Download Acute Interstitial Nephritis

Tubulointristitial
Nephritis
Dr. Hamed Shakhatreh
Consultant nephrologest
Head of nephrology department,Al-basher hospital. M.O.H
Primary interstitial nephropathies make up a
diverse group of diseases that elicit interstitial
inflammation associated with renal tubular cell
damage.
Traditionally, interstitial nephritis has been
classified morphologically and clinically into:
acute and chronic forms.
Acute Interstitial Nephritis
70% Drug hypersensitivity
 30% Antibiotics: PCNs (Methicillin), Cephalosporins, Cipro
 Sulfa drugs
 NSAIDs
 Allopurinol...
15% Infection
 Strep, Legionella, CMV, other bact/viruses
8% Idiopathic
6% Autoimmune Dz (Sarcoidosis, Tubulointerstitial
nephritis/Uveitis)
Drug Causes of AIN
Antibiotics
Cephalosporins, Ciprofloxacin, Ethambutol,
Isoniazid, Macrolides, Penicillins, Rifampin,
Sulfonamides, Tetracycline, Vancomycin
NSAIDs
Almost all agents, including selective COX-2
inhibitors
Diuretics
Furosemide, Thiazides, Triamterene
Miscellaneous
Acyclovir, Allopurinol, Amlodipine, Azathioprine,
Captopril, Carbamazepine, Clofibrate, Cocaine,
Diltiazem, Famotidine, Indinavir, Mesalazine,
Omeprazole, Phenteramine, Phenytoin, Pranlukast,
Propylthioruacil, Quinine, Ranitidine
AIN from Drugs
Renal damage is NOT dose-dependent
May take weeks after initial exposure to drug
 More common is seen several months to a year after use
But as early as 1 week after medication is begun
 Fever (27%)
 Serum Eosinophilia (23%)
 Maculopapular rash (15%)
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Bland sediment or WBCs, RBCs, non-nephrotic proteinuria
WBC Casts are pathognomonic!
Urine eosinophils on Wright’s or Hansel’s Stain
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Also see urine eos in RPGN, renal atheroemboli
Leukocytoclastic vasculitis
Interstitial nephritis
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Acute allergic IN- presents with fever,
maculopapular rash, arthralgia, eosinophilia with
use of certain drugs or systemic infection
UA_ microscopic hematuria, pyuria, non
nephrotic proteinuria, eosinophiluria
Usually resolves after d/c of offending drug and
steroids
Clinical Presentation
AIN of any cause
Nausea
Vomiting
Malaise
Drug-Induced AIN
•Rash
•Fever
•Eosinophilia
•Triad
15%
27%
23%
10%
Laboratory Manifestions

Acute rise in plasma creatinine concentration

Eosinophilia and eosinophiluria

Urine sediment: wbcs, rbcs, white cell casts

Proteinuria (< 1 g/day)
Infectious Causes of
AIN
Bacterial
Corynebacterium diphtheriae,
Viral
legionella, staphylococci,
streptococci, yersinia
CMV, EBV, HIV, HCV, HSV,
hantaviruses, mumps, polyoma
virus
Other
Leptospira, mycobacterium,
mycoplasma, rickettsia, syphilis,
toxoplasmosis
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Acute bilateral pyelonephritis
Flank pain, toxic, febrile
U/A : pyoria, hematuria, proteinuria, bacteriuria
B/C & U/C help to diagnosis
Infiltrative/Autoimmne
Causes of AIN
Sarcoidosis
Sjogren’s
Syndrome
Leukemia
Lymphoma
Systemic lupus erythematosus
TINU SYNDROME
Acute Kidney Injury
Prerenal
Hypovolemia
Decreased cardiac output
Renal vasoconstriction
Intrinsic
Acute Tubular Necrosis
Glomerulonephritis
Vascular disorders
Postrenal
Bladder Neck
Ureteral
Tubular
Renal biopsy
Indications
Uncertainty
of
diagnosis
Advanced
Lack
renal failure
of spontaneous
recovery following
removal of offending
drug
Treatment
Discontinuation
of offending agent
Corticosteroids
 Prednisone 1 mg/kg to a max of 40-60 mg x
1-2 weeks
IV Methylprednisolone 0.5 – 1 g/day x 3
days
AIN PROGNOSIS

