NEPHROTOXICITY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: MECHANISMS, CLINICAL PRESENTATIONS, PREVENTION

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Issue: 
11
Year: 
2017

Professor A. Dyadyk, MD, Honored Science and Technology Worker of Ukraine; T. Kugler, Candidate of Medical Sciences; I. Tsyba, Candidate of Medical Sciences; V. Gnilitskaya, Candidate of Medical Sciences; A. Kaluga Maksim Gorky Donetsk National Medical University

Nonsteroidal anti-inflammatory drugs (NSAIDs) that are among the most popular classes of drugs are a leading cause of renal side effects. The mechanism of action of NSAIDs is associated with blockade of synthesis of renal vasodilator prostaglandins due to inactivation of the enzyme cyclooxygenase. Acute tubulointerstitial nephritis is the most common cause of NSAID-induced kidney injury. In addition, the risk of development and progression of chronic kidney disease has been reported. In this connection, it is necessary to conduct controlled randomized studies of renal complications caused by NSAIDs; the results of these studies will increase awareness of the problem discussed among physicians and pharmacists. It is necessary to strictly regulate the prescription of NSAIDs, to use both their optimal dosages and optimal use duration, and to assess the presence of risk factors for renal complications. To timely diagnose the nephrotoxicity of NSAIDs, a follow-up study of serum creatinine levels should be done calculating glomerular filtration rate, renal concentrating ability (Zimnitsky’s test), and complete urinalysis indices.
Keywords: 
nephrology
nonsteroidal anti-inflammatory drugs
kidneys
glomerular filtration rate
acute kidney injury
tubulointerstitial nephritis
chronic kidney disease
prostaglandins

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References: 
  1. Musu M. et al. Acute nephrotoxicity of NSAID from the foetus to the adult // Eur. Rev. Med. Pharmacol. Sci. – 2011; 15 (12): 1461–72.
  2. Davis A., Registrar G. The dangers of NSAIDs: look both ways // Br. J. Gen. Pract. – 2016; 66 (645): 172–3. DOI: 10.3399/bjgp16X684433.
  3. Pai A. Keeping kidneys safe: the pharmacist`s role in NSAID avoidance in high-risk patients // Pharmacy Today. – 2014; 20 (12): 54–64.
  4. Hörl W. et al. Nonsteroidal Anti-Inflammatory Drugs and the Kidney // Pharmaceuticals (Basel). – 2010; 3 (7): 2291–321.
  5. Zhang X. 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. – 2017; 18: 256. DOI: 10.1186/s12882-017-0673-8.
  6. Rossert J. Drug-induced acute interstitial nephritis // Kidney Int. – 2001; 60 (2): 804–17. DOI: 10.1046/j.1523-1755.2001.060002804.x.
  7. Dreischulte T., Morales D., Bell S. et al. 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. – 2015; 88 (2): 396–403. DOI: 10.1038/ki.2015.101.
  8. Smirnov A.V., Dobronravov V.A. i rabochaja gruppa chlenov Assotsiatsii nefrologov Rossii. Natsional'nye rekomendatsii «Ostroe povrezhdenie pochek: osnovnye printsipy diagnostiki, profilaktiki i terapii». Ch. 1 (2015) // Pochki. – 2016; 2 (16): 63–84.
  9. Smirnov A.V., Dobronravov V.A. i rabochaja gruppa chlenov Assotsiatsii nefrologov Rossii. Natsional'nye rekomendatsii «Ostroe povrezhdenie pochek: osnovnye printsipy diagnostiki, profilaktiki i terapii» (2015). Ch. 2 // Pochki. – 2016; 3 (17): 39–52.
  10. Dudareva L.A., Batjushin M.M. Hronicheskij tubulointerstitsial'nyj nefrit, indutsirovannyj priemom nesteroidnyh protivovospalitel'nyh preparatov: epidemiologicheskie osobennosti i vozmozhnosti rannej diagnostiki // Nefrologija. – 2013; 17 (5): 22–6.
  11. Huerta C., Castellsaque J., Varas-Lorenzo C. et al. Nonsteroidal Anti-Inflammatory Drugs and Risk of ARF in the General Population // Am. J. Kidney Dis. – 2005; 45: 531–9.
