4. A Pattern of renal injury usually characterized by :
• Clinically; Abrupt deterioration in renal function
• Triad of fever ,esinophilia and skin rash.
• Histopathological; inflammation & oedema of interstitium, tubular
atrophy. .
5. • Inflammation Is Limited To Tubules & Interstitium
• Glomeruli & Vessels; Uninvolved Or Minor Changes1ry
• Occur as a consequence of 1ry Glomerular , Vascular Or
Systemic Disease.2ry
• 1ry TIN Whose Etiologic Agent Or Cause Is UnknownIdiopathic
• TIN From Localization Of Live Microorganisms In The KidneyInfectious
• TIN From The Effects Of Systemic Infections
• Kidney Are Usually Sterile
Reactive
6. Acute Chronic
Develops over period of days to several weeks Develops over months or
years.
Associated with AKI Associated with progressive
loss of GFR over time
acute infection of kidneys or delayed
hypersensitivity reaction to medication.
Granulomatous dis, metabolic disorders ,
radiation ,.. Etc
7. Incidence
• 1 % of renal biopsies
during the evaluation of
hematuria or proteinuria.
• 15-27% of cases of
patients hospitalized for
AKI, ; the incidence of
ATIN may be increasing;
more detection.
Misdiagnosed
• Non-specific in clinical features
• Mild forms may be overlooked
• Routine diagnostic tests can’t
confirm or exclude.
Variable Etiology
Management
• Paucity of data in the literature
regarding optimal management
• Large debate on effective therapy
Fate
• Acute, often reversible disease
• Untreated acute TIN may
result in interstitial fibrosis
and irreversible renal injury
14. • Drug-induced AIN is secondary to immune reaction
• AIN occurs only in a small percentage of individuals taking the drug
• AIN is not dose-dependent
• Association with extrarenal manifestations of hypersensitivity
• Recurrence after re-exposure to the drug
17. Clinical
Non specific
Symptoms of AKI
Asymptomatic ↑
Creat
Abnormal urinary
sediment
Hypersensitivity
syd
low-grade fever
70-100%
Skin rash
30-50%
Arthralgia
15-20%
Am Fam Physician. 2003 Jun 15;67(12):2527-2534.
Hematuria
Proteinuria
18.
19. Cells in the cast have nuclei
(unlike RBC casts)
Pathognomonic for Acute
Interstitial Nephritis
21. Imaging
Contrib Nephrol. Basel, Karger, 2016, 188; 39–47
Conventional US does not allow a definitive diagnosis.
67y patient had an AKI from NSAIDs
( Cr 1.1 -to 2.8 mg/dl).
• Kidneys were symmetrical.
• Coronal diameters were >11 cm
• Parenchymal thickness was normal
• But renal structure was altered.
• Cortex; diffusely hyperechoic; interstitial
edema & inflammatory infiltrate
• Medullary pyramids were hypoechoic &
irregular, but CMD was preserved
22. • Doppler wave showed a high
difference between systolic and
diastolic phase, because of the
decrease of diastolic flow.
Imaging
Conventional Doppler US does not allow a definitive diagnosis.
• Hemodynamic variations are
commonly related to severity
and progression of the
anatomical damage.
• RIs are commonly <0.70.
Contrib Nephrol. Basel, Karger, 2016, 188; 39–47
23. The gold standard method for
diagnosis
Done for ALL suspected
patients ??
Biopsy
24. Done for ALL suspected
patients ??
• Probable precipitating
drug can be withdrawn
• Improve readily after
withdrawal of an
offending drug
• Supportive management
can proceed safely with
good outcome
• Not improve after
withdrawal of likely
precipitating drugs
• No contraindications to
renal biopsy
• No refusal to procedure
• Considered for steroid
therapy
Biopsy
25. Biopsy
LM
• Interstitium: edema & lymphocytic infiltration, non-necrotizing
granulomas, fibrosis is initially sparse, but develops later in the
course of the illness.
• Vessles normal
• Glomeruli: normal , GN may has TIN as complication , MC with
NSAIDs, Necrotizing GN or vasculitis is commonly associated
with AIN that, in limited samples with no glomeruli, may be
mistaken as AIN.
• Tubules: Variable tubulitis with associated acute tubular injury
Am J Kidney Dis. 2016;67(6):e35-e36
26. AIN with an interstitial lymphoplasmacytic
infiltrate, edema, and prominent eosinophilic
component (left)
AIN with an interstitial lymphoplasmacytic infiltrate
with eosinophils and associated interstitial
edema
27. Biopsy
LM
IF
• No specific staining
• Linear IgG Anti TBM
Linear deposits of IgG in methicillin-
induced acute interstitial nephritis.
