Interstitial Nephritis– Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- Acute interstitial nephritis (AIN) is an inflammatory response of the kidney involving interstitial edema and, at times, tubular cell damage. It may be an acute reaction or a result of long-term damage.
- System(s) affected: Renal/Urologic; Endocrine/Metabolic; Immunologic
- Synonym(s): Tubulointerstitial nephritis (TIN), Acute interstitial allergic nephritis
- Children exposed to lead poisoning are more likely to develop nephritis as a young adult.
- TIN with uveitis presents in adolescent females.
- Atherosclerotic or ischemic nephritis is more common in the elderly.
- Interstitial nephritis accounts for 10–15% of kidney disease in the US.
- Analgesic-induced nephritis is 5–6× more common in women.
- Peak incidence in women 60–70 years of age
- The elderly have more severe disease and increased risk of permanent damage.
- Early recognition and prompt discontinuation of offending agents
- Remove all sources of heavy metals, including ceramics.
- Avoid further nephrotoxicity.
- Delayed hypersensitivity reaction, usually owing to drugs
- May cause acute renal insufficiency
- Regardless of the severity of the damage to the tubular epithelium, the renal dysfunction generally is reversible, possibly reflecting the regenerative capacity of tubules with preserved basement membrane.
- Chronic interstitial nephritis (CIN):
- Follows long-term exposure to offending agents
- Often found on routine labs or evaluation for hypertension (HTN)
- Characterized by interstitial scarring, fibrosis, and tubule atrophy, resulting in progressive chronic renal insufficiency
- TIN is sometimes associated with uveitis.
- Hypersensitivity to drugs (70%):
- Antibiotics: Penicillin, cephalosporins, sulfonamides, rifampin
- Nonsteroidal anti-inflammatory drugs (NSAIDs)/analgesics (more common in elderly people because of the higher incidence of arthritic disorders in this population)
- Sulfa-containing diuretics
- AIN is associated with primary renal infections such as acute bacterial pyelonephritis, renal tuberculosis, and fungal nephritis.
- Acute transplant rejection
- Immunologic: Systemic lupus erythematosus (SLE), Sjögren syndrome, sarcoidosis, Wegener granulomatosis, cryoglobulinemia
- Idiopathic (isolated or with uveitis)
- Hypersensitivity to drugs (70%):
- Drugs: Analgesics, lithium, antineoplastics, antibiotics, anticonvulsants, antihypertensives, immunosuppressants, diuretics, Chinese herbal medicine
- Heavy metals: Lead, cadmium
- Obstruction: Stones, neoplasm, prostatic hypertrophy
- Metabolic: Hypercalcemia, hyperoxaluria, chronic hypokalemia, cystinosis
- Vascular changes: Cholesterol emboli, HTN, sickle hemoglobinopathy, radiation
- Toxins: Snakebite venom (hemotoxic or myotoxic)
- Other: Balkan-endemic nephropathy, Epstein-Barr virus
Commonly Associated Conditions
- Alport disease
- Medullary cystic disease
- Inflammatory bowel disease
- Multiple myeloma
- Primary biliary cirrhosis
- Fever: 80%
- Transient maculopapular rash: 25–50%
- Acute renal insufficiency:
- Decreased urine output: 50%
- Signs of fluid overload or depletion
- Altered mental status
- Nausea, vomiting
- Decreased urine output or polyuria
- Inability to concentrate urine
- Fanconi syndrome
- Alcohol and illicit drug use
- Exposure to heavy metals
- Tobacco use
- Increased blood pressure
- Altered mental status
- Rash accompanying renal findings in acute AIN
- Pericardial rub if uremic pericarditis
- Lung crackles if fluid overload
- Extremity swelling
- Weight gain from fluid retention
Diagnostic Tests & Interpretation
- Complete blood count (CBC):
- Eosinophilia (80%): Not seen in NSAID-induced AIN
- Elevated blood urea nitrogen (BUN) and creatinine
- Urinalysis with urine lytes
- Hematuria (95%)
- Mild proteinuria (present to variable degrees, usually <1 g/24 h, except in AIN associated with NSAIDs)
- Specific gravity
- Pyuria, white blood cell (WBC) casts
- Serologic testing for immunologic disease: Sarcoidosis, Sjögren syndrome, Wegener granulomatosis, Behçet syndrome
- Lead level:
- Not useful in chronic lead exposure
- >90% of lead resides in bone.
- If chronic lead exposure is suspected, consider EDTA lead mobilization test.
- Liver function tests: Elevated serum transaminase levels (in patients with associated drug-induced liver injury)
- Gallium scan (a negative gallium scan does not preclude the diagnosis because false-negative results can be seen)
- Renal ultrasonography may demonstrate kidneys that are normal to enlarged in size with increased cortical echogenicity, but there are no ultrasonographic findings that will reliably confirm or exclude AIN versus other causes of acute renal failure.
- The role of intravenous pyelography (IVP) remains in question (in many instances, similar information can be obtained by ultrasound without exposing the patient to potentially nephrotoxic contrast dye).
Follow-Up & Special Considerations
Patients who do not recover renal function and those with chronic TIN should receive long-term follow-up care to protect kidneys from further potentially nephrotoxic therapies.
- Renal biopsy is the “gold standard” and definitive method of establishing diagnosis of AIN. However, it is not needed in all patients.
- Indications for renal biopsy: Patients who do not improve following withdrawal of likely precipitating medications, who have no contraindications to renal biopsy and do not refuse the procedure, and who are being considered for steroid therapy are good candidates for renal biopsy.
