Kidney function and use of nonsteroidal anti-inflammatory drugs among elderly people: a cross-sectional study on potential hazards for an at risk population
International Journal of Clinical Pharmacy
Kidney function and use of nonsteroidal anti‑inflammatory drugs among elderly people: a cross‑sectional study on potential hazards for an at risk population
Sara Modig 0
Sölve Elmståhl 0
0 Department of Clinical Sciences in Malmö, Division of Geriatic Medicine, Lund University , Malmö , Sweden
Background Renal elimination normally decreases with age. Nonsteroidal antiinflammatory drugs (NSAIDs) carry a risk of additional kidney damage. Objective The aims of this study were to assess the prevalence of NSAIDs in the elderly (aged ≥ 65) population in Sweden, explore reasons for any possible differences in the level of use and assess their kidney functions. Setting Data were obtained from the cohort study Good Aging in Skåne, Sweden. Patients aged 65 or more were included. Methods Medication lists were collected as well as variables such as cognition and education levels. Glomerular filtration rate was estimated from creatinine and cystatin C. Descriptive statistics and multiple linear regression analysis were used. Main outcome measure: NSAID use among the general elderly population. Results A total of 1798 patients were included. Approximately six percent (n = 105) of the people in the study group were using NSAIDs and of those 82 (78%) bought NSAIDs over the counter (OTC). 42% of those buying NSAIDs OTC showed an estimated glomerular filtration rate below 60 ml/min/1.73 m2. Education level did not affect the use of nonsteroidal anti-inflammatory drugs, nor did age. NSAIDs were more commonly used than other recommended analgesics. Conclusion Many people are unaware of the risks associated with the use of NSAIDs. The findings imply that the frailest elderly use NSAIDs to the same extent as the younger elderly do. It is important that information about safety of these drugs be communicated to both patients and healthcare professionals.
Anti-inflammatory agents; Elderly; Glomerular filtration rate; NSAID; Risk; Sweden
Impacts on Practice
• The findings confirm the importance of medication
reconciliation, and this must include questions about the use
of over-the-counter medications.
• There is a need for information directed towards the
general elderly population, since the findings suggest that
many older people are unaware of the risks associated
with non-steroidal antiinflammatory drugs, including risk
of renal damage.
Department of Clinical Sciences in Malmö, Division
of Family Medicine, Lund University, Malmö, Sweden
• It is essential to plan measures that ensure appropriate
pharmacist counselling regarding non-steroidal
• The communication between prescribers and pharmacists
at community pharmacies is important.
Renal elimination normally decreases with age due to
reduction in both renal blood flow and glomerular filtration
]. In addition, many common conditions among
the elderly, such as hypertension, diabetes and
atherosclerosis, contribute to further reduction of the renal function.
Renal elimination is the most important pharmacokinetic
change that occurs in the elderly . Among the
population from the Good Aging in Skåne (GÅS) study, which
is representative of the Swedish general population, a
significantly decreased renal function after age 80 was
demonstrated. More than 25% of the oldest demonstrated eGFR
below 30 ml/min/1.73 m2, i.e. established renal failure of
chronic kidney disease (CKD) grade 4 [
Swedish nursing home patients, more than half of the population
was found to have a renal failure of CKD grade 3 or more
(< 60 ml/min/1.73 m2) . In an elderly population with
multiple illnesses from Iceland the corresponding proportion
was over 70% [
Many medications are eliminated via the kidneys. Dose
adjustment is therefore often necessary in elderly patients
in order to avoid adverse effects and/or further impairment
of renal function [
]. Some drugs are even contraindicated
for patients with renal impairment. NSAIDs (nonsteroidal
anti-inflammatory drugs) could be useful for
musculoskeletal pain, but are potentially harmful for many elderly people
due to the risk of kidney failure, heart disease or
gastrointestinal bleeding [
]. NSAIDs carry a risk of gradual
decrease of GFR as well as acute kidney damage [
and NSAID users without previous renal disorder had a
three-fold greater risk for developing acute renal failure
compared with non-NSAID users in the general population
in United Kingdom . The Swedish recommendations
state paracetamol as the number one analgesic for elderly
people, with opioids, such as morphine, as the next step
for stronger pain, despite the fact that the latter are
associated with adverse effects, including sedation, dizziness and
even confusion. Opioids should therefore only be used after
strict consideration. These recommendations differ slightly
from the WHO pain ladder, where NSAIDs are included in
