Nephrotic Syndromes Flashcards by Tom O

What is the typical appearance of urine in nephrotic syndrome?

Foamy urine due to proteinuria

How well did you know this?

Not at all

Perfectly

What is the hallmark problem in nephrotic syndrome?

Proteinuria

Increased permeability of the glomerulus to plasma proteins

How well did you know this?

Not at all

Perfectly

In normal physiology, how does the glomerulus prevent certain molecules and proteins from filtration?

Filters by size and charge. Particles that are too large will not get through.
Negatively charged proteins will not get through even if they are small enough (like albumin), due to two negatively charged layers on either side of the lamina densa

How well did you know this?

Not at all

Perfectly

List some general symptoms of nephrotic syndrome

Massive proteinuria (>3.5 g/day)
Hypoalbuminemia
Generalized edema
Hyperlipidemia and lipiduria

How well did you know this?

Not at all

Perfectly

What is the mechanism of hypoalbuminemia in nephrotic syndromes?

Loss of protein in the urine leads to hypoalbuminemia and a drop in plasma colloid osmotic pressure (causing edema)

How well did you know this?

Not at all

Perfectly

What is the mechanism of hyperlipidemia in nephrotic syndromes?

Hypoalbuminemia triggers increased synthesis of lipoproteins in liver

How well did you know this?

Not at all

Perfectly

What is the mechanism of lipiduria in nephrotic syndromes?

Due to the increased permeability of the glomerular basement membrane to lipoproteins

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Typical Clinical Presentation

Edema (ankle, periorbital)
Thrombosis (loss of antithrombin III)
Infections

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Etiology/Pathogenesis

In-situ immune complex formation
Could be due to antibodies against an “intrinsic” renal antigen or a “planted” antigen (that has lodged itself in the basement membrane)

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Where do the immune complexes have their reaction?

Basal surface of the podocytes (the distal zone of the capillary wall)

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Does it cause inflammation?

No!

Immune complex events in the proximal zone of the glomerular capillary wall are much more likely to cause inflammation, but Membranous Nephropathy affects the distal zone.

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Describe the appearance on silver stain and why.

Get a “spike and dome” or “holey” appearance

The podocytes are trying to form a new basement membrane, so they cause the spike and dome appearance

How well did you know this?

Not at all

Perfectly

In older patients diagnosed with membranous nephropathy, what should you do in addition to treatment?

Rule out possible cancer, which could played a role in the immune complex deposition

How well did you know this?

Not at all

Perfectly

What are the granular deposits of Membranous Nephropathy made of?

IgG + Complement

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Prognosis

33% spontaneous remission
33% will need dialysis
33% will have proteinuria without renal failure progression

How well did you know this?

Not at all

Perfectly

Membranous Nephropathy

Treatment

Immunosuppressive drugs
Nonspecific antiproteinuric
Treat the underlying disease
Kidney transplant

How well did you know this?

Not at all

Perfectly

Minimal Change Disease

What is the pathological origin?

Reversible podocyte injury

Derived from…
T cells, cytokines, immune depression, NSAIDs

How well did you know this?

Not at all

Perfectly

Minimal Change Disease

Who is primarily affected?

Children 2-6yo

How well did you know this?

Not at all

Perfectly

Minimal Change Disease

Clinical Presentation

Edema (periorbital, generalized)

How well did you know this?

Not at all

Perfectly

Minimal Change Disease
What is seen on Light microscopy? Immunofluorescence?
Electron microscopy?

Light microscopy and IF look normal.

EM is most critical
See effacement (fusion) of foot processes

How well did you know this?

Not at all

Perfectly

What is a big difference between Minimal Change Disease and Membranous nephropathy?

Minimal Change Disease has no immune complex deposition!

How well did you know this?

Not at all

Perfectly

Minimal Change Disease

Prognosis

Relapsing episodes of nephrotic syndrome

Resolution at puberty

How well did you know this?

Not at all

Perfectly

Minimal Change Disease

Treatment

Steroids

Focal and Segmental Glomerular Sclerosis (FSGS)

Typical Clinical Presentation

Nephrotic Syndrome
Higher incidence of hematuria, reduced GFR, HTN
Non selective proteinuria is more common

FSGS | What groups is it more common in?