- Contraindications: Renal biopsy is contraindicated in bleeding diathesis, solitary kidney, end-stage renal disease with small kidneys, severe uncontrolled HTN and sepsis, or renal parenchymal infection.
- Cellular infiltration with eosinophilia
- In cholesterol microembolism in the kidney, the finding of a characteristic needle-shaped cleft in medium- or small-sized renal arterioles is diagnostic.
- Chronic: Chronic TIN is characterized by tubular atrophy, fibrosis, and cellular infiltration with mononuclear cells.
- Acute renal failure
- Urinary tract obstruction
For AIN, corticosteroids have not been shown to improve outcomes (1)[B].
- Mainstay of treatment is supportive therapy.
- Offending drugs should be discontinued.
- If patient is taking multiple offending drugs, a reasonable clinical approach should include whether any suspected drug can be substituted easily with another medication.
- If renal failure persists after removing agent, attempt medication therapy.
- Prednisone 0.5–2 mg/kg/d PO or equivalent IV dose × 1–2 weeks, followed by a gradual taper over 3–4 weeks
- In patients who do not respond to corticosteroids within 2–3 weeks, treatment with cyclophosphamide (Cytoxan) can be considered.
- Studies support steroid use in chronic, not acute, interstitial nephritis (1)[B],(2),(3)[C],(4)[A].
- Continue corticosteroids for 6 months in patients with sarcoidosis (2)[C].
- Lead toxicity: Repeated chelation therapy may improve renal function (5)[A].
- Succimer 10 mg/kg PO q8h × 5 days, then q12h × 14 days, or
- EDTA 2 g IV/IM; if IM, use with 2% lidocaine.
- SLE nephritis: Steroids plus cyclophosphamide or azathioprine (4)[A]
- Urate nephropathy:
- Allopurinol to decrease urate level (2)[C]
- Use with caution because allopurinol is nephrotoxic.
- Lithium-induced nephritis: Use amiloride as adjunct (2)[C].
- Cidofovir-induced nephritis: Use probenecid as adjunct (2)[C].
- Discontinue offending agent.
- Reduce exposure to other nephrotoxic agents.
- Supportive measures
- Maintain adequate hydration.
- Symptomatic relief for fever, rash, and systemic symptoms
- Control of blood pressure and anemia.
- Correct electrolyte imbalances.
- Dialysis if criteria met
Issues for Referral
Most patients presenting with renal insufficiency, proteinuria, and/or acid-base electrolyte disorders require consultation with a nephrologist.
Patients with acute renal failure or with serious electrolyte or acid-base disorders may require inpatient care until stabilization or resolution.
- Arterial blood gases
- Electrocardiogram (ECG)
- Oliguria or anuria persists
- Severe electrolyte abnormalities
- ECG changes
- Stable vitals, labs, and ECG
- Normal urine production
If patients must remain on nephrotoxic medications, measure renal function, electrolytes, and phosphorus frequently.
- Low fat/low cholesterol
- Low protein (6)[A]
- Low sodium
- Low potassium
Printed materials for patients are available at the National Kidney Disease Education Program, (866) 4-KIDNEY, www.nkdep.nih.gov.
- If the associated AIN is detected early (within 1 week of the rise in serum creatinine) and the drug is discontinued promptly, the long-term outcome is favorable for a return to baseline serum creatinine.
- Renal biopsy reveals extent of damage.
- Recovery within weeks to months
- Acute dialysis is needed for 1/3 of patients before resolution.
- Rarely progresses to end-stage renal disease (ESRD)
- CIN: Can progress to ESRD
- TIN with uveitis:
- Renal disease remits in 1 year if untreated.
- Uveitis has relapsing course, requiring systemic corticosteroids.
- Untreated acute renal failure has a 45–70% mortality.
- Papillary necrosis
- Chronic tubulointerstitial disease may progress to ESRD requiring dialysis or transplantation.
- Analgesics increase the risk of transitional cell cancers of the uroepithelium.
1. Clarkson MR, et al. Acute interstitial nephritis: Clinical features and response to corticosteroid therapy. Nephrol Dialysis Transplant. 2004;19:2778–83.
2. Braden GL, O’Shea MH, Mulhern JG. Tubulointerstitial diseases. Am J Kidney Dis. 2005;46:560–72.
3. Markowitz GS, Perazella MA. Drug-induced renal failure: A focus on tubulointerstitial disease. Clinica Chimica Acta. 2005;351:31–47.
4. Flanc RS, et al. Treatment for lupus nephritis. Cochrane Database Sys Rev. 2004;1:CD002922.
5. Lin JL, Lin-Tan DT, Hsu KH, et al. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med. 2003;348:277–86.
6. Fougue D, et al. Low-protein diets for chronic kidney disease in nondiabetic adults. Cochrane Database Sys Rev. 2006;3.
See Also (Topic, Algorithm, Electronic Media Element)
- 580.89 Acute glomerulonephritis with other specified pathological lesion in kidney
- 582.89 Other chronic glomerulonephritis with specified pathological lesion in kidney
- 583.89 Other nephritis and nephropathy, not specified as acute or chronic, with specified pathological lesion in kidney
- 28689008 interstitial nephritis (disorder)
- 28637003 acute interstitial nephritis (disorder)
- 60926001 chronic interstitial nephritis (disorder)
- The symptoms of AIN are more dramatic and sudden (days to weeks) than those of CIN, which is slower and progressive.
- The best treatment is to 1st remove the offending agent.
- Hypercalcemia is both a cause and an effect of CIN. Treating hypercalcemia slows the progression of CIN.
- Finding eosinophilia on the CBC rules out NSAID-induced AIN.
- The “gold standard” in diagnosing interstitial nephritis is a renal biopsy.