Skip to main content

Advertisement

SpringerLink
Log in

Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration.

Methods

Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days.

Results

Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46–2.15) and 1.38 (1.18–1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09–2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09–1.82, p = 0.008) were also increased in systemic NSAIDs.

Conclusion

Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available, because data sharing will be subject to institutional approval.

References

  1. Tuttle KR, Alicic RZ, Duru OK et al (2019) Clinical characteristics of and risk factors for chronic kidney disease among adults and children: an analysis of the CURE-CKD registry. JAMA Netw Open 2(12):e1918169–e1918169

    Article  PubMed  PubMed Central  Google Scholar 

  2. Davison SN, Rathwell S, George C, Hussain ST, Grundy K, Dennett L (2020) Analgesic use in patients with advanced chronic kidney disease: a systematic review and meta-analysis. Can J Kidney Health Dis 7:2054358120910329

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lefebvre C, Hindié J, Zappitelli M, Platt RW, Filion KB (2019) Non-steroidal anti-inflammatory drugs in chronic kidney disease: a systematic review of prescription practices and use in primary care. Clin Kidney J 13(1):63–71

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang X, Donnan PT, Bell S, Guthrie B (2017) Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol 18(1):256

    Article  PubMed  PubMed Central  Google Scholar 

  5. Orlandi PF, Fujii N, Roy J et al (2018) Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. BMC Nephrol 19(1):150

    Article  PubMed  PubMed Central  Google Scholar 

  6. Heyneman CA, Lawless-Liday C, Wall GC (2000) Oral versus topical NSAIDs in rheumatic diseases. Drugs 60(3):555–574

    Article  CAS  PubMed  Google Scholar 

  7. Lin TC, Solomon DH, Tedeschi SK, Yoshida K, Kao Yang YH (2017) Comparative risk of cardiovascular outcomes between topical and oral nonselective NSAIDs in Taiwanese patients with rheumatoid arthritis. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.006874

    Article  PubMed  PubMed Central  Google Scholar 

  8. Makris UE, Kohler MJ, Fraenkel L (2010) Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol 37(6):1236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lim C, Choo J, Kwek JL, Abdul Kadir H, Tan NC (2021) Non-steroidal anti-inflammatory drug prescription in the young-old and very-old: type, route and burden of cardiovascular risk factors. Nephrol Dialysis Transplant. 36(Supplement_1):gfab092.0065

    Article  Google Scholar 

  10. Terrill M, Soden M, Srivastava V (2020) Survey of Australasian Renal and Rheumatology Specialists investigating topical NSAID use and adverse renal outcomes. Musculoskeletal Care 18(2):134–139

    Article  PubMed  Google Scholar 

  11. Fernando AH, Thomas S, Temple RM, Lee HA (1994) Renal failure after topical use of NSAIDs. BMJ (Clin Res ed) 308(6927):533–533

    Article  CAS  Google Scholar 

  12. Andrews PA, Sampson SA (1999) Topical non-steroidal drugs are systemically absorbed and may cause renal disease. Nephrol Dialysis Transplant 14(1):187–189

    Article  CAS  Google Scholar 

  13. Lim CC, Ang ATW, Kadir HBA et al (2020) Short-course systemic and topical non-steroidal anti-inflammatory drugs: impact on adverse renal events in older adults with co-morbid disease. Drugs Aging 38:147–156

    Article  PubMed  Google Scholar 

  14. Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nash DM, Markle-Reid M, Brimble KS et al (2019) Nonsteroidal anti-inflammatory drug use and risk of acute kidney injury and hyperkalemia in older adults: a population-based study. Nephrol Dialysis Transplant. 34:1145–1154

    Article  Google Scholar 

  16. Kellum JA, Lameire N, Aspelin P et al (2012) Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2(1):1–138

    Google Scholar 

  17. Schneider V, Lévesque LE, Zhang B, Hutchinson T, Brophy JM (2006) Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: a population-based, nested case-control analysis. Am J Epidemiol 164(9):881–889

    Article  PubMed  Google Scholar 

  18. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S (2013) Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ (Clin Res ed). 346:e8525

    Google Scholar 

  19. Chou C-I, Shih C-J, Chen Y-T et al (2016) Adverse effects of oral nonselective and cyclooxygenase-2-selective NSAIDs on hospitalization for acute kidney injury: a nested case–control cohort study. Medicine 95(9):e2645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Horl WH (2010) Nonsteroidal anti-inflammatory drugs and the kidney. Pharmaceuticals (Basel, Switzerland) 3(7):2291–2321

    Article  PubMed  Google Scholar 

  21. Williams AW, Dwyer AC, Eddy AA et al (2012) Critical and honest conversations: the evidence behind the “Choosing Wisely” campaign recommendations by the American Society of Nephrology. Clin J Am Soc Nephrol CJASN 7(10):1664–1672

    Article  PubMed  Google Scholar 

  22. Szeto C-C, Sugano K, Wang J-G, et al (2020) Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations. Gut

  23. Ingrasciotta Y, Sultana J, Giorgianni F et al (2015) Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study. PLoS ONE 10(4):e0122899

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhan M, Doerfler RM, Xie D, et al (2020) Association of opioids and nonsteroidal anti-inflammatory drugs with outcomes in CKD: findings from the CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis

