Term
| What are the 5 principle clinical features of Glomerular disease? |
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Definition
1) Proteinuria
- Heavy is Nephrotic (>3.5g/24h)
- Light may be chronic tubular disease
2) Hematuria- Damage to capillary wall (may be seen in non-glomerular conditions)
3) Edema- seen with heavy proteinuria (osmotic force)
4) Hypertension- Salt and water retention in gomerulonephritis
5) Renal dysfunction- elevated BUN and Creatinine |
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Term
| What differentiateds Glomerulopathy from Glomerulonephritis? |
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Definition
1) Glomerulopathy does not have inflammatory component
2) Glomerulonephritis has inflammatory component (immune complex) |
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Term
| What are the 5 major Glomerular Syndromes? |
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Definition
1) Asymptomatic (isolated) Hematuria
- no HTN, decreased GFR or edema
- Usually NOT glomerular
2) Proteinuria and Nephrotic syndrome
3) Nephritic syndrome
4) RPGN
5) Chronic glomerulonephritis |
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Term
How can you tell whether or not Hematuria has a glomerular origin?
If it does, what is on your ddx? |
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Definition
1) Dysmorphic RBCs and/or RBC casts (glomerulonephritis)
2)
- Thin basement membrane disease (1%, familial, benign)
- IgA nephropathy
- Hereditary Nephritis (Alport Syndrome) |
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Term
| What is the pathogenic basis of the glomerular that produces hematuria and presents with high-frequency nerve deafness and cataracts in young men? |
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Definition
Hereditary Nephritis or "Alport" syndrome
- X-linked (80%) or AD/AR disease with mutation in alpha 5 type IV collagen (COL4A5) gene leading to abnormal glomerular basement membrane synthesis
Affects men more severely than women and eventually causes proteinuria, HTN and renal failure in young men (20 to 30).
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Term
A young male patient presents with cataracts and hematuria, as well as a small amount of proteinuria. His blood pressure is also slightly high.
What would you see on LM, IF and EM analysis? |
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Definition
Hereditary Nephritis (Alport) syndrome presents in young men with hematuria and variable proteinuria. Cataracts is a classic finding and elevated blood pressure suggests advancing state of disease towards HTN.
1) LM
- Focal and segemental or global glomerulosclerosis with interstitial fibrosis and foam cells in advanced form
3) IF
- Absence of BGM staining with antibody to alpha 5 type IV collagen.
4) EM
- Thickened and Thinned BM with splitting and fraying |
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Term
True or False:
Most hematuria is glomerular in origin. |
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Definition
False!
It can occur in renal pelvis, ureters, bladder, prostate or urethra. |
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Term
| How can you distinguish between tubular injury that is leading to proteinuria and glomerular disease causing proteinuria? |
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Definition
UA
Specific gravity and degree of protein
1) Tubular origin will have Isothenuric urine (1.010) with <1+ on dipstick and either tubular cell casts or non.
2) Glomerular disease will have high SG, >3+ protein on dipstick and variable casts (RBC, granular or none). |
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Term
What are the 3 different levels of proteinuria that are generally found in the urine and what are their clinical correlates?
What needs to be done for each? |
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Definition
1) Orthostatic Proteinuria
- <1gm/24h that disappears when supine
- benign
2) Isolated non-nephrotic proteinuria
- 1.5gm-3gm without urine sediment, HTN or renal abnormalities
- No renal biopsy needed
3) Nephrotic syndrome
- >3gm/24h, hypoalbuminemia, hyperlipidemia, edema and lipidiuria
**>40 mg/h in children applies**
Get a biopsy! |
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Term
| What are 4 major clinical features of Nephrotic syndrome. |
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Definition
Remember, >3gm/24 h in adults and >40mg/h in children (infection risk in kids)
1) Edema
- low plasma oncotic pressure and salt/water retention by kidney.
2) Hyperlipidemia
- Increased production of hepatic beta lipoproteins, decreased LPL and dimnished TG to FA conversion.
3) Fatty casts and oval fat bodies
- If proliferative, may see RBC casts as well!