the first step and mild opioids, such as codeine, are
recommended as a second step, before strong opioids [
The Beers Criteria includes avoidance of NSAIDs in
CKD stage 4 and 5 [
] and the STOPP/START criteria
considers the cut-off for use to be < 50 ml/min/1.73 m2
]. Nevertheless, the use of NSAIDs among the elderly
was hazardously high in previous studies. Three out of
four elderly patients discharged from hospital in the
Netherlands after gastrointestinal bleeding were prescribed
NSAIDs again within 7 years [
]. In Italy, 20% of the
general population aged > 65 used NSAIDs in a typical
week and 5.3% were chronic users [
]. In the nursing
home population mentioned above, however, the use of
NSAIDs was low, indicating knowledge exists about the
risks among the Swedish prescribers [
]. These patients
seldom obtain medications over the counter (OTC)
themselves. However, in northern Sweden inappropriate
prescriptions on the basis of impaired renal function were
more common among patients with dementia living in
nursing homes than among those living at home [
educational intervention effectively reduced NSAIDs use
in nursing homes in the US, where prescription of NSAIDs
for these patients was more frequent [
Many NSAIDs are sold OTC in Sweden and the
general population is often exposed to commercial advertising
regarding these drugs. Other European citizens buy NSAIDs
over the counter as well [
]. However, it is not common
knowledge that these drugs are potentially harmful for a
great proportion of the elderly population. Furthermore,
many elderly people are not aware of their decreased
Aim of the study
The aim of this study was to assess how many in the
general elderly population in Scania in Southern Sweden use
NSAIDs regularly or as needed; what level of kidney
function these people have and if there are any variables
associated with possible differences in NSAID use.
The study was approved by the regional ethics committee
at Lund University (LU 744-00). Written informed consent
was obtained from all individual participants included in
the study. The study has been performed in accordance with
the ethical standards as laid down in the 1964 Declaration
The study population was obtained from the ongoing Good
Aging in Skåne (GÅS) study, part of the Swedish National
Study on Aging and Care (SNAC), which has been described
elsewhere in detail [
]. This is a cohort study
representative of the Swedish general population. The original GÅS
population includes 2931 participants aged 60–93 years
old from nine age cohorts. The participants live in five
municipalities of different sizes and are randomized from
the municipality registers with a participation rate of 60%.
Patients aged 65 or more were included in the present
study. The study was designed as a cross-sectional study
of 1832 subjects attending the 6-year re-examination year
2007–2011 out of 2264 survivors from the baseline (follow
up rate 81%).
Information on the study population was collected on the
basis of medical health examinations, psychological
examinations, function tests and survey questions. In order to
assess differences between groups regarding NSAID use,
the following variables were used: education level, sex, age,
place of living (city/countryside, i.e. access to care) and
score level of mini-mental test (MMSE). Investigations were
performed either at the research center or in the patient’s
own home or at nursing homes to avoid selection bias.
Medication data consisted of stated intake from
prescriptions as well as from OTC drugs and was collected by
obtaining the patients’ medication lists, self-reported and/or
written. The medication lists contained information about
drugs used regularly as well as those used “as needed”.
Access was given to medical records in order to check
medications that were prescribed. It should be emphasized that
the self-reporting procedure confers a greater certainty about
which drugs were actually used out of those stated as “as
needed”. The use of systemic NSAIDs was noted, as well as
use of other analgesics, as a marker of chronic pain
condition. In acute pain, systemic or local adverse event rates with
topical NSAIDs were no greater than with topical placebo,
and also in chronic pain, serious adverse events were rare
]. The active substances (ATC groups) that were included
are presented in Table 1, as are also the systemic NSAIDs
that are available OTC in Sweden.
Plasma creatinine (p-Cr) and cystatin C (p-cysC) were
studied for the whole GÅS cohort [
]. P-cysC was, as one batch,
measured by a fully automated particle-enhanced
immunoturbidimetric assay [
] at Lund University Hospital.
Normal reference range of p-cysC is specified as 0.63–1.44 mg/l
(> 50 years) [
P-Cr was measured using a creatininase-based procedure
on the Hitachi Modular P analysis system at Lund University
Hospital. The method is calibrated to IDMS levels. Normal
reference range of p-Cr is specified as 60–100 µmol/l for
men and 50–90 µmol/l for women.
