Chapter 28-9: Interstitial Nephritis

TEXTBOOK PRESENTATION

Classic findings include AKI, hematuria, pyuria with WBC casts, fever, and eosinophilia. The full syndrome is rarely seen today, since it occurs primarily with methicillin-induced acute interstitial nephritis.

DISEASE HIGHLIGHTS

1. Interstitial nephritis is found in 2–3% of all kidney biopsies, and in 15–27% of patients who have a biopsy done for AKI.

2. Etiology

   1. Drug-induced

      1. Accounts for at least 66% of cases of acute interstitial nephritis; up to 90% of cases in some series

      2. Antimicrobial agents and NSAIDs cause the majority of cases; in 2 large series, NSAIDs caused 44% of the drug-induced cases.

      3. Also reported with allopurinol, acyclovir, famotidine, furosemide, omeprazole, phenytoin

   2. Infection-related

      1. 15% of acute interstitial nephritis cases

      2. Can be caused by

         1. Viral infections, such as cytomegalovirus, Epstein-Barr virus, herpes simplex virus, HIV, mumps, and others

         2. Bacterial infections, such as staphylococci, streptococci, Yersinia, Legionella

         3. Other infections, such as mycobacteria, toxoplasmosis, syphilis

   3. Idiopathic

      1. 5–10% of cases

      2. Includes tubulointerstitial nephritis and uveitis syndrome and anti-tubular basement membrane disease

   4. Associated with systemic disease: sarcoidosis, SLE, Sjögren syndrome

3. Prognosis

   1. Most patients improve within 6–8 weeks and return to baseline kidney function.

   2. Predictors of irreversible injury are diffuse infiltrates and frequent granulomas on biopsy, intake of the offending drug for longer than 1 month, delayed response to prednisone, and persistent kidney disease after 3 weeks.

EVIDENCE-BASED DIAGNOSIS

1. Clinical findings

   1. Renal manifestations develop within 3 weeks of exposure in 80% of patients, with an average delay of 10 days (range 1 day to 18 months; longer delays often seen with NSAIDs).

   2. Symptoms develop more rapidly if the patient is rechallenged with the offending drug.

   3. The classic triad of fever, rash, and eosinophilia is seen in only 10–15% of patients.

   4. Table 28-8 summarizes the findings in 2 series reporting 121 cases of acute interstitial nephritis, 90% of which were drug-induced.

The absence of fever, rash, eosinophilia, or eosinophiluria does not rule out interstitial nephritis.

2. Urine eosinophils are less useful than early studies suggested

   1. Sensitivity, 40%; specificity, 72%

   2. LR+, 1.45; LR–, 0.83

3. FE_Na usually > 1%

4. Gallium scan

   1. Substantial renal uptake in acute interstitial nephritis, but uptake also seen in GN, pyelonephritis, and other conditions

   2. Sensitivity and specificity are not well defined.

   3. No uptake with ATN, so possibly useful in distinguishing ATN from acute interstitial nephritis

5. Kidney biopsy is the gold standard and is often necessary to establish the diagnosis. See Table 28-9 for an overview of the indications and contraindications of a kidney biopsy.