Non-steroidal Anti-inflammatory Drug Prescriptions in Living Kidney Donors: A Retrospective Cohort Study

Abstract

French

Background:

Current guidelines recommend that living kidney donors should avoid non-steroidal anti-inflammatory drugs due to their potential nephrotoxic effects. It is unclear if physicians are adhering to this recommendation.

Objective:

Our aim was to determine the proportion of living kidney donors that filled a non-steroidal anti-inflammatory drug prescription post-donation and the proportion with measurement of kidney function post-prescription.

Design:

We conducted a population-based, retrospective cohort study.

Setting:

We identified kidney donors in Alberta, Canada that had accessed the healthcare system in the outpatient, emergency department, or inpatient setting.

Patients:

Adult living kidney donors in Alberta, Canada who donated between 2002 and 2019.

Measurements:

We measured the number of non-steroidal anti-inflammatory drug prescriptions, type of prescribing physician, and evidence of post-prescription measurement of creatinine and potassium.

Methods:

We identified the proportion of donors who filled a non-steroidal anti-inflammatory drug prescription at least 1 year post-donation. We also assessed how many donors underwent laboratory testing for kidney function and potassium within 14 days following the first prescription.

Results:

Of the 759 living kidney donors included in our study, 273 (36%) had at least one non-steroidal anti-inflammatory drug prescription over a median follow-up of 7.2 years (interquartile range 3.5-11.5). The proportion of donors with at least one prescription in follow-up remained stable over time (~10% per year). Family physicians accounted for 66% of all non-steroidal anti-inflammatory drug prescriptions. Approximately, 10% of donors had measurements of serum creatinine or potassium post-prescription.

Limitations:

This study was limited by the inability to capture over-the-counter non-steroidal anti-inflammatory drug use, indication for the prescriptions, and indication for bloodwork being completed in the post-prescription period.

Conclusions:

Over one-third of living kidney donors are prescribed non-steroidal anti-inflammatory drugs despite current guideline recommendations, with only a minority undergoing post-prescription laboratory testing. Further research assessing outcomes following non-steroidal anti-inflammatory drug use is recommended to better inform optimal pain-management strategies for living kidney donors.

Keywords

kidney donation non-steroidal anti-inflammatory drugs prescription monitoring bloodwork

Introduction

Living-donor kidney transplantation is the preferred kidney replacement therapy for individuals with kidney failure as it is associated with superior long-term survival, better quality of life, and lower healthcare costs than maintenance dialysis and deceased-donor kidney transplantation.¹ Every year, over 35,000 living-donor kidney transplants are performed, representing almost 40% of all kidney transplant surgeries.² To improve the living donor experience, a better understanding of donor-related risks and concerns are needed. Living kidney donors identify pain as one of their top ten concerns following donation.³ Previous surveys have shown that 25% of donors have chronic pain post-donation, and 25% have more pain than anticipated.^4,5

The World Health Organization (WHO) includes non-steroidal anti-inflammatory drugs (NSAIDs) in the first step of the therapeutic ladder for pain management, but NSAIDs may not be safe for individuals with reduced kidney function.⁶ NSAIDs have adverse effects on the kidney such as decreased glomerular filtration rate (via altered intraglomerular hemodynamics), risk of interstitial nephritis, glomerulonephritis, renal papillary necrosis, hypertension, and hyperkalemia.^7,8 Importantly, chronic exposure is associated with progression of chronic kidney disease (CKD).⁹ Prior studies found that in the general population, NSAID use was associated with higher rates of acute kidney injury (AKI), with the risk increasing for older adults and those with CKD.^10,11 While living kidney donors have stable kidney function post-donation, the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on “The Evaluation and Care of Living Kidney Donors” recommends that donors avoid potentially nephrotoxic agents, including NSAIDs.^12-15

Currently, there is limited literature on NSAID prescribing practices for living kidney donors. One study from the United States included 23,565 living kidney donors and reported that in the first year post-donation, 0.5%, 2.2%, and 3.3% of donors filled at least one NSAID prescription during the 0-14, 15-183, and 183-365 days post-donation, respectively.¹⁶ While the early use of NSAID prescription fills was low, the authors did not examine prescribing patterns beyond the first year post-donation. Prior studies have reported that >30% of donors have an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² over a mean follow-up of 6.6 years, so longer-term NSAID prescribing practices may be more relevant.¹³

We conducted a retrospective cohort study to inform the use and monitoring related to prescription NSAIDs after living kidney donation. We predicted that physician prescribing of NSAIDs in living kidney donors beyond their first-year donation would be uncommon, and that few would have post-prescription laboratory testing of kidney function.

