Download Tubulo Interstitial Disorders

Tubulo
Interstitial
Disorders
Dr Kishore Kumar Ubrangala
Acute interstitial nephritis (AIN)
 Acute
inflammation within the tubulo-interstitium
 Most
commonly: allergic, particularly to drugs,
Other causes:
toxins,
a variety of systemic diseases,
infections.
 Deterioration
of renal function in drug-induced
AIN: may be dramatic and resemble rapidly
progressive glomerulonephritis.
Acute Interstitial Nephritis-Etiology
 Allergic/Drug induced
 Autoimmune
 Sarcoid
-SLE
 Sjogren’s
 Toxins
 Chinese herb nephropathy
-Heavy metals
 Light chain cast nephropathy
 Infiltrative
 Leukemia
 Lymphoma
 Infections (Legionella, CMV, HIV, Toxoplasma)
Acute Interstitial Nephritis
Causes
 Allergic

interstitial nephritis
Drugs
 Infections


Bacterial
Viral
 Sarcoidosis
Acute bacterial pyelonephritis. A widespread inflammatory infiltrate that includes many neutrophils is seen.
Granulocyte casts (G) are forming within some dilated tubules (T).
Other tubules are scarcely visible because of the extent of the inflammation and damage
ATN
Acute tubular necrosis showing focal loss of tubular epithelial cells (arrows) and
partial occlusion of tubular lumens by cellular debris (D) (H&E stain).
ATN
Acute Tubular Necrosis
The tubular epithelial cells show extensive cytoplasmic
vacuolar change in a case of ethylene glycol poisoning.
Acute Tubular Necrosis
Tubular epithelial degeneration and hyaline amphophilic casts
(positive with immunologic stains for myoglobin) in a patient with
Rhabdomyolysis and myoglobinuric acute tubular necrosis
Acute Interstitial Nephritis-Etiology
 Allergic/Drug induced
 Autoimmune
 Sarcoid
-SLE
 Sjogren’s
 Toxins
 Chinese herb nephropathy
-Heavy metals
 Light chain cast nephropathy
 Infiltrative
 Leukemia
 Lymphoma
 Infections (Legionella, CMV, HIV, Toxoplasma)
Common Causes of Drug Induced AIN



NSAIDS
Antibiotics
 Penicillins
 methicillin
 Ampicillin, amoxacillin, carbenacillin, oxacillin
 Cephalosporins
 Quinolones (ciprofloxacin)
 Anti-tuberculous medications (rifampin, INH, ethambutol)
 Sulfonamides (TMP-SMX, furosemide, thiazides)
Miscellaneous
 Allopurinol, cimetidine, diphenyl hydantin
NSAID vs Beta-lactam AIN
Beta-lactam
Duration of exposure
Fever/rash/eosinophilia
Eosinophiluria
> 3 gm proteinuria
Rate of recovery
Chronic renal failure
Benefit of steroids
2 weeks
80%
80%
< 1%
Fast
Rare
Probably
NSAID
5 months
20%
15%
83%
Slow
Common
Probably not
Allergic Interstitial Nephritis
Clinical Characteristics
 Fever
 Rash
 Arthralgias
 Eosinophilia
 Urinalysis



Microscopic hematuria
Sterile pyuria
Eosinophiluria
Acute Interstitial Nephritis
Drug-induced allergic interstitial nephritis (H&E stain). Note the diffuse
interstitial infiltrate, many red-staining eosinophils, and sparing of the
glomerulus (on the left).
Other Causes
 Renovascular
Diseases
 Atheroembolism
23
Sept 2nd, 2013
Atheroembolic renal disease
(‘Cholesterol' emboli)

Caused by showers of cholesterol-containing
microemboli, arising in atheromatous plaques in
major arteries

Occurs in patients with widespread atheromatous
disease, usually after interventions such as Surgery or
Arteriography
Sometimes - After anticoagulation
1.
2.
3.
Dr Kishore Kumar Ubrangala
24
Sept 2nd, 2013
Atheroembolic renal disease
('cholesterol' emboli)

Loss of renal function, Hematuria and Proteinuria,
and sometimes Eosinophilia & Inflammatory features
which may mimic a small-vessel vasculitis

Accompanying signs of microvascular occlusion in
the lower limbs (e.g. ischaemic toes, livedo
reticularis) are common but not invariable

No specific treatment, but anticoagulation may be
detrimental
Dr Kishore Kumar Ubrangala
Atheroembolic Renal Disease






ARF in patient with erosive atherosclerosis
Often follows aortic manipulation (angiography,
surgery, trauma) or anticoagulation
Pattern is often an acute worsening of renal function
due to showering of emboli, followed by more
insidious progression over several weeks to months
due to ongoing embolization of atheromatous plaques
Livedo reticularis
Nephritic sediment, eosinophilia, eosinophiluria, low
C3
Poor prognosis
Livedo Reticularis
27
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
28
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
Cholesterol Embolization
30
Cholesterol Clefts
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
31
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
32
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
33
Sept 2nd, 2013
Kishore arterioles
Kumar Ubrangala
The yellow fleck trapped at the bifurcation of Dr
retinal
is
probably a platelet-fibrin-cholesterol embolus - Hollenhorst plaque
34
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
35
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
36
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
37
Sept 2nd, 2013
Livedo reticularis
Dr Kishore Kumar Ubrangala
38
Sept 2nd, 2013
Livedo reticularis
Dr Kishore Kumar Ubrangala
39
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
40
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
41
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
Hollenhorst Plaques
42
Sept 2nd, 2013
Dr Kishore Kumar Ubrangala
Hollenhorst Plaques
‘Tubular’ proteinuria




