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Renal Pathology Review

Renal Pathology Review. Medical Diseases of the Kidney Karlene Hewan-Lowe, MD Brody School of Medicine at East Carolina University. Renal Pathology The Osler Institute Review Course. Normal Histology. Renal Pathology The Osler Institute Review Course. Histology Normal Glomerulus

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Renal Pathology Review

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  1. Renal Pathology Review Medical Diseases of the Kidney Karlene Hewan-Lowe, MD Brody School of Medicine at East Carolina University

  2. Renal Pathology The Osler Institute Review Course Normal Histology

  3. Renal Pathology The Osler Institute Review Course • Histology • Normal Glomerulus • Anastamosing capillary network • Architecture is defined with H and E, PAS and Methenamine silver stains • Glomerular capillary wall • Fenestrated endothelial cell • Glomerular Basement membrane 260 – 340 nm • Visceral epithelial cell (Podocyte) • Mesangium • Mesangial cells • Mesangial matrix

  4. Renal Pathology The Osler Institute Review Course • Histology • TubuloInterstitium and Arteries • Proximal convoluted tubules • Distal convoluted Tubules • Interstitium • Architecture defined by Masson’s trichrome stain • Interlobular arteries • Arterioles

  5. Renal Pathology The Osler Institute Review Course • Histologic Alterations in Glomerular Diseases • The kidney has a limited reaction to a myriad of injurious agents • Glomerular hypercellularity • Proliferative glomerulonephritides • Thick glomerular basement membranes • Hyalinization

  6. Renal Pathology The Osler Institute Review Course • Terms Used in the Evaluation of Glomerular Diseases • Diffuse glomerular changes > 50% • Focal glomerular changes < 50% • Global involvement – single glomerulus • Segmental involvement – single glomerulus

  7. Renal Pathology The Osler Institute Review Course • Immunofluorescence Microscopy • Linear capillary wall staining • Anti-GBM disease IgG, C3 • MIDD kappa light chains • Diabetic nephropathy IgG, albumin • DDD C3 • Granular mesangial staining • IgA Nephropathy IgA dominant • ISN/RPS Lupus Class I, II “Full house” • C1q nephropathy C1q

  8. Renal Pathology The Osler Institute Review Course • Immunofluorescence Microscopy • Granular mesangial and capillary wall staining • Membranous GN IgG,C3 • MPGN C3 • WHO Lupus III, IV Full house • Post infectious GN • Diffuse smudgy mesangial and capillary wall staining • Amyloidosis lambda light chains • Fibrillary GN IgG, C3, kappa > lambda • MIDD kappa light chains

  9. Renal Pathology The Osler Institute Review Course • Electron Microscopy • Subepithelial immune complex type dense deposits • Membranous GN Stage I - IV • MPGN • WHO Lupus IV • Post infectious GN “Humps” • Intramembranous (often with mesangial) immune complex type deposits • Dense deposit Disease

  10. Renal Pathology The Osler Institute Review Course • Electron Microscopy • Subendothelial immune complex type deposits • MPGN • ISN/RPS Lupus III, IV Fingerprint, TRS • Cryoglobulinemia Tubular substructure • Pure mesangial immune complex type deposits • IgAN / HSP • ISN/RPS Lupus I, II • C1q nephropathy • Subendothelial immune complex type deposits • ISN/RPS Lupus class III, IV • MPGN Type III • Postinfectious GN

  11. Renal Pathology The Osler Institute Review Course Clinical Patterns of Glomerular Disease

  12. Renal Pathology The Osler Institute Review Course • Clinical Patterns of Glomerular Diseases • Nephrotic Syndrome • Edema • Proteinuria > 3.5 gm/24 hours • Hypoalbuminemia • Hyperlipidemia • Hyerplipiduria

  13. Renal Pathology The Osler Institute Review Course • Clinical Patterns of Glomerular Diseases • Nephritic Syndrome • Hematuria • Red cell casts • Variable levels of proteinuria • Acute or chronic renal failure • Hypertension

  14. Renal Pathology The Osler Institute Review Course • Classification of Glomerular Diseases • Primary renal disease: renal limited injury • Secondary renal disease: systemic disease which involves the kidney Nephrotic Syndrome Nephritic Syndrome Primary Secondary Primary Secondary Minimal Change FSGS Membranous GN MPGN Diabetes Amyloid Post Infectious GN Crescentic GN IgA/HSP SLE Vasculitis

  15. Renal Pathology The Osler Institute Review Course Nephrotic Syndrome

  16. Renal Pathology The Osler Institute Review Course • Minimal Change Disease (Nil Disease, Lipoid Nephrosis) • Clinical Features • Peak age is 2 to 6 years • Severe proteinuria, nephrotic syndrome • Selective proteinuria • Normal renal function • Acute renal failure in adults • Associated with exposure to allergens or immunizations • Associated with Hodgkin’s disease, NSAID therapy

  17. Renal Pathology The Osler Institute Review Course • Minimal Change Disease (Nil Disease, Lipoid Nephrosis) • Pathogenesis • Immune disorder • Circulating permeability factors • Loss of fixed, GCW polyanionic charge • Decreased and altered distribution of nephrin in podocytes