Materials and Methods

Design and Setting

We conducted a population-based, retrospective cohort study using linked healthcare databases within the Alberta Kidney Disease Network (AKDN) that utilizes data from Alberta Health, the provincial health ministry.¹⁷ Over 99% of Alberta residents are registered with Alberta Health and have universal access to hospital care and physician services. We followed guidelines for the reporting of observational studies (Supplemental Table S1) and a protocol approved by the research ethics boards at the University of Alberta and the University of Calgary, with a waiver of patient consent.

Data Sources

We ascertained baseline characteristics, including information about covariates, and outcome data from the AKDN database records (Supplemental Table S2). The Alberta Health database contains information on demographic data, vital statistics, and diagnostic and procedure information for inpatient and outpatient physician services. We linked these data sources to provincial laboratory and pharmaceutical repositories via unique, encoded, patient identifiers. The provincial laboratory data includes serum creatinine and potassium measurements from 2002 onwards. The Pharmaceutical Information Network (PIN) provides data on all prescription medications dispensed in Alberta since January 1, 2008. We used the PIN dataset to identify prescription fills for NSAIDs, including the total number of prescriptions dispensed, number of days supplied, and the physician prescriber specialties. These databases have been previously used for health services research.^13,18-20

Population

We included all prevalent adult living kidney donors (≥18 years old) who underwent donor nephrectomy in Alberta between April 1, 2002, and January 1, 2019 based on the available database. Living kidney donors were identified using an algorithm that required the presence of one diagnostic code for kidney donation (International Statistical Classification of Diseases, Tenth Revision, ICD-10: Z52.4) and one procedural code for kidney procurement or excision (Canadian Classification of Health Interventions, CCI: 1.PC.58, 1.PC.89, or 1.PC.91) (Supplemental Table S2). Similar codes have been used in prior studies to identify living kidney donors.^13,18-20 An algorithm with the ICD-10 and CCI codes was found to have a sensitivity of 97% and a positive predictive value of 90%, when compared to the gold standard of living kidney donor identification by the provincial tissue and organ agency and verification through manual perioperative chart review.²¹

We excluded out-of-province donors, donors age <18 years (0%), and a small proportion of donors (<2%) with missing data such as sex or date of birth. To avoid misclassification of deceased donors, we excluded donors if they died on or before the date of nephrectomy. To avoid misclassification of kidney transplant recipients, we excluded patients with evidence of dialysis or organ transplant, including kidney, prior to donation. The cohort creation is shown in Supplemental Figure S1. A schematic of the study design is presented in Supplemental Figure S2.

Baseline Characteristics

Baseline characteristics were assessed at either April 1, 2008 (to allow for a 3-month look-back window, as the earliest medication dispensing date in the PIN database is January 1, 2008), or the 1-year post-donation date, whichever is later (designated index date). The 1-year post-donation minimum aimed to capture NSAID prescriptions less likely to be attributed to post-operative pain and to reflect long-term practices. In a sensitivity analysis, we restricted the cohort to those who donated from January 1, 2007 onwards to address left-censoring.

The Alberta Health database provided demographics, such as age and sex. While race/ethnicity was not included in the database, approximately 75% of Alberta’s population is white.²² Postal codes were linked to the Canadian Census using the Postal Code Conversion file to determine median neighborhood household income quintile (level 5 being the highest) as well as rural versus urban location of residence. Demographic data were complete except for income quintile (<0.5%); patients with missing income quintile were included in the middle (level 3) category. Pre-donation eGFR and albuminuria were calculated as the mean and median of all outpatient serum creatinine and albuminuria measurements, respectively, in the 1 year prior to the donation date, as previously described.²³ Medical comorbidities were identified based on validated algorithms, whenever possible, using hospital discharge records and physician claims at the index date (Supplemental Table S2).

