Kidney nontumor / medical renal

Tubulointerstitial disease

Other tubular and interstitial disease

Tubulointerstitial nephritis-general

Last author update: 15 December 2021
Last staff update: 19 December 2023

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PubMed Search: Tubulointerstitial nephritis kidney

Sam T. Albadri, M.B.Ch.B., M.Sc.
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Cite this page: Albadri ST. Tubulointerstitial nephritis-general. website. Accessed February 22nd, 2024.
Definition / general
  • Acute interstitial inflammation is commonly associated with involvement of the tubules due to a variety of causes
Essential features
  • Acute inflammation involving tubulointerstitial compartments
  • Might be associated with acute tubular injury or tubulointerstitial scarring
  • Common etiologies include drug, autoimmune, infection, hereditary and idiopathic
  • Acute interstitial nephritis (AIN)
ICD coding
  • ICD-10:
    • N10 - acute pyelonephritis
    • N11 - chronic tubulointerstitial nephritis
    • N12 - tubulointerstitial nephritis, not specified as acute or chronic
    • N13 - obstructive and reflux uropathy
    • N14 - drug and heavy metal induced tubulointerstitial and tubular conditions
    • N15 - other renal tubulointerstitial diseases
    • N16 - renal tubulointerstitial disorders in diseases classified elsewhere
  • Kidney, interstitium and tubules
  • High exposure to nephrotoxic drugs
  • Injury of the tubulointerstitial compartment due to decreased blood supply and increase in metabolic demand
  • Escalating the inflammatory processes by production and activation of cytokines, tissue necrosis factor (TNF) alpha
  • Type IV hypersensitivity reactions in drug induced tubulointerstitial nephritis (Adv Chronic Kidney Dis 2017;24:107)
  • Drugs (J Nephrol 2016;29:611, Am J Kidney Dis 1998;31:108):
    • Accounts for about 60 - 70% of all tubulointerstitial nephritis
    • Allergic (nonsteroidal anti-inflammatory [NSAIDs], antibiotics, proton pump inhibitors [PPI])
    • Toxic (lithium)
  • Autoimmune:
    • Primary (antibrush border antibody [ABBA])
    • Secondary to systemic diseases (Sjögren syndrome, IgG4 related disease, tubulointerstitial nephritis with uveitis) or immune upregulation (check point inhibitor therapy)
  • Infection:
    • Primary kidney (pyelonephritis, BK polyomavirus tubulointerstitial nephritis)
    • Secondary to infection associated glomerulonephritis
  • Hereditary / toxic / metabolic:
  • Idiopathic: 8%
Diagrams / tables

Images hosted on other servers:

Diagnosis of
inherited interstitial
kidney disease

Clinical features
  • Acute or subacute renal failure
  • Subnephrotic range proteinuria
  • Sometimes microscopic hematuria
  • Drug induced tubulointerstitial nephritis: fever, skin rash, arthralgia and eosinophilia (Pediatr Clin North Am 2019;66:111)
  • Clinical history of newly exposure to new drug (allergic etiology) or presence / absence of systemic disease
  • Physical examination; skin rashes (morbilliform, maculopapular, erythroderma and epidermal necrolysis) (Nat Rev Nephrol 2010;6:461)
  • Bilateral normal to increased size of the kidney and diffusely increased cortical hyperechogenicity by renal ultrasound (Nat Rev Nephrol 2010;6:461)
  • Elevation of serum creatinine and blood urea (Clin J Am Soc Nephrol 2017;12:2046)
  • Hyperkalemic
  • Hyperchloremic metabolic acidosis
  • Elevation of eosinophils level (nonspecific)
  • Elevation the level of serum erythrocyte sedimentation rate (ESR) or C reactive proteins
  • Positive proteinuria in dipstick test and microscopic or macroscopic hematuria
Prognostic factors
Case reports
  • 14 year old girl with one sided uveitis and renal involvement (J Med Case Rep 2021;15:443)
  • 28 year old man with a history of ulcerative colitis and sacroiliitis with progressive kidney dysfunction (Intern Med 2019;58:79)
  • 59 year old man with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute kidney injury (AKI) (Clin Kidney J 2021;14:2151)
  • 70 year old man with renal dysfunction, a medical history of bile duct stenosis, an inflammatory pancreatic mass and elevation of serum creatinine and IgG4 (Ren Fail 2019;41:657)
  • Eliminate the causative agents (drugs / toxins)
  • Treat associated systemic disorders
  • Corticosteroid therapy
  • In steroid resistant cases and steroid contraindicated cases, mycophenolate mofetil could be considered (Adv Chronic Kidney Dis 2017;24:94)
  • Azathioprine could be used in cases associated with systemic inflammatory and autoimmune diseases, such as Sjögren syndrome
Clinical images

Images hosted on other servers:

Drug induced tubulointerstitial nephritis

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Sam T. Albadri, M.B.Ch.B., M.Sc.

Interstitial inflammation


Granulomatous interstitial nephritis

Eosinophilic tubulitis

IgG4 related kidney disease


IgG4 immunostain

Immunofluorescence description
  • Granular tubular basement membranes deposits with IgG (IgG4 related tubulointerstitial nephritis)
  • Linear tubular basement membranes deposits (antitubular basement membrane disease) (Curr Opin Nephrol Hypertens 2012;21:279)
Immunofluorescence images

Contributed by Sam T. Albadri, M.B.Ch.B., M.Sc.


Positive stains
Electron microscopy description
  • Nonspecific; evidence of inflammatory cells in the interstitium and tubules
Electron microscopy images

Contributed by Sam T. Albadri, M.B.Ch.B., M.Sc.

Interstitial inflammation and tubulitis


Histopathology kidney - interstitial nephritis

Sample pathology report
  • Kidney, core needle biopsy:
    • Acute and chronic interstitial nephritis, moderate (see comment)
    • Comment: There is no evidence of a glomerular disease of the immune complex type seen on immunofluorescence. Light microscopy exhibits mild acute and chronic interstitial nephritis. Given the positive ANA and SSA and the plasma cell rich infiltrate, this could be due to autoimmune disease, such as Sjögren syndrome. Other possibilities include tubulointerstitial nephritis and uveitis (TINU) syndrome and drug allergies. Clinical correlation is recommended.
Differential diagnosis
Board review style question #1

What is the most common cause of acute tubulointerstitial nephritis?

  1. Drugs
  2. Hereditary
  3. Idiopathic
  4. Sarcoidosis
Board review style answer #1
Board review style question #2
What is the most important histopathologic finding in acute tubulointerstitial nephritis?

  1. Crescentic lesions
  2. Glomerulitis
  3. Inflammation of the interstitium with active tubulitis
  4. Segmental sclerosis of the glomeruli
Board review style answer #2
C. Inflammation of the interstitium with active tubulitis

Comment Here

Reference: Tubulointerstitial nephritis
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