Tubulointristitial Nephritis
A disorder of the interstitium and tubules
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%)
• Bland sediment or WBCs, RBCs, non-nephrotic proteinuria
• WBC Casts are pathognomonic!
• Urine eosinophils on Wright’s or Hansel’s Stain
• Also see urine eos in RPGN, renal atheroemboli
• Leukocytoclastic vasculitis
Interstitial nephritis
• 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)
• Signs of tubulointerstitial damage
Infectious Causes of AIN
Bacterial
Viral
Other
Corynebacterium diphtheriae,
legionella, staphylococci,
streptococci, yersinia
CMV, EBV, HIV, HCV, HSV,
hantaviruses, mumps, polyoma
virus
Leptospira, mycobacterium,
mycoplasma, rickettsia, syphilis,
toxoplasmosis
• Acute bilateral pyelonephritis
• Flank pain, toxic, febrile
• U/A : pyoria, hematuria, proteinuria,
bacteriuria
• B/C & U/C help to diagnosis
Infiltrative/Autoimmune Causes
of AIN
•Sarcoidosis
•Sjogren’s Syndrome
•TINU
•Leukemia
•Lymphoma
•Systemic lupus erythematosus
Acute Renal Failure
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 renal failure
•Lack 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 Management
• Remove offending agent
• Most patients recover full kidney function
in 1 year
• Poor prognostic factors
• ARF > 3 weeks
• Advanced age at onset
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)
Analgesic abuse nephropathy
• chronic interstitial nephritis
• Result from excessive consumption
(Phenacetin & Aspirin)
• Dose dependent (at least 1 kg)
• Being responsible for 1% to 3% of ESRD
cases
• The earliest lesion is thickening of GBM of
vasa recta and capillary medulla then at
later stage, focal area of necrosis in medulla
and fibrosis and atrophy of tubules that
leads to papillary necrosis and calcification.
• Pathogenesis: phenacetin and its
metabolites concentrate in the medulla
where induce the generation of reactive
metabolites
• Aspirin potentiate the toxicity of phenacetin
Bacterial infection
• 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
• The upper and lower poles with compound papilla
in ascending infection
• 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
Consequences of urinary tract
obstruction
•
•
•
•
Reduced glomerular filtration rate
Reduced renal blood flow (after initial rise)
Impaired renal concentrating ability
Impaired distal tubular function
•
•
•
•
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
-Prostacyclin
-Prostraglandi
n E2
h Intratubular
pressure
... due to
... due to
... due to
Disorganised
peristalsis
dilation of
tubules and
ureter
Vasoconstricti
on
-Angiotensin
II
-Thromboxane
A2
-Continuing
obstruction
-vasoconstricti
on
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
• 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
• 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:
•
•
•
•
•
•
1. hyaline casts
2. muddy brown casts
3. RBCs
4. RBC casts
5. Oval fat bodies
6. eosinophils
•
•
•
•
•
•
A. ATN
B. prerenal azotemia
C. glomerulonephritis
D. nephrolithiasis
E. interstitial disease
F. nephrotic syndrome
Question
• 1. 65 year old with H/o HTN, ventricular arrythmias controlled on
Amiodarone, OA on NSAIds presents with puffiness on face on
waking up. Has bilateral pitting dema. UA 3+ prot, 3 RBC., 15-20
WBC
• 24 h prot – 4 g/day
• BUN/creat 80/5
• Serum albumin 2.8, TSH normal. The most likely diagnosis?
• A) amiodarone induced hypothyroidism
• B) RPGN
• C) NSAIDs induced nephrotic sdr and interstitial nephritis