NSAID Prescriptions

The PIN database was used to identify the proportion of living kidney donors who received an NSAID prescription beyond their index date. We included oral formulations and excluded formulations with low systemic absorption such as topical or ophthalmic, as well as formulations less commonly prescribed in the community including rectal, intravenous, and intramuscular formulations (Supplemental Table S3).²⁴ Acetylsalicylic acid was excluded as it is readily available over-the-counter and has the lowest risk of nephrotoxicity.⁸ We assessed the median time from donation and index date to the first prescription as well as the baseline eGFR at the time of the first prescription. The baseline eGFR was based on the mean of all outpatient creatinine measurements in the 1 year prior to the first prescription. We also reported the median number of prescriptions per donor, the number of donors with frequent prescriptions (defined as ≥3 prescriptions during follow-up) and chronic NSAID prescriptions (>30 days/prescription). For the first NSAID prescription only, the PIN database was used to identify relevant baseline medication use up to and including the preceding 120 days, such as opioids, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). At the prescription level, we reported the median days supplied, specialty of prescribing physician, and frequency of each type of NSAID prescribed.

Laboratory Outcomes

For donors with an NSAID prescription, we determined the proportion of donors who had evidence of outpatient, inpatient, or emergency department laboratory testing of serum creatinine or potassium within 14 days of the prescription fill. For donors with multiple NSAID prescription fills, only the first NSAID prescription was considered.

As an exploratory analysis, we determined the incidence of AKI for the living kidney donors with at least one outpatient, inpatient, or emergency department serum creatinine measurement within 14 days of the initial prescription fill. If multiple values were available, the highest value was used. Baseline creatinine was determined using the mean of all outpatient serum creatinine measurements in the one year prior to the prescription fill date. AKI was only considered in those with an available baseline creatinine measurement. AKI was defined as per the 2012 KDIGO AKI guidelines as a serum creatinine increase of ≥50% or ≥26.5 µmol/L (0.3 mg/dL) from their baseline.²⁵ Similarly, we determined the incidence of hyperkalemia post-prescription by identifying those with at least one outpatient, inpatient, or emergency department serum potassium measurement within 14 days of the prescription fill, using the highest value if multiple were available. Hyperkalemia was defined as a serum potassium level ≥5.5 mmol/L.

Statistical Analyses

Descriptive variables were expressed as counts and percentages, medians and interquartile ranges (IQR), or means and standard deviations (SD), as appropriate. We compared baseline characteristics of donors with at least one NSAID prescription with donors who had no NSAID prescriptions using χ², Fisher’s Exact, Kruskal-Wallis, and Student’s t-tests, as appropriate. Donors were followed from the index date until the first occurrence of any of the following events: emigration from the province, death, or end of study period (March 31, 2020). In Alberta, the rate of emigration is <2%.²⁶ We determined the quantiles of the potential follow-up time distribution based on the Kaplan-Meier method applied to the censored times, using the prodlim package in R.²⁷ Statistical analyses were performed using R version 4.2.3 (R-project.org). A P-value of <.05 was used to define statistical significance.

Results

Baseline Characteristics

We identified 759 living kidney donors who met the inclusion criteria in the study period (Supplemental Figure S1). The median potential follow-up time was 7.2 years from the index date (IQR 3.5-11.5). Baseline characteristics are shown in Table 1. The mean age was 45 years (SD 11.6), and 65% were female. The mean pre-donation eGFR was 98.9 mL/min/1.73 m² (SD 15), and of those with measurements, 99% had normal/mild pre-donation albuminuria.

Table 1.

Baseline Characteristics at the Index Date^a (Unless Otherwise Specified) for Living Kidney Donors With and Without Evidence of at Least One NSAID Prescription.

