We questioned 180 patients with end-stage renal disease on maintenance haemodialysis, chronic ambulatory peritoneal dialysis and those who had undergone renal transplantation at the Department of Nephrology, General Hospital, Kuala Lumpur. Twelve patients (6.7%) had consumed excessive quantities ofanalgesics prior to the institution oflong-term dialysis or transplantation. Primary renal disease was considered to be analgesic nephropathy in seven patients (3.9%); in five patients (2.8%), analgesic abuse could have been a contributory factor to end-stage renal failure. Analgesic nephropathy is hence an uncommon cause of end-stage renal disease in Malaysia. However, it is important to be aware of the problem and to institute preventive measures as the cost of treatment for end-stage renal disease is prohibitive

A. Hasnah

Abu Bakar Suleiman

C. M. D. Shaharom

D. Nurul Ashiqeen

Dr. M. Segasothy

H. Siti Sabzah

Jalan Raja Muda

M. Segasothy

Mbbs (mon. Mmed

N. Salbiah

S. I. Yun

S. Nordin

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Med. J. Malaysia Vol. 41 No. 2 June 1986
ANALGESIC NEPHROPATHY AS A CAUSE OF
END-STAGE RENAL DISEASE IN MALAYSIA
M. SEGASOTHY
ABU BAKAR SULEIMAN
A. HASNAH
N. SALBIAH
C.M.D. SHAHAROM
M. Segasothy, MRCP (UK)
Lecturer, Department of Medicine
Faculty of Medicine
Universiti Kebangsaan Malaysia
Jalan Raja Muda
50300 Kuala Lurnpur, Malaysia
Abu Bakar Suleiman, MBBS (Mon.). MMed
FRACP
Consultant Nephrologist and Head, Department of
Nephrology, General Hospital
50586 Kuala Lumpur, Malaysia
A. Hasnah
N. Salbiah
C.M.D. Shaharom
H. Siti Sabzah
D. Nurul Ashiqeen
S. I. Yun
S. Nordin
Medical Students, Universiti Kebangsaan Malaysia
Jalan Raja Muda
50300 Kuala Lumpur, Malaysia
Correspondence:
Dr. M. Segasothy
Department of Nephrology
Royal Melbourne Hospital
Parkville, Melbourne
Victoria 3052, Australia
134
H. SITI SABZAH
D. NURUL ASHIQEEN
S.1. YUN
S. NORDIN
SUMMARY
We questioned 180 patients with end-stage
renal disease on maintenance haemodialysis,
chronic ambulatory peritoneal dialysis and those
who had undergone renal transplantation at the
Department of Nephrology, General Hospital,
Kuala Lumpur. Twelve patients (6.7%) had con-
sumedexcessive quantities ofanalgesics priorto the
institution oflong-term dialysis or transplantation.
Primary renal disease was considered to be
analgesic nephropathy in seven patients (3.9%);
in five patients (2.8%), analgesic abuse could have
been a contributory factor to end-stage renal
failure. Analgesic nephropathy is hence an
uncommon cause of end-stage renal disease in
Malaysia. However, it is important to be aware
of the problem and to institute preventive
measures as the cost of treatment for end-stage
renaldisease is prohibitive.
INTRODUCTION
Analgesic nephropathy (AN) is an important
cause of renal failure in many countries. However
there is marked geographical variation in the
prevalence of AN between countries and even
between different areas within the same country.
The reported figures for AN causing terminal
renal failure requiring dialysis and transplantation
vary from 2.5% in Canada/ 4.8% in Scotland.f
2-10% in the United States," 9.6% in Sweden,
14% in Denmark, 16.7% in Switzerland," 21.5%
in Austratla." and ashigh as44% in Belqlum."In the United States, the proportion of patients
with end-stage renal disease (ESRD) with the
diagnosis of AN varies considerably from region
to region, the figures ranging from 2% in
Californla," 6.25% in the Philadelphia region 7 and
10% in North Carolina." In a retrospective study
of analgesic intake, it was demonstrated that
2.8% of patients with ESRD receiving maintenance
haemodialysis in the Washington, D.C. area had
consumed excessive quantities of analgesic
compounds prior to institution of dialysis."
Likewise in Australia, there is marked regional
variation in the prevalence of AN, with Queens-
land and New South Wales having a higher propor-
tion than the other states.' 0
No work has been done in any Asian country
to determine the proportion of patients with
ESRD caused by AN. The present study was
therefore undertaken to determine the pattern
of analgesic consumption in patients with ESRD
requiring dialysis and transplantation in Malaysia.
MATERIALS AND METHODS
The study population consisted of patients
with ESRD on maintenance haemodialysis, chronic
