Nephrotic Syndrome

Question 1

Five features of nephrotic syndrome

Answer 1

Heavy proteinuria
Hypoalbuminemia
Hyperlipidemia
Lipiduria (oval fat bodies + maltese cross)
Edema

Question 2

Five major clinical causes of nephrotic syndrome

Answer 2

Minimal Change Disease
Focal segmental glomerulosclerosis
Membranous glomerulopathy
Diabetic glomerulosclerosis
Amyloidosis

Question 3

MCD: Pathogenesis

Answer 3

90% of nephrotic syndrome cases in kids 2-6 years. Disorder of the podocyte; leads to defect in glomerular permeability barrier. Increase in size of slit filters regulated by podocyte. (Circulating “permeability factors,” immune related)

Question 4

MCD: Etiology

Answer 4

Unclear but mainly suspected immunologic mechanism: we see remissions w/ steroids or cytotoxic agents; T cell abnormalities; disease onset also associated w/ lymphoma in some patients.

Occasionally MCD can occur as drug rxn in pts w/ NSAIDS or lithium.

Question 5

Nephrotic Syndrome Rx

Answer 5

Treat both primary disease (immune modulating) and symptoms!
Symptoms: Low sodium diet, loop diuretics
Statins for hyperlipidemia
ARBs/ACE i’s to induce remission of proteinuria + decrease BP
Anticoagulation in some for ^ clotting factors

Question 6

MCD Gross pathology

Answer 6

Pale, lipid rich kidneys

due to nephrotic syndrome

Question 7

MCD micropathology

Answer 7

“Nil” disease because minimal changes seen on light microscopy. Glomeruli look normal. No immune deposits. But can see proximal tubules stuffed w/ lipid materials

Question 8

MCD treatment

Answer 8

HIGHLY responsive to steroids. 50% will never get recurrence.

Question 9

Fogal Segmental Glomerulosclerosis (FSGS) cause

Answer 9

Podocyte disease; uncertain whether it represents a progressed MCD or if it’s a separate entity.
Note: Can be unresponsive to corticosteroid therapy

Question 10

FSGS morphology/histology

Answer 10

It’s FOCAL, involves a specific subset of glomeruli. The uninvolved glomeruli demonstrate changes of MCD (normal by light microscopy w/ diffuse foot processes)

• Hyaline deposits (entrapped plasma proteins in areas of sclerosis)
• involves only a PORTION OF THE TUFT
• -> lesions can progress to global glomerulosclerosis
• IgM and C3 in sclerotic lesions

Question 11

FSGS etiology

Answer 11

• Primary/idiopathic FSGS: Unclear, but we see foot process effacement, altered adhesion to GBM and increased permeability of the glomerulus that may be caused by circulating permeability factors
• Genetic: podocyte mutations
• Viral: HIV can actually infect these cells (give HAART. See tubular microcysts on microscopy)
• Drug induced: eg Heroine
• Adaptive FSGS: result of increased hemodynamic stress on glomerulus; ex: in obesity, reflux nephropathy, renal agenesis, any chronic renal disease. Common consequence of reduction in functioning nephrons during course of any renal disease. Hypertrophy of glomerulus can be adaptive initially but over time becomes maladaptive –> sclerosing

Question 12

Membranous Glomerulopathy (MG) morphology

Answer 12

Not glomerulonephritis because there is no proliferation of inflammatory cell infiltration of the glomerulus.
Light microscopy: diffuse and global uniform thickening of GBMs
- ALL GLOMERULI affected uniformly!
- Spikes on GBM (silver stain)
- Bumps on GBM (trichrome red)
- Fluorescence: IgG and C3 dposits on peripheral GBM

Question 13

MG clinical features

Answer 13

• Most common cause of NS in white adults
• ## insidious onset

Question 14

MG etiology

Answer 14

• 60% of cases are primary, mediated by antibody to a specific podocyte antigen Phospholipase A2 receptor.
• 40% are secondary

Question 15

4 causes of 2ndary MG

Answer 15

• Infections (hep B, C, syphilis, schistosomiasis, malaria)
• Autoimmune diseases (SLE, RA)
• Neoplasm (lung/breast/colon/stomach carcinoma)
• Meds (gold, Hg, D-penicillin)
• usually remit after fixing the underlying problem_

Question 16

MG pathogenesis

Answer 16

Primary: AUTOIMMUNE. Binding of circulating antibody to podocyte antigen through in site immune complex formation in subepithelium.
HEYMANN NEPHRITIS is prototype.
–> antigen-antibody complex shed off clathrin-coated pits of podocyte into subepithelial space, forming deposits.
Secondary has similar process, but it’s likely that antigen is non-glomerular. Ex; viral antigens in hep B and C.

Question 17

Renal vein thrombosis

Answer 17

Dangerous complication of nephrotic syndrome. Seen almost exclusively in pts w/ MG. Due to hypercoagulable state from increased hepatic synth of fibrinogen and coag factors.

Question 18

Diabetic Nephropathy pathogenesis

Answer 18

Most common renal disease leading to dialysis and transplantation.

• Progressive thickening of capilary and arteriolar basement membranes (microangiopathy) which is present in every organ but reaches greatest severity in kidneys and retina.
• Excessive synthesis of collagenous proteins and glycoproteins from abnormal glucose metab.
• Leads to glycosylation of BM proteins and the formation of advanced glycation end products (AGE - can see w/ immunostain).

Question 19

Diabetic nephropathy morphology

Answer 19

• thickening of basement membranes
• Can be diffuse or nodular
• nodular from exuberant increase in mesangial matrix, forms large nodules.
• basement membrane thickening and expansion. individual glomeruli are seen w/ increase in mesangial matrix (KW nodules), it’s uniform. you also have thickening of tubule basement membrane
• hyalinosis in glomerulus and arterioles
• can see glomerular microaneurysms

Question 20

RX of membranous nephropathy

Answer 20

Conservative therapy
Corticosteroids
Alternating steroids/cytotoxics
cyclosporine
mycophenolate
ACTH
Rituximab

Question 21

DM neph gross pathology

Answer 21

Enlarged kidney due to increase in all renal compartments

Question 22

Stages of Diabetic renal disease

Answer 22

1: hyperfiltration
2: clinically silent
3. incipient nephropathy
4. overt nephropathy
5. ESRD

Question 23

Hyalinosis

Answer 23

Insudation of plasma proteins into thickened basement membranes. Appear as waxy, homogenous, eosinophilic material containing focal lipid dropletx. Common in DM.

Can also see in intima or media or arterioles

Question 24

Rx for proteinuria

Answer 24

ARB’s and ACE I’s

Question 25

Renal Amyloidosis pathogenesis

Answer 25

Deposition of amorphous eosinophilic hyaline substance in tissues. Can be local or systemic in body.
- Two major forms are primary (AL) and secondary (AA);
Cause:
1) dysproteinemias (myeloma, B CEll lymphomas, macroglobulinemia, occult plasma cell dyscrasia): increased light chains (lambda tends to be particularly common myeloma)
2) chronic inflammatory or infectious states (TB, chronic bronchiectasis, osteomyelitis, RA, ankylosing spondylitis, IBS)

Question 26

Amyloidosis Morphology and Clinical Features

Answer 26

May deposit in all four renal compartments (glomeruli, vessels, tubular basement membranes, interstitium)
- As glomeruli incrreasingly replaced by amyloid deposits, there is a reduction in glomerular filtration rate, leading to renal insufficiency and CRF.

Question 27

Amyloid gross path

Answer 27

large kidneys, pale and waxy