Robbins Basic Pathology: Nephrotic Syndrome

Question 1

What is Nephrotic syndrome?

Answer 1

Nephrotic syndrome is a complex of signs and symptoms characterized by

(1) massive proteinuria > 3.5g/dL
(2) Hypoalbuminemia
(3) generalized edema
(4) hyperlipidemia and lipiduria

Question 2

How do the signs of nephrotic syndrome develop?

Answer 2

A derangement of the capillary walls in the glomeruli leads to increased filtration of proteins from the plasma.

Increased filtration of albumin leads to decreased plasma oncotic pressure and fluid leaves the vascular system resulting in edema.

Decreased fluid volume activates RAAS and Na+ and water reabsorption is increased, which further exacerbates the problem.

Question 3

Is nephrotic syndrome in children usually primary or seconday?

Answer 3

Usually nephrotic syndrome in children in primary

Question 4

Is nephrotic syndrome in adults usually primary or secondary?

Answer 4

Usually in adults nephrotic syndrome is secondary.

Question 5

What are the three most frequent systemic causes of nephrotic syndrome in adults?

Answer 5

(1) Diabetes
(2) Amyloidosis
(3) SLE

Question 6

What are the primary Nephrotic diseases?

Answer 6

(1) membranous GN
(2) Minimal change disease
(3) Focal segmental glomerulosclerosis
(4) Membranoproliferative GN
(5) IgA nephropathy

Question 7

What is minimal change disease?

Answer 7

A relatively benign cause of nephrotic syndrome in children.

Question 8

what is the epidemiology of MCD?

Answer 8

MCD is the most common cause of nephrotic syndrome in children. most common between the ages of 1 and 7

Question 9

What is the pathogenesis of MCD?

Answer 9

There is no clearly established pathogenesis for MCD. However, it has been suggested that T cell mediated damage to podocytes causes the effeacement of foot processes leading to the nephrotic syndrome.

Question 10

What happens when corticosteroids are given in MCD?

Answer 10

The podocytes return to normal the the proteinuria remits.

Question 11

What does MCD look like with light microscopy?

Answer 11

The glomeruli look normal under light microscopy.

Question 12

What does MCD look like under the electron microscope?

Answer 12

(1) effacement of the foot processes
(2) Proximal convoluted tubule cells are laden with protein and lipid secondary to nephrotic syndrome.
(3) Epithelial cell vacuolization, micrvillus formation, and focal detachment.

Question 13

What is the typical presentation of MCD?

Answer 13

An otherwise healthy child with an insidious onset of nephrotic syndrome.

(1) proteinuria >3.5g/dL
(2) generalized edema
(3) hypoalbuminemia
(4) hyperlipidemia/lipiduria

Question 14

What is the treatment for MCD?

Answer 14

Short course corticosteroids will usually cause restoration of podocyte morphology followed by correction of the proteinuria. However, relapse is common.

Question 15

What is the prognosis for MCD?

Answer 15

For children the prognosis is good with more than 90% responding to short course corticosteroids. Less than 5% will progress to chronic renal failure. However, two thirds will typically relapse and some of those patients may become steroid dependent. In adults the response rate to corticosteroids is lower and the relapse rate is higher.

Question 16

What factors can cause FSGS?

Answer 16

(1) drugs or infection (HIV, heroin)
(2) Other GN disorders (IgA nephropathy)
(3) Maladaption to nephron loss
(4) Inherited defect in podocyte proteins
(5) FSGS can be a primary disease

Question 17

What is the pathogenesis of FSGS?

Answer 17

The pathogenesis is unknown. However, it has been suggested that a circulating mediator causes damage to the podocytes which results in the proliferation of the ECM and deposition of hyaline masses.

Question 18

What are the light microscope findings associated with FSGS?

