Nephrotic Syndrome & Acute Glomerulonephritis in Childhood Flashcards
Nephrotic syndrome
It is a common kidney problem in childhood:
• It affects both males and female, with a higher (male or female ?)frequency in younger children and similar
prevalence in older children
• _____________ have the highest incidence of childhood nephrotic syndrome while steroid resistant NS is more common in _________ children
male
South Asians
black
What is Nephrotic Syndrome?
• It is a manifestation of _________ disease
characterized by _________ _________, massive _________, _________ and
_________.
glomerular
generalized oedema ; massive
proteinuria
hypoalbuminaemia ;
hypercholesterolemia.
_____________ and _______________ must be present to make a diagnosis of nephrotic syndrome
Hypoalbuminaemia & massive proteinuria
Hence NS is not a disease in itself but a
manifestation of a disease affecting the
_____________ of the ___________ ; this disease may be intrinsic to the kidney or extrinsic to it.
permselectivity
glomeruli
Oedema
• Usually ___________ .
• First noticed on the ________ (the ________ region) then the _______ and subsequently the ________ (resolution occurs in the same order).
The scrotum or labia may also be swollen
generalized. ; face
periorbital ; legs ;abdomen
Oedema
Initially the ________ oedema resolves while _________, but as the oedema increases the resolution when upright may no longer be remarkable
facial
upright
Oedema
Two theories explain the cause of the oedema:
– Underfill theory: the oedema is due to decreased ————— leading to increased __________ of __________ and __________ in the kidneys
– Overfill theory: the oedema is due to primary increased __________ of __________ in the kidneys
oncotic pressure ; absorption
sodium ; water
re-absorption ; sodium
Proteinuria
• The proteinuria is ________ or _________-range. it is mostly ________.
• On dipstick it is usually ≥______
massive; nephrotic
albumin; 3+
Massive or nephrotic-range proteinuria is defined as
– >_______mg/m2/24hr or
– >____mg/m2/hr or
– urine protein : creatinine ratio >____
1000
40
2
The proteinuria is due to increased permeability of the glomeruli to albumin:
• The increased permeability may be due to
– (a) an unknown circulating factor induced by a disorder of __________________ (most common reason) or
– (b) _________ abnormality of the __________ due to ________ disorders
– The increased urinary loss of albumin results in hypoalbuminaemia (serum albumin <_____g/dl)
T cell immunity
structural; glomeruli; genetic
2.5
The _________ is the major determinant of
glomerular permeability
podocyte
Hypercholesterolemia
• _______________ and _______________ are elevated
• Hypercholesterolemia is serum cholesterol >____mmol/l or >______mg/dl
Both triglycerides
cholesterol
5mmol/l ;?200mg/dl
The hypercholesterolemia is due to
– Increased _________ of ____________ by the __________
– Decreased activity of __________________
synthesis ; lipoprotein
Liver
lipoprotein lipase
Increased risk of Infection
• Children with NS are at an increased risk of infection especially from ___________ organisms such as ___________, ___________.
The infections commonly include ———— , _________ and _________
encapsulated
streptococcal pneumoniae ; H. Influenzae.
sepsis ; cellulitis ; peritonitis
Increased risk of infection
This is due to
– Decreased ____________ from loss of __________ in urine, especially ________
– Functional ________
– Ascites & oedema
– Concomitant use of ___________ such as ___________, cyclophosphamide etc
opsonization ; complements
factor B ; hyposplenism
immunosuppressants ; steroids
Increased risk of thrombosis
• May manifest as ___________ ,
gangrene, deep vein thrombosis, renal vein
thrombosis or stroke
• The increased thrombosis is due to
– Increased serum levels of _________ : ____,____,____,_____
– Decreased serum levels of _________ such as _______,________ and ________
– Hypovolemia & immobility
pulmonary embolism,
procoagulants: factors II,
V, VII, VIII
anticoagulants
antithrombin III, protein C & S
Increased risk of acute kidney injury
• Commonly due to __________ of the
kidneys but may be due to renal vein
thrombosis, adverse effects of drugs such as ____________ or _________ or a co-manifestation of the underlying disease as a ______,________
hypoperfusion
ACE inhibitors ; ARB
MPGN ; FSGS
Classification of Nephrotic Syndrome
• Age at onset
(a) Congenital NS: occurring between ____________ of life: usually due to genetic disorders
(b) Infantile NS: occurring between ____________
(c) Childhood NS: Occurring from ____________ of life
0-3 months
4-11 months
12 months of life
Classification of Nephrotic Syndrome
• Due to disease intrinsic or extrinsic to the kidneys
(a) primary (idiopathic) NS: not due to ____________________.
