28. Acute nephritic syndrome. Acute renal injury.

Question 1

what is the pathophysiology of nephritic syndrome

Answer 1

inflammation of the glomerulus
damages the glomerular capillary basement membrane resulting in heamturea
forming red blood cell casts
when they passing the tubules they become dysmorphic RBC - acanthocytes

damaged podocytes - less than 3.5g proteinurea / day

leukocytes can also be leaked - sterile pyuria

there is reduced GFR - oliguria
leading to azotemia
and increase creation

reduced gfr - stimulations RAAS - hypertension

Question 2

what re the different causes of glomerulonephritis that can cause nephritic syndrome

Answer 2

acute proliferative glomerulonephritis :

1) In children, the most common cause of acute glomerulonephritis is post-streptococcal glomerulonephritis
caused by group A-beta hemolytic streptococci
Only a few strains of the bacteria are nephritogenic
(immune complex mediated)

non strep acute proliferative
2) meningococcemia, staphylococcal endocarditis (immune complex mediated) , and pneumococcal pneumonia

MEBRANOPROLIFERATIVE GLOMERULONEPHRITIS (occurs mainly in children)
3) viral infections mainly hepatitis B, hepatitis 

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2) crescentic/ rapidly progressive glomerulonephritis,
- Anti-GBM antibody-mediated disease (e.g., Goodpasture syndrome)
- immune complex nephritides : postinfectious glomerulonephritis,

lupus nephritis - MEBRANO PROLIFERATIVE GLOMERULONEPHRITIS
(occurs mainly in children)

IgA nephropathy,

Question 3

what are the typical signs and symptoms of nephritic syndrome ?

Answer 3

onset - abrupt

hematurea - tea/ cola coloured urine
hypertension - headache
edema - periorbital first
oliguria

azotemia related symptoms - fatigue , axterixis (flapping tremor) , decreased alertness and confusion

JVP - raised

USUALLY SELF LIMITING IN CHILDREN BUT MAY LEAD TO RAPIDLY PRORGRESSIVE

Question 4

what is the general treatmnet of nephritic syndrome?

Answer 4

low sodium diet
water restriction

if porteinure or hypertension - ACEI or ARB
is severe hypertension of edema - diuretics

severe renal insuffiency - hemodialysis and possibilities of transplantation

Question 5

when is the onset of nephritic syndrome in acute post strep glomerulonephritis ?

Answer 5

seven to ten days after a streptococcal throat or

2-3 weeks after a skin infection (impetigo

Question 6

post strep GN most commonly seen in

Answer 6

children of 3–12 years

Question 7

what re the symptoms of post strep GN ?

Answer 7

pharyngitis - sore throat , tonsillitis 
non bullous impetigo 
erysipelas 
fever 
malaise 
Peritonsilar abcess

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nephritic syndrome - usually self limiting
but can go to rapidly progressing glomerulonephritis

Question 8

DIAGNOSIS OF POST STREP GN?

Answer 8

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Normocytic, normochromic anemia

Possibly elevated BUN and creatinine (often transient)

↑ Antistreptolysin-O titer (ASO) (particularly following streptococcal infection of the pharynx)

↑ Anti-DNase B antibody (ADB) titer (particularly following streptococcal infection of the soft tissue)

↓ C3 complement

Urinalysis: nephritic sediment (e.g., hematuria and RBC casts, mild proteinuria)

Ultrasound: enlarged kidneys

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Renal biopsy (not performed in most cases)
Indication: suspected rapidly progressive glomerulonephritis

Light microscopy:
Glomeruli are globally and diffusely enlarged
diffuse hypercellularity in mesangial and endothelial cells
infiltration of monocytes and polymorphonuclear cells.
all of this block the capillary

Immunofluorescent : IgG/M , C3

granular
garland pattern, the starry sky pattern, and the mesangial pattern

The starry sky pattern is an irregular, finely granular pattern with small C3 deposits on glomerular basement membrane This pattern is often seen in the early phase.

may turn into the mesangial pattern, which is characterized by granular deposition of C3 with or without immunoglobulin G. - closely related to resolving

sometimes deposits are large and densely packed and aggregate into a garlandlike pattern. These correspond to the humps on the subepithelial side of the glomerular capillary wall seen with electron microscopy
These types of deposits may persist for months and may be associated with the persistence of proteinuria and the development of glomerulosclerosis

Electron microscopy:
“humps” = dome shaped = subepithelial immune complexes (between epithelial cells and the glomerular basement membrane)

Question 9

treatment of post strep

Answer 9

for edema - low sodium , low protein diet , loop diuretics
hypertension - ACE inhibitors / arb
persisting strep infection - penicillin g bezathine
severe course of disease - glucocorticoids and temporary need for dialysis

Question 10

what re the different types of membranoproliferative glomerulonephritis ?