ambulatory peritoneal dialysis (CAPD) and those
who had undergone renal transplantation at the
Department of Nephrology, General Hospital,
Kuala Lumpur. Data on analgesic consumption
by the patients in this study were obtained by
interview using standardised questionnaires by
the authors.
Patient charts were also reviewed to determine
the cause of renal failure, urographic abnorma-
lities, renal biopsy findings and other relevant
investigations performed. Significant analgesic
abuse was defined as "a minimum total of 2 kg of
aspirin, phenacetin, paracetamol and other com-
pounds alone, or in combination prior to the
institution of long-term dialysis or transplanta-
tion".
RESULTS
Glomerular disease was considered to be the
cause of end-stage renal failure in 56 (31.1%),
135
tubulointerstitial disease in 25 (13.9%), vascular
disease in nine (5.0%), systemic disease in 12
(6.7%), and "unknown" in 78 (43.3%)(Table I).
The high incidence of "unknown" aetiology in
our study is due to the late presentation of many
patients when diagnostic procedures cannot be
performed. One patient was diagnosed as having
AN on the basis of a history of excessive con-
sumption of analgesics (pafacetarnoll and the
demonstration of renal papillary necrosis on
intravenous urogram.
Significant analgesic abuse was noted in 12
patients (6.6%) (Table I). There were seven males
and five females with an age range of 31 to 61
TABLE I
DIAGNOSIS OF PATIENTS WITH END-STAGE
RENAL FAILURE
Classification Frequency
Glomerulonephritides (GN) 56 131.1%)
Chronic GN 33
Membraneous GN 4
Focal glomerulosclerosis 6
Rapidly progressive GN 5
Mesangiocapillary GN 6
Post-streptococcal GN 2
Tubulointerstitial Nephropathies 25 (13.9%)
Analgesic nephropathy 1
Chronic pyelonephritis 3
Vesico-ureteric reflux 4
Polycystic kidney disease 4
Chronic urate nephropathy 7
Obstructive nephropathy 6
Vascular Nephropathies 9 15.0%)
Nephrosclerosis 9
Systemic Diseases 12 16.7%)
Diabetes mellitus 8
Systemic lupus erythematosus 4
Unknown 78 (43.3%)
Total 180 (100.0%)years (mean 39.2 years). Paracetamol is the
commonest analgesic consumed, seven having
consumed paracetamol singly (2,100 to 6,600 g)
and one having consumed paracetamol (1,500 g)
in combination with Chap Harimau (Tiger Brand)
(1,400 g) which is the local proprietary compound
analgesic containing aspirin, phenacetin and
caffeine (Table 11). One patient had consumed
only Indomethacin (7,300 capsules). Two patients
were unable to specify the amount of analgesics
they had had consumed but they did state that
they have been consuming analgesics excessively,
one for nine years and the other for 28 years. The
major reasons for consuming analgesics were
headache for seven patients, and arthritis in three
patients.
Primary renal disease was considered to be
AN in seven patients (3.9%) on clinical grounds.
In five patients (2.8%) of whom two had renal
calculi, two had chronic glomerulonephritis and
one had polycystic kidney disease, analgesic
abuse could have been a contributory factor
in the development of end-stage renal failure.
DISCUSSION
Previous studies have shown that analgesic abuse,
renal papillary necrosis and AN are prevalent in
TABLE II
AMOUNT OF ANALGESICS CONSUMED
the Malaysian population. In a survey conducted
on three different groups of population, it was
found that 0.5 - 2.0% of the people surveyed
had consumed more than 2 kg of analgesics,
an amount sufficient to cause renal damage.!!
In a retrospective radiological study of the 1,011
intravenous urograms done at the Department
of Nephrology, General Hospital, Kuala Lumpur
from 1968 to 1981,20 had renal papillary necrosis
of which two were due to diabetes mellitus and
the rest due to AN.! 2
In a prospective study performed on patients
admitted to the medical and renal wards of
General Hospital, Kuala Lumpur, from January
1982 to February 1983, 12 new cases of AN were
docurnented.l :' Since then a further 13 cases have
been documented.' 4
This study has demonstrated that 6.7% of
patients with ESRD receiving maintenance dialysis
or transplantation in Malaysia consumed excessive
quantities of analgesic compounds prior to the
institution of dialysis or transplantation. Primary
renal disease was considered to be AN in 3.9% of
patients, and in 2.8% of patients, consumption of
analgesic compound may have contributed to