4) Hyper-coagulable
- Liver synthesis of coagulation factors (renal vein thrombosis and PE) |
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Term
| What is on the typical nephrotic syndrome ddx? (hint: 4 primary and 3 secondary) |
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Definition
Primary
1) Minimal change (nil disease)
2) Focal segmental glomerulosclerosis (FSGS)
3) Membranous nephropathy
4) Membranoproliferative glomerulonephritis (MPGN)
Secondary
1) Diabetic nephropathy
2) Lupus nephritis
3) Dysproteinemia and Amyloidosis |
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Term
How can UA help you distinguish between Nephritic Syndrome, Nephrotic Syndrome and Chronic GN?
What does each suggest about underlying etiology |
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Definition
1) Nephritic
- RBC (hematuria), granular and RBC cast, variable proteinuria
- Suggests Proliferative GN or vasculitis
2) Nephrotic
- Heavy proteinuria, free fat droplets, oval fat bodies, fatty casts (maltese crosses)
- Suggests non-proliferative GN
3) Proteinuria, variable hematuria, BROAD WAXY CASTS, granular casts |
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Term
What is the typical workup for a patient with suspected glomerulonephritis?
Which tests are always run and which only in particular clinical contexts? |
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Definition
1) Electrolytes, glucose, BUN and creatinine, lipid profile
2) Serologic for C3 and C4
Depending on context
1) ANA
2) Strepozyme titer
3) Serum and urine electrophoresis with immunofixation
4) ANCA
5) Liver function, hep B/C serology
6) Cryoglobulins
7) Anti-glomerular basement membrane antibody |
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Term
How do you manage Proteinuria and Nephrotic Syndrome?
4 Steps |
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Definition
1) Salt restriction
2) ACE-i or ARB
3) Judicious use of diuretics for edema
4) Lipid lowering agents (hyperlipidemia) |
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Term
A young asian boy presents with massive edema and signs of Pneumonia.
His bp of 125/78 and he has a normal CrCl.
His urine has a bland sediment with oval fat bodies, fat casts and 3+ proteinuria
What do you see on microscopy? |
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Definition
Nephrotic syndrome with bland sediment in young asian males that are normotensive and have preserved renal function suggests MINIMAL CHANGE.
Treat with Steroids, and if no response, give Cyclophosphamide.
1) LM- normal glomeruli
2) IF- negative
3) EM- fusion of podocyte foot processes with cytoplasmic microcysts and podocyte microvilli transformation. |
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Term
| What is the pathogenesis/treatment of the nephrotic syndrome that presents with normal IF and EM findings in normotensive young males with preserved renal function? |
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Definition
1) Pathogenesis
- T-cell mediated attack of Podocytes leading to fusion and microvillus transformation.
- Disrupted negative charge distributed causes permeability to protein.
2) Treat with Steroids, or Cyclophosphamde is steroids don't work. |
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Term
A 45 year old african american male with a h/x of HTN presents with hematuria.
Microscopic evaluation shows the following results:
LM- Focal, Segmental glomerulosclerosis with hyaline insudates and glomerular tip lesions of capillary tuft as well as some glomerular hypertrophy.
IF- Focal segmental IgM and C3 in sclerotic areas
EM- Effacement of foot processes, cytoplasmic vacuolization, sclerotic loop with foamy cells and collagen fibers. No immune deposits
What is the path/treatment of this nephrotic syndrome? |
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Definition
Focal Segmental Glomerulosclerosis
1) Hyperfiltration injury, altered T-cell function and primary visceral epithelial injury may be involved.
2) May respond to steroids, but can also use cyclosporine, tacrolimus and mycophenolate mofetil.
- Use Ace-i and statins for HTN and hyperlipidemia. |
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Term
A 45 year old white male with a h/x of renal vein thrombosis presents.
UA shows heavy proteinuria, fatty casts.
Microscopy shows the following:
LM- Normocellular glomerulus with THICK capillary wall, epimembranous spikes, and train tracks. Silver stain shows thick BM
IF- Diffuse granular deposites outlining membrane with IgG and C3.
EM- Diffuse epimembranous (SUBEPITHELIAL) electron dense deposits.
What is the pathogenesis/treatment of this condition? |
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Definition
While male with signs of Nephrotic syndrome
Microscopy is consistent with stage IV Membranous Glomerulonephritis
1- Thickened capillary wall
2- Epimembranous spikes (new BM)
3-4- Train tracks
Pathogenesis
- Autoantibody to glomerular antigen (primary form) or "planted" antigen (secondary/drug-induced) leading to sub-epithelial IC deposits that activate complement.
