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Chronic tubulointerstitial nephritis (CTIN) is an inflammatory process that involves the peritubular space or interstitium of the kidneys resulting in interstitial scarring with fibrosis, a lymphomonocytic infiltrate, tubular dilation, and atrophy. These forms of injury are very similar regardless of the inciting cause. Usually asymptomatic, it presents as a slowly progressive impairment in renal function leading to chronic kidney disease (CKD). Any structural damage, either glomerular, tubular, or a direct injury to the interstitium from an acute nephritis that has not appropriately resolved can amount to CTIN.

The most common etiologies are medication-induced lesions and infections. However, a wide variety of other diseases can lead to CTIN, including heavy metal toxicities or exposures, chronic obstructive nephropathy, reflux disease, nephrolithiasis, immunologic disease, metabolic disorders, genetic disease, neoplasia, and chronic renovascular, ischemia (Table 38–1). The following will provide an overview of select causes of CTIN.

Table 38–1.Causes of chronic tubulointerstitial disease.


  • Most common cause of drug induced CTIN

  • Seen with phenacetin, acetaminophen, aspirin, and NSAIDs

  • Presents with CTIN, papillary necrosis, hypertension

  • Despite association with nephropathy, number of patients is relatively low given the total amount of non-narcotic analgesics prescribed or available without prescription

Lithium-Induced Renal Disease
  • Approximately 15–20% of patients treated with lithium will develop kidney disease

  • Latent period to development of ESRD is approximately 20 years

  • Renal manifestations include: FSGS, MCD, distal RTA, diabetes insipidus, and CTIN

  • Stopping lithium may delay progression, but progression to ESRD tends to occur if serum creatinine >2.5 mg/dL

Aristolochic Acid Nephropathy
  • Exposure through herbal supplements containing ingredients from Aristolochia species

  • Rapid progression to ESRD of approximately 2 years

  • Biopsy reveals hypocellular infiltrate with severe fibrosis

  • 40–45% prevalence of urothelial carcinomas

  • Treatment with glucocorticoids may delay progression to ESRD

  • Balkan endemic nephropathy is a prolonged variant of AAN with progression to ESRD occurring over decades

Renal Sarcoidosis
  • Immune mediated disease affecting several organs including lungs and kidney

  • Renal involvement can be in the form of hypercalcemia with AKI to CTIN with granulomatous lesions

  • Glucocorticoids remains first line of therapy

  • Anterior uveitis usually occurs after nephritis

  • CTIN is ...

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