Answer 10

immune complex mediated - MPGN type 1 
- SLE 
by hep b or hep c (cyroglobulinemia) 
HBV
monoclonal gammopathy 
idiopathic 

complement mediated - type2 /dense deposit disease / C3F
NO ASSOCIATIO WITH IMMUNE COMPLEX UNLIKE TYPE 1 and 3

Type III
immune complexes and complements are found deposited in the subepithelial space

Question 11

what are the clinical features specific for membranoproliferative GN type 2

Answer 11

develop drusen - deposts within the bruch’s membrane and beneath the retinal epithelium = lipodystrophy =over time vision deteriorates , macular detachment

Question 12

diagnosis of mebranoproliferative GN ?

Answer 12

Sle
Ana titre ratio of 1:80
Anti phospholipid antibodies - 
Anti cardiolipi n antibody
Lupus anticoagulant
Anti B2 GPI anybody

Complement- low c3 and c4

Specific antibody
Anti dsDNA anybody

Anti sm anybody

Leukocytosis
Thrombocytopnea
HEMOLYTIC anemia r

——-

BOTH NEPHROTIc AND NEPHRITIC SYNDROME

renal biopsy and light microscopy

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LM with H&E or PAS stain shows mesangial ingrowth, which leads to thickening and splitting of the glomerular basement membrane (tram-track appearance)
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IF
type 1 and 3 - IgG and C3
type 2 - C3 alone

hep C
granular depositionof IgM and C3 and BOTH kappa and lambda light chains
IgG may or may not be present
similar pattern for viruses

monoclonal gammapathies - monotype kappa or lambda light chains

autoimmune - full house pattern
gG and Igm , iGa , c1q , c3 , kappa andlambda light chains

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EM =
type 1
subendothelila and mesangial immune deposits and tram track appearance

type 2 -
DDD dense - more aggressive with high c3
ribbon like appearance of the subendothelilal space of the basement membrane and mesangium
INTRAMEMBRANOUS depositions

c3GN = not dense deposition and not intamembranous ,
light depositions in mesangium and sub endothelium

type 3 = sub endothelial and mesangial and subepithelial

Question 13

treatment for MPGN?

Answer 13

monoclonal gammapopathy - plasma infusion

immune complex mediated MPGN
evaluated for virus or AI and be treated for that
and underlying disease

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idiopathic immune complex mediated MPGN 
C3GN 
DDD
are what is left 
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normal GFR and non nephrotic range proteinurea = ACEI

GFR LOW /NEphrotic range proteinurea / severe histological changes - CRESCENTS /
progressive even with ACEI / elevated serum creatinine

prednisolone 1mg/kg for 12-16 weeks and ACEI

add cyclophosphamide if no response for three to six months

no response to cyclo = stop it and go to trial with rituximab

rapidly progressive MPGN - glucocorticoids and cyclophospimde

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Glucocorticoids and rituximab
not good very effective in DDD

genetic mutation in complement pathway - inhibit of MAC - eculizumab

due to h defects - periodic infusion of fresh frozen plasma infusion

Question 14

why should membranoproliferative GN not be confused with membranous gn ?

Answer 14

both have basement membrane thickening however mebranoproliferative Gn there is also mesangium thickening

Question 15

what is the etiology of aport syndrome ?

Answer 15

x linked dominant inheritance
can also be autosomal rececissev and autosomal dominant
more severe in males

defect in type 4 collagen

Question 16

what re the clinical features in aport syndrome ?

Answer 16

often asymptomatic

sensorineural hearing loss

ocular - retinopathy and anterior lenticonus - CANT SEE

Nephritic syndrome
chronic kidney disease and ESRD between 16-35

Question 17

WHAT AI STHE DIAGnosis for aport syndrome ?

Answer 17

nephritic test

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skin biopsy - confirmatory - shows absence of collagen 4 alpha 5 chains

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renal biopsy

LM - mesangial cell proliferating and sclerosis

EM - basket weave appearance of the glomerular basement membrane , splitting and alternative irregular thinning and thickening

immunostaining - absence of type 4 collage in the basement mean

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molecular genetic testing

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audiometry
ophthalmic evalautaion

Question 18

what is the treatment for alport syndrome ?

