Nephrotic Syndrome

primary nephrotic syndrome causes

-also: diabetes, lupus

Membranoproliferative GN (type 1 MPGN)

-associated with chronic infections -thickening and lobular appearance --> doesnt look like an xmas tree, more like a grapefruit TYPE II [complement disorder] • Typically presents in childhood • Nephrotic Syndrome, Hypertension •Has low C3 + normal C4 (alternative pathway of complement due to presence of C3 Nephritic factor) • Often poorly responsive to therapy • May be a candidate for new agents that block complement pathway (such as ecluzimab) TYPE I: classical complement process (C4) TYPE II: alternative complement pathway (C3)

Minimal Change disease

-nephrotic disease of children -associated with allergies LAB: -normal light microscopy -negative immunoflourescence -EM with foot process fusion **Podocytes express CD80 --> begin to act like a dendritic cell --> responds well to steroids PATHOGENESIS: -circulating factor --> podocyte injury (Foot process fusion; Expression of CD80 in podocytes) --> proteinuria TREATMENT -corticosteroids (prednisone) -short course of oral xytoxan if relapse more than 3 times -tends to relaps 3-5 times

HIV Nephropathy

-treated with anti-retroviral drugs GENETIC PREDISPOSITION -APOL1 mutation in african americans increases risk for nephropathology in HIV infected patients -mutation protects against sleeping sickness

Discuss the pathogenesis of the nephrotic syndrome.

NEPHROTIC SYNDROME: disease that causes disruption of podocyte and barrier to protein -podocytes control proteinuria --> with damage, allows more protein through CLINICAL: -**Proteinuria - (>3.5 g/day) -Hypoalbuminemia - (<3.0 g/dl) -Edema -Hyperlipidemia -Lipiduria (lipoproteins go up, with leak in the kidney they end up in the urine --> looks like maltese cross) **UA with high protein must have high albumin to be nephrotic OTHER COMPLICATIONS 1) Hypercoagulable state - Increased coagulation factors (fibrinogen, factors V, VIII, IX, X) - Decreased anti-thrombin III - Increased platelet aggregation to stimuli • Infections 2) Increased risk for bacterial infections (peritonitis, pneumonia) - Mechanism: loss of immunoglobulins (IgG) + complement components (factor B) -Decreased Vitamin D Levels (Loss of vitamin D binding protein) MANAGEMENT • Low salt diet • Diuretics • BP control • Other measures -cholesterol lowering drugs -ACE inhibitors to decrease proteinuria by lowering glomerular pressure -Vit D (25-OH Vit D) replacement Normal or slightly low protein diet

Focal Segmental Glomerulosclerosis (FSGS)

Nephrotic syndrome FOCAL: some glomeruli are normal, others are not SEGMENTAL: some portions are worse than others SCLEROSIS: Scarring *worse disease than minimal change because there is scarring, harder to treat

Describe the anatomy and function of the glomerulus.

PODOCYTES: Have interdigitating foot processess -podocyte slit diagram controls proteinuria -nephrin molecules stick out and form the slit diaphragm --> primary barrier for protein to get into the urine**

Membranous Nephropathy

basement membrane is thickened **christmas tree PATHOGENESIS: Mediated by antibodies to phospholipase A2 Receptor on podocyte -antibodies cross BM and attacks podocytes **ANTI-PLA2 *associated with mercury used in skin cream to lighten skin TREAT: steroids MALIGNANCY -cancer present in 6-11% of membranous nephropathy -types of malignancies: carcinoma

Identify and discuss the major causes and treatment of idiopathic nephrotic syndrome.

• Low salt diet • Diuretics • BP control • Other measures -cholesterol lowering drugs -ACE inhibitors to decrease proteinuria by lowering glomerular pressure -Vit D (25-OH Vit D) replacement Normal or slightly low protein diet