editorial: special report www.kidney-international.

org

Endemic rise in cases of acute kidney

injury in children in Indonesia and Gambia: OPEN
what is the likely culprit and why?
Tungki Pratama Umar1, Nityanand Jain2 and Henri Azis3
A sudden rise in the cases of acute kidney injury (AKI) has been reported in Indonesia and
Gambia that has been linked to the consumption of tainted syrup medications for cough,
colds, pain, and fever. Preliminary investigations revealed multiple lapses in quality control
during manufacturing including substitution of diethylene glycol (DEG) and ethylene
glycol (EG) for the more expensive but non-toxic solvent glycerol. In this editorial report,
we shed light upon the current situation and urge the investigating authorities to make
those responsible accountable to regain public trust.
Kidney International (2023) 103, 444–447; https://doi.org/10.1016/j.kint.2022.12.004
KEYWORDS: acute kidney injury; cough syrups; diethylene glycol; Gambia; Indonesia
Copyright ª 2022, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the
CC BY license (http://creativecommons.org/licenses/by/4.0/).

1
Department of Medical
Profession, Faculty of Medicine,
Universitas Sriwijaya,
Palembang, Indonesia;
2
Statistics Laboratory, Faculty
of Medicine, Riga Stradiņs
University, Riga, Latvia; and
3
Pediatric Department,
Regional General Hospital Dr.
HM Rabain, Muara Enim,
Indonesia
Correspondence: Tungki
Pratama Umar, Faculty of
Medicine, Sriwijaya University,
Dr. Moh. Ali St, RSMH Complex,
Palembang, Indonesia 30126.
E-mail: tungkipratama@gmail.
com; or Nityanand Jain,
Statistics Laboratory, Faculty of
Medicine, Riga Stradiņs
University, Dzirciema Street 16,
Riga, Latvia, LV-1007. E-mail:
nityapkl@gmail.com
Received 25 October 2022;
revised 5 December 2022;
accepted 6 December 2022;
published online 4 January
2023
T
here has recently been a sudden increase
in the hospitalizations and deaths of
children who developed acute kidney
injury following the consumption of cough and
antipyretic syrups in Indonesia and Gambia.
This situation has not only panicked the
affected societies but has implications beyond
their borders. The World Health Organization
(WHO) is concerned about the possibility of
illegal redistribution of these contaminated
syrups in other international markets.1
What is the current situation?
In Gambia, as of November 1, 2022, 70 deaths
of children, mostly aged <5 years, have been
reported. These deaths were associated with the
ingestion of adulterated anti-histamine and
cough-and-cold syrups, manufactured in a
single batch in 2021 by an Indian pharmaceu-
tical company. The incident prompted the
WHO to issue a global medical product alert
against the 4 contaminated products (Table 1),1
followed by an inspection and shutdown of the
production facility by the Indian authorities.
Gambian authorities have so far been able to
recall about 83% of the tainted syrup bottles.
However, the WHO and the Gambian National
Regulator (Medicines Control Agency) have
advised caution because direct causation has
not yet been established.
Indonesia, on the other hand, has had a
more difficult time dealing with the soaring
number of cases of acute kidney injury–affected
children. As of November 15, 2022, the country
has reported >324 cases along with 199 deaths
(Figure 1), which have been linked to the
consumption of at least 8 locally produced
syrups. Toxicologic testing detected traces of
diethylene glycol (DEG) or ethylene glycol (EG)
in 7 of the 11 tested children, and a kidney
biopsy resulted positive for calcium oxalate, an
alcohol dehydrogenase metabolite of DEG/EG.2
Indonesian authorities have since implemented
a blanket ban on the sale of all syrup medica-
tions, and have advised the use of powder,
tablet, or capsule forms of such drugs for an
indefinite period.3
Gambian authorities have estimated an
associated mortality rate of about 90%, whereas
Indonesian figures put the mortality rate
around 61.4%. These levels of mortality are
significantly higher than those previously re-
ported for pediatric patients with acute kidney
injury, even in critical care wards (6.4%–
32.3%).4
What is behind this sudden increase?
Both countries have identified excessive DEG/
EG contamination in syrup medications as the
probable common cause behind these cases,
particularly paracetamol-containing prepara-
tions (used for fever, cough, cold, and pain).1
Both DEG and EG are odorless, water-miscible
organic compounds with a sweetish taste,