  18. Renal Pathology The Osler Institute Review Course • Minimal Change Disease (Nil Disease, Lipoid Nephrosis) • Light Microscopy • Normal glomeruli • Foam cells • Resorbtion droplets in the PCT • Immunofluorescence Microscopy • No staining for G, A, M, C3, C1q, kappa, lambda

  19. Renal Pathology The Osler Institute Review Course • Minimal Change Disease • Electron Microscopy • Foot process effacement and microvillous transformation • Prognosis • Remission in 8 weeks with steroid therapy • No tendency to progress to chronic renal disease

  20. Renal Pathology The Osler Institute Review Course • Focal Segmental Glomerulosclerosis • Clinical Features • Heavy, non selective proteinuria • Nephrotic Syndrome • Microhematuria • Hypertension • Idiopathic FSGS • Secondary FSGS • HIVAN Heroin abuse • Morbid obesity Unilateral renal agenesis • Vesicoureteral reflux

  21. Renal Pathology The Osler Institute Review Course • Focal Segmental Glomerulosclerosis • Pathogenesis of FSGS • Hyperfiltration/hyperperfusion injury • Circulating permeability factor • Most cases are sporadic • Few cases are associated with genetic abnormalities • Viral infections - HIV, parvovirus B19

  22. Renal Pathology The Osler Institute Review Course • Focal Segmental Glomerulosclerosis • Light Microscopy • Juxta-medullary glomeruli • Focal glomerular involvement • Segmental glomerulosclerosis • Foam cells • Peripheral hyalinosis • Tubular atrophy and interstitial inflammation

  23. Renal Pathology The Osler Institute Review Course • Focal Segmental Glomerulosclerosis • Columbia Classification • FSGS, NOS • Typical course • Collapsing Type • Poor prognosis • Tip Lesion • ? Better prognosis • Perihilar variant • Secondary FSGS

  24. Renal Pathology The Osler Institute Review Course Focal Segmental Glomerulosclerosis • Immunofluorescence Microscopy • IgM and C3 in the sclerosed glomerular segments • Electron Microscopy • Podocyte injury • Protein droplets in podocytes • Lamellar subepithelial reduplication of the glomerular basement membrane • Foot process effacement and microvillous transformation

  25. Renal Pathology The Osler Institute Review Course Focal Segmental Glomerulosclerosis • HIV Associated Nephropathy • HIV positive African American male • Short clinical history • Late manifestation of HIV infection • Rapid progression to end stage renal disease • Collapsing variant of FSGS • Microcystic tubular dilatation • Mononuclear interstitial inflammation • Tubuloreticular structures in endothelial cells

  26. Renal Pathology The Osler Institute Review Course • Membranous Glomerulonephritis • Clinical Features • Most common cause of nephrotic syndrome in non-diabetic adults • Insidiuous onset of heavy proteinuria • Most common de novo glomerulonephritis in renal allografts

  27. Renal Pathology The Osler Institute Review Course Membranous Glomerulonephritis • Secondary MGN • Infection • Hepatitis B, Hepatitis C, Syphilis, Parastic disease • Drugs • Mercury, Gold, penicillamine, NSAID, Catopril, formaldehye • Neoplasms • Renal carcinoma, lung, stomach, breast, • Hematolymphoid neoplasms, pancreas, melanoma, seminoma • Autoimmune Disease • SLE, pemphigoid, MCTD, thyroiditis • Others • Diabetes, renal vein thrombosis, Sjogren’s, sarcoid, cryoglobulinemia, SCD

  28. Renal Pathology The Osler Institute Review Course Membranous Glomerulonephritis • Light Microscopy • Normocellular glomerulus • Thickened glomerular basement membranes • Spikes and rings seen on Jones methenamine silver • Variable interstitial fibrosis • Interstitial foam cells may be present D’Agati Columbia-Presbyterian University

  29. Renal Pathology The Osler Institute Review Course Membranous Glomerulonephritis • Immunofluorescence Microscopy • Granular IgG and C3 in the peripheral capillary wall • Electron Microscopy • Supepithelial electron dense deposits • Subendothelial and mesangial deposits in secondary membranous GN • Thickened basement membrane • Foot process effacement and microvillous transformation

  30. Renal Pathology The Osler Institute Review Course • Membranous Glomerulonephritis • Ehrenreich and Churg - Morphologic Classification • Stage I • Subepithelial electron dense deposits, normal GBM • Stage II • Subepithelial electron dense deposits surrounded by cup-like extensions of the glomerular basement membranes • Stage III • Subepithelial deposits, variable electron density, neomembranes are present on the surface of the deposit • Stage IV • Irregularly thickened GBM and no deposits

  31. Renal Pathology The Osler Institute Review Course • Membranous Glomerulonephritis • Prognosis • Slow deterioration to renal failure • Corticosteroids and cytotoxic agents may be beneficial in idiopathic membranous GN • Secondary membranous GN may regress

