28. Acute nephritic syndrome. Acute renal injury. Flashcards
what is the pathophysiology of nephritic syndrome
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
what re the different causes of glomerulonephritis that can cause nephritic syndrome
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,
what are the typical signs and symptoms of nephritic syndrome ?
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
what is the general treatmnet of nephritic syndrome?
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
when is the onset of nephritic syndrome in acute post strep glomerulonephritis ?
seven to ten days after a streptococcal throat or
2-3 weeks after a skin infection (impetigo
post strep GN most commonly seen in
children of 3–12 years
what re the symptoms of post strep GN ?
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
DIAGNOSIS OF POST STREP GN?
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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)
treatment of post strep
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
what re the different types of membranoproliferative glomerulonephritis ?
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
what are the clinical features specific for membranoproliferative GN type 2
develop drusen - deposts within the bruch’s membrane and beneath the retinal epithelium = lipodystrophy =over time vision deteriorates , macular detachment
diagnosis of mebranoproliferative GN ?
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
treatment for MPGN?
monoclonal gammapopathy - plasma infusion
immune complex mediated MPGN
evaluated for virus or AI and be treated for that
and underlying disease
==== idiopathic immune complex mediated MPGN C3GN DDD are what is left ======== 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
why should membranoproliferative GN not be confused with membranous gn ?
both have basement membrane thickening however mebranoproliferative Gn there is also mesangium thickening
what is the etiology of aport syndrome ?
x linked dominant inheritance
can also be autosomal rececissev and autosomal dominant
more severe in males
defect in type 4 collagen
what re the clinical features in aport syndrome ?
often asymptomatic
sensorineural hearing loss
ocular - retinopathy and anterior lenticonus - CANT SEE
Nephritic syndrome
chronic kidney disease and ESRD between 16-35
WHAT AI STHE DIAGnosis for aport syndrome ?
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
what is the treatment for alport syndrome ?
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
what causes lupus nephritis
genetic predisposition - HLA-DR2 and HLADR3
genetic deficiency of classic pathway complement - C1q , c2, c4
what i the pathophysiology of lupus nephritis ?
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
other then nephritic syndrome what are the clinical manifestation of lupus nephritis?
joints - arthritis arthralgia
skin - molar rash - butterfly
raynaud phenomena
photosensitvity
Limbman sack endocarditis
Oral ulcers
non scarring species
diagnosis of SLE
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
what is the treatment for lupus nephritis ?
oral corticosteroids
immunosuppressants - mycophenolate and cyclophosphamide
ACE inhibitors
what is the pathophysiology of good pasture syndrome ?
abnormal plasma cell production of anti - GBM - against collagen type 4
attack the alveoli and glomeruli basement membrane
and activate the complement cascade
what are the clinical manifestations of good pasture syndrome
lungs antedate the kidney
hemoptysis
cough
dyspnea
nephritic syndrome symptoms
what is the diagnosis of good pasture’s disease ?
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
when is the peak incidence of good pasture syndrome ?
6-30 years
what is the treatmnet for good pasture syndrome ?
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
what is AKI ?
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
what is the etiology and classification of AKI ?
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
how to differential between prerenal ,intrinsic and post renal ?
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
Children with AIN clinical characteristics ?
rash, fever, arthralgias, eosinophilia, and pyuria with or without eosinophiluria.
Specific therapy for AIN includes
withdrawal of the drug implicated in causing the AIN. In addition, corticosteroids may aid in the resolution of the renal failure
what is hemolytic ureic syndrome ?
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).
who does hemolytic ureic syndrome occur in ?
mainly children under 5 years of age
what causes hemolytic uremic syndrome?
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
what are the clinical features of HUS?
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
what is the diagnosis of HUS ?
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
what is the treatment of HUS?
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
what is the complication of hus?
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
what is the diagnosis or intrinsic kidney injury ?
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
how can we treat post renal acute kidney injury ?
Postrenal: Remove outflow obstructions with Foley catheter insertion,
an indwelling bladder catheter, nephrostomy,
or stenting.
what is the cause of henoch scholen purpura ?
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
clinical features of henoch scholen purpura?
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
===== Kidneys IgAV nephritic syndrome or worst nephrotic syndrome ====== scrotal swelling, pain, and tenderness
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central and peripheral nervous system
headaches, seizures,
how can you diagnose henoch scholen purpura / iga vascultidis ?
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
what is the treatmnet for henoch scholen purpura ?
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
difference between henoch scholen purpura and iga nephropathy ?
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