  25. Katsuno T, Togo K, Ebata N et al (2021) Burden of renal events associated with nonsteroidal anti-inflammatory drugs in patients with osteoarthritis and chronic low back pain: a retrospective database study. Pain Ther 10:443–455

  26. Dreischulte T, Morales DR, Bell S, Guthrie B (2015) Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin–angiotensin system inhibitors in the community increases the risk of acute kidney injury. Kidney Int 88(2):396–403

    Article  CAS  PubMed  Google Scholar 

  27. Schjerning A-M, McGettigan P, Gislason G (2020) Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol 17:1–11

    Article  Google Scholar 

  28. Navaneethan SD, Schold JD, Arrigain S, Jolly SE, Nally JV (2015) Cause-specific deaths in non–dialysis-dependent CKD. J Am Soc Nephrol 26(10):2512–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chertow GM, Lee J, Kuperman GJ et al (2001) Guided medication dosing for inpatients with renal insufficiency. JAMA 286(22):2839–2844

    Article  CAS  PubMed  Google Scholar 

  30. Yamamoto T, Nakayama I, Kawakatsu Y et al (2019) Effects of pharmacist participation in chronic kidney disease (CKD) network and CKD manual distribution on drug-related kidney injury. Pharmacoepidemiol Drug Saf 28(6):887–896

    Article  CAS  PubMed  Google Scholar 

  31. Martin M, Wilson FP (2019) Utility of electronic medical record alerts to prevent drug nephrotoxicity. Clin J Am Soc Nephrol 14(1):115–123

    Article  CAS  PubMed  Google Scholar 

  32. Pham PC, Khaing K, Sievers TM et al (2017) 2017 update on pain management in patients with chronic kidney disease. Clin Kidney J 10(5):688–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Persons O (2009) Pharmacological management of persistent pain in older persons. J Am Geriatr Soc 57(8):1331–1346

    Article  Google Scholar 

  34. Novick TK, Surapaneni A, Shin J-I et al (2018) Prevalence of opioid, gabapentinoid, and NSAID use in patients with CKD. Clin J Am Soc Nephrol 13(12):1886–1888

    Article  PubMed  PubMed Central  Google Scholar 

  35. Muanda FT, Weir MA, Ahmadi F et al (2022) Higher-dose gabapentinoids and the risk of adverse events in older adults with CKD: a population-based cohort study. Am J Kidney Dis 80(1):98-107.e101

    Article  CAS  PubMed  Google Scholar 

  36. Agoritsas T, Merglen A, Shah ND, O’Donnell M, Guyatt GH (2017) Adjusted analyses in studies addressing therapy and harm: users’ guides to the medical literature. JAMA 317(7):748–759

    Article  PubMed  Google Scholar 

  37. Signorello LB, McLaughlin JK, Lipworth L, Friis S, Sørensen HT, Blot WJ (2002) Confounding by indication in epidemiologic studies of commonly used analgesics. Am J Ther 9(3):199–205

    Article  PubMed  Google Scholar 

  38. Secrest MH, Platt RW, Dormuth CR et al (2020) Extreme restriction design as a method for reducing confounding by indication in pharmacoepidemiologic research. Pharmacoepidemiol Drug Saf 29:26–34

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the SingHealth Health Services Research Center for providing de-identification service and the SingHealth Research Office for administrative support.

Funding

This research was supported by the SHF-Foundation Research Grant (SHF/HSRHO014/2017).

Author information

Authors and Affiliations

  1. Department of Renal Medicine, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore, 169856, Singapore

    Su Hooi Teo, Jason Chon Jun Choo, Jia Liang Kwek, Huijun Huang, Manish Kaushik & Cynthia Ciwei Lim

  2. SingHealth Polyclinic, Singapore, Singapore

    Ngiap Chuan Tan & Andrew Teck Wee Ang

  3. Health Services Research Unit, Singapore General Hospital, Singapore, Singapore

    Hanis Bte Abdul Kadir

  4. Department of Endocrinology, Singapore General Hospital, Singapore, Singapore

    Yong Mong Bee

Authors
  1. Su Hooi Teo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ngiap Chuan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason Chon Jun Choo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia Liang Kwek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanis Bte Abdul Kadir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Mong Bee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huijun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manish Kaushik
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrew Teck Wee Ang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cynthia Ciwei Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to and approved the final version of this manuscript for submission.

Corresponding author

Correspondence to Cynthia Ciwei Lim.

Ethics declarations

Conflict of interest

All authors declare no relevant conflict of interest.

Ethics approval

For manuscripts that report the results of a clinical trial, a statement confirms that the study was approved (or granted exemption) by the appropriate institutional and/or national research ethics committee (including the name of the ethics committee) and certifying that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent

Waiver of informed consent for use of de-identified electronic medical record data was approved by the SingHealth Centralized Institutional Review Board (2018/2567).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 28 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teo, S.H., Tan, N.C., Choo, J.C.J. et al. Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration. Int Urol Nephrol 55, 679–686 (2023). https://doi.org/10.1007/s11255-022-03344-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-022-03344-9

Keywords

Search

Navigation