The levels of p-cysC and p-Cr were used as markers for
glomerular filtration rate (GFR). Estimated GFR (eGFR)
was calculated with the cystatin C-based CAPA [
the creatinine-based LM-Rev (Revised Lund-Malmö Study
equation without body weight measure)—equations [
as commonly used in Scania, Sweden. The mean of the two
estimated GFR-values was used, as recommended as the
generally best estimate for adults [
CAPA : eGFR = 130 × cystatin C−1.069 × age−0.117 − 7,
Descriptive statistics (frequencies, mean values and
proportions) were used to describe the use of NSAIDs and the
kidney function in the population.
Multiple linear regression analysis was performed with
the use of NSAIDs as a dependent variable to assess if
there were any explanation models for possible differences
in NSAID use. The following independent variables were
chosen: sex (male = 0, female = 1), age, education level
(elementary school not completed/elementary school/
secondary school/one or more year extra or university
degree), place of living (urban and rural settings as a proxy
for access to in-patient and outpatient) and score level of
mini-mental test (MMSE). Two analyses were performed,
aDate for examination was missing for 34 cases
one with NSAID use dichotomized as Yes/No and one with
NSAID use split into No use/OTC use/NSAID prescribed,
The independent variables were checked for
multicollinearity with Tolerance and Variation Inflation factors
(VIF). No signs of multicollinearity were detected.
Analyses were performed in IBM Corp. SPSS Statistics
for Windows, Version 22.0, Armonk, NY, released 2013.
P value < 0.05 was regarded as statistically significant
and set a priori.
A total of 1798 persons were included. Mean age was 75
(SD 9.1) years; 56% were men. Mean eGFR (mean from
capa and Lmrev) was 64.8 ml/min/1.73 m2. Characteristics
of the study population are shown in Table 2.
NSAIDs were used on a daily basis or as needed by 105
persons (5.8%). The mean eGFR was 64.0 (31.1–100.1) in
this group. Of those taking NSAIDs, 23 were prescribed
the medicine [mean eGFR = 64.8 (39.8–95.3)] and 82 were
buying it OTC [mean eGFR = 63.8 (31.1–100.1)]. A total
of 42% of those buying NSAIDs over the counter showed an
eGFR below 60 ml/min/1.73 m2. The most frequently used
NSAID was ibuprofen (200–400 mg). Four persons reported
the use of two different NSAIDs similarly. The regular use
of other analgesics (paracetamol, opioids or drugs for
neuropathic pain) as a marker for chronic pain condition was
reported by 83 persons. Table 3 shows the use of NSAIDs
among the study population and within the groups of
The multiple linear regression showed that female sex
(beta = 0.029; 95% CI = 0.005–0.052) was weakly but
significantly associated with NSAID use (p = 0.018). This was
also true when NSAID use was split into no
use/OTC/prescribed (beta = 0.042; 95% CI = 0.012–0.073; p = 0.007).
The other independent variables (age, level of education,
access to care and score level of mini-mental test) did not
contribute to the model in any of the analyses. The
respective R2 values were 0.007 and 0.009.
This study on the general elderly population in southern
Sweden shows that more than one out of 20 among the study
population, which is representative of Sweden as a whole,
use potentially hazardous anti-inflammatory medication.
Even elderly people with moderate kidney function decline
(CKD grade 3) use NSAIDs, which suggests that many are
unaware of the risks associated with this medication. Age or
education degree did not affect the use of NSAIDs. However,
there was a small but significant association between female
sex and NSAID use.
Among those who showed a kidney function decline to
grade three (n = 487), 8.0% used NSAIDs. Most of them
(31 out of 39) bought these medications OTC. This
finding stresses the importance of asking patients about OTC
use and of informing them about risks. This is even more
NSAID use, n (%)
important if the patient is receiving treatment with other
medications that are dependent on kidney function for their
elimination, i.e. metformin, digoxin and spironolactone [
Even occasional intake of NSAIDs might cause acute kidney
] with an according risk of accumulation and even
fatal outcome. This study, however, did not assess the
contemporary use of medications other than analgesics.
In Sweden it is relatively easy to buy NSAIDs OTC and
the majority of the NSAID users in the study bought the
drug OTC. Broadly speaking, every supermarket offers
these products. Paracetamol tablets, however, are since
2015 (but not during the study period) only sold at
pharmacies, due to repeated intentional self-harm acts. It would
therefore not be surprising if the average elderly person
was of the belief that NSAIDs are less dangerous than
paracetamol. Consequently, it is important to provide
information that these are not risk-free medications. Nurses
who give advice to patients with momentary pain from
the musculoskeletal system should not suggest NSAID for
elderly people. Likewise, the communication between
physicians and staff who meet these patients at the pharmacies
could be developed and expand [
]. Physicians must also
avoid prescribing these drugs for patients at risk of kidney
failure as well as gastrointestinal bleeding and heart
failure. Physicians should instead choose drugs in accordance
with the most recent guidelines. Primary care patients with
gonarthrosis did not report any difference in knee pain
severity between those taking paracetamol or diclofenac.
