3. Introduction
Medications are a common cause of kidney injury .
The medication history is an absolutely fundamental component of renal
medicine.
Consideration should be given when any drug prescribed for patient with
renal insufficiency .
4. Risk factors for drug nephrotoxicity
The innate kidney
toxicity of the offending
agent.
Drug factorsKidney factors Patient factors
Old age
Female sex
CKD
AKI
High renal blood flow,
which approximates 25% of
cardiac output, exposes the
kidney to significant drug
conc
Insoluble drug and/or
metabolite with
intratubular crystal
Precipitation
Combination between
nephrotoxic drugs
Volume depletion:
Vomiting, diarrhea, poor
fluid intake, fever,
diuretic use, or effective
volume depletion (CHF,
liver disease with ascites)
Immune response genes
increasing allergic drug
response
Biotransformation of drugs
to nephrotoxic metabolites
and reactive oxygen species
(aminoglycoside –platinum )
Extensive tubular cell
uptake of potential
nephrotoxic drugs via
transport systems
5. Pathophysiology of drug-induced nephropathy
Multiple drugs can affect the same site, e.g. acute tubular necrosis, can be
caused by aminoglycosides and amphotercin B
dyes and many other drugsA single drug can affect different sites in the kidney, e.g. NSAIDs can cause
interstitial nephritis ,glomeruloral disease and prerenal azotemia
6. Classification of drug induced kidney
Injury
Therapeutic agents associated with kidney injury can be classified based
on the category of the agent or the clinical kidney syndrome .
2-Acute
3-Acute
1-Prerenal/
functional
2-Acute
tubular
necrosis
(ATN )
3-Acute
interstitial
nephritis
(AIN )
5-
Glomerular
Disease
6-
Obstructive
nephropathy
4-Chronic
interstitial
nephritis
7. 1- Drug induce Functional
(Hemodynamically mediated) AK I
Caused by a decrease in intraglomerular pressure through the
vasoconstriction of afferent arterioles or the vasodilation of efferent
arterioles
NSAIDsNSAIDs
Cyclosporin
Tacrolimus
ACEI
ARB
8. 1-Functional (Hemodynamically mediated) AK I
NSAID Calcineurin inhibitor
Cyclosporin
Tacrolimus
ACE I /ARB
Mechanism VC (afferent
arteriole)
VC (afferent
arteriole)
VD of the efferent arteriole
presentation Increase, SCr
Can occur within
days of starting
therapy
Increase, SCr
Can occur within
days of starting
therapy
S.Cr increases within 3-5
days up to 30%
therapy therapy
Prevention Paracetamol Monitor serum
cyclosporine and
tacrolimus
concentrations
-Initiate low dose+ gradual
titration
-Monitor SCr
-Avoid use of concomitant
NSAIDs.
10. 2-Drugs induce acute tubular necrosis
Aminoglycosides Cisplatin & carboplatin Amphotercin
Gradual rise in SCr
concentrations after 6–10
days of therapy
-Electrolyte wasting
SCr peaks 10–12 days
after therapy starts
-Electrolyte wasting
-scr increase after
administration of 2-
3 gm
-Electrolyte wasting
-Avoid use in high-risk Use smallest dose possible Intravenous
Presentation
afferentafferent
arteriolar vc ,
causing
a hemodynamic
reduction in the
GFR.
-Avoid use in high-risk
patients.
-Maintain adequate
hydration.
-Use extended-interval
(once-daily)
Use smallest dose possible
and decrease frequency of
administration
-Aggressive intravenous
hydration: 1–4 L within
24 hours of high-dose
cisplatin or carboplatin
Intravenous
hydration:Nacl
0.9%
At least 1 L/day
before each dose
prevention
11. 3-Tubulointerstitial disease
Involves the renal tubules and the surrounding interstitium
1-Acute (allergic)
-Allergic hypersensitivity reaction that affects the
interstitium of the kidney
-Classic” presentation of skin rash, arthralgia,
and eosinophilia is more commonly occurs in association
with certain drugs, such as penicillin derivatives,
2-Chronic
(Irreversible )
-Shows interstitial
fibrosis
with certain drugs, such as penicillin derivatives,
compared with NSAIDs
No clinical symptoms or signs are sensitive
or specific enough to establish a definitive diagnosis.
-The GFR typically falls 7 to10 days after starting the
medication.
