Nephrotic Syndrome Flashcards
Five features of nephrotic syndrome
Heavy proteinuria Hypoalbuminemia Hyperlipidemia Lipiduria (oval fat bodies + maltese cross) Edema
Five major clinical causes of nephrotic syndrome
Minimal Change Disease Focal segmental glomerulosclerosis Membranous glomerulopathy Diabetic glomerulosclerosis Amyloidosis
MCD: Pathogenesis
90% of nephrotic syndrome cases in kids 2-6 years. Disorder of the podocyte; leads to defect in glomerular permeability barrier. Increase in size of slit filters regulated by podocyte. (Circulating “permeability factors,” immune related)
MCD: Etiology
Unclear but mainly suspected immunologic mechanism: we see remissions w/ steroids or cytotoxic agents; T cell abnormalities; disease onset also associated w/ lymphoma in some patients.
Occasionally MCD can occur as drug rxn in pts w/ NSAIDS or lithium.
Nephrotic Syndrome Rx
Treat both primary disease (immune modulating) and symptoms!
Symptoms: Low sodium diet, loop diuretics
Statins for hyperlipidemia
ARBs/ACE i’s to induce remission of proteinuria + decrease BP
Anticoagulation in some for ^ clotting factors
MCD Gross pathology
Pale, lipid rich kidneys
due to nephrotic syndrome
MCD micropathology
“Nil” disease because minimal changes seen on light microscopy. Glomeruli look normal. No immune deposits. But can see proximal tubules stuffed w/ lipid materials
MCD treatment
HIGHLY responsive to steroids. 50% will never get recurrence.
Fogal Segmental Glomerulosclerosis (FSGS) cause
Podocyte disease; uncertain whether it represents a progressed MCD or if it’s a separate entity.
Note: Can be unresponsive to corticosteroid therapy
FSGS morphology/histology
It’s FOCAL, involves a specific subset of glomeruli. The uninvolved glomeruli demonstrate changes of MCD (normal by light microscopy w/ diffuse foot processes)
- Hyaline deposits (entrapped plasma proteins in areas of sclerosis)
- involves only a PORTION OF THE TUFT
- -> lesions can progress to global glomerulosclerosis
- IgM and C3 in sclerotic lesions
FSGS etiology
- Primary/idiopathic FSGS: Unclear, but we see foot process effacement, altered adhesion to GBM and increased permeability of the glomerulus that may be caused by circulating permeability factors
- Genetic: podocyte mutations
- Viral: HIV can actually infect these cells (give HAART. See tubular microcysts on microscopy)
- Drug induced: eg Heroine
- Adaptive FSGS: result of increased hemodynamic stress on glomerulus; ex: in obesity, reflux nephropathy, renal agenesis, any chronic renal disease. Common consequence of reduction in functioning nephrons during course of any renal disease. Hypertrophy of glomerulus can be adaptive initially but over time becomes maladaptive –> sclerosing
Membranous Glomerulopathy (MG) morphology
Not glomerulonephritis because there is no proliferation of inflammatory cell infiltration of the glomerulus.
Light microscopy: diffuse and global uniform thickening of GBMs
- ALL GLOMERULI affected uniformly!
- Spikes on GBM (silver stain)
- Bumps on GBM (trichrome red)
- Fluorescence: IgG and C3 dposits on peripheral GBM
MG clinical features
- Most common cause of NS in white adults
- ## insidious onset
MG etiology
- 60% of cases are primary, mediated by antibody to a specific podocyte antigen Phospholipase A2 receptor.
- 40% are secondary
4 causes of 2ndary MG
- Infections (hep B, C, syphilis, schistosomiasis, malaria)
- Autoimmune diseases (SLE, RA)
- Neoplasm (lung/breast/colon/stomach carcinoma)
- Meds (gold, Hg, D-penicillin)
- usually remit after fixing the underlying problem_
MG pathogenesis
Primary: AUTOIMMUNE. Binding of circulating antibody to podocyte antigen through in site immune complex formation in subepithelium.
HEYMANN NEPHRITIS is prototype.
–> antigen-antibody complex shed off clathrin-coated pits of podocyte into subepithelial space, forming deposits.
Secondary has similar process, but it’s likely that antigen is non-glomerular. Ex; viral antigens in hep B and C.
Renal vein thrombosis
Dangerous complication of nephrotic syndrome. Seen almost exclusively in pts w/ MG. Due to hypercoagulable state from increased hepatic synth of fibrinogen and coag factors.
Diabetic Nephropathy pathogenesis
Most common renal disease leading to dialysis and transplantation.
- Progressive thickening of capilary and arteriolar basement membranes (microangiopathy) which is present in every organ but reaches greatest severity in kidneys and retina.
- Excessive synthesis of collagenous proteins and glycoproteins from abnormal glucose metab.
- Leads to glycosylation of BM proteins and the formation of advanced glycation end products (AGE - can see w/ immunostain).
Diabetic nephropathy morphology
- thickening of basement membranes
- Can be diffuse or nodular
- nodular from exuberant increase in mesangial matrix, forms large nodules.
- basement membrane thickening and expansion. individual glomeruli are seen w/ increase in mesangial matrix (KW nodules), it’s uniform. you also have thickening of tubule basement membrane
- hyalinosis in glomerulus and arterioles
- can see glomerular microaneurysms
RX of membranous nephropathy
Conservative therapy Corticosteroids Alternating steroids/cytotoxics cyclosporine mycophenolate ACTH Rituximab
DM neph gross pathology
Enlarged kidney due to increase in all renal compartments
Stages of Diabetic renal disease
1: hyperfiltration
2: clinically silent
3. incipient nephropathy
4. overt nephropathy
5. ESRD
Hyalinosis
Insudation of plasma proteins into thickened basement membranes. Appear as waxy, homogenous, eosinophilic material containing focal lipid dropletx. Common in DM.
Can also see in intima or media or arterioles
Rx for proteinuria
ARB’s and ACE I’s
Renal Amyloidosis pathogenesis
Deposition of amorphous eosinophilic hyaline substance in tissues. Can be local or systemic in body.
- Two major forms are primary (AL) and secondary (AA);
Cause:
1) dysproteinemias (myeloma, B CEll lymphomas, macroglobulinemia, occult plasma cell dyscrasia): increased light chains (lambda tends to be particularly common myeloma)
2) chronic inflammatory or infectious states (TB, chronic bronchiectasis, osteomyelitis, RA, ankylosing spondylitis, IBS)
Amyloidosis Morphology and Clinical Features
May deposit in all four renal compartments (glomeruli, vessels, tubular basement membranes, interstitium)
- As glomeruli incrreasingly replaced by amyloid deposits, there is a reduction in glomerular filtration rate, leading to renal insufficiency and CRF.
Amyloid gross path
large kidneys, pale and waxy
