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acute interstitial nephritis

Etiology: 1) allergic reaction 2) pharmacologic causes (most common, 70%) [10] a) antibiotics (most common, 35% of total cases) [10] 1] penicillins, esp methicillin (anti-tubular basement membrane antibodies) 2] cephalosporins 3] anti-tuberculous medications a] rifampin b] isoniazid c] ethambutol 4] sulfonamides 5] fluoroquinolones [14] a] ciprofloxacin b] levofloxacin 6] vancomycin 7] pentamidine b) antiviral: indinavir c) NSAIDs (large doses), COX2 inhibitors d) diuretics (sulfa derivatives) 1] thiazides 2] furosemide (Lasix) 3] bumetanide (Bumex) e) H2 blockers: cimetidine f) proton pump inhibitors [10] g) allopurinol, phenytoin & phenindione cause 1] exfoliative dermatitis 2] hepatitis 3] acute interstitial nephritis h) cyclosporin A - acute renal vasoconstriction i) phenobarbital j) levetiracetam (Keppra) [13] k) interferon alpha l) mesalamine [4] 3) infection a) streptococcus b) leptospirosis c) Rocky Mountain spotted fever d) Legionella e) Epstein Barr virus f) cytomegalovirus g) HIV h) toxoplasmosis i) polyoma BK virus in renal transplant patients 4) infiltrative malignancies a) lymphoma b) leukemia: leukemic infiltration c) multiple myeloma 5) autoimmune a) lupus nephritis b) Sjogren's syndrome c) sarcoidosis (most common among autoimmune disorders) [10] 6) toxins a) Chinese herb nephropathy b) heavy metal toxicity: germanium, lead c) myeloma cast nephropathy 7) renal transplant rejection 8) radiation 9) acute pyelonephritis Pathology: - often caused by hypersensitivity to a medication - acute interstitial infiltrate a) mononuclear cells b) eosinophils (less frequently) Clinical manifestations: 1) generally occurs after 7-10 days of drug exposure - prior drug exposure may result in earlier onset [4,7] 2) fever 90% 2 weeks duration 3) arthralgias (25%) 4) rash (25%) 5) acute renal failure is generally non-oliguric 6) not associated with flank pain [5] Laboratory: 1) urinalysis: a) sterile pyuria (100%); may be as few as 5-10 WBC/hpf [4] b) hematuria (95%), no RBC casts c) proteinuria (75%) - < 2.5 mg/mg of creatinine (not nephrotic range) d) urinary leukocyte casts in the urine sediment - brown granular casts not observed [4] e) eosinophils in urine: eosinophiluria (50%) - not specific, not needed for diagnosis [4] 2) renal insufficiency (60%) a) increased serum creatinine - gradual increase in serum creatinine 7-10 days after drug exposure [4] b) increased serum urea nitrogen 3) renal biopsy sometimes needed for diagnosis 4) complete blood count - may show eosinophilia (23%) [16] Radiology: 1) renal ultrasound may show renal papillary necrosis 2) gallium scan or indium scan can be helpful Management: 1) discontinue use of offending pharmaceutical agent & observe [19] 2) prednisone 60 mg QOD for 2-4 weeks [4,6] - generally reserved for patients who do not respond to discontinuation of offending agent [4,19] - improves recovery, diminishes need for dialysis [6] 3) specific therapy for specific etiology 4) dialysis may be necessary 5) recovery is variable - 47% with complete recovery of renal function - 38% with partial recovery of renal function [10] - ~100% if offending drug stopped immediately after onset of acute renal failure [4,20]

Related

chronic interstitial nephritis (analgesic nephropathy, drug-induced chronic interstitial nephritis)

Specific

acute uric acid nephropathy

General

interstitial nephritis acute inflammation acute kidney disease

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
  2. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 266
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 612
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021
  5. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004 - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  6. Gonzalez E et al Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int. 2008 Apr;73(8):940-6. Epub 2008 Jan 9. PMID: 18185501
  7. Praga M, Gonzalez E. Acute interstitial nephritis. Kidney Int. 2010 Jun;77(11):956-61 PMID: 20336051 Free Article - Praga M, Sevillano A, Aunon P, Gonzalez E. Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury. Nephrol Dial Transplant. 2015 Sep;30(9):1472-9. Review. PMID: 25324356
  8. Appel GB. The treatment of acute interstitial nephritis: More data at last. Kidney Int. 2008 Apr;73(8):905-7. PMID: 18379525
  9. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol. 2010 Aug;6(8):461-70 PMID: 20517290
  10. Blank ML et al A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 2014 Oct; 86:837 PMID: 24646856 - Muriithi AK et al. Biopsy-proven acute interstitial nephritis, 1993 - 2011: A case series. Am J Kidney Dis 2014 Oct; 64:558 PMID: 24927897
  11. Fogazzi GB, Ferrari B, Garigali G, Simonini P, Consonni D Urinary sediment findings in acute interstitial nephritis. Am J Kidney Dis. 2012 Aug;60(2):330-2. PMID: 22677261
  12. Raghavan R, Eknoyan G. Acute interstitial nephritis - a reappraisal and update. Clin Nephrol. 2014 Sep;82(3):149-62. Review. PMID: 25079860 Free PMC Article
  13. Lowes R New FDA Watch List Flags More Drugs Medscape Internal Medicine. July 3, 2017 http://www.medscape.com/viewarticle/882425
  14. Farid S, Mahmood M, Abu Saleh OM et al. Clinical manifestations and outcomes of fluoroquinolone- related acute interstitial nephritis. Mayo Clin Proc. 2018 Jan;93(1):25-31 PMID: 29157532 http://www.mayoclinicproceedings.org/article/S0025-6196(17)30695-X/fulltext
  15. Muriithi AK, Nasr SH, Leung N. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin J Am Soc Nephrol 2013 Nov; 8:1857. PMID: 24052222 Free PMC Article
  16. NEJM Knowledge + Question of the Week. Jam 23, 2019 https://knowledgeplus.nejm.org/question-of-week/1148/ - Grad YH, Seifter JL, Levy BD, Loscalzo J. Clinical problem-solving. Bitter pills. N Engl J Med. 2010 Nov 4;363(19):1847-51 PMID: 21047229 Free PMC Article https://www.nejm.org/doi/full/10.1056/NEJMcps0904937
  17. Krishnan N, Perazella MA. Drug-induced acute interstitial nephritis: pathology, pathogenesis, and treatment. Iran J Kidney Dis. 2015;9(1):3-13 PMID: 25599729 Free article
  18. Moledina DG, Perazella MA. Drug-induced acute interstitial nephritis. Clin J Am Soc Nephrol CJASN. 2017;12(12):2046-2049 PMID: 28893923 PMCID: PMC5718279 Free PMC article https://cjasn.asnjournals.org/content/12/12/2046
  19. NEJM Knowledge+ Nephrology/Urology
  20. Perazella MA. Diagnosing drug-induced AIN in the hospitalized patient: a challenge for the clinician. Clin Nephrol. 2014 Jun;81(6):381-8. PMID: 24691017 PMCID: PMC4326856 Free PMC article.