AINES en ERC 2020
AINES en ERC 2020
1, 63–71
doi: 10.1093/ckj/sfz054
Advance Access Publication Date: 20 May 2019
Original Article
ORIGINAL ARTICLE
ABSTRACT
Background. Chronic kidney disease (CKD) management focuses on limiting further renal injury, including avoiding
nephrotoxic medications such as non-steroidal anti-inflammatory drugs (NSAIDs). We performed a systematic review to
evaluate the prevalence of primary care NSAID prescribing in this population.
Methods. We systematically searched MEDLINE and Embase from inception to October 2017 for observational studies
examining NSAID prescribing practices or use in CKD patients in a primary care setting. The methodological quality of
included studies was assessed independently by two authors using a modified version of the Agency for Healthcare
Research and Quality’s Methodological Evaluation of Observational Research checklist.
Results. Our search generated 8055 potentially relevant publications, 304 of which were retrieved for full-text review. A total
of 14 studies from 13 publications met our inclusion criteria. There were eight cohort and three cross-sectional studies, two
quality improvement intervention studies and one prospective survey, representing a total of 49 209 CKD patients. Cross-
sectional point prevalence of NSAID use in CKD patients ranged from 8 to 21%. Annual period prevalence rates ranged from
3 to 33%. Meta-analysis was not performed due to important clinical heterogeneity across study populations.
Conclusions. Evidence suggests that NSAID prescriptions/use in primary care among patients with CKD is variable and
relatively high. Future research should explore reasons for this to better focus knowledge translation interventions aimed
at reducing NSAID use in this patient population.
Keywords: chronic kidney disease, nephrotoxicity, non-steroidal anti-inflammatory drugs, primary care, systematic review
63
64 | C. Lefebvre et al.
prevalence rates in the general population [23]. As the purpose follow-up period. Data from included studies were synthesized
of our study was to evaluate prescriptions by health care qualitatively via systematic review rather than quantitatively
practitioners, we did not assign a major flaw to studies using via meta-analysis due to important clinical heterogeneity
such sampling methods. However, we did assign a minor across studies. As there were only two studies comparing
flaw to studies that used claims data that restricted to NSAID use in CKD patients to that in non-CKD patients, we did
insured patients. MORE also assigns flaws to studies based on not present relative effect measures [25, 26].
absolute cut-offs for participant response rates and exclusions
from analysis, whereas we also considered whether studies
assessed differences between responders and non-responders
RESULTS
and between included and excluded patients. For the Our search generated 8055 potentially relevant publications
assessment of internal validity, we specifically evaluated (Figure 1). After removal of duplicates and title/abstract
whether NSAID prevalence was assessed objectively, whether screening, 304 articles were retrieved for full-text review. Of
it relied on patient recall for <6 months or patient recall these, 12 met our inclusion criteria, 2 of which were derived
for >6 months, assigning no flaw, a minor flaw or a major from a single publication [27]. Two additional studies were
flaw, respectively. identified through reference screening of included articles. A
total of 14 studies from 13 separate publications were thus
Statistical analysis included in our review.
Table 1. Characteristics of studies assessing point prevalence of NSAID use among patients with CKD
a
Values are given for whole study population.
b
Prospective cohort.
c
Retrospective cohort.
SD, standard deviation; eCCr, estimated creatinine clearance; C–G, Cockcroft–Gault formula; OTC, over the counter; HTN, hypertension; NR, not reported; EMR, elec-
tronic medical record; MDRD, Modification of Diet in Renal Disease equation.
studies [25, 28, 34], two studies of quality improvement inter- comorbidity other than CKD (e.g. diabetes, hypertension, mus-
ventions [35, 36] and one prospective survey [37]. One publica- culoskeletal complaints and gout) [26, 35–37]. Two studies
tion described two separate CKD populations, which were were not specifically based in a primary care practice. One was
considered independently in our analysis [27]. Two studies conducted using claims data from a major New York State
were performed within a single primary practice center [27]. insurer and was eligible for inclusion because the authors
The remaining studies were conducted across two or more specifically provided prescription data for patients who
practices, four of which grouped data from >100 practices us- had not been seen by a nephrologist and were therefore
ing centralized electronic medical records databases [21, 26, considered primary care patients [32]. The other study was
29, 30]. conducted in a nursing home and was included because >96%
Study populations varied widely (Tables 1 and 2). The mean of the patients were regularly followed by a primary care
age ranged from 47 to 83 years, with all patients >18 years of physician and a very small proportion were followed by
age. Four studies selected their patient population based on medical specialists [25].
NSAIDs in CKD | 67
Table 2. Characteristics of studies assessing period prevalence of NSAID use among patients with CKD
Allen et al. [31] Multispecialty 11 774 (60) 73 (12) Two eGFRs separated NSAID prescrip- 2008–9 10 (9–10)
(USA) group practice by at least 3 months tion in the
of 15 ambula- (MDRD) EMR
tory health Stage 3: 97%
centers in Stage 4: 3%
Massachusetts
(only 10% fol-
lowed by a
nephrologist)
a
Values are given for whole study population.
b
Patients with a known renal disorder or impairment, type 1 or 2 diabetes mellitus, hypertension, cardiovascular disease, peripheral vascular disease, hyperlipidemia
and structural urological disorders.
c
All patients within this eGFR stage also had 30 mg/day of albuminuria.
SD, standard deviation; MDRD, Modification of Diet in Renal Disease equation; EMR, electronic medical record; NR, not reported; OTC, over the counter.
