肾脏病学慢性肾小管间质肾炎
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• Metabolic disorders--younger individuals.
Etiology
• Drugs (eg, analgesics, lithium, cyclosporine, tacrolimus) • Heavy metals (eg, lead, cadmium, mercury) • Infection(acute pyelonephritis) • Obstructive uropathy, nephrolithiasis, reflux disease • Immunologic diseases (eg, lupus, Sjögren syndrome,
Content
• Epidemiology • Etiology • Pathophysiology • 诊断 • 治疗 • Prognosis
Epidemiology
• Primary tubulointerstitial diseases (ie, diseases of the renal tubules and interstitium sparing the glomeruli) constitute 10-15% of all kidney diseases both in the United States and around the world.
Chronic Tubulointerstitial Nephritis
CHENG KAIYUAN
• Chronic TIN is a frequent cause of ESRD, characterized by the clinical manifestation of tubular dysfunction and progressive chronic renal failure and pathological changes of tubular atrophy, inflammatory cell infiltration of interstitial nephritis and fibrosis.
primary glomerulopathies, sarcoidosis, vasculitis, antineutrophil cytoplasmic antibody [ANCA]–associated vasculitides, Wegener granulomatosis, and chronic transplant nephropathy) • Neoplasia (eg, myeloma, leukemia, amyloidosis) • Metabolic diseases (eg, hypercalcemia, cystinosis, potassium depletion, hyperoxaluria) • Genetics (eg, Alport syndrome, medullary cystic disease) • Miscellaneous (eg, Balkan endemic nephropathy, Chinese herb/aristolochic acid nephropathy)[5, 6]
Injury, necrosis Injury,breakage
chronic +~++ +~++
+~++++ atrophy thickeness
Pathophysiology
TGF-β
+
-
production
degradation
collagen
fibrogenesis
*
*
*
ຫໍສະໝຸດ Baidu
Kidney biopsy. This image shows chronic tubulointerstitial nephritis. The interstitium is expanded by fibrosis, with distortion of tubules and periglomerular fibrosis. Glomeruli do not show pathologic changes (hematoxylin and eosin, 20 X).
Pathophysiology
• Chronic tubulointerstitial nephritis is characterized by interstitial scarring, fibrosis, and tubule atrophy, resulting in progressive chronic renal insufficiency.
• Analgesic nephropathy is 5-6 times more common in women --women taking more analgesics than men. --greater sensivity
• All toxic nephropathies are related to the cumulative effects, more frequently with advancing age.
• Activation of nuclear transcription factors, such NFκB in injured kidney cells, with consequent transcription and release of proinflammatory cytokines into the interstitium, appears to be a major mechanism
Acute vs Chronic
Morphology features
interstitium
Cell infiltration
edema
fibrosis
tubule
epithelium
Basement membrane
morphology
glomerulus
vessel
acute +~++++ +~++++
Etiology
• Drugs (eg, analgesics, lithium, cyclosporine, tacrolimus) • Heavy metals (eg, lead, cadmium, mercury) • Infection(acute pyelonephritis) • Obstructive uropathy, nephrolithiasis, reflux disease • Immunologic diseases (eg, lupus, Sjögren syndrome,
Content
• Epidemiology • Etiology • Pathophysiology • 诊断 • 治疗 • Prognosis
Epidemiology
• Primary tubulointerstitial diseases (ie, diseases of the renal tubules and interstitium sparing the glomeruli) constitute 10-15% of all kidney diseases both in the United States and around the world.
Chronic Tubulointerstitial Nephritis
CHENG KAIYUAN
• Chronic TIN is a frequent cause of ESRD, characterized by the clinical manifestation of tubular dysfunction and progressive chronic renal failure and pathological changes of tubular atrophy, inflammatory cell infiltration of interstitial nephritis and fibrosis.
primary glomerulopathies, sarcoidosis, vasculitis, antineutrophil cytoplasmic antibody [ANCA]–associated vasculitides, Wegener granulomatosis, and chronic transplant nephropathy) • Neoplasia (eg, myeloma, leukemia, amyloidosis) • Metabolic diseases (eg, hypercalcemia, cystinosis, potassium depletion, hyperoxaluria) • Genetics (eg, Alport syndrome, medullary cystic disease) • Miscellaneous (eg, Balkan endemic nephropathy, Chinese herb/aristolochic acid nephropathy)[5, 6]
Injury, necrosis Injury,breakage
chronic +~++ +~++
+~++++ atrophy thickeness
Pathophysiology
TGF-β
+
-
production
degradation
collagen
fibrogenesis
*
*
*
ຫໍສະໝຸດ Baidu
Kidney biopsy. This image shows chronic tubulointerstitial nephritis. The interstitium is expanded by fibrosis, with distortion of tubules and periglomerular fibrosis. Glomeruli do not show pathologic changes (hematoxylin and eosin, 20 X).
Pathophysiology
• Chronic tubulointerstitial nephritis is characterized by interstitial scarring, fibrosis, and tubule atrophy, resulting in progressive chronic renal insufficiency.
• Analgesic nephropathy is 5-6 times more common in women --women taking more analgesics than men. --greater sensivity
• All toxic nephropathies are related to the cumulative effects, more frequently with advancing age.
• Activation of nuclear transcription factors, such NFκB in injured kidney cells, with consequent transcription and release of proinflammatory cytokines into the interstitium, appears to be a major mechanism
Acute vs Chronic
Morphology features
interstitium
Cell infiltration
edema
fibrosis
tubule
epithelium
Basement membrane
morphology
glomerulus
vessel
acute +~++++ +~++++