PATTERNS OF RENAL INJURY
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1 PATTERNS OF RENAL INJURY
2 Normal glomerulus
3 podocyte
4 Glomerular capillaries electron micrograph
5 THE CLINICAL SYNDROMES 1. The Nephrotic Syndrome 2. The Acute Nephritic Syndrome 3. Rapidly Progressive Glomerulonephritis 4. Asymptomatic Hematuria / Proteinuria 5. The Chronic Nephritic Syndrome (Chronic Renal Failure)
6 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
7 THE NEPHROTIC SYNDROME Proteinuria (>3.5g/day) Hypoalbuminemia Hyperlipidemia Lipiduria Edema Bland urine sediment
8 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
9 THE NEPHROTIC SYNDROME The structural abnormality shared by all nephrotic conditions or diseases with heavy proteinuria is diffuse simplification or fusion of the foot processes of the glomerular visceral epithelial cells.
10 MINIMAL CHANGE DISEASE DIFFUSE EPITHELIAL CELL DISEASE
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12 Preserved podocytic foot processes Minimal change disease EM shows one capillary loop covered with simplified "fused foot processes". No electron dense deposits are seen.
13 CLINICAL CONDITIONS ASSOCIATED WITH MINIMAL CHANGE DISEASE 1. Idiopathic minimal change disease (lipoid nephrosis, nil disease): MINIMAL CHANGE DISEASE/FGS/MesPGN complex 2. Secondary forms of minimal change disease: - associated with drug use, with or without interstitial nephritis - associated with IgA nephropathy, diabetes mellitus, and other primary glomerulopathies - Hodgkin's disease, other lymphoproliferative processes
14 FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS (FGS) 1. IDIOPATHIC OR PRIMARY FGS 2. SECONDARY FGS 3. SEGMENTAL GLOMERULAR SCARRING
15 FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS (FGS) 1. IDIOPATHIC OR PRIMARY FGS 2. SECONDARY FGS 3. SEGMENTAL GLOMERULAR SCARRING
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17 Primary FGS: EM, low power, showing diffuse obliteration and simplification of foot processes (fusion) in a glomerulus not involved by the segmental collapse. This is indistinguishable from MCD.
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20 Secondary FGS, unilateral renal agenesis: EM details of the capillary walls. There are relatively well preserved foot processes (arrows). The "fusion" (arrowheads) occurs in general much more focally in these secondary forms of FGS when compared to the more diffuse obliteration of foot processes in the primary forms.
21 FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS (FGS) 1. IDIOPATHIC OR PRIMARY FGS 2. SECONDARY FGS 3. SEGMENTAL GLOMERULAR SCARRING
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23 MEMBRANOUS GLOMERULOPATHY
24
25 IgG
26 * * *
27 CONDITIONS ASSOCIATED WITH MEMBRANOUS NEPHROPATHY 1.- Idiopathic Membranous Nephropathy 2.- Autoimmune Diseases - SLE and RA - Hashimoto's disease, Grave's disease, - MCTD, Sjögren's syndrome, - primary biliary cirrhosis, - bullous pemphigoid, dermatitis herpetiformis, ankylosing spondylitis, small bowel enteropathies
28 CONDITIONS ASSOCIATED WITH MEMBRANOUS NEPHROPATHY 3.- Infectious or Parasitic Diseases - Hepatitis B and C - Syphilis - Filariasis,schistosomiasis, malaria, leprosy, enterococcal endocarditis 4.- Drugs - Au, Hg, Penicillamine, Captopril, - NSAIDs - Hydrochlorothiazide, Trimethadione, - Chlormethiazole
29 THE CLINICAL SYNDROMES 1. The Nephrotic Syndrome 2. The Acute Nephritic Syndrome 3. Rapidly Progressive Glomerulonephritis 4. Asymptomatic Hematuria / Proteinuria 5. The Chronic Nephritic Syndrome (Chronic Renal Failure)
30 THE ACUTE NEPHRITIC SYNDROME Hematuria (red cell casts, dysmorphic RBCs) Oliguria Azotemia Hypertension Edema
31 THE ACUTE NEPHRITIC SYNDROME Diseases characterized by the acute nephritic syndrome are associated invariably with deposition of immune complexes in the more proximal layers of the glomerular capillary wall, in close proximity to the endothelial cell surfaces.
