THE MALIGNANT COUPLE:

PHENACETIN
NEPHROPATHY-
UROTHELIAL TUMORS

Scientific coordinators:
MITITIUC IRINA,PhD
HOGAS SIMONA,MD
Author: Pricop Mariana
Coauthors: Pricop Daniela
Biru Diana
-Madalina
PHENACETIN
• Phenacetin, introduced in
1887, was used principally
as an analgesic, and was
one of the first synthetic
fever reducers to go on the
market.

• It is also known
historically to be the first
analgesic without anti-
inflammatory properties.
PHENACETIN
• Phenacetin was widely used until the third quarter of
the twentieth century, but was then largely replaced
by non-carcinogenic drugs.

• Some branded phenacetin-based preparations

continued to be sold, but with the phenacetin
replaced by safer alternatives.

• A popular brand of phenacetin was Roche's Saridon,

which was reformulated in 1983 to contain
propyphenazone, paracetamol and caffeine.

• Paracetamol is a metabolite of phenacetin with

similar analgesic and antipyretic effects, but the new
formulation has not been found to have phenacetin's
carcinogenicity.
PHENACETIN
NEPHROPATHY-
UROTHELIAL TUMORS
• 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.

• Risk factors include:

* Use of OTC analgesics containing more than one
active ingredient
* Chronic headache
* Chronic backache or musculoskeletal pain
* Emotional or behavioral changes
* History of dependent behaviors including smoking,
alcoholism, and excessive use of tranquilizers
* Pain with menstrual periods
PHENACETIN
NEPHROPATHY-
UROTHELIAL TUMORS
The cardinal features of the Analgesic
Syndrome:
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS

• In general, phenacetin is metabolized by

acetaminophen after dehydration in the liver and
thereafter it undergoes either sulfate acid or
glutamic conjugation in the kidneys;

• The remaining free phenacetin is then excreted into

the urine. Excessive acetaminophen results in the
depletion of glutathione and the accumulation of
acetaminophen oxides and an activated reaction
may thus occur.
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
• The reflux of acetaminophen into the kidneys and its
concentration in the renal medulla contribute to the
inhibition of prostaglandin synthesis, thus leading to
renal medullary ischemia and renal papillary
necrosis.

• The resulting tubular obstruction promotes an

enlargement of the renal cortex and the formation of
a histological background of interstitinal nephritis.
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
• Regarding the development of urotherial tumor
associated with phenacetin abuse, N-hydroxylation
products, the intermediate metabolite of phenacetin
such as N-hydroxy-p-phenetidine and 2-
hydroxyphetidine, seemed to be potential
carcinogens.

• The process of carcinogenesis in urotherium by

exposure of the potential carcinogens in phenacetin
metabolic products are considered to take at least
10 years under excessive .

• Therefore, almost all reported cases of urotherial

tumor associated with phenacetin abuse had a
history of excessive phenacetin use for more than 10
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
PHENACETIN ABUSE
Double target on
reno-urinary system
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
• Specific kidney injuries
– renal papillary necrosis
- chronic interstitial nephritis
(the neprhopathy is a result from decreased blood flow to
the kidney
rapid consumption of antioxidants subsequent oxidative
damage )

• This damage may lead to progressive chronic renal

failure, abnormal urinalysis
results high blood pressure and anemia. A
proportion of individuals with phenacetin
nephropathy may develop end-stage kidney disease.

• Also the phenacetin abuse is directly related to the

urothelial tumors.
• Phenacetin abuse-daily consume for at least 5
years(minimum total dose=2-7kg)
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS

Drug-induced acute interstitial

nephritis
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS

Papillary necrosis
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS

B.I.,male,65years old,Pascani

• 1978-amputation left leg

• Pain in the amputated leg -> chronical abuse of

phenacetin -3-60 tablets/day for 19 years (30 kg)

• Microscopic hematury-high suspicion of vesical

tumors

• 1997-phenacetin nephropathy
PHENACETIN NEPHROPATHY-
UROTHELIAL TUMORS

S.F.,female,75years old,Iasi

• Abuse of phenacetin-headaches->3-6 tablets/day for

20 years(4-8kg)

• 2000-CRF stage 5,peritoneal dialysis

• 2001-after 5 episode of peritonitis->hemodialysis

• 2007-multiple vesical tumors ->endoscopic resection

• 2009-fever with unknown etiology-suspicion of

metastasis
Conclusions
“in memoriam phenacetin nephropathy”

 The asociation between phenacetin and urothelial

tumors is a reality .

 Every patient with phenacetin nephropathy needs

to be closely observed for urothelial tumors

 The cases of phenacetin nephropathy are among

the last ones because products containing
phenacetin the drug was withdrawn from the market
in Western countries in the 1980s and also in Japan
in 2001.

 The evolution is slowly progression to chronic renal

failure

 Stoping the phenacetin ingestion can stabilize the

Stop to the consumption of over the
counter pain medications!

It could affect permanently and

irreversible your reno-urinary system!
THANK YOU!