Tubulointerstitial Diseases

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Tubulointerstitial Diseases

• Dr. Raid Jastania

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Objectives

• By the end of this session the student should be
  able to
• Describe the types of Acute tubular necrosis and
  its clinical importance
• Know the features of Acute and Chronic
  pyelonephritis, and the risk factors
• Understand the special issues in Drug-induced
  interstitial nephritis

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Tubulointerstitial Diseases

• Acute tubular necrosis
• Acute pyelonephritis
• Chronic Pyelonephritis
• Drug-induced interstitial nephritis

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Acute Tubular Necrosis

• The most common cause of acute renal failure
• Clinicopathological entity
• Reversible lesion
• Destruction of tubular epithelium
• Acute suppression of renal function (urine
  gt400ml/day)

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Causes of acute renal failure

• Pre renal, renal, post renal
• Acute tubular necrosis
• Glomerular disease. RPGN
• Vascular disease. Polyarteritis nodosa
• Acute papillary necrosis
• Diffuse cortical necrosis

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Types of Acute Tubular Necrosis

• 1. Ischemic
• 2. Nephrotoxic

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Types of Acute Tubular Necrosis

• 1. Ischemic
• State of hypoperfusion
• Eg. Trauma, septicemia, acute pancreatitis,
  hypotension, shock

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Types of Acute Tubular Necrosis

• 2. Nephrotoxic
• Heavy metals mercury
• CaCl4
• Antibiotics. Gentamicin

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Pathogenesis

• 1. Tubular injury
• 2. Blood flow disturbance (persistent, severe),
  (Endothelial cell injury)

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Pathogenesis

• 1. Tubular injury
• Sensitive to ischemia and toxins
• Injury
• Functional defect increase Na delivery to distal
  tubules vasoconstriction
• Cytokines vasoconstriction
• Tubular debris block urine outflow increase
  the pressure
• Fluid leak in interstitium collapse of tubules

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Pathogenesis

• 1. Tubular injury
• 2. Blood flow disturbance (persistent, severe),
  (Endothelial cell injury)

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Pathogenesis

• 2. Blood flow disturbance (persistent, severe),
  (Endothelial cell injury)
• Vasoconstriction
• Endothelial injury release of endothelin,
  decrease in nitric oxide
• Others renin-angiotensin, norepinephrine)

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Pathogenesis
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Morphology

• Subtle findings, similar in ischemic and toxic
• Interstitium- edema, mild acute inflammation
• Proximal tubules
• Necrosis
• Rupture of basement membrane
• Proteinaceous cast in distal and collecting
  tubules
• Tamm-Horsfall protein
• Epithelial regeneration

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Clinical course

• 1. Initiating phase 36 hours
• Hypotension, decrease urine output, rising urea
• 2. Maintenance phase 2-6 days
• Low urine output 50-400 ml/day
• Ureamia, fluid overload
• 3. Recovery
• Increase urine output (upto 3L/day)
• Electrolyte imbalance
• Risk of infections

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Tubulointerstitial nephritis

• Causes
• Infectious Bacterial, viral, fungal, parasitic
• Non-infectious Physical (radiation) Chemical
  (toxins, drugs), metabolic, Ischemic, Immune
• Acute pyelonephritis
• Chronic pylelonephritis

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Acute Pyelonephritis

• UTI
• Commonly bacterial
• Gram negative E.coli, Proteus, Klebsiella,
  Pseudomonas, Enterobacter
• Risk factors
• Anomalies, Instrumentation,
• Obstruction, bladder dysfunction, reflux
• Pregnancy
• DM. Immunosuppression

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Acute Pyelonephritis

• Routes of infections
• Hematogenous
• Ascending infection
• Adhesion to mucosa colonization of urethra
  ascending of infection
• Femalegtmale

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Acute Pyelonephritis

• Morphology
• One or both kidneys
• Sharp yellow abscess on the surface
• Necrosis, pus (neutrophils)
• WBC casts
• Pyonephrosis
• Papillary necrosis (DM, obstruction, Analgesic)
• Sharp yellow necrosis at the apex of the pyramid
• Cystitis hypertrophy, trabeculation

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Acute Pyelonephritis

• Symptoms
• Pain at the costovertebral angle, fever, chills,
  malaise
• Urine pyuria, bacteria
• Dysuria, frequencey, urgency
• Natural history
• Self-limiting
• Recurrent
• chronic

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Chronic Pyelonephritis

• Interstitial inflammation and scarring with
  deformity of the pelvicalyceal system
• 1. Chronic obstructive pyelonephritis
• Recurrent infections
• 2. Reflux nephropathy
• Vesico-ureteral reflux
• infections