Treatment is CONTROVERSIAL
(1/3 Rule)
- 1/3 spontaneous remission
- 1/3 partial remission/slow deterioration
- 1/3 progress to ESRD over 20 years |
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Term
What are teh following LM findings and in what context are they found?
1) Thickened capillary wall
2) Epimembranous spikes (new BM)
3-4) Train tracks |
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Definition
All found in Membranous Glomerulonephritis, which is the most common idiopathic nephrotic syndrome in caucasian adults (Male dominance).
Remember, SUBEPITHELIAL DEPOSITS
1) Seen initially in stage 1, where there are only IC deposits
2) Symbolic of new BM being laid down. Spikes and deposits become new BM.
3-4) Replicated BM looks like "train tracks" |
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Term
| What is the pathogenesis of the most common cause of nephrotic syndrome in adults? |
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Definition
Diabetic Nephropathy (also most common cause of ESRD in USA)
Increased renal hyper-filtration and non-enzymatic glycosylation leads to hyaline arteriolsclerosis and damages BM. |
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Term
After finding the following microscopic findings, how would you proceed with treatment?
1) LM- Mesangial matrix expansion with marked nodular accumulation of mesangial matrix.
You also see striking PAS positivity, arteriolar hyaline sclerosis and arterial intimal thickening.
2) IF- nonspecific linear IgG staining and albumin
3) EM- Lamellar thickening of glomerular BM, mesangial matrix, lipid droplet, NO immune complex deposits |
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Definition
The LM gives it away, as this nodular glomerulosclerosis is "Kimmelsteil-Wilson lesion"
This is found in Diabetic Nephropathy (other mesangial expansion patter would be diffuse glomerulosclerosis).
1) Control Blood glucose (insulin)
2) BP control (ACe-i)
3) Smoking cessation
4) Control hyperlipidemia
5) Protein restriction. |
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Term
| What are the 2 major patterns of mesangial matrix expansion seen in Diabetic Nephropathy? |
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Definition
1) Nodular Glomerulosclerosis- Nodular accumulation of mesangial matrix- KIMMELSTEIL-WILSON lesion
2) Diffuse Glomerulosclerosis |
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Term
The following microscopic findings are seen.
LM: Positive congo red staining with green-bifringence
EM: Small non-branching fibrils in mesangial glomeruli
What are the 2 primary biochemical forms of the protein found in this disease? |
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Definition
Amyloidosis.
1) Amyloid of immunoglobin (Amyloid AL)- consisting of light chains and fragments of LC's called "Bence Jones Proteins"
2) Amyloid associated with chronic inflammatory states (Amyloid AA) |
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Term
| What does it mean if you see striking amyloid deposits in liver, spleen, kidneys and adrenals? |
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Definition
Secondary Amyloidosis!
Primary is found in heart, GI tract, skin, nerves and tongues. |
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Term
A patient presents with bone pain and a right-arm fracture. You find monoclonal immunoglobulin in his serum and urine.
On microscopy, you see the following
LM: Intraluminal protinaceous casts is distal nephron (may produce giant cell inflammation and tubular atrophy over time).
IF: confirms casts as light chains
What is the pathogenesis/treatment of this disease? |
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Definition
Myeloma Cast Nephropathy from Multiple Myeloma
1) Patients with multiple myeloma who produce unbalanced LC (Bence Jones protein that form insoluble casts in tubules.
2) Hydration, plasmapheresis and chemotherapy. |
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Term
A patient with nephrotic syndrome and asytomatic albuminuria gets a renal biopsy.
LM: congo-red negative and PAS positive in glomeruli and tubules, but not in vessels.
EM: granular, electron dense material
What is the course of treatment? |
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Definition
Light-Chain Deposition Disease (Kappa chain)
Kappa chain deposits will look like amyloid but will be congo-red negative and PAS positive.
Renal failure is the rule so with Melphalan and Prednisone (prevent deterioration of renal function, but HIGH MORBIDITY). |
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Term
Which Nephrotic syndrome has each of the following?
1) Segmental sclerosis
2) Silver stain- thick BM, spikes, train track
3) Normal glomeruli with fused foot processes on EM
4) Nodular sclerosis with KW lesion
5) Congo red-positive, green birefringence and fibrils on EM |
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Definition
1) Focal segmental glomerulosclerosis (FSGS)
2) Membranous glomerulonephritis
3) Minimal change
4) Diabetic nephropathy
5) Amyloidosis |
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