It is sometimes helpful to identify the type of protein in
the urine.
Low molecular weight proteins may appear in the urine
in larger quantities than 150 mg/day, indicating failure
of reabsorption by damaged tubular cells, i.e. 'tubular
proteinuria'.
This can be demonstrated by analysis of the size of
excreted proteins or by specific assays for such proteins
(e.g. β2-microglobulin, molecular weight 12 kDa, Retinol
binding protein-RBP, Alpha 1 microglobulin,
Immunoglobulin light chains etc.).
The amounts of such protein rarely exceed 1.5-2 g/24
hours (maximum PCR 150-200 mg/mmol), and
proteinuria greater than this almost always indicates
significant glomerular disease.
AIN: Diagnosis
 Renal
biopsy is usually required to confirm the
diagnosis
 Shows
intense inflammation, with PMNLs and
lymphocytes surrounding tubules and blood
vessels and invading tubules (tubulitis), and
occasional eosinophils (especially in druginduced disease).
 The
degree of chronic inflammation in a biopsy
is a useful predictor of the eventual outcome
for renal function.
AIN: Management
 Some
patients with drug-induced AIN recover
following withdrawal of the drug alone,
 but
corticosteroids (e.g. prednisolone 1
mg/kg/day) accelerate recovery and may
prevent long-term scarring.
 Dialysis
is sometimes necessary but is usually
only short-term
 Other specific causes: Treat if possible
Chronic Interstitial Nephritis
Chronic Interstitial Nephritis
Chronic Interstitial Nephritis
Toxic causes of CIN






The combination of interstitial nephritis and tumours of the
collecting system is seen in
'Chinese herb nephropathy' (a rapidly progressive
syndrome caused by mistaken identity of ingredients in
herbal preparations),
in analgesic nephropathy, and
in Balkan nephropathy (an endemic chronic nephropathy).
A plant toxin found in Aristolochia clematis is probably
responsible for the herb nephropathy and possibly also for
Balkan nephropathy.
Confusing Cortinarius species for wild edible or 'magic'
mushrooms causes a devastating irreversible renal tubular
toxicity encountered occasionally in Scandinavia and
Scotland.
Papillary necrosis and analgesic
nephropathy
The renal papillae and may necrose in




Diabetes mellitus
rarely in Infections
Sickle-cell disease and
occly in other conditions
Necrosed papillae may cause ureteric obstruction and
renal colic. Papillary necrosis is difficult to identify other
than on pyelography.

Long-term ingestion (years to decades) of certain
NSAIDs may cause CIN and renal papillary necrosis.
Lead Nephropathy
 Kidney
– main route of Lead elimination
 C/C Lead Nephropathy – frequently ass. with
Gout & Hypertension.
 Htn: reduced synthesis of eicosanoids
direct effect on vascular sm m cells
abnormalities in RAS axis
effect on sodium-lithium countertransport
system
Uric Acid: Enhanced reabsorption / reduced
secretion/altered purine metabolism
Hypokalemia, Hypercalcemia
Clinical and biochemical features





Most patients present in adult life with CKD, HTN & small
kidneys.
CKD is often moderate (stage 3) but, because of
tubular dysfunction, electrolyte abnormalities are
typically more severe (e.g. hyperkalaemia, acidosis).
Urinalysis abnormalities: Non-specific.
A minority of patients present with salt-losing
nephropathy, causing hypotension, polyuria and
features of sodium and water depletion (e.g. low BP &
JVP).
Impairment of urine-concentrating ability and sodium
conservation places patients with CIN at risk of
superimposed ARF with even moderate salt and water
depletion during an acute illness.
CIN
 Hyperkalaemia
may be disproportionate
in CIN or in diabetic nephropathy
because of hyporeninaemic
hypoaldosteronism.
 Renal
tubular acidosis is seen most often
in myeloma, sarcoidosis, cystinosis,
amyloidosis and Sjögren's syndrome.
Sickle-cell nephropathy
Chronic complications of microvascular occlusion:

Changes most pronounced in the medulla, where the vasa recta are
the site of sickling because of hypoxia and hypertonicity.

Loss of urinary concentrating ability and polyuria are the earliest
changes

Distal renal tubular acidosis and impaired potassium excretion are
typical.

Papillary necrosis is very common.

A minority of patients develop ESRD. (This is managed according to the
usual principles, but response to recombinant erythropoietin is poor in
the presence of haemoglobinopathy).

Patients with sickle trait have an increased incidence of unexplained
microscopic haematuria, and occasionally overt papillary necrosis.
Balkan Nephropathy