Characteristic	Total(N = 759)	Donors with ≥1NSAID prescription(n = 273)	Donors without NSAID prescription(n = 486)	P value
Age, years, mean [SD]	44.5 [11.6]	43.6 [11.3]	45.0 [11.7]	.11
18-30	111 (15)	45 (16)	66 (14)	.32
31-50	380 (50)	140 (51)	240 (49)
>50	268 (35)	88 (32)	180 (37)
Sex
Male	269 (35)	100 (37)	169 (35)	.61
Female	490 (65)	173 (63)	317 (65)	.61
SES
Level 1 (lowest)	128 (17)	68 (25)	60 (12)	<.001
Level 2	169 (22)	73 (27)	96 (20)
Level 3 (middle)	172 (23)	51 (19)	121 (25)
Level 4	135 (18)	41 (15)	94 (19)
Level 5 (highest)	155 (20)	40 (15)	115 (24)
Residence
Urban	675 (89)	236 (86)	439 (90)	.10
Rural	84 (11)	37 (14)	47 (10)	.10
Distance to transplant center, km, median [IQR]	29.1 [14.3-162.9]	30.4 [16.8-169.4]	28.4 [13.3-140.8]	.04
<50	471 (62)	157 (58)	314 (65)	.24
50.1-150	115 (15)	44 (16)	71 (15)
150.1-300	79 (10)	34 (12)	45 (9)
>300	94 (12)	38 (14)	56 (12)
Year of nephrectomy
2002-2010	324 (43)	179 (66)	145 (30)	<.001
2011-2019	435 (57)	94 (34)	341 (70)	<.001
Years from donation to index date, median [IQR]	1.0 [1.0-1.8]	1.0 [1.0-3.6]	1.0 [1.0-1.0]	<.001
Pre-donation eGFR, mL/min/1.73 m ² , mean [SD]	98.9 [15]	101.4 [15.3]	97.6 [14.6]	.002
≥90	498 (66)	183 (67)	315 (65)	<.001
80-89	129 (17)	33 (12)	96 (20)
70-79	69 (9)	23 (8)	46 (9)
60-69	12 (2)	3 (1)	9 (2)
≤59	0	0	0
Missing	51 (7)	31 (11)	20 (4)
Pre-donation albuminuria category
None/Mild	704 (93)	241 (88)	463 (95)	<.001
Moderate	6 (1)	2 (1)	4 (1)
Severe	0	0	0
Missing	49 (6)	30 (11)	19 (4)
Medical comorbidities
Hypertension	114 (15)	37 (14)	77 (16)	.4
Gout	19 (3)	12 (4)	7 (1)	.01
Chronic pain	198 (26)	81 (30)	117 (24)	.09
Migraine	115 (15)	44 (16)	71 (15)	.58
Osteoarthritis	134 (18)	59 (22)	75 (15)	.03
Rheumatoid arthritis	6 (1)	3 (1)	3 (1)	.47
Systemic lupus erythematosus	3 (0)	0	3 (1)	.19

Note. Data are presented as count (percent), mean [SD], or median [IQR]. eGFR = estimated glomerular filtration rate; IQR = interquartile range; NSAID = non-steroidal anti-inflammatory drugs; SD = standard deviation; SES = socio-economic status.

Index date is defined as 1-year post-donation date or April 1, 2008, whichever is later.

Primary Outcome

Of the 759 donors, 273 (36%) had at least one NSAID prescription during follow-up. Donors with at least one NSAID prescription were more likely to be from lower socio-economic status (SES), have an earlier donation date, higher pre-donation eGFR, and co-morbid gout and osteoarthritis at the index date. There was no significant difference between donors with and without a prescription with respect to baseline hypertension, chronic pain, migraine, rheumatoid arthritis, and systemic lupus erythematosus.

Characteristics of NSAID Use

The median time from index date to first NSAID prescription was 2.9 years (IQR 1.1-5.1) and none of the donors with an NSAID prescription had an eGFR <30 mL/min/1.73 m² (Table 2). The median number of prescriptions per donor was 2 (IQR 1-4, rage 1-113). The proportion of donors each year with at least one prescription remained stable over time (~10% of the cohort per year; Figure 1). Of the 273 donors with at least 1 NSAID prescription, 104 (38%) of donors filled 3 or more prescriptions and 26 (10%) of donors had at least 1 prescription for greater than 30 days.

Table 2.

Characteristics of NSAID Use in Living Kidney Donors.