-Drugs such as the NSAIDs and proton pump inhibitors
(PPIs) may not develop AIN for many weeks or months
after initial exposure
-Slow decline in
kidney function
-No systemic
Symptoms
14. Lithium
Lithium
Chronic tubulointerstitial nephritis
Most commonly encountered after >= 10 years of therapy
Risk factor Long duration of use
Elevated serum concentrations
Repeated episodes of AKI from lithium toxicity.
presentation (a) Often asymptomatic, with slow progression over years
(b) May be recognized by slow increases in blood pressure (BP) or
BUN and SCr
Prevention Maintaining the lowest serum lithium concentrations possible,
avoiding dehydration, and monitoring kidney function closely
15. 5-Glomerular disease
Proteinuria is the hallmark of glomerular disease and may occur with or
without a decrease in GFR.
NSAIDs Minimal change ( most common ) -membranouse
nephropathy is a relatively rare complication
Lithium Minimmal change -focal segmental glomerulosclerosisLithium Minimmal change -focal segmental glomerulosclerosis
Interferon (α, β, γ) A variety of glomerular lesions, including minimal
change disease and focal segmental glomerulosclerosis
16. 6-Postrenal
(obstructive nephropathy )
Renal tubular obstruction Extrarenal urinary tract obstruction
Tissue degradation
product
Drugs precipitation
Uric acid Sulfonamides
Results from obstruction of the flow of urine after glomerular filtration
BPH can
worsened by
anticholinergic
Bladder outlet or
ureteral
obstructionUric acid
intratubular
precipitation after
tumor lysis after
chemotherapy
Sulfonamides
Methotrexate
Acyclovir
Ascorbic acid
Myoglobin
intratublar
precipitatons after
drugs induce
rhabdomyolysis
(Statin-fibrate)
Needle like crystals
observed in
leukocytes found on
urinalysis can
prompt diagnosis
anticholinergic obstruction
from fibrosis
after
cyclophosphamide
for hemorrhagic
cystitis
--------------------- Prevention
Hydration and
concomitant
Mesna
administration
17. Pseudo-nephrotoxicity
Drugs that inhibit the
tubular secretion of Cr
Trimethoprim, cimetidine
Drugs that increase BUN Corticosteroids, tetracycline
Drugs that interfere with SCr
assay
Cefoxitin and other cephalosporins
20. Sodium phosphate preparations
Agent Use Adverse events Comment
Sodium
phosphate
preparations
as purgatives
for bowel
cleansing before
diagnostic
colonoscopy.
-AKI
-Hypocalcemia and
hyperphosphatemia
Occur with excessive
dosing or use in
patients with underlying
kidney disease.
oral sodium
phosphate-based
products should not be
used in patients with
underlying
kidney disease, volume
depletion, or
electrolyte
abnormalitiesabnormalities
Recently, the
possibility of CKD
developing in patients
receiving phosphate-
containing enemas was
raised. Clinicians
should remain vigilant
for this possibility.
21. Case 2
.
Iv acyclovir 10 mg/kg /dose q 8hr
Duration 14- 21 day
30 -year-old man with CNS infection (encaphlitis)
75 kg
Normal kidney function
No hepatic impairment
Duration 14- 21 day
Do you need any precautions during
administration ?
22. Case 2 cont.,
.
For iv infusion
Avoid rapid IV infusion
Infuse over 1 hr to avoid renal damage
Maintain adequate hydration of the patient
Crystal nephropathy
Typically develops within 24 to 48 hours of acyclovir administration,
with an incidence of 12% to 48% when acyclovir is administered as a
rapid IV bolus .
23. Case 3
.
Regarding vancomycin adverse effects, which one of the following choices
is CORRECT?
A. Acute kidney injury (AKI)
B. Ototoxicity in combination with aminoglycosides
C. Red man syndrome
D. Thrombocytopenia
E. All of the above
24. Case 4
.
-Both triamterene and amiloride are potassium sparing
diuretics, but triamterene is more likely to cause what
problem not seen with amiloride?
1. Increased calcium nephrolithiasis
2. Increased uric acid nephrolithiasis
3. Less diuresis compared to Amiloride3. Less diuresis compared to Amiloride
4. Metabolite caused nephrolithiasis
25. Case 5
Which one of the following drugs is associated with stone
formation?
A. Vitamin C
B. Acyclovir
C. Indinavir
D. All of the above
26. Case 6
72-year-old man with bipolar disorder and hypertension is treated
with lithium (Li). His physician added enalapril 10 mg/day for
improvement of his hypertension and possible congestive heart
failure.
Two months later, he was confused and admitted to the hospital withTwo months later, he was confused and admitted to the hospital with
LI toxicity.
27. Case 6 cont.,
Which one of the following choices explains his Li toxicity?
A. Combination of Li and an angiotensin converting enzyme-inhibitor (ACE-
I) enhances Li toxicity
B. No relationship exists between Li and ACE-Is
C. Combination of an ACE-I and Li enhances estimated glomerular filtration
rate (eGFR)
D. Combination of an ACE-I and Li has no effect on eGFRD. Combination of an ACE-I and Li has no effect on eGFR
E. None of the above
28. Case 7
.