Most common type of childhood NS; 90% of childhood NS in children aged 1-10 years
(b) Secondary NS: due to a systemic or extra-renal disease such as SLE, henoch-schonlein purpura, HBV, HCV, HIV,
lymphoma, sickle cell disease. They become more common as children get older.
to any systemic disease.
Classification of Nephrotic Syndrome
Histology
(a) Minimal change NS: __________ histologic form in children.
Normal renal histology on both light and immunoflourescent microscopy. On electron microscopy there is __________ of the __________ of the __________
(b) Focal segmental glomerulosclerosis: _________________ histologic form of childhood NS. Only 20-30% of children with FSGS are sensitive to
steroids
(C) __________ GN
(c) __________ glomerulonephritis
(d) __________ __________: _____ in childhood
commonest ; effacement
foot process ; podocytes
second commonest ; Membranoproliferative
Mesangioproliferative
Membranous nephropathy ; rare
Classification of Nephrotic Syndrome
• Response to steroids:
• Steroid __________ NS: most children have SSNS
• Steroid ___________ NS
Steroid sensitive
Steroid resistant
_______________ is the most important way of classifying NS
Response to steroids
_______________ is the most important way of classifying NS
Response to steroids
Minimal Change Nephrotic Syndrome
• Commonest histology on biopsy of children
• >90% of children with MCNS are steroid ————-
• MCNS can be differentiated clinically from other histologic forms of childhood NS by the the following:
– Age between _____
– __________ renal function
– __________ complement
– __________ of hypertension or pulmonary oedema
– __________ of extra-renal disease such as skin rash, joint pains, anaemia
– __________ of family history
– __________ of active urinary sediment e.g. red blood cell
casts
sensitive; 1-10yr
Normal; Normal; Absence; absence; absence; absence
Indications for Kidney Biopsy in Nephrotic Syndrome
Kidney biopsy is reserved for children with NS presenting with the following:
a. Age outside _________
b. Significant _________
c. Gross _________
d. _________ disease such as SLE, HSP, SCD
e. _________tension
f. Persistently ______ serum complement levels
g. Steroid _________
h. With severe steroid toxicity
Generally kidney biopsy is done when it is not likely that the child has MCNS
1 yr to 10 yr
renal failure
hematuria
Systemic disease
Hypertension
low ; resistance
Differential Diagnosis of NS
• ________ ________ syndrome
• Acute or chronic ______________
• _______ failure
• Other causes of hypoalbuminaemia such as severe ___________________ , _________ enteropathy
• Severe ________ disease
Acute nephritic syndrome
kidney disease
Heart failure
protein-energy malnutrition
protein
losing enteropathy
liver disease
Treatment of Children with Idiopathic Childhood NS
Definitive Therapy
Drug of choice is __________; it is given to all children with idiopathic childhood NS
Dose: ____mg/m2 daily for 6 weeks
If the child goes into remission during this period then at the end of 6 weeks
prednisolone is reduced to _____mg/m2 alternate day for 6 weeks. If the child remains in remission then prednisolone is tapered slowly over the next 4 weeks.
Total duration of steroid: ______ weeks
Single daily dose is preferred to divided doses because side effects are less
prednisolone; 60mg/m2
40mg/m2 ; 16 weeks
Treatment of children with idiopathic childhood NS
Supportive Therapy
___________ antagonist or ___________ inhibitors
___________ & ___________ supplementation, c
H2 receptor antagonist
proton pump inhibitors
Vitamin D & calcium supplementation, m
Some common definitions
•Relapse: urinary protein excretion >______mg/m2/hr; ≥____ by dipstick on ____ consecutive days
•Remission: urinary protein excretion <____mg/m2/hr; nil or trace by dipstick for ___consecutive days
•Frequent relapses: _____ or more relapses in ________ of initial response; ____ or more relapses in any 12 mo
> 40mg/m2/hr; ≥3+ ; 3
<4mg/m2/hr; ; 3 consecutive days
two ; 6 months
4 or more relapses in any 12 mo
Some common definitions
•Steroid dependence: occurrence of _______________________ during steroid therapy or within ____________ of its
cessation
•Steroid resistance: failure to achieve _________ after ________ of daily therapy with _______________ at a dose
of _____mg/m2/day
2 consecutive relapses
2 weeks ; remission
8 weeks ; oral prednisolone
60mg/m2/day
Acute Glomerulonephritis (AGN)
• This is defined as a pathologic process characterized by _________ and _________ of glomerular cells(endothelial, mesangial and epithelial) and infiltration by ___________.
inflammation ; proliferation
neutrophils.
