Tubulointerstitial diseases

Tubulointerstitial diseases are characterized by acute or chronic inflammation of the renal tubules and interstitium. Acute interstitial nephritis is commonly caused by hypersensitivity reactions to drugs, but infection or systemic disease may also precipitate the disease. Common causes of chronic nephritis include drug toxicity (especially analgesics), metabolic disease (e.g., uric acid nephropathy), and other underlying conditions (e.g., multiple myeloma). Typical symptoms in both acute and chronic nephritis are painless hematuria (without RBC casts) and pyuria. Depending on the underlying disease, nephritis may present with additional symptoms such as rash, arthralgias, and fever in the case of allergic interstitial nephritis. The most important diagnostic modalities are lab tests (increased blood urea nitrogen and creatinine) and urinalysis, although a kidney biopsy may be indicated in selected cases. Treatment usually consists of supportive measures and addressing the underlying cause (e.g., discontinuing medication). All diseases affecting the renal tubules can ultimately lead to chronic renal failure.

• Definition: an acute inflammation of the renal interstitium and tubules that causes a decline in renal function over a period of days to several weeks ^[1]
• Etiology ^[2]
  • Medications
  • Infections: Mycoplasma, Streptococci, Brucella, Legionella, hantavirus, Leptospira, CMV, EBV, Mycobacterium tuberculosis
  • Systemic diseases: Sjogren syndrome, systemic lupus erythematosus (SLE), sarcoidosis
  • Autosomal dominant tubulointerstitial kidney disease: a rare genetic disorder that causes progressive renal dysfunction

“Please RSVP:” Rifampin, Sulfa drugs and the V (5) Ps (Protone pump inhibitors, Pain killers (NSAIDs), “Pee pills” (diuretics), Penicillins, and Phenytoin) are the drugs that cause interstitial nephritis.

• Definition: a chronic inflammation of the renal interstitium and tubules that usually progresses to end-stage renal disease (ESRD) after months or years ^[6]
• Etiology
  • Drugs ^[7]
    • NSAIDs and acetaminophen (most common cause)
    • Mesalazine
    • Lithium
    • Chemotherapy drugs (e.g., cisplatin, ifosfamide)
    • Calcineurin inhibitors (e.g., cyclosporine, tacrolimus)
    • Nucleoside inhibitors (e.g., cidofovir, tenofovir)
    • Aristolochic acid: can cause Chinese herb nephropathy
      • A rapidly progressive interstitial nephropathy associated with herbal medicine
      • Patients are typically young women with a history of ingesting weight reduction pills.
  • Toxins: cadmium, lead
  • Systemic diseases: multiple myeloma, Sjogren syndrome, SLE, sickle cell disease
  • Metabolic diseases: hyperuricemia, hypercalcemia, hyperoxaluria, hypokalemia

• Definition: coagulative necrosis of the renal medullary pyramids and papillae
• Etiology (often multifactorial)
  • Acute pyelonephritis
  • Obstruction of the urinary tract
  • Sickle cell disease and sickle cell trait
  • Tuberculosis
  • Cirrhosis of the liver
  • NSAIDs; (due to inhibition of prostaglandin-mediated vasodilation in the vasa recta)
  • Renal transplant rejection
  • Diabetes mellitus
  • Systemic vasculitis
• Pathophysiology
  • Usually occurs bilaterally
  • Ischemia → necrosis and sloughing of the papillae → ureteral obstruction → possible scarring
• Clinical features (can be acute or chronic)
  • Patients with a chronic course are usually asymptomatic or only present with mild symptoms.
  • Flank pain, colicky pain
  • Hematuria (microscopic or macroscopic)
  • Proteinuria
  • Fever, chills
  • Acute kidney injury
• Diagnostics: See “Diagnostics” below and in “Pyelonephritis.”
• Therapy: See “Treatment” below and in “Pyelonephritis.”

POSTCARDS: Pyelonephritis, Obstruction, Sickle cell disease, Tuberculosis, Cirrhosis, Analgesics (NSAIDs), Renal transplant rejection, Diabetes mellitus, and Systemic vasculitis are the causes of renal papillary necrosis.

• Blood: ↑ BUN and creatinine
• Urinalysis
  • Tubular proteinuria
  • Hematuria with no RBC casts or acanthocytes (in contrast to glomerulonephritis)
  • Sterile pyuria
  • WBC casts
• Ultrasound: initial imaging test
  • Acute nephritis: The kidneys appear edematous and enlarged.
  • Chronic nephritis: The kidneys often appear shrunken.
• CT scan: test of choice for renal papillary necrosis ^[10]
  • Bilateral calcifications of the renal papilla
  • Filling defects in papillary necrosis
  • Small kidneys in chronic nephritis
• Intravenous urography
  • Irregular papillae
  • Ring shadows
  • Filling defects in the renal pelvis
  • Small contrast-containing cavities in the papillary regions
• Kidney biopsy: often nonspecific histological findings

• Treat underlying disease
• Monitor kidney function
• Consider glucocorticoids
• In selected cases, (temporary) dialysis

1. Kodner CM, Kudrimoti A. Diagnosis and management of acute interstitial nephritis.. Am Fam Physician. 2003; 67 (12): p.2527-34.
2. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series. American Journal of Kidney Diseases. 2014; 64 (4): p.558-566. doi: 10.1053/j.ajkd.2014.04.027 . | Open in Read by QxMD
3. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nature Reviews Nephrology. 2010; 6 (8): p.461-470. doi: 10.1038/nrneph.2010.71 . | Open in Read by QxMD
4. Mulay SR, Anders H-J. Crystal nephropathies: mechanisms of crystal-induced kidney injury. Nature Reviews Nephrology. 2017; 13 (4): p.226-240. doi: 10.1038/nrneph.2017.10 . | Open in Read by QxMD
5. Nast CC. Medication-Induced Interstitial Nephritis in the 21st Century. Adv Chronic Kidney Dis. 2017; 24 (2): p.72-79. doi: 10.1053/j.ackd.2016.11.016 . | Open in Read by QxMD
6. Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring.. Pediatr Nephrol. 2017; 32 (4): p.577-587. doi: 10.1007/s00467-016-3394-5 . | Open in Read by QxMD
7. Uetrecht J. Adverse Drug Reactions. Springer Science & Business Media ; 2009
8. Faiman BM, Mangan P, Spong J, Tariman JD. Renal Complications in Multiple Myeloma and Related Disorders. Clin J Oncol Nurs. 2011; 15 : p.66-76. doi: 10.1188/11.cjon.s1.66-76 . | Open in Read by QxMD
9. Fored CM, Ejerblad E, Lindblad P, et al. Acetaminophen, Aspirin, and Chronic Renal Failure. N Engl J Med. 2001; 345 (25): p.1801-1808. doi: 10.1056/nejmoa010323 . | Open in Read by QxMD
10. Jung DC, Kim SH, Jung SI, Hwang SI, Kim SH. Renal Papillary Necrosis: Review and Comparison of Findings at Multi–Detector Row CT and Intravenous Urography. RadioGraphics. 2006; 26 (6): p.1827-1836. doi: 10.1148/rg.266065039 . | Open in Read by QxMD