Glomerular disease

Glomerular Disease wiht nephritic and nephrotic syndrom

1. Glomerular Disease Yousaf Khan Lecturer Renal Dialysis IPMS-KMU

2. Glomerular disease Group of disease Affect of glomerular and inflammatory in nature Immunologically mediated It may be primary or secondary.

3. Primary Glomerular disease Minimal change glomerular disease Membranous glomerulonephritis Membranoproliferative glomerulonphritis IgA nephropathy Acute diffuseproliferative glomerulonephritis

4. Secondary Glomerular nephritis Common SLE Polyarteritisnodosa Diabetes mellitus Amyloidosis Malarial nephropathy Uncommon: Sarcoidosis Rheumatoid arthritis Hemolytic uremicsyndorm AIDS nephropaty

5. Pathogenesis Circulating immune complex deposition: Antigen + Antibody – deposition in glomeruli – binding with complement – inflammation – glomerular injury. Antigen may be exogenous or endogenous 2. Antibodies directed against antigen on glomerular capillary membrane : Anti – GBM antibody disease – antigen fixed in the GBM e.g good pasture syndrome Antibodies against non GBM antigen

6. Nephrotic syndrome Clinical complex characterized by Heavy proteinuria (3.5 g/day) Hypoalbuminemia Edema Hypelipidemia Hyperlipiduria Proteinuria: daily loss of protein 3.5 gm or more of protein Injury to the capillary wall of the glomeruli result – increase permeability to the plasma protein – allow to – escape from plasma

7. Pathogenesis Hypoalbuminemia : Proteinuria – decrease serum albumin level Generalized edema: Hypoalbuminemia – result decrease colloid osmotic pressure Hyperlipidemia: Hypoalbuminemia triggers increase sysnthesis of all form of plasma protein including lipoprotein – hyperlipidemia. Hyperlipiduria : Hyperlipoproteinemia – increase permeability results in hyperliduria

8. Etiology of nephrotic syndrome Primary glomerular disease: Minimal change nephropathy Focal segmental glomerulosclerosis Membranous GN Secondary GN associated with systemic disease: Diabetic nephropathy Amyloidoisis Drugs: penicillamine , gold, mercury, cadmium Allergic reaction

9. Clinical features Edema: Upper and lower limb Children more obvious on the face Intense edema of scrotum or vulva may occur Bilateral hydrothorax Edema of intestine causes anorexia, diarrhea and vomiting. Malnutrition: Malnutrition may be due to protienuria , frequent infection and muscle wasting. Hypercoagulability: Hypercoagulability manifest as peripheral arterial or venous thrombosis renal vain thrombosis and pulmonary embolism

10. Investigation Urine D/R – Proteinuria 24 hr urinary protien - > 3 g/day Serum albumin – less than 3 g/dl and total serum protein < 6 mg/dl Low- density lipoprotien is elevated but HDL is usually normal. Raised ESR due to increase serum fibrinogen Blood sugar for diabetes and antinuclear factor for SLE. Serology and renal biopsy.

11. Complication and menagement Protein malnutrition Hypercoagulabilty – due to rise in many clotting factors Impaired resistance to infection Sepsis, blood loss and hpovolemia may lead to acute oliguric renal failure Management: Diet Diuretics Hypercholesterlemia Hypercoagulability Oliguric renal failure

12. Membranous glomerulonephritis Slowly progressive disease Most common between 30 to 50 year Characterized by diffuse thickening of GBM Cause by deposition of immune complex on the epithelial side of the GBM.

13. ETIOLOGY Primary 85% membranous nephropathy caused by autoantibodies that cross-react with antigens expressed by podocytes . Secondary causes Infections (chronic hepatitis B, syphilis, malaria ) Malignant tumors, particularly carcinoma of the lung and colon and melanoma Systemic lupus erythematosus and other autoimmune conditions Exposure to inorganic salts (gold, mercury) Drugs (penicillamine, captopril, nonsteroidal antiinflammatory agents )

14. Pathogenesis: Membranous glomerulonephritis is a form of chronic immune complex nephritis Morphology: Feature of light microscope Diffuse thickening of glomerular basement membrane Feature of electron microscope: Apparent thickening of GBM is caused by subepitheial deposits that are separated from each other by small spike in GBM matrix.

15. Clinical feature of membranous GN Insidious development of nephrotic syndrome. In contrast to minimal change disease the proteinuria is non selective (albumin and globulin both are excreted) Usually does not response to corticosteroid therapy About 40% lead to renal failure after 2- 20 years 60% although proteinuria persist yet they do not progress to renal failure

16. Nephritic syndrome Inflammatory process causing renal dysfunction Over days to week that may or may not resolve. More than 50% loss of nephron function Characterized by Hematuria with RBC casts Proteinuria (usually non rephrotic range) Hypertension Edema Oliguria uremia

17. Glomerual disease with nephritic presentation Post- Streptococcal GN IgA nephropaty Goodpasteur sysndrom Polyarteritits nodosa Acute interstitial nephritis

18. Investigation: Urinalysis Dysmorphic red cell Red cell cast Proteinuria Serum chemistries Renal biopsy Treatment: Reduction of hypertension Salt water restriction Diuretics

19. Rapidly progressive Glomerulonephitis Yousaf Khan Lecturer Renal Dialysis IPMS-KMU

20. RPGN Clinical syndrome Characterized by loss of renal function Laboratory finding – nephritic syndrome – severe oliguria About 50% cases are idiopathic while 50% are related to the systemic disease. Histological finding associated with RPGN is the presence of cresents

21. Types of RPGN Type I RPGN: Anti-GBM disease Characterized by deposition of IgG and C3 on GBM anti-GBM antibodies cross react with pulmonary alveolar basement membrane –to produce clinical picture of pulmonary hemorrhage along with renal hemorrhage – good pasture syndrome. Type II RPGN (Immune – complex mediated disease) Complication of any of immune complex nephritis such as poststrptococcal GN, SLE, IgA nephropathy ets Type III: Characterized by lack of anti GBM antibodies or immune complex by immunoflurescent and electron microscope. In serum antineutrophilic cytoplasmic antibody Associated with some systemic vasculitis

22. Morphology Presence of crescents in most of the glomeruli Crescents are formed by proliferation of the parietal epithelial cells of bowman capsule Crescents eventually obliterate the bowman space and compress the glomeruli resulting oliguria

23. Clinical feature Like nephritic syndrome But more marked oliguria and azotemia 90% patient required dialysis and transplantation.

24. Thank You