Tubulointerstitial diseases

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Renal pathology tutorial for nephrologists

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Tubulointerstitial diseases

  1. 1. TUBULOINTERSTITIAL DISEASES
  2. 2. Acute Tubular Necrosis <ul><li>Histopathology: </li></ul><ul><li>Tubules with low epithelial lining, single cell necrosis, epithelial apical surface blebbing, cytoplasmic vacuolization, luminal distension, cellular debris and casts in the lumens </li></ul><ul><li>Ischemic injury tends to be more subtle and patchy; affecting S3 segments of proximal tubules and thick ascending limb of loops of Henle </li></ul><ul><li>Toxic injury is associated with more extensive damage; affecting proximal tubules </li></ul><ul><li>Myoglobin/hemoglobin casts: large pigmented casts in the distal tubules. The casts can be stained using specific immunoperoxidase stain for myoglobin in tissue sections. </li></ul><ul><li>Regenerative changes: nucleomegaly, high nuclear-to-cytoplasmic ratio, mitotic figures, cytoplasmic basophilia </li></ul><ul><li>Ethylene glycol poisoning: marked swelling and vacuolization of the proximal tubule cytoplasm (distal tubules spared), oxalate crystal deposition </li></ul>
  3. 6. Acute interstitial nephritis <ul><li>Histopathology: </li></ul><ul><li>Interstitial inflammatory infiltrate composed mainly of lymphocytes, with admixed macrophages, plasma cells, eosinophils, and neutrophils </li></ul><ul><li>Invasion of the tubular epithelium by inflammatory cells (tubulitis) is commonly seen </li></ul>
  4. 8. Chronic interstitial nephritis <ul><li>Histopathology: </li></ul><ul><li>Tubular atrophy and interstitial fibrosis </li></ul><ul><li>Atrophic tubules may contain PAS-positive &quot;hyaline&quot; casts; other atrophic tubules may be very small, without prominent lumen, resembling endocrine gland acini (&quot;endocrine type atrophy) </li></ul><ul><li>Patchy non-specific interstitial inflammation </li></ul><ul><li>Glomeruli are usually spared; in advanced cases, different degrees of secondary focal sclerosis </li></ul>
  5. 9. Granulomatous interstitial nephritis <ul><li>Definition: </li></ul><ul><li>A form of interstitial nephritis characterized by the presence of necrotizing or non-necrotizing granulomas.{1},{2},{3},{4} </li></ul><ul><li>Classification: </li></ul><ul><li>Non-necrotizing GIN - more common; no necrosis, but lymhocytes, macrophages, epitheliod cells, giant cells, sometimes eosinophils, plasma cells </li></ul><ul><li>Necrotizing GIN - presence of central caseating necrosis in the granulomas, usually seen in infectious processes (mycobacterial or fungal nephritis) </li></ul>
  6. 10. <ul><li>Etiology: </li></ul><ul><li>Drug induced processes, most common (nearly 17-45% of all causes){5},{6}, {7} </li></ul><ul><li>Sarcoidosis (about 15-40% of all cases){8},{9} </li></ul><ul><li>Idiopathic GIN (about 10% of all cases){4}, {1} </li></ul><ul><li>Wegener granulomatosis {10}, {11} </li></ul><ul><li>Foreign body giant cell type reaction {1} </li></ul><ul><li>Xanthogranulomatous pyelonephritis (XPN){12}, {13} </li></ul><ul><li>Tuberculosis and other mycobacterial infections (BCG-induced GIN) {14},{15} </li></ul><ul><li>Histoplasmosis and other fungal infections (usually systemic) {16},{17} </li></ul>
  7. 13. Acute Pyelonephritis <ul><li>Histopathology: </li></ul><ul><li>Patchy interstitial inflammation by polymorphonuclear leukocytes, involving both, cortex and medulla; sometimes microabscess formations </li></ul><ul><li>Polymorphonuclears may be seen under the urothelium in inner medulla, if this is sampled </li></ul><ul><li>Some tubules contain neutrophils and cellular debris in their lumens (pus casts) </li></ul>
  8. 16. Chronic pyelonephritis <ul><li>Histopathology: </li></ul><ul><li>Cortical thinning due to extensive tubular atrophy and interstitial fibrosis </li></ul><ul><li>&quot;Thyroidization&quot; of the kidney: atrophic tubules contain large acellular, PAS-positive, proteinaceous, &quot;hyaline&quot; casts </li></ul><ul><li>Patchy non-specific interstitial inflammation </li></ul><ul><li>Glomeruli are usually spared; in advanced cases, different degrees of secondary focal sclerosis </li></ul>
  9. 18. Light chain cast nephropathy <ul><li>Major complication of multiple myeloma (MM) or other plasma cell dyscrasias (PCD) due to formation of large Bence-Jones protein casts in distal tubules and collecting ducts, eliciting multinucleated giant cell reaction and brisk interstitial inflammation and leading into acute and progressive renal failure </li></ul><ul><li>Etiology: </li></ul><ul><li>Abnormal plasma cell clone (or other neoplastic cell population) produces an abnormal protein (paraprotein), that filters through the glomerulus and has affinity of forming casts within distal tubules and collecting ducts </li></ul>
  10. 19. <ul><li>Histopathology: </li></ul><ul><li>Large, waxy, refractile, laminated distal tubular casts </li></ul><ul><li>The casts are often PAS-negative; however, PAS-variable staining can be seen in older, long-standing casts, as they aquire glycosilated material and change staining properties </li></ul><ul><li>Multinucleated giant cell reaction and brisk interstitial inflammation </li></ul><ul><li>Glomeruli are typically unremarkable </li></ul><ul><li>Concomittant monoclonal immunoglobulin deposition disease or amyloid deposition is very rare </li></ul><ul><li>Immunofluorescence: </li></ul><ul><li>Immunofluorescence is often restricted to a single light chain (frequently kappa); older casts may lose light chain specificity </li></ul><ul><li>Electron microscopy: </li></ul><ul><li>EM is usually not helpful; casts may contain needle shaped crystals </li></ul>
  11. 21. Oxalosis
  12. 22. Nephrocalcinosis <ul><li>Definition: </li></ul><ul><li>Deposition of non-polarizable calcium phosphate crystals in the tubules </li></ul><ul><li>Etiology: </li></ul><ul><li>Use of bowel-cleansing preparations which contain phosphate (commonly used in various gastrointestinal procedures, including colonoscopy); the patients do not have hypercalcemia or other risk factors for development of nephrocalcinosis. Most patients have normal renal function prior to colonoscopy and many are hypertensive and being treated with agents that are known to be associated with reduced perfusion pressure. {1}, {2}, </li></ul>
  13. 23. <ul><li>Histopathology: </li></ul><ul><li>Non-polarizable calcifications in the distal tubules and collecting ducts </li></ul>
  14. 26. Urate Nephropathy <ul><li>Histopathology: </li></ul><ul><li>Needle-shaped crystals, with surrounding interstitial inflammation (sometimes with giant cells), usually in inner medulla </li></ul><ul><li>Crystals are water-soluble. Therefore, to be visualized, alcohol fixation is needed; birefringent under polarized light </li></ul>

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