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Most patients recover full kidney function in 1
year
Poor prognostic factors
AKI > 3 weeks
 Advanced age at onset

Chronic Tubulointerstitial Disease
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chronic interstitial nephritis (CIN) follows a
more indolent course and is characterized by
tubulointerstitial fibrosis and atrophy associated
with interstitial mononuclear cell infiltration.
Over time, glomerular and vascular structures
are involved, with progressive fibrosis and
sclerosis within the kidney
Causes of chronic interstitial nephritis

Toxins( analgesic nephropathy, lead nephropathy)

Infection (chronic pyelonephritis)
Autoimmune( Sjogren syndrome, SLE, renal
rejection)
Metabolic( hyperuricemia, hypercalcemia)
Radiation
Neoplastic infiltration( leukemia, lymphoma,
multiple myeloma)
Hereditary renal diseases(ADPKD,MCD,MSK)
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Analgesic abuse nephropathy
chronic interstitial nephritis
 Result from excessive consumption
(NSAID & Aspirin)
 Dose dependent (at least 1 kg)
 Being responsible for 1% to 3% of ESRD
cases
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Bacterial infection
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bacterial infection of the renal parenchyma causes
interstitial nephritis
infection without anatomical abnormality seldom
produces permanent damage
obstruction (stones, prostate etc) in combination
with infection can cause progressive disease
tuberculosis causes extensive destruction from
granulomata, fibrosis and caseation
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At first, interstitial edema and PMN
infiltration, then formation of irregular
abscesses and eventually scars
Risk factors:
diabetes mellitus
obstruction
delayed antimicrobial therapy
severe infection with ATN
reflux nephropathy
papillary necrosis
Urinary tract obstruction
Consequences of urinary tract
obstruction
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Reduced glomerular filtration rate
Reduced renal blood flow (after initial rise)
Impaired renal concentrating ability
Impaired distal tubular function
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Nephrogenic diabetes insipidus
Renal salt wasting
Renal tubular acidosis
Impaired potassium concentration
Reduced RBF leads to renal ischemia tubular atrophy
Phase A
Phase B
Intraluminal
pressure
RBF
GFR
... due to
... due to
... due to
obstruction
h Peristalsis
Vasodilation
h Intratubular
pressure
Prostacyclin
Prostraglandi
n E2
... due to
... due to
... due to
Disorganised
peristalsis
dilation of
tubules and
ureter
Vasoconstricti
on
Angiotensin
II
Thromboxan
e A2
Continuing
obstruction
vasoconstrict
ion
Acute urinary tract obstruction
Functional consequences
Ureteric and tubular pressure
Renal blood flow (RBF)
GFR
0
6
Hours
12
baseline
18

myeloma
Bence-Jones protein (light chains from malignant
plasma cell clone) causes interstitial nephritis,
tubular obstruction(cast nephropathy) and
amyloid deposition
 Myeloma kidney :the classic pathologic include
THP+LC casts in dilated, atrophic distal tubuls
with infiltration monocyte & macrophage &
plasma cells that produce giant cells
 LCs are nephrotoxic through direct injury of
tubular epithelial cells & intrarenal obstruction
from cast formation
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Predisposing factors:
LC concentration
LC isoelectric point
intraluminal PH
tubular flow rate
presence of Tamm-Horsfall Pr
Hypercalcemic Nephropathy

Chronic hypercalcemia is seen in
Hyperparathyroidism
Sarcoidosis
Multiple myeloma
Vitamin D toxicity
Metastasis bone disease
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Hypercalcemia decrease GFR through renal
vasoconstriction
Calcium deposition in distal nephron and
interstitial that leads to mononeuclear cell
infiltration and tubular necrosis
Defective concentration ability, poliuria,
nocturia
Nephrocalcinosis & nephrolitiasis
WBC Casts
Cells in the cast have
nuclei
(unlike RBC casts)
Pathognomonic for
Acute Interstitial
Nephritis
Match:
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1. hyaline casts
2. muddy brown casts
3. RBCs
4. RBC casts
5. Oval fat bodies
6. eosinophils
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A. ATN
B. prerenal azotemia
C. glomerulonephritis
D. nephrolithiasis
E. interstitial disease
F. nephrotic syndrome
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