Nephrotic syndromes (Johnson)

Question 1

What are four common clinical features of nephrotic syndrome?

Answer 1

1) Infection: (loss of Ab)
2) Hypercoagulable: increased risk of thrombosis and accelerated atherogenesis (increased liver production of clotting factors - especially in the RENAL VEIN. Also increase the LDL/HDL ratio which is atherogenic. For some reason Antithrombin III is lost in the urine more than other clotting factors.)
3) Stunted growth/osteomalacia (Vit D loss), Protein malnutrition (if severe)
4) Loss of albumin leads to drug toxicity (must adjust drug dosages), hypotension, and edema

Question 2

As contrasted with nephrotic syndrome, nephritic syndrome presents with:

Answer 2

Microhematuria
Red cell casts
Non-nephrotic proteinuria
Decreased GFR
Hypertension
Edema

Question 3

What are the four major histologic patterns assx with Idiopathic nephrotic syndrome?

Answer 3

Minimal change disease, 
Idiopathic focal and segmental glomerulosclerosis (FSGS), Membranous nephropathy (MN), 
Membranoproliferative glomerulonephritis (MPGN).

Question 4

Classical presentation (age) for someone with Focal Segmental Glomerulosclerosis? (FSGS)

Answer 4

20s to 40s. African Americans get this at higher rates due to a mutation. Associated with HIV.

Question 5

Classical presentation (age) for patient with Minimal Change Disease?

Answer 5

2-4 y/o

Question 6

[HY] Tell about Minimal Change Disease [Minimal Change Nephropathy].

Answer 6

Classical presentation in 2-4 y/o. Presents with rapid onset severe edema, lethargy. Long term prognosis is good. Treatment with a short course of steroids.

Pathology: NO CHANGE VISIBLE
No immune globulin or complement on immunofluorescence. [The absence of granular staining for IgG and C3 and the absence of subepithelial
electron dense deposits excludes early membranous nephropathy.]

Proteinuria due to “podocyte food effacement” visible on EM. Albumin is lost, but not Ab.

Pathoma: Assx with Hodgkin lymphoma. Foot process damage due to cytokines–>Reed-sternberg cell production of cytokines cause MCD.

Question 7

[HY] Focal Segmental Glomerulosclerosis (FSGS). Talk about it. Intelligently, please.

Answer 7

Classical presentation is 20-40 African American populations. Resistant to treatment, poor prognosis. Treat with 6mo course of steroids.

**HTN and/or microhematuria can differentiate FSGS from MCD

4 Types:
Idiopathic
HIV assx
heroin nephropathy (IV DRUG ABUSE)
Secondary FSGS (hyperfiltration = loss of nephron overtaxes remaining functional units)

Pathology: Focal Segmental (see, the name describes it) destruction of glomerulus, immunofluorescence generally negative but may show IgM and C3 in sclerotic areas. EM will show foot process effacement. Poor prognosis. Many progress to ESRD

Question 8

[HY] Membranous Nephropathy. Tell me about it.

Answer 8

Classically assx with older adults (50-60) with a male predominance.

Associations: (Bugs, drugs, tumors and rheum)
chronic infection (especially hepatitis B)
drugs (gold and penicillamin
LUPUS (type V membranous)
CANCER (lung, breast and GI tract)

50% end stage renal failure, 25% continued nephrotic syndrome, 25% spontaneous remission over 10-20 years

Pathology:
THICKENED MEMBRANE
IF = subEPIthelial granular deposits of IgG and C3
Immune complex deposition (Ab targeted to Phospholipase A2 [PLA2].

Why no PMN infiltrate? Because complement released in Bowmans space ends up in the urine (not blood).

**BUGS, DRUGS, TUMORS and RHEUM must be worked up if making a diagnosis of MN

Question 9

What are the primary renal diseases that cause nephrotic syndrome (5)

Answer 9

Minimal Change Disease (MCD)
Focal Segmental Segmental Glomerulosclerosis
Membranous Nephropathy (MN)
Membranoproliferative Glomerulonephritis (MPGN)
Hereditary Nephrotic Syndrome

Question 10

What are systemic diseases that can cause nephrotic syndrome?

Answer 10

Diabetes, Amyloid, SLE

Question 11

What are the three functions of the mesangial cell?

Answer 11

1) secrete GBM
2) phagocytosis/cytokine and growth factor secretion
3) contraction

Question 12

What is the “maltese cross” on microscopic urinalysis

Answer 12

Fatty casts in the urine, due to lipiduria and increased glomerular pore size (due to hyperlipidemia).

Question 13

What is the presentation of renal vein thrombosis?

Answer 13

Flank pain, enlarged kidney on US, and hematuria.

Question 14

Membranoproliferative Glomerulonephropathy

Answer 14

52 y/o female. 3 wk hx of cough, fever, chills, burning on urination. Workup is done urine sediment shows RBC TNTC, RBC casts. Meets criteria for nephrotic syndrome AND nephritic syndrome (RBC casts). She has pitting edema, lung rales.

Pathology: Hypercellular (diffuse endocapillary proliferative process). Basement membrane duplication (tram-tracking). IF shows big huge deposits on the capillary loops (IgG) between the layers of basement membrane. EM shows dark deposits on the subendothelial side, with a second membrane forming beneath to wall it off.

Question 15

Amyloidosis

Answer 15

Kidney involved 85% of the time. Usually present with nephrotic range proteinuria. Charecteristic apple green birefringence on Congo stain.

Question 16

Diabetes

Answer 16

The primary cause of chronic renal failure (38%, then HTN 25%). Get hyaline arteriolar disease (narrowing of the vessels) as well as a glomerular lesion (nodular expansion of the matrix). This can build up so much that it kills the mesangium, making it hypocellular. Big pink nodules, thickening of GBM.

Increased risk of pyelonephritis (susceptibility to infection, and ischemia due to vascular disease [necrosis of the papillae])

Question 17

HTN renal disease

Answer 17

Thickening of vessels (hyaline formation) Leads to granular appearance (gross) of kidney. Onion skin lesion of the arteriole with malignant hypertension.

Question 18

Uremia primary consequence

Answer 18

Occurs when all renal functions are compromised.

1) acidosis
2) fluid retention, edema, CHF, HTN
3) cardiac arrythmias (K+ imbalance)
4) PO4 - secondary hyperparathyroidism (hyperplastic parathyroids they are huge)

Azotemia and drug toxicity (drugs metabolized by kidney won’t be excreted efficiently)

Endocrine fxns are compromised. Anemia of chronic disease, HTN (renin), 2nd step of vitamin D activation doesn’t work, so get osteomalacia

Neurologic problems, infections, bleeding disorders, pericarditis, etc. etc.

Question 19

What’s so special about the edema assx with Nephrotic syndrome/kidney disease?

Answer 19

People can lie flat! That’s why you get periorbital edema. This differentiates it from liver, heart failure edema. The edema is more centralized in kidney disease.