Answer 18

ace / arb for porteinurea
reduce salt in your diet
diuretics

kidney transplant is the only definitive treatmnet
complication GB syndrome can occur due to newly developed collagen type 4 antigens

Question 19

what causes lupus nephritis

Answer 19

genetic predisposition - HLA-DR2 and HLADR3

genetic deficiency of classic pathway complement - C1q , c2, c4

Question 20

what i the pathophysiology of lupus nephritis ?

Answer 20

mesangial and/or subendothelial deposition of immune complexes (e.g., anti-dsDNA antibodies, anti-Sm antibodies) → expansion and thickening of mesangium, capillary walls, and/or glomerular basement membrane

Question 21

other then nephritic syndrome what are the clinical manifestation of lupus nephritis?

Answer 21

joints - arthritis arthralgia

skin - molar rash - butterfly
raynaud phenomena
photosensitvity

Limbman sack endocarditis

Oral ulcers
non scarring species

Question 22

diagnosis of SLE

Answer 22

ANA test >1:80
evaluate EULAR/ACR

serum protein - low c3 and c4

ANTIPHOSPHOLIPID ANTIBODIES - ANTICARDIOLIPIN ANTIBODIES
ANTI b2gpi antibodies
lupus anticoagulant

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SLE specific antibodies
ant-dsDNA
anti - Sm antibody

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lupus nephritis - kidney biopsy

Question 23

what is the treatment for lupus nephritis ?

Answer 23

oral corticosteroids

immunosuppressants - mycophenolate and cyclophosphamide

ACE inhibitors

Question 24

what is the pathophysiology of good pasture syndrome ?

Answer 24

abnormal plasma cell production of anti - GBM - against collagen type 4

attack the alveoli and glomeruli basement membrane
and activate the complement cascade

Question 25

what are the clinical manifestations of good pasture syndrome

Answer 25

lungs antedate the kidney
hemoptysis
cough
dyspnea

nephritic syndrome symptoms

Question 26

what is the diagnosis of good pasture’s disease ?

Answer 26

serum antibody -ELISA assay for circulating anti-GBM antibodies

renal biopsy immunofluorescence
prescence of anti GBM antibodies- IgG and complement (C3) along the basement membrane. Predominantly, subclass IgG-1
specifically showing a strong linear ribbon-like appearance

x ray/ ct - alveolar haemorrhages
A chest radiograph shows patchy parenchymal opacifications, which are usually bilateral and bibasilar. The apices and costophrenic angles are generally spared

Question 27

when is the peak incidence of good pasture syndrome ?

Answer 27

6-30 years

Question 28

what is the treatmnet for good pasture syndrome ?

Answer 28

may be critically ill on presentation - Urgent hemodialysis often is needed for standard indications, and intubation for respiratory failure

Upon diagnosis, patients should be started on prednisone, cyclophosphamide, and daily plasmapheresis

daily plasmapheresis is performed until anti-glomerular basement membrane antibodies are undetectable 1.5-times plasma volume on a daily basis for at least 5 days, followed by a change to alternate day for an additional 6-7 treatments. Replacement is usually with fresh-frozen plasma or 5% albumin

with steroid 6 months and 3 moths cyclophosphamide continuing months until full remission is achieved

Rituximab

f therapy is initiated early: full recovery of renal function
without treatmnet rapid progressive

Question 29

what is AKI ?

Answer 29

Acute kidney injury (AKI) (previously called acute renal failure) is characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately

Question 30

what is the etiology and classification of AKI ?

Answer 30

Pre-renal injury
Decreased true intravascular volume
= In children, gastroenteritis is the most common cause of hypovolemia and can result in pre renal AKI

adrenal diseases, central or nephrogenic diabetes insipidus, i burns, and in disease states associated with third space losses, such as sepsis, nephrotic syndrome,

Congenital and acquired heart diseases

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Intrarenal
Acute tubular necrosis (vasomotor nephropathy)

Rapidly progressive glomerulonephritis

HEMOLYTIC UREMIC SYNDROME - MOST COMMON CAUSE OF AKI in children

secondary to medications (eg, aminoglycosides, NSAIDs)

Acute interstitial nephritis (AIN) as a result of a reaction to a drug or due to idiopathic AIN. Children with
Medications commonly associated with AIN include methicillin and other penicillin analogs, cimetidine, sulfonamides

Renal artery thrombosis
Renal vein thrombosis

contrast nephropathy

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Postrenal
congenital malformation in the kidney and collecting system
Bilateral ureteral obstruction
posterior urethral valves, bilateral ureteropelvic junction obstruction or
bilateral obstructive ureteroceles

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intrinsic in neonates
cortical necrosis and renal vein thrombosis, occur more commonly in neonates
maternal drugs in utero that interfere with nephrogenesis such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and nonsteroidal anti-inflammatory drugs

Question 31

how to differential between prerenal ,intrinsic and post renal ?

