5/6 Chronic Glomerulonephritis

Question 1

what are the classification of chornic glomerulonephrtis ?

Answer 1

minimal change disease = mostly in children

measngioproliefartive glomerulonephritis IgM

focal and segmnetal sclerosis and hyalinosis

mebranous glomerulonephrtis

idiopathic IgA berger = NEPHRITIC

Question 2

what is the diagnosis of minimal change disease ?

Answer 2

nephrotic syndrome =SELECTIVE ALBUMINUREA WITHOUT evidence of hypertension and hematuria - the only one with selective

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renal function is preserved

no changes when viewing kidney biopsy specimens under light microscopy,

Under immunofluorescence, there are no immunoglobulins or complement deposits

= hence minimal change disease

electron microscopy =
hallmarks of the disease were discovered.
diffuse loss of visceral epithelial cells foot processes podocyte effacement,
vacuolation, and growth of microvilli on the visceral epithelial cells, allowing for excess protein loss in the urine

Question 3

etiology of minimal change disease ?

Answer 3

unknown - idiopathic

Question 4

clinical presentation of minimal change disease ?

Answer 4

nephrotic syndrome

swellings that often occur suddenly, most prominent in the morning, initially covering the eyelids and the face, and later on spreading across the limbs, in the sacral region and can generalize to anasarca with leak in the body cavities.

abdominal discomfort due to ascitis , diarrhea

edema of scrotum

increased tendency for infection and thrombotic events

Question 5

what is the treatment for minimal change disease

Answer 5

everything for nephrotic syndrome

albumin infusion

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high dose methyl prednisolone replaced by by oral prednisolone
= good reposes then we taper it

if not effective add
cyclophosphamide/ cyclosporin - monitoring of bone marrow and gonadal toxicity

high dose of immunovenin if still not responsive

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ACE inhibitors to reduce protein

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statins

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direct and indirect anticoagulants

iv heparin , the end of the month switched to indirect anticoagulant (dabigartan)

Question 6

mesangioproliferative glomerulonephritis is classified as a ?

Answer 6

type 2 lupus nephritis

Question 7

what is the pathophysiology of mesangioproliferative GN?

Answer 7

Mesangial use endocytosis degrade circulating immunoglobulin.

This normal process stimulates mesangial cell proliferation and matrix deposition.

Therefore, during times of elevated circulating immunoglobulin (i.e. lupus / IgA nephropathy) increased number of mesangial cells and matrix

we can also find but not necessary to find IgM and C3 deposits in the mesangium which is why the disease is also called igm nephorpathy

Question 8

what is the diagnosis of mesangioproliferatve glomerulonephritis ?

Answer 8

immunoflorecence - igm and c3 deposits in mesangium

LM - varied mesangial proliferation affecting ALL glomeruli to the same extent

Question 9

what is the clinical presentation of mesangioporliferative glomerulonephritis

Answer 9

nephrotic syndrome
hematuria is established for majority of patients
igm positive have more nephrotic syndrome
HOWEVER igM negative have macroscopic hematourea

Question 10

what is the treatmnet of MSGN ?

Answer 10

pulse treatmnet with methylprednisolone

add cyclosphosphamide monthly pulses
or
if iGm positive - cytosporin a

immunovenin if still not responsive

then oral prednisone

anticoagulants such as IV heparin

Question 11

focal segmental glomeruloscelrosis is the most common what ?

Answer 11

most common cause of nephrotic syndrome in adults

esp african american and hispanic

Question 12

what is the characteristics of FSGS

Answer 12

it has subacute lesions , segmental sclerotic changes , poor prognosis and resistance to corticosteroid therapy

Question 13

what is the classification of FSGS?

Answer 13

primary = when no underlying cause is found =
role of circulating permeability factor
because FSCG rapidly occurs in graft of renal transplant , however if plasmaphoresis is done before transplant the disease is limited

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secondary = underlying cause is identified

presents with kidney failure

toxins = such as heroin , pamidronate

familial = mutatation in nephron and podocin

HIV infection

hypertension , DM and obesity causing glomerular hyper filtration = mechanical stress on podocytes

Question 14

what are the pathological variants of FSGS?

Answer 14

1 glomerulus with endocapillary hypercellularity involving at least 25% of the tuft and causing occlusion of the capillary lumen/lumina

collapsing variant = higher risk for ESRD = heavy proteinurea
one glomerulus segmnetal or global obliteration of the glomerular capillary by wrinkling and collapse of the glomerular basement membrane because of podocyte hypertrophy and hyperplasia

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glomerular tip lesions variant = low risk

at least 1 segmental lesion involving the tip domain (ie, the outer 25% of the tuft next to the origin of the proximal tubule

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cellular variant =
intermediate isk

perihilar variant :
of at least one glomerulus with perihilar hyalinosis with or without sclerotic lesions

not otherwise specified variant

Question 15

how do we diagnose focal segmental glomerulosclerosis ?

Answer 15

massive non selective porteinurea

microscopic hematurea in pronounced mesangial proliferation

progressive decrease in GFR

increase in serum urea and creatinine

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LM : segmental sclerosis and hyalinosis

IM : most commonly negative
maybe I’m , C1 and C3 inside the sclerotic regions

EM : effacement of podocyte foot process

Question 16

what is the clinical presentation of FSGS?

Answer 16

hypertension and deterioration of renal function - oligourea - usual find
nephrotic syndrome

Question 17

management of FSGS?

Answer 17

extremely important to differentiate the primary from the secondary because the secondary leads to more cases in ESRD , and to treate the underlying disease

ACE AND arb

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in primary forms
corticosteroids - prendisole
cycopphsophamide
cyclosporin a

anticoagulants

renal transplant has not been success due to frequent reoccurrence

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Question 18

what is the pathopsyiology of membranous glomerulonephritis ?
and clinical presentation?