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Chronic Pyelonephritis

• Morphology
• One or both kidneys
• Uneven scarring/inflammation (lymphocytes, plasma
  cells)
• Papillary blunting and calyceal deformities
• Dilation/atrophy of tubules, colloid casts
  (thyoidization)
• Vascular changes
• Secondary focal segmental glomerulosclerosis

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Chronic Pyelonephritis

• Clinical
• Late presentation renal insufficiency,
  hypertension
• Contracted kidneys
• Tubular dysfunction polyruia/nocturia

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Drug-induced interstitial nephritis

• Acute drug-induced interstitial nephritis
• Antibiotics
• NSAIDs
• Diuretics
• Begin 15 days after exposure
• Fever, eosinophilia, rash
• acute renal failure, hematuria, proteinuria

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Drug-induced interstitial nephritis

• Acute drug-induced interstitial nephritis
• Pathogenesis
• Immune mechanism, hypersensitivity
• Drug is trapped in the kidney during secretion
• Results in injury
• ? Type I, high IgE
• ? Type IV, granuloma

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Drug-induced interstitial nephritis

• Acute drug-induced interstitial nephritis
• Morphology
• Edema
• Inflammatory infiltrate lymphocytes,
  macrophages, eosinophils
• Sometimes granulomas
• NSAIDs may cause minimal change disease

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Drug-induced interstitial nephritis

• Analgesic Nephropathy
• Chronic users
• Chronic interstitial nephritis
• Renal papillary necrosis
• Aspirin, acetaminophen, caffeine, codeine

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Drug-induced interstitial nephritis

• Analgesic Nephropathy
• Pathogenesis
• Unclear, papillary necrosis, inflammation
• Oxidative damage
• Aspirin inhibits prostaglandin synthesis
  (vasoconstriction)

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Drug-induced interstitial nephritis

• Analgesic Nephropathy
• Morphology
• Papillae yellow brown, lipofuscin pigment
• inflammation
• Coagulative necrosis
• Clacification
• Scarring
• Vessels basement membrane thickening (analgesic
  microangiopathy)

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Drug-induced interstitial nephritis

• Analgesic Nephropathy
• Clinical
• Chronic renal failure
• Hypertension
• Anemia
• Increase risk of transitional cell carcinoma

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Case presentation
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• A twelve-year-old boy presents to his family
  physician with a history of a sore throat and
  fever. The sore throat began about 3 days
  previously a fever of 39C developed in the last
  day. Physical examination reveals a
  well-developed, well-nourished boy of appropriate
  size for age in mild distress. His temperature is
  39.5C, pulse 90 (nl 60-100/min), blood pressure
  100/75, and respirations 20 (nl 8-16/min).
  Examination of the oropharynx reveals a red,
  inflamed throat and tonsils with exudate.
  Otherwise, the exam is unremarkable.

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• A swab from his throat is used to test for the
  presence of streptococcal antigens (streptozyme
  test), and it is positive. When the physician
  suggests an injection of penicillin, the child
  throws a wall-eyed fit, and the physician
  relents, prescribing a ten-day course of
  ampicillin.

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• After two or three days of treatment, the boy
  begins to feel better, and has less throat pain.
  However, his mother notes a red, macular rash
  over his chest and back, and the boy complains of
  itching. Calamine lotion is applied for a day or
  two without relief, and the fever recurs, this
  time with the complaint of joint aches. When the
  child becomes listless and loses his appetite,
  his mother returns him to the doctor, who
  performs further lab tests

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• Urinalysis
• pH 7, yellow-brown
• protein - 2
• blood - 1
• glucose - neg
• leukocyte esterase - 3

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• Micro
• 5-10 RBCs/HPF
• 10-20 WBCs/HPF
• no bacteria
• few hyaline casts
• (nl 0-2 RBCs or WBCs/HPF)

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• WBC
• 12,000/mm3
• 52 neutrophils
• 5 bands
• 28 lymphocytes
• 15 eosinophils

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• Creatinine 2.1 mg/dL
• BUN 40 mg/dL
• ASO 350 U/mL
• Liver function tests normal
• 24-hour urine protein 500 mg/24 hr

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• The child is hospitalized, and a renal biopsy is
  performed. The ampicillin is discontinued, a
  course of tapering steroids is begun, and the
  patient is discharged.

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Objectives

• By the end of this session the student should be
  able to
• Describe the types of Acute tubular necrosis and
  its clinical importance
• Know the features of Acute and Chronic
  pyelonephritis, and the risk factors
• Understand the special issues in Drug-induced
  interstitial nephritis