Furthermore, the patients more frequently reported minor
adverse events after taking diclofenac (64%) than
paracetamol (46%) [
The regular use of other analgesics (paracetamol, opioids
or drugs for neuropathic pain) as a marker for chronic pain
condition was reported by 83 persons (4.6%). This was less
than those using NSAIDs, which 105 elderly people (5.8%)
did. This finding implies that NSAIDs might be used as a
first choice drug, instead of analgesics recommended for
elderly, especially paracetamol. This was seen previously
in Germany, where ibuprofen was the most frequently used
], while in Norway paracetamol use was twice
as common as NSAID use [
The regression did not show an association between age
and NSAID use. This is risky since it implies that the oldest,
although they are most likely frailer and have lower kidney
function, use these medications to the same extent as the
younger elderly do. In the general Italian population, the
older age groups even showed an increased risk of chronic
NSAID use, according to a survey performed in 2002 [
Furthermore, in Germany in 2014–2015 a fifth of the
nursing home patients, who often are the frailest and oldest, were
prescribed NSAIDs, regardless of kidney function state [
In Sweden, physicians seem to be more careful with NSAID
prescriptions to the frailest patients [
]. However, the
problem with OTC use still remains. This implicates that there is
a need for developing the role of community pharmacists in
providing counselling to the patients regarding NSAID use.
In a previous Swedish study, lower education level has
been shown to be associated with a higher risk of hazardous
medication use [
]. In the present study, however,
education level was not found to associate with NSAID use, and
nor was cognition level (MMSE). The small but significant
association between female sex and NSAID use was not
surprising. The fact that women use more analgesics, both
prescribed and OTC, has been shown previously [
The medication lists that were collected contain data
about prescription drugs as well as OTC drugs. This is a
strength compared to studies with collected data from the
Swedish Prescribed Drug Register [
]. Access was given
to medical records in order to check medications that were
prescribed. However, medication data refers to stated intake
from prescriptions as well as OTC. Other strengths that
should be pointed out are that home visits were performed
in order to minimize selection bias of healthier individuals.
The study design with urban and rural areas increases the
generalization of our findings.
One weakness of the study is that it was not possible to
decide if the study person used NSAIDs regularly or more
seldom, when it was reported as “as needed”. However, even
a single intake of NSAID carries a risk of causing acute
kidney failure [
] and the risk of myocardial infarction
was recently found to be greatest during short term daily
use of an NSAID [
]. It is also not possible to guarantee
that all occasionally used NSAIDs were reported.
Furthermore, it was not known how many of the patients taking
NSAIDs who had an increased risk for adverse effects of
those drugs, such as recent gastrointestinal bleeding, cardiac
failure or renal failure. Missing data were most frequently
seen regarding blood samples (258/1832). However, we had
no reason to believe that the kidney function was different
in this group.
Future research should focus on interventions to decrease
NSAID, targeting prescribers and personnel at community
pharmacies as well as elderly in general. Such studies could
have the potential to form the basis of future strategies for
optimizing drug use among the elderly. Assessing the
knowledge about NSAIDs among older people who buy these
medications OTC at pharmacies could be helpful in
customizing information directed at the general elderly population
in Sweden. Even more, perhaps regulation of OTC
dispensing to the elderly should be a priority?
Almost six percent of the elderly in our study
population were using NSAIDs, which are potentially hazardous
medications for this population. The majority bought these
medications over the counter, without prescription. Among
those buying NSAIDs over the counter, almost half showed
an eGFR below 60 ml/min/1.73 m2, suggesting that many
people are unaware of the risks associated with the use.
Education level did not affect the use of nonsteroidal
antiinflammatory drugs, nor did age. The latter is risky since it
implies that the oldest, although they most likely are frailer
and have lower kidney function, use these medications to the
same extent as the younger elderly do. Many pain patients
choose these medications as their first choice, instead of
other recommended analgesics. It is important to provide
the information that these are not risk-free medications,
especially to the general population but also to physicians.
Acknowledgements We are most grateful to all participants of the
GÅS project and their next of kin. We are indebted to Patrick Reilly
for his expertise and advice in editing the manuscript.
Conflicts of interest The authors declare that they have no conflict of
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