Answer 18

(1) focal segmental involvement of glomeruli
(2) Increased mesangial matrix
(3) obliterated capillaries
(4) deposition of hyaline masses
(5) lipid droplets

Question 19

What are the electron microscopy findings associated with FSGS?

Answer 19

electron microscopy shows effacement of the foot processes.

Question 20

What are the signs of FSGS?

Answer 20

(1) proteinuria >3.5g/dL
(2) generalized edema
(3) hypoalbuminemia
(4) hyperlipidemia/lipiduria
(5) hematuria (different than MCD)
(6) hypertension (different than MCD)

Question 21

What is the prognosis for FSGS?

Answer 21

FSGS rarely remits on its own and 50% progress to chronic renal failure within 10 years. Response to corticosteroids is poor.

Question 22

What is collapsing glomerulopathy?

Answer 22

A variation of FSGS that is characterized podocyte hyperplasia and collapse of the glomerular tuft. This is associated with a poor prognosis.

Question 23

What is Membranous nephropathy?

Answer 23

A slowly progressing nephrotic syndrome characterized by sub-epithelial Ig containing deposits along the GBM.

Question 24

What is the epidemiology of membranous nephropathy?

Answer 24

membranous nephropathy is most common between 30 and 50 years of age.

Question 25

What conditions can cause membranous nephropathy?

Answer 25

85% are idiopathic but 15% are secondary to (1) infection (HBV, syphilis, Malaria) (2) malignancy (lung, colon, melanoma) (3) SLE (and other AI diseases) (4) Inorganic salts (gold, mercury) (5) drugs (penicillamine, captopril, NSAIDs)

Question 26

What is the pathogenesis of membranous nephropathy?

Answer 26

In membranous nephropathy sub-epithelial immune complex deposition leads to MAC mediated damage of podocytes and mesangial cells. In response the cells release proteases and ROS which cause further damage. In response to the damage excessive ECM is laid down.

Question 27

What are the microscopic findings associated with membranous nephropathy?

Answer 27

diffuse thickening of the GBM

Question 28

What are the electron microscopy findings associated with membranous nephropathy?

Answer 28

(1) sub-epithelial immune complex deposition (2) spike and dome appearance of sub-epithelial humps. (as new matrix is added) (3) effacement of foot processes.

Question 29

What are the immunoflourescense findings associated with membranous nephropathy?

Answer 29

Granular immune complex deposition along the GBM.

Question 30

What are the signs and symptoms of membranous nephropathy?

Answer 30

Normal signs of nephrotic syndrome (1) proteinuria >3.5g/dL (non-selective with globulins as well as albumin) (2) hypoalbuminemia (3) generalized edema (4) hyperlipidemia/lipiduria

Question 31

What is the prognosis for membranous nephropathy?

Answer 31

(1) 40% progress to renal failure within 20 years (2) proteinuria persists in 60% of cases (3) 10-30% have partial or complete remission.

Question 32

What is Membranoproliferative Glomerulonephritis (MPGN) and how are type I and II diferentiated?

Answer 32

A sometimes nephrotic disease with altered GBM and proliferation of glomerular cells. Type I is characterized by sub-endothelial deposits. Type II is characterized by intramembranous deposits.

Question 33

What is the pathogenesis of Type I MPGN?

Answer 33

Circulating immune complexes are deposited in the sub-endothelial space. This is commonly caused by diseases with high antigen load such as (1) HBV/HCV infections (2) SLE (3) infected Atrioventricular shunts (4) Extra renal infections with high antigen load.

Question 34

What is the pathogenesis of Type II MPGN?

Answer 34

Also known as Dense deposit disease type II MPGN is caused fundamentally by excessive complement activation. It is believed that auto-antibodies against C3 convertase which stabilize the complex are responsible for excessive activation of complement. Defective factor H has also be suggested as a cause of excessive complement activation.

Question 35

What is the typical presentation of MPGN?

Answer 35

50% will present with nephrotic syndrome although some may present with nephritic syndrome or a combination of both.