Major Glomerular Diseases Flashcards
Normal Function of the Glomerelus
layers of the glomerelus
Glomerelus: Role approx. 50-100 capillaires per glomerelus
- responsible for the filteration of the blood into the bowmans capsule (specifically into the filtrate)
- composed of fenestrated capillaries which allow for exchange of larger molecules (but not entire cells) so things like water, ions, sodium, glucose, urea) from teh blood into the filterate
- has a regulation system of the afferent and efferent arterioles to dictate the pressures within the glomereulus which aid in diffusion of molecules from high to low pressures/concentrations
3 layers
- fenistrated capillary endothelium
- basement membrane (attaches to the capillaries)
- podocytes: epithelial cells with foot processes that attach to the basement membrane
- podocytes allow for a size “gap” to exisit – things that are small enough to fit through will filter about of the high presssure capillary into the filtrate
- EXCEPT: the podocytes are negatveily charges – thus things with a negative charge (ALBUMIN, IgG & other proteins) wont pass through
is protein normally filtered through the golmereulus?
what proteins are normally found in the urine?
normally – a MINIMAL amount of protein is lost in the urine
such a small amount that its not picked up on urine dipstick
- average loss is approx. < 150- 160 mg/day (of 50 million)
- majority (85%) is reuptaken in the PCT
- breakdown of proteins within the urine normally: albumin (40%), (40%) Tamm-Horsfall proteins (immune proteins of the glom.) & small amounts of the IgG and IgA proteins
proteinuria: is an abnormal increase in the amount of protein found within the urine
what is the spectrum of disease processes which are a result of a dysfunctioning glomerulus
key characterisics of each
NEPHROTIC v NEPHRITIC syndromes
nephOrtic — prOtein in the urine
nephrItic — Inflammation
Nephritic: inflammatory processes which are impacting the glomereulus: destroying the SIZE barrier
resulting in
- hypertension
- hematuria (RBC in blood)
- red blood cell casts
- pyuria (infection/inflammatory)
- MILD proteinuria (< 3 g/day)
- edema (think of withing dependent areas of the body)
- increased BUN and creatitine in the blood ( because poor GFR leads to back up)
Nephrotic: characterized by a loss of protein into the urine due to a destruction of the charge barrier – podocytes negative charge is impacted & then albumin and negatively charged protiens pass – damage to the basement membrane
resulting in…
- proteinuria ( > 3 g/day) (albumin)
- hypoalbuminemia (in the blood)
- edema (peripheral)
- hyperlipidemia & oval bodies (lipids) in urine (drop protein triggers lipoprotein production)
- “bland urine” meaning no cells (or minimal)
- hypercoagulable state (lost protein C & S regulators)
- hypertension
Types of Nephritic Syndrome
3 classes of the pathololgy
- post-infectious glomerulonephritis
- IgA Nephropathy
- Antiglomerular Basement Membrane Disease
Others
- lupus
- small vessel vasculitis (wagners granuloma)
- membranoproliferative glomerunonephritis
- mesangioproliferative glomerunonphritis
3 classes of how inflammation does this
- antibodies cause vasculitis (damange the membrane and thus the size barrier)
- antibodies DIRECTLY target the basement membrane of the glom.
- antibodies from other pathologies DEPOSIT into the glomerulus capillary bed & inflammation occurs – damange the barrier
Post-Infectious Glomerulonephritis
etiology
presentation
Etiology
- body fights an infection –> mounts an immune response with compliment (IgG response & the antibodies deposit in the kidney & damage)
- most commonly: group A beta-hemolyic strep infections cause this 1-3 WEEKS after an untreated infection (7-10 days) (strep or impetago)
- can also occur during an ongoing infection
other etiologies include…
- staph aureus
- viral (hep b/c, HIV, CMV, EBV)
- fungal, micobacteria, malaria, syphilis
affects: males, ages 2-14 years old most commonly
Presentation
- a nephritic syndrome by nature
- hematuria
- pyuria
- edema
- HTN
- RBC casts on urinalysis
- HA, malaise, anorexia, flank pain
- could have protein in the nephrotic range
Post-Infectious Glomereuralnephritis
- diagnosis
- treatment
Diagnosis
- serologic ASO titer : indicates they had a recent infection (not treated or partially) (and they tell you they were recently sick)
- serum compliment (C3) levels will be low (deposited in kidneys)
Kidney Biopsy: not often done but would see
- proliferative injury of the bx. (hypercellular)
- immunoflorescence IgG & C3 in mesangium and basement membrane
- electron microscopy: “humps” of subepitheal depostis of the inflammatory contents
Treatment
- if underlying infection still active: identify and treat
- supportive management
- salt retention, diuretics (for hypertension)
- renal failure is rare: most will resolve in 3-6 weeks
IgA Nephropathy - “Berger’s Disease”
Etiology
Presentation
one of the most common glomerulonephrititis worldwide
common in kids
Etiology
- immune complexs of the IgA deposit in the kidney and create inflammation & damange the size barrier
- Patho: a deficient O-linked glycosylation (mutation) in the IgA molecule that leads it to deposit in the kidney
- Primary reasons: genetic
- Secondary: hepatic cirrhosis causes, celiac, infection (HIV, CMV)
Presentation
- a single episode of gross hematuria, usually preceeeded by a URI or viral episode first (1-2 days before the hematuria)
- 1-2 days post illness help differentiates this from Post-infectious glmo. because that will take 1-3 weeks
IgA Nephropathy
Diagnosis
Treatment
Diagnosis
- no serological test will point you in the direction of IgA nephropathy – all complements will be normal
Kidney Biopsy
- Mesanigal cell proliferation showing focal glomerulonephritis
- on immunoflorescence: see diffuse IgA and C3 deposits
Treatment (1/3 will get better, 1/3 stay like this, 1/3 ESRD)
- tailored to the pts. risk of it progressing to ESRD
- ACE/ARB for those with proteinuria, HTN or declining renal function
- corticosteroids may help, but minimal evidence in stopping progression
- cytoxic agents: cyclophosphomide or mycophenolat mofetil
- transplant for those in ESRD
if it becomes a chronic situation –> normal renal function but they will have microscopic hematuria
Signs that they might decline into Renal Failure
- proteinuria > 1 g/day !! thats a lot….