32 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
33
34 IgM
35 E D D
36
37 CONDITIONS ASSOCIATED WITH DIFFUSE PROLIFERATIVE GLOMERULONEPHRITIS Acute Postinfectious Glomerulonephritis: bacterial: streptococcal, staphylococcal, pneumococcal, and typhoid fever viral: varicella, mumps, ECHO and Coxsackie, infectious mononucleosis, hepatitis B, hepatitis C with cryoglobulins, measles Other: syphilis, leptospirosis, toxoplasmosis, falciparum malaria Diffuse proliferative lupus nephritis Dense Deposit Diseases (MPGN type II), early phase Essential mixed cryoglobulinemia, early phase
38 MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)
39
40
41 US * C * D * D C End C CL
42 US CL
43 CONDITIONS ASSOCIATED WITH A MEMBRANOPROLIFERATIVE PATTERN OF INJURY 1. IMMUNE COMPLEX-MEDIATED DISEASES 2. THROMBOTIC ANGIOPATHIES 3. DEPOSITION DISEASE 1. IMMUNE COMPLEX-MEDIATED DISEASES Chronic infections: - Viral: hepatitis B, hepatitis C and essential mixed cryoglobulinemia - Bacterial: endocarditis, infected ventriculo-atrial (or jugular) shunt, multiple visceral abscesses, leprosy, meningococcal meningitis - Protozoa: malaria, schistosomiasis - Other infections: mycoplasma,?borreliosis, Leishmaniasis; parasitic diseases Miscellaneous: Chronic liver disease (cirrhosis and alpha1-antitrypsin deficiency)
44 CONDITIONS ASSOCIATED WITH A MEMBRANOPROLIFERATIVE PATTERN OF INJURY 1. IMMUNE COMPLEX-MEDIATED DISEASES: Autoimmune diseases: SLE Sjögren syndrome Rheumatoid arthritis Inherited complement deficiencies, in particular C2 deficiency Idiopathic forms of MPGN (unknown association): MPGN type I MPGN type II or dense deposit disease and partial lipodystrophy MPGN type III
45 CONDITIONS ASSOCIATED WITH A MEMBRANOPROLIFERATIVE PATTERN OF INJURY 2. CHRONIC AND HEALED THROMBOTIC MICROANGIOPATHIES: - Healing phase of HUS/TTP - The syndrome of circulating anti-phospholipid (anti-cardiolipin) antibodies - Nephropathy associated with bone marrow transplantation - Drug-associated thrombotic angiopathies - Sickle cell anemia and polycythemia - Dysfibrinogenemia and other pro-thrombotic states - Transplant glomerulopathy
46 Mes End
47 CONDITIONS ASSOCIATED WITH A MEMBRANOPROLIFERATIVE PATTERN OF INJURY 3. PARAPROTEIN DEPOSITION DISEASES: - Glomerulopathies associated with cryoglobulinemia - Waldenström macroglobulinemia - Immunotactoid glomerulopathy - Immunoglobulin light chain or heavy chain deposition diseases - POEMS syndrome (Polyneuropathy, Organomegaly, - Endocrinopathy, m-protein, Skin change) - Fibrillary glomerulonephritis
48 RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Rapid decline in renal function (over several days or few weeks) Active urine sediment Usually no edema and no hypertension
49 RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Clinical conditions that evolve with rapidly progressive decline in renal function and an active urine sediment are usually characterized by an inflammatory process that results in the formation of cellular crescents within Bowman s space (crescents).
50 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and / or Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
51 CLINICAL CONDITIONS ASSOCIATED WITH FOCAL PROLIFERATIVE AND NECROTIZING GLOMERULONEPHRITIS - IgA nephropathy/ Henoch-Schoenlein purpura - Various vasculitides, early phase. - Early idiopathic crescentic glomerulonephritis, including Goodpasture's syndrome - Immune complex-mediated diseases Lupus nephritis, WHO class III Postinfectious Glomerulonephritis (SBE)
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53
54
55
56 CRESCENTIC GLOMERULONEPHRITIS Idiopathic or primary crescentic glomerulonephritis: - Type I, anti-gbm disease - Type II, immune complex-mediated -Type III, pauci immune (ANCA-associated) Vasculitides (ANCA-associated): microscopic form of polyarteritis nodosa, Wegener's granulomatosis Churg-Strauss syndrome Drug-induced vasculitides Other primary glomerulonephritides: post-infectious GN, IgA nephropathy, MPGN, etc. Systemic diseases (SLE, RA, H-S purpura)
57 IgG
58
59
60
61 ASYMPTOMATIC HEMATURIA (PROTEINURIA) Hematuria or proteinuria (persistent microhematuria) Usually normal renal function (early during the course) Usually no hypertension or edema
62 ASYMPTOMATIC HEMATURIA/PROTEINURIA These conditions are characterized morphologically either by focal necrotizing and/or inflammatory lesions of the glomeruli or by basement membrane anomalies that result in greater capillary fragility.
63 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
64 MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS - IgA Nephropathy - Idiopathic Mesangioproliferative GN - Recovery phase of a postinfectious glomerulonephritis - SLE WHO Class II, mesangial form, and other IC-mediated diseases - Some of the deposition diseases
65
66 IgA
67
68 CLINICAL CONDITIONS ASSOCIATED WITH GLOMERULAR BASEMENT MEMBRANE ABNORMALITIES Hereditary nephritis: Classical Alport syndrome Autosomal recessive hereditary nephritis Autosomal dominant hereditary nephritis Thin basement membrane disease (TBMD) Nail-patella syndrome or hereditary osteoonychodysplasia Lecithin-cholesterol acyltranferase deficiency Resolving immune complex mediated GN
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70
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72 CHRONIC NEPHRITIC SYNDROME Azotemia Active urine sediment (variable) Proteinuria (variable) Past history of RPGN, nephrotic syndrome, or nephritic syndrome Hypertension
73 CHRONIC RENAL FAILURE CHRONIC NEPHRITIC SYNDROME The structural equivalent of this syndrome is endstage renal disease, with widespread global glomerular obsolescence (sclerosis), tubular atrophy, interstitial fibrosis, and variable degree of arterial and arteriolar sclerosis. A more precise diagnosis can often be established by immunohistochemical and ultrstructural studies.
74 THE BASIC STRUCTURAL PATTERNS OF GLOMERULAR INJURY 1.- Epithelial Cell Disease (Minimal Change Disease) 2.- Focal Segmental Glomerulosclerosis 3.- Membranous Nephropathy 4.- Diffuse Proliferative Glomerulonephritis 5.- Membranoproliferative Glomerulonephritis 6.- Crescentic Glomerulonephritis 7.- Focal Proliferative and Necrotizing Glomerulonephritis 8.- Mesangial Proliferative Glomerulonephritis 9.- Basement Membrane Abnormalities 10.- Focal Global Glomerulosclerosis
75
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