Donor-level characteristics	Donors with ≥1 NSAID prescription n = 273
Time from index date to first prescription, years	2.9 [1.1-5.1]
Donation era: 2002-2010	3.5 [1.2-4.1]
Donation era: 2011-2019	2.0 [0.9-3.9]
Time from donation to first prescription, years	5.0 [2.7-8.2]
Donation era: 2002-2010	6.6 [3.9-9.6]
Donation era: 2011-2019	3.0 [1.9-4.9]
eGFR (mL/min/1.73 m²)^a
≥90	19 (7)
60-89	102 (37)
45-59	57 (21)
30-44	3 (1)
15-29	0
<15	0
Missing	92 (34)
Number of prescriptions, per donor (minimum, maximum)	2 [1-4] (1-113)
≥3 prescriptions during follow-up	104 (38)
≥1 chronic NSAID prescription (>30 days)	26 (10)
Concurrent medication use ^b
Opioid	82 (30)
Anticoagulant	3 (1)
Antiplatelet	4 (1)
ACE inhibitor	5 (2)
ARB	7 (3)
Beta-blocker	3 (1)
CCB—dihydropyridine	4 (1)
Diuretic—non-loop	5 (2)
Diuretic—loop	2 (1)
Statin	23 (8)
PPI	56 (21)
H₂-blocker	2 (1)
Prescription-level characteristics	Total NSAID prescriptions n = 1,234
Median days supplied	15 [7-30]
Prescriber
Family physician	819 (66)
Psychiatrist	71 (6)
Emergency department physician	15 (1)
Nephrologist	0 (0)
Other	42 (3)
Missing	287 (23)
Type of NSAID prescription
Naproxen	392 (32)
Diclofenac	269 (22)
Celecoxib	161 (13)
Indomethacin	145 (12)
Ketorolac	132 (11)
Ibuprofen	116 (9)
Other	19 (2)

Note. Data are presented as N (%) or median [IQR]. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker; eGFR = estimated glomerular filtration rate; H₂-blocker = histamine blocker; IQR = interquartile range; NSAID = non-steroidal anti-inflammatory drug; PPI = proton pump inhibitor.

Based on the mean of all outpatient creatinine measurements in the 1 year prior to the first prescription.

Determined by evidence of prescription in the 120 days prior to the first NSAID prescription.

Figure 1.

Proportion of living kidney donors with at least one NSAID prescription per year in follow-up.

At the prescription level, there were 1,234 NSAID prescriptions. The median number of days supplied was 15 (IQR 7-30). Family physicians accounted for 66% of NSAID prescriptions and there were no documented prescriptions from kidney specialist physicians. The most common NSAIDs prescribed were naproxen (32%) and diclofenac (22%). Of the donors with an NSAID prescription, 30% also filled at least one prescription for an opioid in the preceding 120 days.

Post-Prescription Laboratory Testing

Only a minority of living donors had an outpatient, inpatient, or ED measurement of serum creatinine (12%, n = 33) or potassium (12%, n = 32) within 14 days following first NSAID prescription (Table 3). Of the donors that underwent post-prescription laboratory testing, 2/25 (8%) developed AKI, and 1/32 (3%) had hyperkalemia.

Table 3.

Outcomes Within 14 Days Following First NSAID Prescription in Living Kidney Donors.

Outcome	Donors with ≥1 NSAID prescriptionn = 273
Post-prescription outpatient, inpatient, or ED laboratory measurement
Serum creatinine	33 (12)
Serum potassium	32 (12)
Adverse outcomes
AKI within 14 days of those with serum creatinine^a	2/25 (8)
Hyperkalemia within 14 days of those with serum potassium^b	1/32 (3)

Note. Data are presented as N (%). AKI = acute kidney injury; ED = emergency department; KDIGO = Kidney Disease: Improving Global Outcomes; NSAID = non-steroidal anti-inflammatory drug.

AKI was defined as per the 2012 KDIGO AKI guidelines as a serum creatinine increase of ≥50% or ≥26.5 µmol/L (0.3 mg/dL), restricted to donors who had outpatient serum creatinine measurements in the 1 year prior to the prescription fill date to determine baseline compared to an outpatient, inpatient, or ED laboratory measurement in the 14 days after the prescription fill date.

Hyperkalemia was defined as an outpatient, inpatient, or ED serum potassium ≥5.5 mmol/L in the 14 days after the prescription fill date.

Sensitivity Analysis

When we restricted the analysis to living kidney donors who donated after January 1, 2007, our results were similar, in that 28% of donors (158/559) had an NSAID prescription from their 1-year post-donation date onwards.