  12. Ungprasert P. et al. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies // Eur. J. Intern. Med. – 2015; 26 (4): 285–91. DOI: 10.1016/j.ejim.2015.03.008.
  13. Chel'tsov V.V. NPVS – nefropatii // Klin. nefrologija. – 2011; 5: 17–23.
  14. Schlondorff D. Renal complications of nonsteroidal anti-inflammatory drugs // Kidney Int. – 1993; 44 (3): 643–53.
  15. Crofford L. COX-1 and COX-2 tissue expression: implications and predictions // J. Rheumatol. Suppl. – 1997; 49: 15–9.
  16. Adegboyega P. et al. Immunohistochemical expression of cyclooxygenase-2 in normal kidneys // Appl. Immunohistochem. Mol. Morphol. – 2004; 12: 71–4.
  17. Komhoff M. Cyclooxygenase-2 selective inhibitors impair glomerulogenesis and renal cortical development // Kidney Int. – 2000; 57: 414–22.
  18. Jonson A. NSAIDs and increased blood pressure. What is clinical significance? // Drug Safety. – 1997; 17: 277–89.
  19. Brodsky S., Nadashy T. Acute and chronic tubulointerstitial nephritis. Heptinstall’s Pathology of the Kidney. Ch. 25 / Philadelphia: Wolters Kluwer, 1111–65.
  20. Gambaro G., Perazella M. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors // J. Intern. Med. – 2003; 253 (6): 643–52.
  21. Karateev A.E., Nasonov E.L., Jahno N.N. i dr. Klinicheskie rekomendatsii «Ratsional'noe primenenie nesteroidnyh protivovospalitel'nyh preparatov (NPVP) v klinicheskoj praktike» // Sovrem. revmatol. – 2015; 9 (1): 4–23 DOI: 10.14412/1996-7012-2015-1-4-23.
  22. Perazella M., Luciano R. Review of select causes of drug-induced AKI // Expert Rev. Clin. Pharmacol. – 2015; 8 (4): 367–71 DOI: 10.1586/17512433.2015.1045489.
  23. Baker R. Acute tubulointerstitial nephritis: overview. Oxford Textbook of Clinical Nephrology (4 ed.) 2016. Section 4. Chapter 83: 669–677.
  24. Kelly C., Neilson E. Tubulointerstitial diseases. Brenner and Rector's the Kidney edited by Karl Skorecki et al. 10 ed. / Elsevier, 2016; Ch. 36: 1209–30.
  25. Krishnan N., Perazella M. Drug-induced acute interstitial nephritis // Kidney Dis. – 2015; 9: 3–13.
  26. Leonard Ch. et al. Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury // Pharmacoepidemiol. Drug Safety. – 2012; 21: 1155–72.
  27. Nast C. Medication-Induced Interstitial Nephritis in the 21st Century // Adv Chronic Kidney Dis. – 2017; 24 (2): 72–9.
  28. Baker R., Pusey C. The changing profile of acute tubulointerstitial nephritis // Nephrol. Dial. Transplant. – 2004; 19: 8–11.
  29. Rossert J., Fischer E. Acute interstitial nephritis. In: Johnson R., Feehally J., eds. Comprehensive clinical nephrology / St Louis, Mosby, 2000; 62.1–62.9.
  30. Perazella M., Markowitz G. Drug-induced acute interstitial nephritis // Nat. Rev. Nephrol. – 2010; 6 (8): 461–70.
  31. Izzedine H., Guetin V. Drug-induced acute tubulointerstitial nephritis. Oxford Textbook of Clinical Nephrology (4 ed.) Section 4. Chapter 84: 679–86.
  32. Neilson E. Pathogenesis and therapy of interstitial nephritis // Kidney Int. – 1989; 35: 1257.
  33. Chang C., Gershwin M. Drugs and autoimmunity--a contemporary review and mechanistic approach // J. Autoimmun. – 2010; 34: J266–75.