  32. Renal Pathology The Osler Institute Review Course • Membranoproliferative GN Type I • Clinical Features • More common in children • Uncommon in adults > 60 years of age • Prodrome of an upper respiratory infection • Hypertension • Proteinuria - always present, moderate to heavy , poorly selective • Hematuria - macroscopic hematuria is uncommon • Nephritic Syndrome • Nephrotic Syndrome • Altered renal function - decrease GFR, Elevated BUN, Creatinine • Hypocomplimentemia • Circulating immune complexes (20%)

  33. Renal Pathology The Osler Institute Review Course Membranoproliferative GN Type I • Glomeruli • Enlarged, hypercellular tuft • Lobular accentuation • Infiltrating monocytes and neutrophils • Crescents (2 - 10%) • Thick peripheral glomerular membranes • Silver stain - Double contours • Tubules • Hyaline (protein and lipid) droplets in tubular epithelium • Tubular atrophy • Interstitium • Interstitial fibrosis, foam cellsIflammatory cells • Vessels • Arteriosclerosis • Vasculitis (Cryoglobulinemia)

  34. Renal Pathology The Osler Institute Review Course • MPGN Type II – Dense Deposit Disease • Clinical Features • Children and young adults • URI prodrome in ~50% of patients • Proteinuria with hematuria • Nephrotic syndrome is the most common presentation • Acute nephritic syndrome (16 – 38%) • Partial lipodystrophy • C3 – low, fluctuating, normal • C1q, C4 – normal • C3NeF - IgG autoantibody against complement inhibitory proteins • Factor B, Properdin – low

  35. Renal Pathology The Osler Institute Review Course MPGN Type II – Dense Deposit Disease • Pathology • Glomeruli • Thick GBM • Hypercellular tuft • Leukocyte infiltration • Mesangial sclerosis • Immunofluorescence • C3, IgM - segmental • Electron Microscopy • Undulating ribbon-like deposits in the GBM, mesangium and tubular basement membranes

  36. Renal Pathology The Osler Institute Review Course • Membranoproliferative GN • Prognosis • Uniformly poor • Prognosis for Type II is generally worse than Type I • Response to alpha interferon - MPGN associated with Hepatitis C • Type II MPGN has 90% recurrence rate in allograft kidney

  37. Renal Pathology The Osler Institute Review Course • Glomerular Diseases with a Membranoproliferative Pattern • Diabetic glomerulosclerosis • Cryoglobulinemic Glomerulonephritis • Systemic Lupus nephritis (WHO Class IV) • Fibrillary glomerulonephritis • Hepatitis viral infection • Chronic liver disease • Light chain deposition disease • Lecithin-cholesterol acyltransferase deficiency

  38. Renal Pathology The Osler Institute Review Course • Diabetic Nephropathy • Clinical Features • Ten year or more history of diabetes mellitus • Microalbuminuria is an early clinical feature • Type I diabetes mellitus has good correlation between renal disease and severity of fundoscopic findings • Hypertension is common

  39. Renal Pathology The Osler Institute Review Course • Diabetic Nephropathy • Etiology and Pathogenesis • Irreversible glycosylation of the glomerular basement membranes • Growth factors • Genetic susceptibility • Glomerular hyperperfusion or hyperfiltation injury

  40. Renal Pathology The Osler Institute Review Course • Diabetic Nephropathy • Light Microscopy • Diffuse increase in mesangial matrix • Sclerotic mesangial nodules • Fibrin cap (peripheral hyalinosis) • Capsular drop • Hyaline arteriolosclerosis of the afferent and efferent arterioles • Arteriosclerosis • Protein droplets in tubular epithelium • Glycogen in tubules - Armani Ebstein anomaly • Pyelonephritis • Papillary necrosis

  41. Renal Pathology The Osler Institute Review Course • Diabetic Nephropathy • Immunofluorescence Microscopy • IgG - low intensity linear accentuation of the glomerular basement membrane • Albumin - low intensity linear accentuation of the glomerular basement membrane • IgM and C3 in sclerosed glomerular segments • Electron Microscopy • Podocytes show foot process effacement • Uniformly thick glomerular basement membrane • Expanded mesangial matrix

  42. Renal Pathology The Osler Institute Review Course • Diabetic Nephropathy • Prognosis • Progression to end stage renal failure ranges from 3 to 20 years • Renal failure • 40% of Type I diabetics • 20% Type II diabetics • Recurs in allograft kidney • Control of hyperglycemia and hypertension delays the progression of diabetic nephropathy

  43. Renal Pathology The Osler Institute Review Course • Amyloidosis • Clinical Features • AL Type amyloid - Plasma cell dyscrasia • Most common is AL monoclonal light chain, l > k • Overt myeloma is present in 10 – 20% • AA Type amyloid - Chronic inflammatory diseases • Osteomyelitis, TB, leprosy, rheumatoid arthritis • Neoplasms - Renal cell carcinoma • Familial Mediterranean Fever • Severe proteinuria • Nephrotic syndrome

  44. Renal Pathology The Osler Institute Review Course Amyloidosis • Light Microscopy • Smudgy, homogenous deposits in glomeruli, tubular basement membranes, peritubular capillaries and blood vessels • Deposits are weakly PAS positive and silver negative • Detection: Congo Red, antibody to AA, Thioflavine T

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