Answer 31

urine osmolality, urine sodium concentration, the fractional excretion of sodium, and the renal failure index, have all been proposed to be used to help differentiate pre-renal injury from hypoxic/ischemic AKI

Renal tubules are working appropriately in pre-renal injury and are able to conserve salt and water appropriately, whereas, in vasomotor nephropathy, the tubules have progressed to irreversible injury and are unable to conserve salt appropriately

pre-renal injury the tubules respond to decreased renal perfusion by appropriately conserving sodium and water such that the urine osmolality is greater than 350 mosmol/l, (400-500 - older children)
urine sodium is less than 20-30mEq/l, (10-20)
and the fractional excretion of sodium is less than 2.5 percent (1percent)
Serum BUN:creatinine ratio > 20:1
Fractional excretion of sodium

Intrinsic
BUN:creatinine ratio < 15:1.

urine sediments
Hyaline casts

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intrinsic

urine osmolality is less than 350 mosmol/l,
the urine sodium is greater than 30–40 mEq/l,
and the fractional excretion of sodium is greater than 2.0%.

Muddy brown, epithelial, or granular casts (ATN)
RBC casts (glomerulonephritis) 
Fatty casts (nephrotic syndrome)

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post renal

urine sediment absent
urine osmolality - <350

Question 32

Children with AIN clinical characteristics ?

Answer 32

rash, fever, arthralgias, eosinophilia, and pyuria with or without eosinophiluria.

Question 33

Specific therapy for AIN includes

Answer 33

withdrawal of the drug implicated in causing the AIN. In addition, corticosteroids may aid in the resolution of the renal failure

Question 34

what is hemolytic ureic syndrome ?

Answer 34

thrombotic microangiopathy in which microthrombi, consisting primarily of platelets, form and occlude the arterioles and capillaries. These occlusions result in the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI).

Question 35

who does hemolytic ureic syndrome occur in ?

Answer 35

mainly children under 5 years of age

Question 36

what causes hemolytic uremic syndrome?

Answer 36

bacterial toxins, most commonly the Shiga-like toxin (verotoxin ) of enterohemorrhagic Escherichia coli (E. coli)
transmitted via contaminated fod

shiga toxin - shigella dysenteriae

strep pneumonia infection

Question 37

what are the clinical features of HUS?

Answer 37

diarrhoea illness commences for the past 5-10 days
bloody stools
dehydration

thrombocytopenia
- petechia , purpura
mucosal bleeding

micorangiopathic hemolytic anemia 
fatigue 
dyspnea 
pallor 
jaundice 

irritability

seizures occur

impaired renal function 
hematurea , protein urea 
oliguria 
anuria 
volume overload 

2) Atypical HUS:
• have a similar microangiopathic syndrome, only that they have a preceding or concomittend pneumonia

Question 38

what is the diagnosis of HUS ?

Answer 38

diarrhea and presence of toxin-producing e.coli have resolved by the time HUS is diagnosed

peripheral blood smear reveals microangiopathic hemolysis schistocytes

haematology 
reduced hemoglobin 
reduced haptoglobin 
increased indirect bilirubin 
increased reticulocytes 
Increased ldh 

coagulation profile
deceased platelets
normal or slightly elevated pt and aptt
increased FDP and D- dimer results

serum chemistry - increased BUN and creation

urinanalysis - hematurea and proteinurea

Question 39

what is the treatment of HUS?

Answer 39

Volume substitution → Early hydration during the diarrheal phase may lessen the severity of renal
insufficiency
isotonic hydration

• control of hypertension (not with diuretics or RAAS drugs!) → CCB such as amlodipine

Dialysis:
◦ 50%of patients require a period of dialysis
◦ Peritoneal dialysis is widely used for pediatric patients

Red blood cell transfusions

Transfuse platelets only if the patient has active bleeding ( should be avoided because they may add to the thrombotic microangiopathy)

• Antibiotics and antidiarrheal agents may increase the risk of developing HUS (—> lysis of bacteria and more release of toxins)

anti motility drugs not given

• Most children (>95%) with the classical HUS survive the acute phase and recover normal renal function

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atypical hus
plasma therapy +immunosuppresive therapy

eculizmab

renal +liver transplant

Question 40

what is the complication of hus?