- HTN
- abnormal GFR at time of presentation
- severe changes on biopsy: like tubulointersistial fiberosis or crescents (sclerosis)
Henoch-Schonlein Purpura
IgA nephropathy
etiology
- a small vessel leukocytosis vasculitis that results in IgA nephropathy as the IgA deposit in the vessel walls
- more common in kids
Presentation
- IgA deposit in the skin, and kidneys resulting in…
- palpable purpura (butt and lower back)
- arthraligas
- abdominal pain
- renal lesions (on biopsy) will appear just like normal IgA nephropathy
Antiglomerular Basement Membrane Disease (AGBM)
Etiology
Presentation
Etiology: a DIRECT auto-antibody which is developed to attack the basement membrane of the glomerelus
- however –> because the basement membrane of the glomerelus is so similar to that of the alveoli –> it can attack the lungs as well
Goodpasture’s syndrome: the lungs and kdieny effected
- think of younger men or older (bimodal)
- smokers!!!
- have hemoptysis (lung hemorrhage) & glomereular symptoms (hematuria)
Presentaion
- hemopytisis and hemorrahge of lungs (GP)
- glomereural symptoms (hematuria, edema, HTN, etc.)
AGBM
Diagnosis
Treatment
prognosis
Diagnosis
- detection of anti-GBM antibodies (most pts.)
- serum compliments will be normal
Kidney Biopsy: important aspect of finding out GPs
- focal and segmental necrosis – destorying the capillaries via proliferation
- crescent formation in the bowman’s space
- interstitial nephritis with fiberosis
- tubular atrophy
- linear IgG staining along the GBM when immunoflorescence
Treament (all together)
- 8-10 weeks of plasma exchange (daily for the first 2 weeks)
- induction therapy: prednisone and cyclophosphamide to immunosuppress
- refractory disease: Rituximab
kidney transplant: wait 6 months until the antibodies are no longer detected (as you titer the anti-GBM amoutn should decrease)
Prognosis
- if creascents > 50% on the biopsy with fiberosis
- serum creatitine > 6-7 (indicates the kdineys aren’t working well anymore)
- olgiuria
- needing diaylsis on presentation
Types of Nephrotic Syndromes
NephrOtic syndrome –> think protein in uria; but otherwise a bland urine sediment
- minimal hematuria, high protein, high lipids, edema, HTN, hypercoaguable
Types
- Minimal change disease (MCD)
- Membranous Nephropathy (MN)
- Focal Segmental Glomerulosclerosis (FSGS)
- Diabetic Nephropathy
others include
- Glomerular Deposition Diseases (Light Chain, renal amyloidosis, fibrillary- immunotactoid glomerulopathy)
Minial Change Disease
Etiology
Presentations
Etiology
- 80% of the nephrotic syndomres in kids is MCD ; can be in adults but not as common
- can be assocaited with hodgkin’s lymphoma, allergies, NSAID use
- can be occuring (and commonly presents as) post URI
- the problme here: an underlying autoimmune conditions in which the podocytes are damaged, flattened and no negative charge leaks protiens out
Presentation
- abrupt onset of edema around the eyes for kids
- nephrotic syndrome: HTN, frothy urine (proteins), hypercoaguable state
- acellular urine specimen
- may see microscopic hematuria
- may see atopy or allergic symptoms
- may have decreased renal function
kidney biopsy
- no obvious lesions
- microscopy: lost foot processes of teh epithelial cells with weakened gaps
Minimal Change Disease
Treatment
Relaspe
Treatment
- steroid use for 4-8 weeks!
- adults may need longer: 16 weeks ofr treatment
- immunosupressive drugs (cyclophosphomide, cyclosporines, rituximab) are reserved for refractory
Relapse
- can occur in 70-75% of kids
- early relapse = more common to relapse
- steroid resistance MCD can develop into FSGS
Membranous Nephropathy (MN)
Etiology
Presentation
Etiology
most common cause of primary nephrotic syndrome in adults
- adult disease primarily, rarely in kids
- predispose you to developing renal vein thrombosis
- antibodies (either podocyte antigen reactivty or others from secondary causes) deposit in the glomeruarl space, impact the podocytes and their charge –> leak protein into urine
Primary Causes :
- circulating antibodies (PLA2R) is majority
- type17A are the other antibody which can deposity
Secondary Causes:
- infection (Hep B, Hep C, endocarditis, syphilis)
- cancer (Carcinomas)
- drugs (NSAIDS, captopril)
- autoimmune (lupus)
- other systemic diseases
Presentation
- normal glomerural nephroric disease symptoms
- disease course is variable