AGN
• The clinical spectrum of AGN may be ————- with or without __________ , __________ syndrome, nephrotic syndrome or rapidly progressing __________
• _____________________ is the most common
clinical presentation of AGN
hematuria ; proteinuria
acute nephritic syndrome
GN ; Acute nephritic syndrome
Causes of AGN
Post infective
(a)________________________
(b)Other bacteria such as other streptococci, staphylococcus
(c)Viruses such as cytomegalovirus, mumps, Epstein-Barr virus,
Hepatitis B, Hepatitis C virus
Non post infective
(a)Connective tissue disroders: ______
(b)Vasculitis: ______________________ , polyarteritis nodosa, wegener’s granulomatosis
Primary Kidney Disease
Such as _______ nephropathy, ______________ GN,
Idiopathic rapidly progressive GN
Group A beta hemolytic streptococcus
SLE ; Henoch-Schonlein purpura,
IgA nephropathy
Membranoproliferative GN,
Post Streptococcal AGN (PSAGN)
PSAGN & ________________ are used interchangeably
Acute nephritic syndrome
PSAGN is the (suppurative or non-suppurative?) complication of streptococcal
pharyngitis or skin infection
• AGN occurs __________ after pharyngitis or skin infection; the longer duration applies to skin infection.
•Some strains of streptococci are known to be more nephritogenic:
strain ____ (following pharyngitis)
strain ——- (following skin infection)
non-suppurative
1-3 weeks
strain 12
strain 49
In developing and tropical countries, ___________-associated PSAGN is more common than _________-associated PSAGN
• No known racial predilection
pyoderma
pharyngitis
Pathogenesis of PSAGN
•It is an ____________ reaction following ____________ infection
•The immunological reaction may be due to trapping of circulating ____________ in the ____________ or insitu formation of one (the later is more likely).
•The antigens in these complexes may be either components of streptococci or the glomeruli itself (___________).
•The two major streptococcal proteins now recognized as Ag in PSAGN are
_____________________________ (NSAP) and _______________________________ (NAPIr)
•These Ag activate complements commonly via the ___________ pathway leading to proliferation of glomerular cells and infiltration by non glomerular cells such as __________ and __________
The proliferation of glomerular cells leads to __________ of the glomeruli leading to reduced glomerular filtration, oedema, hypertension and oliguria. Damage to the _______ leads to hematuria with or without
proteinuria
immunological ; streptococcal
immune complexes ; glomeruli ; molecular mimicry
Nephritis Strain Associated Protein (NSAP) ; Nephritis Associated Plasmin Receptor (NAPIr)
alternate; neutrophils and monocytes
occlusion ; GBM
Clinical Features of AGN
•Most common presentation is acute nephritic syndrome: ________
(85%), ________, ________ (50-90%), ________ (~100%) and ________(PH2O2)
The oedema is first noticed on the face, and rarely associated with ________.
•The hypertension is due to ________ and may be complicated by ________ and ________
•The hematuria is usually _______scopic giving urine the ________ appearance.
• On microscopy there are numerous ______________ casts and ___________
red cells (characteristic)
•Acute kidney injury occurs in some children and may be severe
enough to require dialysis (rapidly progressive GN)
•Other non-specific features include malaise, lethargy, fever,
abdominal pain and headache
oedema; oliguria
hypertension ; hematuria
proteinuria ; ascites
water retention ;heart failure ; encephalopathy
microscopic ; smoky
red cell casts ; dysmorphic red cells
Prognosis
• The short term prognosis is _________ .
• The long term prognosis may not be as good as previously reported: prevalence of
_________ or _________ may be higher in
persons with PSAGN followed up for several years
excellent.
proteinuria or hematuria