Deposits along TBM are shown on IF
microscopy. These antibodies
recognize either a component of the
TBM or a methicillin metabolite
(dimethoxyphenylpenicilloyl) bound to
the TBM. (Courtesy Dr. B Mougenot,
Paris VI University, Paris.)
EM • No specific finding
• Some cases with NSAIDs-induced AIN, concurrent induction of MCD
with extensive foot process effacement.
29. • Withdrawal of medications that are likely to cause AIN is the most
significant step in early management of suspected or biopsy-proven
AIN.
• Avoid volume depletion or overload
• Identify and correct electrolyte abnormalities
• Symptomatic relief for fever and systemic symptoms
• Avoid use of nephrotoxic drugs
• Adjust drug dosages for existing level of renal function
• Dialysis if indicated
30. As an immune-mediated
disorder immune
suppressive therapy has
been the mainstay of
treatment for decades.
• The effectiveness of steroids for
treatment of AIN is debated.
• There are no RCT to support the use
of corticosteroids in treatment of AIN
31. • Outcome from two studies involving <25 cases each, in which
corticosteroid therapy was found to accelerate renal recovery and
improve the final baseline serum creatinine
• Small case reports have demonstrated rapid diuresis, clinical
improvement, and return of normal renal function within 72 hours
after starting steroid treatment
32. Multicentre retrospective study including 61 patients with biopsy-proven
DI-AIN, 52 of whom were treated with steroids.
Kidney International, Volume 73, Issue 8, 2008, 940–946
33. • retrospective study of 60 patients with
biopsy proven AIN over a 12 year period
in whom (n=42) only had complete FU
• 60% received corticosteroid therapy
while the remainder received supportive
care only
No difference in outcome was observed
between the two groups with respect to the
median serum creatinine at time points of 1,
6 and 12 months following diagnosis
34. Treatment with steroids did
not affect recovery status
at 6 months
October 2014Volume 64, Issue 4, Pages 558–566
35. • Guided by the clinical course following
withdrawal of offending medications &
delayed recovery of renal function
• A reasonable dosage is prednisone, 1
mg per kg per day orally (or equivalent
intravenous dose) for two to three
weeks followed by a gradually tapering
dose over three to four weeks.
39. Nephrol. Dial. Transplant. (2004)19 (11): 2778-2783.
• Retrospective study of all cases (n=60) of AIN found by reviewing 2598
native renal biopsiesover a 12 year period
40. Cause
The cause of AIN had no impact
on recovery at 6 months
October 2014Volume 64, Issue 4, Pages 558–566
Longer duration of drug exposure
correlate with bad outcome
41. • Small kidney by U/S
• Longer duration renal failure lasts for >3 weeks
• Two series have shown worse prognosis with increasing age
• NO correlation with peak creatinine concentration
Correlates of poor recovery:
Med Balt1977; 56: 483–491Nephrol 1984; 22: 55–60Nephrol 1980; 14: 263–273
Cause
Clinical
42. • Higher degree of tubular atrophy and interstitial fibrosis
• Presence of interstitial granulomas on biopsy were marginally
significant correlates of prognosis.
• Diffuse (versus patchy) inflammation on biopsy; excess
number of neutrophils. However, recent studies have not
supported a correlation between the degree of cellular
infiltration or tubulitis and outcome
AJKD October 2014 (64), 4: 558–66 Nephrol Dial Transplant 1989; 4: 205–15
Correlates of poor recovery:
Cause
Clinical
Histo-
pathology
Nephrol Dial Transplant 1990 5:94–9
43. • Longer time from onset of AKI or biopsy to starting steroid
treatment correlate with worse recovery
Cause
Clinical
Histo-
Pathology
October 2014Volume 64, Issue 4, Pages 558–566
Steroid
Therapy
45. • Dramatically decreased with
widespread of antibiotics
• AIN occurring in patients treated
with antibiotics should not always be
attributed to the drug
• The clinical presentation depends
mostly on the underlying infection
• Steroids not recommended
46. • Extrarenal symptoms of sarcoidosis in about 90% of patients mostly
LN, lung, eye, or liver involvement.
• Granulomatous interstitial nephritis Hypercalcemia
Sarcoidosis
• Clinically significant interstitial nephritis is rare in Sjögren syndrome
• Usually results in chronic tubular dysfunction
Sjogren syd
• Interstitial infiltrates rich in IgG4-positive plasma cells and immune
deposits along the TBM
• Can be associated with a membranous GN
IgG4
• Most commonly in girls of pubertal age; ocular pain and visual
impairment, or pseudoviral, with fever, myalgia
• Prognosis worse in adults
TINU Syd
• Acute rejection Drug induced
• Infection : polyoma virus acute ↑ RF & decoy cells in urine
Renal Tx
recipient