A 26-year-old woman with sickle cell disease with serum creatinine of 1.4
mg/dL (eGFR <30 mL/dL) is admitted for seizure disorder.
She is on meperidine 50 mg BID for pain by his primary care physician. Her
pain was controlled for many weeks. She does not want to change her
medication.
What is the cause of seizure ?
29. Case 8
.
60 year old male admitted to nephrology department
begun on ciprofloxacin for UTI, patient on theophylline for
asthma .
Patient developed confusion , seizure after 3 days of admission .
What is the cause of seizure ?
30. Quinolone antibiotic may decrease the metabolism of
theophylline
Theophylline / Quinolone may augment the seizure producing
potential of each individual agent
Case 8 cont.,
An empiric reduction in the dosage of theophylline ( 25 – 50 % )
Consider using another antibiotic ( other than ciprofloxacin)
32. Case 9
56 year old female CKD – Spontaneous bacterial peritonitis
weight 60 kg - height 160 cm- sCr 2mg/dl
(ceftrixone- cefotaxime)
..
Ceftrixone not avialable in the pharmacy ?
33. Case 9 cont.,
Renal impairment may necessitate a dose reduction, an extension in
the dosing interval, or a combination of both.
Such alterations will depend on the degree of renal dysfunction (or form of
renal replacement therapy).
35. Case 10
.
Oseltamiver dose as a treatment for influenza in different
modalities of dialysis
IHD CAPD
30 mg Immediately and then 30 mg 30 mg immediately as a single dose30 mg Immediately and then 30 mg
after every HD session for 5 days
( Assume 3 hemodialysis sessions in
the 5-days period )
30 mg immediately as a single dose
(Single dose provide a 5days
duration)
36. Case 11
.
Do you need special precautions for this patient ?
60 year old female on regular hemodialysis has catheter realted
blood stream infection(CRBSI ) on tineam (imipenem /
cilastatin ) 500 mg q 12 hr (based on blood culture )
Do you need special precautions for this patient ?
37. Case 11 cont.,
.
Dosing changes in patients with HD may be necessary because of
Drug dosing in hemodialysis
Dosing changes in patients with HD may be necessary because of
-Accumulation caused by kidney failure
-or because the procedure may remove the drug from the circulation
38. Case 12
.
Which is not effectively removed by hemodialysis?
1. Amphetamines
2. Phenobarbital
3. Digoxin
4. Chlorpropamide
39. Case 13
.
Which one of the following drugs does NOT need supplementation
following hemodialysis (HD)?
A. Vancomycin
B. Gentamicin
C. Piperacillin/tazobactam
D. Meropenam
E. PhenytoinE. Phenytoin
40. Case 14
.
55 year old male on Peritoneal dialysis ( PD) admitted to
nephrology
department with Peritonitis
His current medications
Ciprofloxacin Iv
Vancomycin Iv
Calcium carbonate
Ciprofloxacin 250 mg oral q 12hr
Vancomycin Iv
Calcium carbonate
????????
Calcium carbonate
Calcium carbonate
41. Interaction
oral calcium
Salts
ScurlfateSevelemer
Ciprofloxacin should be separated by 2 hr to prevent chelation interactionCiprofloxacin should be separated by 2 hr to prevent chelation interaction
reducing ciprofloxacin absorption .
(Administer ciprofloxacin 1st )
Oral zinic Milk
Oral
magnesium
and alumnium
antacid
42. Case 15
.
35 year old female admitted to nephrology department
Current medication sheet
Azathiopurine
Prednisone ( oral )
Allopurinol
Calcium carbonate
Comment on current medications
Calcium carbonate
43. Case 15 cont.,
.
Azathiopurine
Allopurinol may
increase serum
conc of active
Reduce dose of
azathiopurine to
1/3
To ¼ the usual
dose
Allopurinol
conc of active
metabolite (s) Monitor
Systemic toxicity
(heamatologic
toxicity
, nasuea and
vomiting )
45. Case 16
.
35 year old female , renal transplant , HCV admitted to nephrology department
seek advice due to increase in the serum level of tacrolimus
Current medication sheet
-Tacrolimus
-Myfortic
-Prednisone
Patient has start qureveo for hcv
The nephrologist ask for tacrolimus level
46. Case 16 cont.,
.
Tacrolimus
Ombitasvir
Paritaprevier
Avoid combination
May increase serum conc
of tacrolimus
Management
-When combination
the typical
tacrolimus dose
required to
maintain
therapeutic
ConcParitaprevier
Ritonavir
of tacrolimus Conc
was 0.5 mg
q 7 days