Answer 40

CNS
Seizures
Paresis
Stroke

GI tract
Hemorrhagic colitis
Bowel necrosis, perforation, stricture
Peritonitis

Heart: ischemia and fluid overload

Pancreas: transient or permanent diabetes mellitus

Liver: hepatomegaly, transaminase elevations

Question 41

what is the diagnosis or intrinsic kidney injury ?

Answer 41

Markedly elevated serum CPK level

Hyperkalemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, hyperuricemia, and/or dyslipidemia (especially hypertriglyceridemia) may be seen.
Low Hb (anemia) due to decreased EPO

Urine test findings
Renal tubular epithelial cells or granular, muddy brown, or pigmented casts

Urine dipstick is positive for blood but negative for RBCs in rhabdomyolysis

Question 42

how can we treat post renal acute kidney injury ?

Answer 42

Postrenal: Remove outflow obstructions with Foley catheter insertion,
an indwelling bladder catheter, nephrostomy,
or stenting.

Question 43

what is the cause of henoch scholen purpura ?

Answer 43

occurs in less than 10 years!

preceding infection
Up to 90% of cases preceded by viral or bacterial infection 1–3 weeks prior

Most commonly an upper respiratory tract infection caused by group A Streptococcus [4]
GI infections also possible

Question 44

clinical features of henoch scholen purpura?

Answer 44

Skin: (∼ 100% of cases)

Symmetrically distributed, raised, erythematous macules or urticarial lesions that coalesce into palpable purpura

Most common sites: the lower extremities, buttocks,

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Joints:
arthritis/arthralgia, most common in the ankles and knees

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Gastrointestinal tract

Colicky abdominal pain (may be severe enough to mimic an acute abdomen)

Can cause intussusception

Bloody stools or melena

Nausea/vomiting

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Kidneys 
IgAV nephritic syndrome
or worst nephrotic syndrome 
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scrotal swelling, pain, and tenderness

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central and peripheral nervous system
headaches, seizures,

Question 45

how can you diagnose henoch scholen purpura / iga vascultidis ?

Answer 45

Serum chemistry - BUN and creatinine high

Complete blood cell count with differential
↑ Platelet count
Thrombocytopenia would indicate a condition other than IgAV.

Mild normochromic anemia may appear as a result of GI bleeding

increased wbc

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IgA in serum high
low complements
Strep infection - streptolysin O

skin biopsy - leukocytoclastic vasculitis with igA and C3 immune complex deposition in small vessels = hallmark

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nephritic urineanalysis

renal biopsy
lm - mesangial proliferation
IF -mesangial iga deposits c3 and fibrin

Question 46

what is the treatmnet for henoch scholen purpura ?

Answer 46

bad prognosis signs are - hypertension
proteinurea fre than 1g/24 hours
rapidly progressive crescentic glomerulonephritis

IgAV are self-limiting
only require supportive care (e.g., pain management)

Systemic glucocorticoids for severe abdominal pain not relieved by NSAIDs
IV fluids to maintain hydration

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renal

patients with isolated hematurea / persistent proteinurea >1mg/day
or no porteinurea
/ normal GFR / no signs of progressive disease / normal serum creatinin
general interventions to slow progression
ACE and ARB

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nephrotic range porteinurea despite ACE and ARB
renal biopsy with more severe histological changes but no chronic changes
rising creatinin
reduced GFR

therapy with prednisolone such as minimal change disease
and the following therapy for nephrotic syndrome

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progressive active disease
heamturea with increasing porteinurea and serum creating despite ace and arb and glucorticoids

two regimens used
IV methylprednisolone 0.5-1g/kg /day
for three consecutive days at the beginning months one , three and five
with alternating daily oral prednisone 0.5mg/kg for six months

avid pulse therapy
2mg/kg prednisone every other day for two months
with rapid taper to dose of 0.5mg/kg every other day for additional four months

still persistent

prednisone 1mg/kg for two three months with tapering down to maintenance of 10mg/day
and
cyclophosphamide 1.5mg/kg/day orally for three months

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crescentic glomerulonephritis
IV pulse glucocorticoids + cyclophosphamide

iv methylprednisolone 3 days followed by oral prednisolone for to to three months then slow taper to maintenance
with IV cyclophosphamide monthly for three months atleast

can use azathioprine
micophenolate

Question 47

difference between henoch scholen purpura and iga nephropathy ?

Answer 47

extrarenal clinical signs found only in HSPN

15 and 30 years for a diagnosis of IgAN, whereas HSPN is mainly seen in childhood

Nephritic and/or nephrotic syndromes are more often seen at presentation in HSPN.

HSPN has been described in association with hypersensitivity