Tubulointerstitial Diseases
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Transcript of 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 >400ml/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
• Female>male
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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 39°C 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 39.5°C, 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