444 Kidney International (2023) 103, 444–447

Kidney International (2023) 103, 444–447

Table 1 | Characteristics of the suspected cough-and-cold medications that have been since removed from distribution
Variable Gambia Indonesia

Product name Promethazine Kofexmalin Makoff Baby Magrip N Termorex Flurin DMP Unibebi Unibebi Unibebi Paracetamol Paracetamol Vipcol Syrup
Oral Solution Baby Cough Syrup Cold Syrup Syrup Syrup Cough Syrup Fever Syrup Fever Drops Drops Syrup,
Cough Peppermint
Syrup

Reported Promethazine Pheniramine CTM, Paracetamol, Paracetamol Paracetamol, Paracetamol, Paracetamol Paracetamol Paracetamol Paracetamol Paracetamol,
active maleate, phenylephrine phenylephrine CTM, guaifenesin, guaifenesin,
ingredients ammonium HCl, and HCl, and CTM pseudoephedrine and CTM menthol, and
chloride, dextromethorphan HCl, and CTM
and menthol HBr dextromethorphan
HBr

Indication Nausea and Cough Cough Cough and flu Fever Cough and flu Cough and flu Fever Fever Fever Fever Cough and flu
for use vomiting, and
antiallergic
agent

Packaging, ml 100 125 100 100 60 60 60 60 15 15 60 60

Manufacturer Maiden Maiden Maiden Maiden Konimex Yarindo Universal Universal Universal Afi Farma Afi Farma Afi Farma
Pharmaceuticals Pharmaceuticals Pharmaceuticals Pharmaceuticals Farmatama Pharmaceutical Pharmaceutical Pharmaceutical Pharmaceutical Pharmaceutical Pharmaceutical
Limited Limited Limited Limited Industries Industries Industries Industries Industries Industries

Manufacturing India India India India Indonesia Indonesia Indonesia Indonesia Indonesia Indonesia Indonesia Indonesia
country

Distribution ML21-202 ML21-199 ML21-203 ML21-198 DBL781300 DTL03327 DTL722630 DBL8726 DBL192630 GBL180170 GBL010170 DTL780170
permit 3537A1 08637A1 3037A1 301237A1 3336A1 7636A1 4237A1 6637A1
number/lot (batch:
numbera AUG22A06)

Manufacture December December December 2021 December 2021 August 2022 N/A N/A N/A N/A N/A N/A N/A
date 2021 2021

editorial: special report

Expiration November November November 2024 November 2024 August 2025 N/A N/A N/A N/A N/A N/A N/A
date 2024 2024