African Americans and Hispanics

FSGS | Pathogenesis

Irreversible injury to podocytes Some glomeruli (not all) will show an increase in mesangial matrix-like substance, leading to obliteration of the capillaries and sclerosis See effacement of epithelial foot processes on EM in all glomeruli

FSGS | Which glomeruli tend to be involved in the initial stages? As it progresses?

Juxtamedullary glomeruli only in initial stages Global sclerosis, tubular atrophy, and interstitial fibrosis in later stages

FSGS | Prognosis

Progression to renal failure

FSGS | Treatment

Initially, may be responsive to steroids though it will become resistant over time. In kidney transplants, FSGS may recur

FSGS | List some of the many etiologies

HIV-associated Parvavirus B19 Heroin Sickle Cell disease Steroid use HTN Low birth weight Obesity

FSGS | What genetic mutations are commonly involved?

Mutations in genes encoding slit diaphragm proteins. NPHS1 or NPHS2 -- play a role in maintaining normal glomerular filtration barrier

Which gene is associated with higher risk in adult African American onset of FSGS?

Apolipoprotein L1

HIV-associated FSGS | What is seen on H&E stain of the glomerulus?

"Collapsing FSGS" No obliteration and solidification of the capillaries Instead, the glomerulus looks collapsed

``` Membranoproliferative Glomerulonephritis (MPGN) Typical Clinical Presentation ```

Nephrotic syndrome na dhematuria

``` Membranoproliferative Glomerulonephritis (MPGN) Etiology/Pathogenesis ```

Primary immune complex formation with classic complement activation Could be secondary to chronic autoimmune disorders, hepatitis, endocarditis, bacterial infections

``` Membranoproliferative Glomerulonephritis (MPGN) What is the classic appearance on EM? ```

Glomerular capillary wall has two visible lines "Tram track" appearance There are dense irregular dots that are immune complex (IgG+C3) deposits in the subendothelial space

``` Membranoproliferative Glomerulonephritis (MPGN) Lab Tests ```

Low complement levels

``` Membranoproliferative Glomerulonephritis (MPGN) Prognosis ```

Progress to renal failure

``` Membranoproliferative Glomerulonephritis (MPGN) Treatment ```

Treat the underlying disease

Dense Deposit Disease (DDD) | Typical Clinical Presentation

Nephrotic syndrome with hematuria

Dense Deposit Disease (DDD) | Who most commonly gets it?

Older children

Dense Deposit Disease (DDD) | Pathogenesis

Sustained activation of complement via alternative pathway (non-Ab mediated) Sustained activation of complement is due to stabilized C3 convertase, often due to C3 nephritic factor

Dense Deposit Disease (DDD) | What is the appearance on EM?

Ribbon-like dense appearance of the lamina densa

Dense Deposit Disease (DDD) | What is most commonly the factor that causes sustained complement activation?

C3 nephritic factor

Dense Deposit Disease (DDD) | Prognosis

Progress to renal failure | Recurrence in transplants

Diabetes | What is the hallmark lesion/pathology of diabetic nephropathy?

Thick glomerular basement membrane due to non-enzymatic glycosylation of the basement membrane. Therefore, the wall of the membrane is thicker and the kidney lumen is narrower

Diabetes | In what vessel does hyaline/protein material tend to accumulate?

Efferent arterioles in the kidney

Amyloidosis | What is the basic pathological issue?

Abnormally folded protein (Beta plated sheets) accumulating outside cells

Amyloidosis | What stain should be used for diagnosis?

Congo Red stain

What kind of malignancy is amyloidosis commonly involved with?

Plasma cell malignancy

How do you diagnose/detect amyloidosis?

Tissue screening (such as a fat biopsy) Deposits of amyloid may be present in both the kidney and adipose tissue

Symptoms of Amyloidosis

``` Nephrotic syndrome (proteinuria) Heart involvement (could cause restrictive cardiomyopathy) Submandibular swelling Raccoon eyes Macroglossia ```

SLE | Who is most commonly affected?

Young women

SLE | What is the basic pathological problem?

Chronic formation of circulating immune complexes in blood

SLE | What is a kidney biopsy used for in SLE?

Staging of SLE | If the kidney is badly affected with diffuse proliferative necrosis, then treat that patient more aggressively