Answer 18

immune complex in subeipthelium! - between podicytes and gbm

the antigens may be part of the basement membrane - which are M type phospholipase A2 receptor
or neutral endopeptidase -expressed in the podocyte surface lining the basement membrane

or deposited there from systemic circulation

immune complex forms the MAC

inflammation of the basement membrane , PODOCYTES

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initially, proteinuria may be mild, and nephrotic syndrome may develop at a later stage.
nephrotic syndrome

The swelling could appear without any other symptoms and later disappear spontaneously

Arterial hypertension and worsing of the renal function

Question 19

what re the causes for membranous glomerulonephritis ?

Answer 19

primary
caucasians
idiopathic - antigen targets

secondary
immune complex deposition by cationic bovine serum albumin seen in cows milk and beef protein

autoimmun - sle
infection such as - hep c , hep b , HIV , syphilus

drugs - captopril and nsaids
organic gold

lung carcinoma, colon carcinoma, lymphoma, leukemia

Question 20

diagnosis of membranous glomerulonephritis ?

Answer 20

High-grade non-selective proteinuria,
in a small percentage of patients there is a microscopic haematuria

Hypoproteinaemia with hypoalbuminemia and hyperlipidemia is observed.
Coagulation status shows a tendency to hypercoagulability

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serum c3 are usually low esp in case of viral hep c
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LM :
1) diffuse thickening of basement membrane
GBM appears to be spiked and holey appearance appearance - Swiss cheese).

em : spike and dome pattern of basement membrane
podocyte effacement
subepitheila deposits - as it progresses these deposits cleared and leave cavities - can then become sclerosed and hylainsed

IMF= granular deposition of immunoglobulin and complement along basement membrane

Question 21

what is the treatment of membranous glomerulonephritis ?

Answer 21

immunovenin

anti-proteinuric
ACE inhibitors or ARB’s

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ponticelli regiment :

Starts with a 3-day pulse of methylprednisolone cyclophsopamide alternating with corticosteroid (mixed results) such as prednisolone

On the second month, the corticosteroid treatment stops and the oral intake of cyclophosphamide or chlorambucil iniciated for one month.

Corticosteroids and cytostatics alternate for a total of 6 months

corticosteroid must always be combined with one of the mentioned above or these :

chlorambucil

cyclosporin

tacrolimus

rituximab

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Besides the Pontichelli regiment there is the pulse treatment with corticosteroids and cyclophosphamide that we treate of idiopathic nephrotic syndrome.

A very good effect in patients is the tacrolimus

spontaneous remission common and higher remission rates with anti proteinuria therapy

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progression - dialysis

Question 22

complication of membranous glomerulonephritis

Answer 22

more prone to thromboembolism than other nephrotic syndrome diseases

Question 23

what is the etiology berger disease ?

Answer 23

idiopathic
most likely upper respiratory tract infection or go infection triggered - isa antibodies form immune complex that are deposited in kidney (TYPE 3 HYPERSENTITIVTY)

secondary :
systemic disease - henoch
chrons ,
sjoren syndrome

neoplasma 0 giga monoclonal gammopathy , lung carcinoma
infectious toxoplasmosis

Question 24

what is the clinical features of berger disease ?

Answer 24

asymptomatic - microscopic hematurea
with
recurring epodes of gross hematurea may have flank pain

hypertension is initially absent but may develop

it may progress into rpgn or nephrotic syndrome

Question 25

what is the diagnosis of iga nephropathy ?

Answer 25

• perisitant microhematurea
  Dysmorphic erythrocytes with erythrocyte cylinders are found in the sediment

in flare ups or intercurrent infections - gross hematurea

low to moderate proteinurea mostly less than 2g/24

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or nephrotic syndrome findings
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GFR usually remains unchanged

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serum iga elevated

C3 levels are generally normal so is the rest of the complement panel

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renal biopsy - usually indicated only when severe progression f disease such as hypertension increases , creating levels increase
proteinurea

lm - mesangial proliferation

IMF : mesangial iga deposits
with C3
maybe also igG and ism

EM - mesangial immune complex deposits

Question 26

what is the treatmnet for berger disease ?

Answer 26

patients with recurrent macroscopic haematuria, recommendations include aggressive hydration.

patients with just isolated hematurea
- monitor kidney function and start treatmnet if progresses

symptoms usually resolve spontaneously for these patients

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persistence of proteinurea above 1g/24hr and hypertension -
acei and arb
polyunsaturated fatty acids
corticosteroids at a conventional dose for two years

pronounced nephrotic syndrome in histological variation, appropriate to administer corticosteroid pulse then conventional corticosteroid

for proteinuria below 1 g/24h, the arterial pressure should be maintained below 130/80 mmHg

With proteinuria above 1 g/24h it should not exceed 125/75 mmHg.

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severe or rapidly progressive = glucocorticoids plus ,cyclophosphamide / azathioprine

selective plasma plasmapheresis synchronized with cytostatic therapy.

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high chance of reoccurrence with renal transplant

Question 27

what is the pathopshyiology of isa nephropathy ?

Answer 27

iga depostion in mesangium

thought to produce mac

b lymphocytes also produce glycan specific antibody of the egg class directed at the abdonamlly gluycsilated igA1

Question 28

about 20 percent of isa can develop kidney failure and what is a good prognostic indicator of that ?

Answer 28

These 20% were usually with expressed high arterial pressure and proteinuria above 2 g/24 h or with nephrotic syndrome.