Packaging English English English English Indonesian Indonesian Indonesian Indonesian Indonesian Indonesian Indonesian Indonesian
language
CTM, Chlorphenamine maleate; N/A, data not available.
The data have been collected from World Health Organization advisories: Medical Product Alert N 6/2022: substandard (contaminated) pediatric medicines (dated October 5, 2022)1; and Medical Product Alert N 7/2022:
substandard (contaminated) pediatric liquid dosage medicines (dated November 2, 2022).
a
Lot number is used for Gambian medications, whereas distribution permit number is used for Indonesian medications.
445
editorial: special report
Figure 1 | Distribution of cases and deaths in different provinces of Indonesia (as reported by the Indonesian Ministry of Health on
November 15, 2022). The authors remain neutral with regard to the territorial disputes.
commonly used as industrial solvents and in
the manufacturing of antifreeze, dyes, and
brake fluids.5
Active pharmaceutical compounds, like
paracetamol, are non–water soluble and require
nontoxic solvents, like glycerol and propylene
glycol, to provide a liquid base. In addition,
these solvents act as preservatives, thickeners,
and sweetening agents, and confer antimicrobial
properties.5,6 Manufacturers illegally replace
glycerol and propylene glycol with toxic DEG/
EG or cheaper grades of the nontoxic solvents,
which are tainted with DEG/EG, thereby leading
to poisoning. The minimum lethal dose for
DEG is yet to be determined but is estimated to
range from 0.014 to 0.35 mg/kg.6
The toxicity of DEG/EG is primarily deter-
mined by their metabolite glycolaldehyde, which
can hinder numerous aspects of cellular meta-
bolism while also exacerbating cellular damage.
The formation of oxalic acid and calcium oxalate
monohydrate crystals, which can cause cerebral
edema and kidney failure, related to tubular sys-
tem blockade and injury, can be seen within 8 to
24 hours of consumption of a lethal dose. If un-
treated, death from multiorgan failure typically
occurs within 24 to 36 hours of glycol ingestion.5,6
For pediatric patients presenting with DEG-
associated acute kidney injury, treatment in-
volves concurrent hemodialysis with fomepi-
zole (alcohol dehydrogenase inhibitor)
administered over 4 hours. In resource-limited
settings, peritoneal dialysis with oral ethanol
(0.8–1.0 ml/kg loading dose, followed by 0.15
ml/kg per hour of 95% ethanol diluted in or-
ange juice) is suggested.6 However, caution
must be observed while administering ethanol,
given its toxic effects.
Is this the first time?
Regrettably, the present incidents are not the
first time that spurious DEG/EG-containing
446
syrups have been identified as a cause of
pediatric morbidity and mortality. More than
300 child deaths have been reported in the
past due to the consumption of tainted
syrups.6 Just 2 years ago, India reported 12
deaths due to the consumption of locally
produced tainted cough syrups, the fourth
such incident in the country after 1998 (33
deaths), 1986 (14 deaths), and 1973 (14
deaths). Other countries, like the United
States, Panama, Haiti, South Africa, and
Bangladesh, have also reported deaths due to
cough syrup–related DEG/EG poisonings.5,6
Clearly, such incidents highlight lapses in
regulatory oversight, implementation, and
cross-country checks of the pharmaceutical
industry. These incidents negatively shape
public trust and opinion toward the medical
and pharmaceutical sectors.
Root cause analysis of the problem
Indian authorities found multiple lapses in the
production process of these medicinal syrups,
including bypassing quality checks of raw
products, mislabeling product shelf life, and
missing records and logbooks, among others.
According to the All-India Organization of
Chemists and Distributors, none of the prod-
ucts produced by the implicated pharmaceu-
tical company is available for sale in India.
Although Indian authorities pointed out that
final approval and sale of the drugs is the onus
of the importing country, Gambian authorities
noted their limited resource capacity, which
can only prioritize quality checks on antima-
larial drugs, antibiotics, and pain killers, rather
than cough syrups. Indonesia, on other hand,
has now promised stricter scrutiny of the
pharmaceutical sector while increasing imports
of antidotes (fomepizole injections) from
Singapore and Australia. A pilot study from
2014 highlighted that most of the drugs made
Kidney International (2023) 103, 444–447

in India and sold in Africa are of poorer quality
than those sold in India or other countries,
exposing an exporting bias based on cutting
costs and maintaining company reputation.7
Developing countries have always struggled
with drug regulation and control because of a
lack of resources.8 This is becoming increasingly
difficult, particularly in the light of the current
coronavirus disease 2019 (COVID-19) situa-
tion, which necessitates providing funds for
other purposes, such as medical care and social
assistance. Relatively lenient rules for punish-
ment are another cause promoting adulteration
and the sale of counterfeit drugs. In addition,
India’s non-inclusion in WHO standards for
national bodies that regulate medication stan-
dards globally is a serious concern, given India’s
reputation as the “Pharmacy of the World.”
Understandably, parents of young children
are now unsure of the medications that they
have recently purchased, and the possible
consequences of administering DEG- and EG-
contaminated drugs to their children before
definitive findings are released by the author-
ities. In such perilous times, it is necessary that
the companies and individuals responsible be
made accountable and the investigation find-
ings be made public. National regulators should
make sure that companies adhere to the WHO
Good Manufacturing Practice Guidelines and
follow the international certification scheme
for medications meant for export.6 Such mea-
sures will help not only to regain public trust
but also prevent the spread of misinformation
and hesitancy.
DISCLOSURE
All the authors declared no competing interests.
Kidney International (2023) 103, 444–447
editorial: special report
AUTHOR CONTRIBUTIONS
TPU and NJ conceptualized the present study and
were responsible for data collection, synthesis, and
writing the initial draft of the article. NJ was
responsible for visualizations, while project
administration was done by TPU. Supervision was
done by HA. All authors were involved in
preparing the final draft of the article. The authors
have read and agreed on the final version for
publication.
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