Discussion

Pain is a common concern for living kidney donors post-nephrectomy, but there is minimal evidence regarding the safety and efficacy of pain-management strategies in this population. Guidelines caution against NSAID use after living kidney donation, but information on prescribing patterns and related care is limited. In our study of 759 living kidney donors identified through comprehensive database linkage in one Canadian province, 36% of donors filled at least 1 NSAID prescription in follow-up. Family physicians accounted for 66% of NSAID prescriptions. Only a minority of donors had post-prescription laboratory testing for serum creatinine or potassium, and the risk of AKI or hyperkalemia was uncommon in these donors.

The proportion of donors who filled an NSAID prescription was higher than anticipated considering guideline recommendations to avoid NSAID use after kidney donation, a recommendation based on concerns for potential nephrotoxicity.¹⁴ In the previously mentioned study from the United States, 5% of living kidney donors filled an NSAID prescription in the first year post-donation.¹⁶ Our study found a higher proportion (~10% per year) since we captured longer-term prescribing practices beyond the first year. We could not capture indication for NSAID prescription, but possible explanations for the high prescribing rate include lack of awareness of guidelines by prescribers or clinical necessity. Within our cohort, donors with an NSAID prescription were more likely to be from lower SES, which may be associated with lower health literacy²⁸ or an increased burden of comorbidities.²⁹ We also found that donors with an NSAID prescription were more likely to have an earlier donation date, suggesting the development of post-donation comorbidities leading to acute or chronic pain. A history of gout and osteoarthritis at the index date was associated with increased NSAID prescription fills, and while chronic pain at the index date was not associated, up to 25% of donors experience chronic pain post-donation.⁵ A similar study of kidney transplant recipients in Alberta also found that prescribing rates were greater than expected with 11% of recipients filling an NSAID prescription.²³

It is notable that the guideline recommendation to avoid NSAIDs in living kidney donors is based on expert opinion, rather than evidence, due to the limited available evidence. There are few studies assessing post-donation NSAID use and short- and long-term effects on kidney function.¹⁵ In the general population, a meta-analysis found a pooled odds ratio of AKI with current NSAID use of 1.73 (95% CI 1.44-2.07), acknowledging variability between the studies.¹⁰ Compared to the general population, living kidney donors may be at higher risk of AKI given their solitary kidney, but also at lower risk given that they are a healthier subset of the population with a surgical reduction in eGFR, rather than dysfunction due to a disease process. Early post-donation, one study assessed the effect of intraoperative ketorolac infusion verses normal saline during donor nephrectomy.³⁰ There was no significant impact on the 1- and 1.5-year post-donation eGFR, which suggests that short-term NSAID use in donors may be safe. In our study, the risk of AKI was 8% and hyperkalemia was 3% for donors that had evidence of post-prescription laboratory testing. This may reassure providers that the risk of kidney injury for donors receiving NSAID prescriptions is low, even in those whom we assume to be at higher risk given the early post-prescription bloodwork. However, only a minority of donors in our study (12%) had early post-prescription bloodwork and not all the donors in our study with post-prescription bloodwork had a baseline creatinine measurement in the previous year, so our ability to assess for associations between NSAID use and kidney dysfunction is limited. In addition, without formal chart reviews, we are unable to determine whether the cause of AKI was directly due to nephrotoxicity from the NSAID versus the concurrent illness the NSAID was prescribed to treat. Finally, comparison to a control group would be needed to confirm if the risk of AKI or hyperkalemia is greater for donors than the general population.

Given that pain management is a priority issue for living kidney donors, the uncertainty about NSAID safety in this population is concerning, as NSAIDs are considered a first-line analgesic.^3-6 More individuals are being included as donor candidates despite having comorbidities commonly treated with NSAIDs, such as rheumatoid arthritis, which makes NSAID safety for kidney donors an increasingly relevant topic.^31,32 Without NSAIDs, acetaminophen becomes the alternative first-line treatment option for donors, and if ineffective, leaves opioids as the next step on the WHO three-step analgesic ladder.⁶ The adverse effects of opioids have been extensively documented with the primary concern being dependence and risk for overdose.³³ While neither opioids nor NSAIDs have been well studied in the donor population, when comparing the risks, short-term NSAIDs may be a safer option.³⁴ Other medications gaining popularity in the general population for pain management include certain anticonvulsants, antidepressants, and dopamine receptor antagonists, but these have also not been well studied in living kidney donors.^35,36 Overall, further research is needed to assess optimal pain-management strategies in living kidney donors to characterize efficacy and safety.

