Nephrotic Syndromes Flashcards
What is the typical appearance of urine in nephrotic syndrome?
Foamy urine due to proteinuria
What is the hallmark problem in nephrotic syndrome?
Proteinuria
Increased permeability of the glomerulus to plasma proteins
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
List some general symptoms of nephrotic syndrome
Massive proteinuria (>3.5 g/day)
Hypoalbuminemia
Generalized edema
Hyperlipidemia and lipiduria
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)
What is the mechanism of hyperlipidemia in nephrotic syndromes?
Hypoalbuminemia triggers increased synthesis of lipoproteins in liver
What is the mechanism of lipiduria in nephrotic syndromes?
Due to the increased permeability of the glomerular basement membrane to lipoproteins
Membranous Nephropathy
Typical Clinical Presentation
Edema (ankle, periorbital)
Thrombosis (loss of antithrombin III)
Infections
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)
Membranous Nephropathy
Where do the immune complexes have their reaction?
Basal surface of the podocytes (the distal zone of the capillary wall)
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.
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
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
What are the granular deposits of Membranous Nephropathy made of?
IgG + Complement
Membranous Nephropathy
Prognosis
33% spontaneous remission
33% will need dialysis
33% will have proteinuria without renal failure progression
Membranous Nephropathy
Treatment
Immunosuppressive drugs
Nonspecific antiproteinuric
Treat the underlying disease
Kidney transplant
Minimal Change Disease
What is the pathological origin?
Reversible podocyte injury
Derived from…
T cells, cytokines, immune depression, NSAIDs
Minimal Change Disease
Who is primarily affected?
Children 2-6yo
Minimal Change Disease
Clinical Presentation
Edema (periorbital, generalized)
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
What is a big difference between Minimal Change Disease and Membranous nephropathy?
Minimal Change Disease has no immune complex deposition!
Minimal Change Disease
Prognosis
Relapsing episodes of nephrotic syndrome
Resolution at puberty
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
