prevent Contrast Nephrotoxicity
Which is best proven prevention strategy?

NS 1-2 mL/kg/hr starting 12 hours pre and
continued 12 hours post-procedure

Sodium Bicarbonate 150mEq/L D5W infused at
3mL/kg/h x 1 hours pre, then 1mL/kg/h x 6 hours
post-procedure

N-acetylcysteine 600mg PO BID x 4 doses on
day prior to and on day after admin of contrast
Which of the following is an example of a
preventive measure to avoid nephrotoxicity?

Using alternatives to nephrotoxic drugs

Adequate hydration

Avoiding use of contrast dye in patients taking aminoglycosides

Recognizing a 50% rise from baseline creatinine is considered
acute renal failure

All of the above are correct
Drug-Induced Acute Renal Dysfunction

Acute Renal Failure
- Prerenal
NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
- Intrinsic – ATN vs AIN
ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media
AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine,
NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
- Obstructive
Methotrexate, Acyclovir, Indinavir, Rhabdomyolysis (Statins)
CLASSIFICATIONS

Anuric: < 50ml/day urine output

Oliguric: 50-400ml/day urine output

Non-oliguric: >400ml/day urine output
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