68 | C. Lefebvre et al.
FIGURE 3: Forest plot of studies assessing period prevalence of NSAID prescription/use among CKD patients in primary care, expressed as yearly prevalence. NS, not
specified.
CKD and NSAID definitions Stages 1 and 2 [33]. Three studies relied on recorded CKD diag-
The definition of CKD differed substantially across studies. nostic and procedure codes without specific staging informa-
Seven studies required a single low estimated GFR (eGFR) value tion [27, 29, 30].
[25, 26, 28, 33, 35–37]. Three studies required two separate eGFR Nine studies assessed NSAID prescriptions using patients’
values separated by at least 3 months [31, 32, 34]. Of the studies medical records [25–27, 29, 31, 33, 35, 36], of which five specifically
using eGFR, the severity of CKD among included patients varied excluded low-dose aspirin from reported estimates [27, 33, 35,
widely (Tables 1 and 2) [26, 28, 33, 37]. Only one study consid- 36]. Two studies reported on prescriptions reimbursed by either a
ered microalbuminuria, allowing for the identification of CKD national health provider [30] or by private insurance [32]. Two
NSAIDs in CKD | 69
studies used patient-administered questionnaires [28, 34] and was seen in the year following patient entry into dialysis (30%).
one used physician-completed study forms [37] to assess NSAID Furthermore, another study [31] reported only a small decrease
use. Only one study provided a list of included NSAIDs [30]. (from 24% to 20%) in inappropriate medication prescriptions be-
tween CKD patients whose physicians had recognized their di-
agnosis versus those whose physicians had not, although data
Quality assessment
for NSAIDs alone were not available.
All the studies had at least a moderate risk of bias Only one study evaluated the indication for NSAID prescrip-
(Supplementary data, Tables SA3 and SA4). Eleven studies were tion and found that the overwhelming majority were prescribed
considered to have a moderate risk of sampling bias and all but for osteoarticular disease [30]. Although alternative therapies
one failed to provide age-adjusted prevalences. Two studies exist, NSAIDs may offer superior pain relief in conditions such
were deemed to be at a high risk of bias [28, 37]. The first had a as arthritis, and our findings may reflect instances where alter-
sample size of eight CKD patients and relied on questionnaire natives to NSAIDs have been attempted but were unsuccessful
data to assess NSAID use, with a 26% response rate [28]. [40]. Thus, despite recommendations to avoid NSAIDs in CKD
Furthermore, patients could be excluded based on their treating patients, it may be difficult to do so, given the potential benefi-
Foundation for Health Research (FRQS)] in partnership with 15. Gill PJ, Roberts NW, Wang KY et al. Development of a search
Fondation des Étoiles. R.W.P. holds the Albert Boehringer I filter for identifying studies completed in primary care. Fam
Chair in Pharmacoepidemiology at McGill University. K.B.F. Pract 2014; 31: 739–745
was supported by a Junior II salary support award from the 16. Messner DA, Moloney R, Warriner AH et al. Understanding
FRQS. practice-based research participation: the differing motiva-
tions of engaged vs. non-engaged clinicians in pragmatic
clinical trials. Contemp Clin Trials Commun 2016; 4: 136–140
CONFLICT OF INTEREST STATEMENT 17. Rengerink KO, Kalkman S, Collier S et al. Series: pragmatic
trials and real world evidence: Paper 3. Patient selection
None declared. Results presented in this article have not
challenges and consequences. J Clin Epidemiol 2016; 89:
been published previously in whole or part, except in ab-
173–180
stract format.
18. Litvin C, Nietert P, Wessell A et al. Recognition and manage-
ment of chronic kidney disease in primary care. Am J Kidney
Dis 2011; 57: 646–647
31. Allen A, Forman J, Orav J et al. Quality of chronic kidney dis- 36. Keohane DM, Dennehy T, Keohane KP et al. Reducing inap-
ease care in primary care. J Gen Intern Med 25: S373 propriate non-steroidal anti-inflammatory prescription in
32. Arora P, Elkin PL, Eberle J et al. An observational study of the primary care patients with chronic kidney disease. Int J
quality of care for chronic kidney disease: a Buffalo and Health Care Qual Assur 2017; 30: 638–644
Albany, New York metropolitan area study. BMC Nephrol 37. Lioté F, Lancrenon S, Lanz S et al. GOSPEL: prospective survey
2015; 16: 199 of gout in France. Part I: design and patient characteristics
33. Martinez-Ramirez HR, Jalomo-Martinez B, Cortes-Sanabria L (n ¼ 1003). Joint Bone Spine 2012; 79: 464–470
et al. Renal function preservation in type 2 diabetes mellitus 38. Akbari A, Swedko PJ, Clark HD et al. Detection of chronic kid-
patients with early nephropathy: a comparative prospective ney disease with laboratory reporting of estimated glomeru-
cohort study between primary health care doctors and a ne- lar filtration rate and an educational program. Arch Intern
phrologist. Am J Kidney Dis 47: 78–87 Med 2004; 164: 1788–1792
34. McIntyre NJ, Fluck R, McIntyre C et al. Treatment needs and 39. Wyatt C, Konduri V, Eng J et al. Reporting of estimated GFR in
diagnosis awareness in primary care patients with chronic the primary care clinic. Am J Kidney Dis 2007; 49: 634–641
kidney disease. Br J Gen Pract 2012; 62: e227–e232 40. Towheed TE, Maxwell L, Judd MG et al. Acetaminophen for