further renal deterioration. In Malaysia, analgesic
consumption would appear to be an uncommon
cause of ESRD: These figures however may not
reflect the true percentage of patients with ESRD
due to AN as it is well known that many patients
with AN will deny analgesic abuse.' 5
* Unidentified (5,100 tab) - 1; Indomethacin (7,300 cap)
- 1; Unable to remember - 2.
Amount
(kg)
0 0.25
0.26 0.50
0.51 1.0
1.1 2.0
2.1 5.0
> 5.1
Excessive
No.
16
15
7
5
4
4
4*
Percentage
of total
population
8.9
8.3
3.9
2.8
2.2
2.2
2.2
136
There is considerable international and regional
variation in the apparent incidence of AN. One of
the most likely causes for this is the variation in
the consumption of analqesics.! 6 There is however
a problem in attempting to define the incidence
of AN as there is no common agreement on the
definitions of abuse and use of analgesics, while
the actual drugs taken and the various combina-
tions used vary widely, even in different parts of
the same country.
Authors employ different criteria concerning
the frequency of analgesic intake such as daily,
several times a day, at least twice weekly, etc.,
and some surveys are carried out on a communityTABLE III
CLINICAL CHARACTERISTICS OF PATIENTS EXCESSIVE ANALGESIC CONSUMPTION
Asthma 2,100
Headache 2,900
Headache, 4,400
backache
Headache 5,500
Headache 5,700
Gout 5,100
(tab)
Headache Excessive
Headache 2,400
Giddiness 6,600
6-8/day, 3 vrs 4.5 yrs
101day, 3 y rs 6.5 yrs
2-3/day, 14 yrs 2.5 y rs
2/day, 7 yrs 6 mths
28 yrs 5 mths
4/wk, 23 yrs 11 mths
2-6/day, 9 vrs 4 yrs
Patient's Cause of Analgesics
age (vr.) end-stage consumed
and sex* renal disease
381 M AN Paracetamol
381 M AN Paracetamol+
Chap Harimau
30 1 F AN Paracetamol
341 M AN Paracetamol
32 1 F AN Paracetamol
611 M AN Unidentified
421 M AN Unidentified
341 M Calculi Paracetamol
31 1 F Chronic Paracetamol
Glomeru-
lonephjitis
Reason Amount
(g)
Dose
8/wk, 10 yrs
2/day, 4 yrs
Duration
of dialysis/
transplantation
11 mths
1.5 yrs
44 1 F Chronic Paracetamol Headache 5,100 2/day, 14 yrs 2.5 yrs
Glomeru-
"
lonephritis
31 / M Calculi, Indomethacin Gout 7,300 2/day, 10 vrs 5 mths
gout (cap)
4
55 1 F Polycystic Paracetamol Arthralgia Excessive 9 yrs 8 vrs
kidney
*M - Male; F - Female.
basis, while others have been conducted in highly
selected groups of individuals such as factory and
office workers or hospital patients.l " The varia-
tion in the consumption of analgesics might be
determined by local, social, cultural factors as
well as the role played by advertislno.l "
Variation in factors which modify suscepti-
bility to the nephrotoxicity might also account
for the geographical variation in the true incidence
ofAN.
1 6
Recognition of the disease and awareness of
137
analgesic abuse is a very important factor account-
ing for the variation in the incidence of AN. AN
is often not reooqnised and this is underlined by
the recent "discovery" of the condition in a
number of countries where it was formerly consi-
dered to be rare.
1 6 The conclusion of many
authors is remarkably similar in that they all
acknowledge that AN is a major problem which
has not been appreciated oreviouslv.' 6
We conclude that analgesic abuse and AN do
exist in Malaysia. Significant consumption of
analgesics occurred in 6.6% of our patients withESRD requrnnq dialysis or transplantation. In
3.9% of the patients the primary renal disease
was considered to be AN whilst in 2.8% of the
patients analgesic abuse could have been a contri-
butory factor in the development of end-stage
renal failure. Although analgesic consumption is
an uncommon cause of ESRD its significance
cannot be underestimated. AN is essentially a
preventable disease and the long-term outlook is
optimistic if patients stop analgesic abuse as renal
function will improve with the cessation of drug
consumption.
1 7 Thus it is important to be aware
of the existence of analgesic abuse and to institute
preventive measures as well as to advise patients
to stop the regular use of analgesics as the cost of
definitive treatment for ESRD is prohibitive.
ACKNOWLEDGEMENT
We thank the staff of the Department of
Nephrology, in particular T. Satkunasingam, Lim
Poh Poh and Chong Kwai Fong for having
provided cooperation in this study, and Saiyah
for typing the manuscript.
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