  34. Singh N., Ganguli A, Prakash A. Drug-induced kidney diseases // J. Assoc. Physicians India. – 2003; 51: 970–9.
  35. Kasiske B., Keane W. Laboratory assesment of renal biopsy. Brenner and Rector's the Kidney edited by Karl Skorecki et al. 10 ed. / Elsevier, 2016; 1137–74.
  36. Walker P. The renal biopsy // Arch. Pathol. Lab. Med. – 2009; 133: 181–8.
  37. Radford M. Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs // JAMA. – 1996; 276 (6): 466–9.
  38. Warren G., Korbet S., Schwartz M. et al. Minimal change glomerulopathy associated with nonsteroidal antiinflammatory drugs // Am. J. Kidney Dis. – 1989; 13 (2): 127–30.
  39. Mohammed S. Risk factors for occurrence and recurrence of diabetic foot ulcers among Iraqi diabetic patients // Diabet Foot Ankle. – 2016; 7: 29605. DOI: 10.3402/dfa.v7.29605.
  40. Pirani C. et al. Renal toxicity of nonsteroidal anti-inflammatory drugs // Contrib. Nephrol. – 1987; 55: 159–75.
  41. Batjushkin M.M. Rol' anal'getikov i nesteroidnyh protivovospalitel'nyh preparatov v razvitii interstitsial'nogo porazhenija pochek // Nefrologija i dializ. – 2008; 8 (3): 239–43.
  42. Pentjuk O.O. Nefrotoksichnіst' lіkars'kih zasobіv: klіnіchnі projavi, patofіzіologіchnі mehanіzmi ta pіdhodi do lіkuvannja // Rats. farmakoterapіja. – 2009; 1: 21–7.
  43. Blowey D. Nephrotoxicity of over-the-counter analgesics, natural medicines and illicit drugs // Adolesc. Med. – 2005; 16: 31–43.
  44. Sigitova O.N., Arhipov E.V. Tubulointerstitsial'nyj nefrit // Vestn. sovr. klin. meditsiny. – 2010; 3 (3): 45–9.
  45. Gonzales E., Gutierrez E., Galeano C. et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis // Kidney Int. – 2008; 73 (8): 940–6.
  46. Muriithi A., Leung N., Valeri A. et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series // Am. J. Kidney Dis. – 2014; 64: 558–66.
  47. Clarcson M. et al. Acute iterstitial nephritis% clinical features and response to corticosteroid therapy // Nephrol. Dial. Transplant. – 2004; 19 (11): 2778–83.
  48. Nderitu P., Doos L., Jones P. et al. Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review // Family Practice. – 2013; 30: 247–55. DOI: 10.1093/fampra/cms086.
  49. Kohlhagen J. et al. Does regular use of non-steroidal anti-inflammatory drugs increase the risk of renal disease? // Nephrology. – 2002; 7 (1): 5–11 DOI: 10.1046/j.1440-1797.2002.00069.x.
  50. Agodoa L., Francis M., Eggers P. Association of analgesic use with prevalence of albuminuria and reduced GFR in US adults // Am. J. Kidney Dis. – 2008; 51: 573–83.
  51. Yaxley J., Litfin T. Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a systematic review // Ren. Fail. – 2016; 38 (9): 1328–34. DOI: 10.1080/0886022X.2016.1216708.
  52. Muhin N. i soavt. Porazhenie pochek, obuslovlennoe zloupotrebleniem neopioidnymi anal'getikami // Vrach. – 2006; 3: 34–7.
  53. Chang Yu-Kang. Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) // Medicine (Baltimore). – 2015; 94 (38): e1362. DOI: 10.1097/MD.0000000000001362.
  54. Schwarz A., Krause P., Kunzendorf U. et al. The outcome of acute interstitial nephritis: Risk factors for the transition from acute to chronic interstitial nephritis // Clin. Nephrol. – 2000; 54: 179–90.
  55. Ingrasciotta Y., Sultana J., Giorgianni F. et al. Association of Individual Non-Steroidal Anti- Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study // PLoS One. – 2015; 10 (4): e0122899. DOI: 10.1371/journal.pone.0122899.
  56. Armstrong E., Malone D. The impact of nonsteroidal anti-inflammatory drugs on blood pressure, with an emphasis on newer agents // Clin. Ther. – 2003; 25: 1–18.