Our study has strengths. It involves a large Canadian cohort of 759 donors with little loss to follow-up and a pharmaceutical database capturing all NSAID prescriptions. Furthermore, we were able to access all laboratory measurements performed within the province, and the measurements have been standardized across laboratories to reduce inter-laboratory variation. A limitation of our study is the inability to distinguish between NSAID prescriptions that were filled and not taken, potentially overestimating NSAID use. Conversely, we were unable to capture over-the-counter NSAIDs which likely underestimates use. We did not have information regarding indication for NSAID prescriptions, but did assess comorbidities at the index date that allowed us to infer it. We are also limited by indication bias for the post-prescription laboratory measurements. We are unable to infer if the laboratory testing was routine, in response to the illness the NSAID was treating, or for monitoring following the NSAID prescription. Finally, our findings may not be generalizable as Alberta has a predominately White population with universal access to health care.²² Given this, our study may not be as generalizable to jurisdictions with more diverse patient populations or alternative health care systems.

Conclusions

Over one-third of living kidney donors are prescribed NSAIDs beyond their first year post-donation. Given current guideline recommendations, educational initiatives for family practitioners and pharmacists may be beneficial. However, the potential risk of NSAIDs must be weighed against the benefit for each patient with consideration of the adverse events associated with alternative treatment options, such as opioids. If NSAID use is necessary, short durations with minimal doses are preferable, but there is no available evidence to guide safe NSAID use in this population. Further research is recommended to assess outcomes following NSAID use to better inform guidelines and safe prescribing practices for living kidney donors.

Supplemental Material

sj-docx-1-cjk-10.1177_20543581251368782 – Supplemental material for Non-steroidal Anti-inflammatory Drug Prescriptions in Living Kidney Donors: A Retrospective Cohort Study

Supplemental material, sj-docx-1-cjk-10.1177_20543581251368782 for Non-steroidal Anti-inflammatory Drug Prescriptions in Living Kidney Donors: A Retrospective Cohort Study by Mikayla I. Laube, Robert R. Quinn, Pietro Ravani, Krista L. Lentine, Alix Clarke, Rachel Jeong, Jason Bau and Ngan N. Lam in Canadian Journal of Kidney Health and Disease

Footnotes

Acknowledgements

This study is based in part on data provided by Alberta Health and Alberta Health Services. The interpretation and conclusions contained herein are those of the researchers and do not necessarily represent the views of the Government of Alberta or Alberta Health Services. Neither the Government of Alberta nor Alberta Health or Alberta Health Services express any opinion in relation to this study.

List of Abbreviations

ACE, angiotensin-converting enzyme; AKDN, Alberta Kidney Disease Network; AKI, acute kidney injury; ARB, angiotensin receptor blocker; CCI, Canadian Classification of Health Interventions; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ICD-10, International Statistical Classification of Diseases, Tenth Revision; IQR, interquartile range; KDIGO, Kidney Disease: Improving Global Outcomes; NSAID, non-steroidal anti-inflammatory drug; PIN, Pharmaceutical Information Network; SES, socio-economic status; SD, standard deviation; WHO, World Health Organization.

ORCID iDs

Robert R. Quinn

Pietro Ravani

Alix Clarke

Ngan N. Lam

Ethics Approval

We followed a protocol approved by the research ethics boards at the University of Alberta and the University of Calgary.

Consent to Participate

A waiver of patient consent was provided by the research ethics boards at the University of Alberta and the University of Calgary.

Consent for Publication

Not applicable.

Author Contributions ML and NNL conceived of the study and research design. AC performed the data analysis. ML, AC, and NNL participated in data interpretation. ML drafted the manuscript.

All authors critically revised the manuscript and accept accountability for the integrity of the data and data analysis.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. KLL is supported by the Mid-America Transplant Endowed Chair in Transplantation.

Data Availability

We are not able to make our dataset available to other researchers due to our contractual arrangements with the provincial health ministry (Alberta Health), who is the data custodian. Researchers may make requests to obtain a similar dataset at

Supplemental Material

Supplemental material for this article is available online.

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