Clinical manifestations and diagnosis of acute

interstitial nephritis
• Acute interstitial nephritis (AIN) is a renal
lesion that causes a decline in renal function
and is characterized by an inflammatory
infiltrate in the kidney interstitium.
 Etiology
Drugs
-Virtually any drug can cause AIN
 most common drug causes
1) Nonsteroidal anti-inflammatory agents
(NSAIDs), including selective cyclooxygenase
(COX)-2 inhibitors
2) Penicillins and cephalosporins
3) Rifampin
4) Antimicrobial sulfonamides, including
trimethoprim-sulfamethoxazole
5) Diuretics, including loop diuretics such as
furosemide and bumetanide, and thiazidetype
diuretics
6) Ciprofloxacin and, perhaps to a lesser degree,
other quinolones
7) Cimetidine (only rare cases have been
described with other H-2 blockers such as
ranitidine)
 Continue
8) Allopurinol
9) Proton pump inhibitors (PPIs) such as
omeprazole and lansoprazole
10) indinavir
11) 5-aminosalicylates
• The development of drug-induced AIN is not
dose dependent,
• Recurrence or exacerbation can occur with a
second exposure to the same or a related drug
• Several studies have shown an association
between PPIs and AIN .
• The interval between the onset of these drugs
and detection of AIN is very variable (from one
week to nine months), although 10 to 11
weeks is the most common interval.
• PPIs are one of the most frequently prescribed
drug classes worldwide.
• Studies have suggested that repeated episodes
of PPI-induced AIN, many of them undetected,
can contribute to the development of chronic
kidney disease (CKD).
• An association between consumption of PPI and
the presence of CKD has been found in
epidemiological studies
 CLINICAL FEATURES

• With AIN from any cause, patients may

present with nonspecific signs and symptoms
of acute renal dysfunction.
• These may include the acute or subacute
onset of nausea, vomiting, and malaise.
• However , many patients are asymptomatic
 Continue
• Patients usually do not have significant
proteinuria, and nephrotic syndrome occurs in
<1 percent of patients with AIN .
 Continue
• An exception occurs among patients who have
nonsteroidal anti-inflammatory drug (NSAID)-
induced AIN, which may occur concurrently
with NSAID-induced membranous
nephropathy or minimal change disease
 Continue
• Classically , patients with drug-induced AIN
were reported to have symptoms and/or signs
of an allergic-type reaction, including rash,
fever , and eosinophilia .
 Continue
• However , in a more recent review of three
series that totaled 128 patients with AIN (of
whom 70 percent had drug-induced disease),
these findings of a typical allergic response
were relatively less common at presentation :
a) Rash – 15 percent
b) Fever – 27 percent
c) Eosinophilia – 23 percent
d) Triad of rash, fever , and eosinophilia – 10
percent
• Thus, the originally described classic triad is
less commonly observed than initially
reported.
• some agents, such as NSAIDs and proton
pump inhibitors (PPIs), are less commonly
associated with fever , rash, and eosinophilia
compared with other agents
 No typical range of onset for medication-
induced AIN
• the latent period may be as short as one day
with rifampin or as long as 18 months with an
NSAID
Tubulointerstitial nephritis and uveitis (TINU)
syndrome
• — Some patients with interstitial nephritis
have the TINU syndrome.
 Continue
• Patients present with interstitial nephritis and
uveitis and occasionally with systemic findings
including fever , weight loss, fatigue, malaise,
anorexia, asthenia, abdominal and flank pain,
arthralgias, myalgias, headache, polyuria,
and/or nocturia.
 Laboratory and radiographic findings

1) Increased plasma creatinine

2) Eosinophilia and eosinophiluria – Although
eosinophilia (defined by an absolute blood
eosinophil count of ≥500 eosinophils/microL)
is only found in 25 to 35 percent of AIN
cases , its finding in a patient with AKI with
no other apparent cause should raise the
suspicion of drug-induced AIN.
 Eosinophiluria
• defined by eosinophils that account for more
than 1 percent of urinary white cells by Hansel
stain , has been associated with AIN.
 Continue
• However , urinary eosinophils are not useful in
distinguishing AIN from other causes of AKI,
and the absence of eosinophiluria does not
exclude the possibility of AIN.
 Example
• Five-hundred sixty-six patients had both a
kidney biopsy and a test for urinary
eosinophils performed for AKI.
• Among 179 patients who had a positive test
for urinary eosinophils (defined as ≥1 percent
of urinary white cells), only 28 had AIN on
biopsy .
• Conversely , among 387 patients who had a
negative test for eosinophils, 63 had biopsy-
proven AIN.
 Continue
• In this study , urinary eosinophils were found
in multiple other kidney diseases, including
acute tubular necrosis and crescentic and
proliferative glomerulonephritis .
 A characteristic urine sediment
• – The urine sediment usually reveals white
cells, red cells, and white cell casts .
• Red blood cell casts, which are typically seen
in glomerulonephritis, have also been
described in AIN, although this is rare
 High fractional sodium excretion
• – The fractional excretion of sodium (FENa)
may be >1 percent, which is in part indicative
of tubular damage.
A definitive diagnosis of AIN

Renal biopsy
Treatment of acute interstitial nephritis

• Acute interstitial nephritis (AIN) classically

presents as acute renal failure (ARF) after the
use of known offending drugs and is
associated with the typical urinary findings of
pyuria, hematuria, and white cell casts
 TREATMENT
• — Discontinuation of the potential causative
agent is a mainstay of therapy , and
immunosuppressive therapy has been
employed if there is no subsequent
improvement in kidney function by three to
seven days.
• The most important aspect of therapy of AIN
is cessation of the potentially offending agent
(or treatment of the underlying infection).
 Glucocorticoid therapy
• — Immunosuppressive therapy has been
employed to treat AIN that persists despite
discontinuation of the offending agent
• The optimal dose and duration of therapy are
unclear.
• One approach is to administer prednisone at
a dose of 1 mg/kg per day (to a maximum of
40 to 60 mg) for a minimum of one to two
weeks, beginning a gradual taper after the
serum creatinine has returned to or near
baseline, for a total therapy duration of two to
three months.
 Continue
• Most patients will improve in the first one to
two weeks.
• In patients with more severe acute renal
failure (ARF), therapy may be initiated with IV
methylprednisolone (0.5 to 1 g/day for three
days)